2009

Fourth National Report on Human Exposure to Environmental Chemicals
Fourth National Report on Human Exposure to 

Environmental Chemicals 

2009

Department of Health and Human Services 

Centers for Disease Control and Prevention 
Fourth National Report on Human Exposure to Environmental Chemicals i

 Contents

Contents

Introduction 1

What’s New in this Report 2

What’s Different in this Report 3

Data Sources and Data Analysis 4

Interpretation of Report Data: Important Factors 8

Chemical and Toxicological Information 9

Acrylamide 11

Acrylamide hemoglobin adducts 11

Glycidamide hemoglobin adducts 12

Cotinine 15

Cotinine 15

N,N-Diethyl-meta-toluamide (DEET) 19

N,N-Diethyl-meta-toluamide (DEET) 19

Disinfection By-Products (Trihalomethanes) 22

Bromodichloromethane 22

Dibromochloromethane (Chlorodibromomethane) 23

Tribromomethane (Bromoform) 24

Trichloromethane (Chloroform) 25

Environmental Phenols 27

Benzophenone-3 (2-Hydroxy-4-methoxybenzophenone) 28

Bisphenol A (2,2-bis[4-Hydroxyphenyl] propane) 30

4-tert-Octylphenol (4-[1,1,3,3- Tetramethylbutyl] phenol) 34

Triclosan (2,4,4’- Trichloro-2’-hydroxyphenyl ether) 38

Fungicides 40

Pentachlorophenol 40

ortho-Phenylphenol 43

Herbicides 46

Acetochlor 47

Acetochlor mercapturate 48

Alachlor 50

Alachlor mercapturate 51

Atrazine 53

Atrazine mercapturate 53

2,4-Dichlorophenoxyacetic Acid 57

Metolachlor 61

Metolachlor mercapturate 62

2,4,5-Trichlorophenoxyacetic Acid 64

Insecticides/Pesticides 67

Carbamate Insecticides 67

Carbofuran 68

Carbofuranphenol 68

Propoxur 71
 ii Fourth National Report on Human Exposure to Environmental Chemicals 

Contents

2-Isopropoxyphenol 72

Organochlorine Pesticides 75

Aldrin and Dieldrin 77

Aldrin 77

Dieldrin 79

Chlordane and Heptachlor 81

Oxychlordane 81

Heptachlor Epoxide 84

trans-Nonachlor 86

Dichlorodiphenyltrichloroethane (DDT) 89

p,p’-Dichlorodiphenyltrichloroethane (DDT) 89

p,p’-Dichlorodiphenyldichloroethene (DDE) 91

o,p’-Dichlorodiphenyltrichloroethane 93

Endrin 97

Hexachlorobenzene 100

Hexachlorocyclohexane 104

beta-Hexachlorocyclohexane 104

gamma- Hexachlorocyclohexane (Lindane) 106

Mirex 109

2,4,5-Trichlorophenol and 2,4,6-Trichlorophenol 112

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 117

Diethylphosphate (DEP) 120

Dimethylphosphate (DMP) 122

Diethylthiophosphate (DETP) 124

Dimethylthiophosphate (DMTP) 126

Diethyldithiophosphate (DEDTP) 128

Dimethyldithiophosphate (DMDTP) 130

Organophosphorus Insecticides: Specific Metabolites 134

Chlorpyrifos, Chlorpyrifos-methyl 135

3,5,6-Trichloro-2-pyridinol 135

Coumaphos 140

3-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one/ol 141

Diazinon 143

2-Isopropyl-4-methyl-6-hydroxypyrimidine 143

Malathion 146

Malathion dicarboxylic acid 146

Methyl Parathion, Ethyl Parathion 149

para-Nitrophenol 149

Pirmiphos-methyl 153

2-(Diethylamino)-6-methylpyrimidin-4-ol/one 154

Pyrethroid Pesticides 156

Cyfluthrin 159

4-Fluoro-3-phenoxybenzoic acid 160
Fourth National Report on Human Exposure to Environmental Chemicals iii

 Contents

Cyfluthrin, Cypermethrin, Permethrin 163

cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 163

trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 165

Deltamethrin 168

cis-3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid 169

Cyhalothrin, Cypermethrin, Deltamethrin, Fenpropathrin, Permethrin, Tralomethrin 172

3-Phenoxybenzoic acid 173

Metals 176

Antimony 176

Arsenic 180

Arsenic, Total 180

Arsenic (V) Acid 182

Arsenobetaine 184

Arsenocholine 186

Arsenous (III) Acid 187

Dimethylarsinic Acid 188

Monomethylarsonic Acid 189

Trimethylarsine oxide 190

Barium 193

Beryllium 196

Cadmium 199

Cesium 205

Cobalt 208

Lead 212

Mercury 218

Molybdenum 227

Platinum 230

Thallium 233

Tungsten 236

Uranium 239

Perchlorate 243

Perchlorate 243

Perfluorochemicals 247

Perfluorobutane sulfonic acid (PFBuS) 248

Perfluorodecanoic acid (PFDeA) 249

Perfluorododecanoic acid (PFDoA) 251

Perfluoroheptanoic acid (PFHpA) 251

Perfluorohexane sulfonic acid (PFHxS) 252

Perfluorononanoic acid (PFNA) 252

Perfluorooctanoic acid (PFOA) 253

Perfluorooctane acid (PFOS) 253

Perfluorooctane sulfonamide (PFOSA) 254

2-(N-Ethyl-perfluorooctane sulfonamido) acetic acid (Et-PFOSA-AcOH) 254
 iv Fourth National Report on Human Exposure to Environmental Chemicals 

Contents

2-(N-Methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) 255

Perfluoroundecanoic acid (PFUA) 255

Phthalates 258

Benzylbutyl Phthalate 262

Mono-benzyl phthalate (MBzP) 262

Dibutyl Phthalates 265

Mono-isobutyl phthalate (MiBP) 265

Mono-n-butyl phthalate (MnBP) 267

Dicyclohexyl Phthalate 270

Mono-cyclohexyl phthalate (MCHP) 270

Diethyl Phthalate 272

Mono-ethyl phthalate (MEP) 272

Di-2-ethylhexyl Phthalate 275

Mono-2-ethylhexyl phthalate (MEHP) 275

Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) 277

Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) 279

Mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) 281

Di-isononyl Phthalate 284

Mono-isononyl phthalate (MiNP) 284

Dimethyl Phthalate 287

Mono-methyl phthalate (MMP) 287

Di-(n-octyl) Phthalate 290

Mono-(3-carboxypropyl) phthalate (MCPP) 290

Mono-n-octyl phthalate (MOP) 292

Phytoestrogens 295

Daidzein 296

O-Desmethylangolensin 298

Enterodiol 300

Enterolactone 302

Equol 304

Genistein 306

Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153) 311

2,2’,4-Tribromodiphenyl ether (BDE 17) 312

2,4,4’-Tribromodiphenyl ether (BDE 28) 313

2,2’,4,4’-Tetrabromodiphenyl ether (BDE 47) 314

2,3’,4,4’-Tetrabromodiphenyl ether (BDE 66) 314

2,2’,3,4,4’-Pentabromodiphenyl ether (BDE 85) 315

2,2’,4,4’,5-Pentabromodiphenyl ether (BDE 99) 315

2,2’,4,4’,6-Pentabromodiphenyl ether (BDE 100) 316

2,2’,4,4’,5,5’-Hexabromodiphenyl ether (BDE 153) 316

2,2’,4,4’,5,6’-Hexabromodiphenyl ether (BDE 154) 317

2,2’,3,4,4’,5’,6-Heptabromodiphenyl ether (BDE 183) 317

2,2’,4,4’,5,5’-Hexabromobiphenyl (BB 153) 318
Fourth National Report on Human Exposure to Environmental Chemicals v

 Contents

Polychlorinated Biphenyls—Non-Dioxin-Like 321

2,4,4’-Trichlorobiphenyl (PCB 28) 322

2,2’,3,5’-Tetrachlorobiphenyl (PCB 44) 326

2,2’,4,5’-Tetrachlorobiphenyl (PCB 49) 327

2,2’,5,5’-Tetrachlorobiphenyl (PCB 52) 328

2,3’,4,4’-Tetrachlorobiphenyl (PCB 66) 330

2,4,4’,5-Tetrachlorobiphenyl (PCB 74) 332

2,2’,3,4,5’-Pentachlorobiphenyl (PCB 87) 334

2,2’,4,4’,5-Pentachlorobiphenyl (PCB 99) 336

2,2’,4,5,5’-Pentachlorobiphenyl (PCB 101) 338

2,3,3’,4’,6-Pentachlorobiphenyl (PCB 110) 340

2,2’,3,3’,4,4’-Hexachlorobiphenyl (PCB 128) 342

2,2’,3,4,4’,5’and 2,3,3’,4,4’,6-Hexachlorobiphenyl (PCB 138 & 158) 344

2,2’,3,4’,5,5’-Hexachlorobiphenyl (PCB 146) 346

2,2’,3,4’,5’,6-Hexachlorobiphenyl (PCB 149) 348

2,2’,3,5,5’,6-Hexachlorobiphenyl (PCB 151) 350

2,2’,4,4’,5,5’,-Hexachlorobiphenyl (PCB 153) 352

2,2’,3,3’,4,4’,5-Heptachlorobiphenyl (PCB 170) 354

2,2’,3,3’,4,5,5’-Heptachlorobiphenyl (PCB 172) 356

2,2’,3,3’,4,5’,6’-Heptachlorobiphenyl (PCB 177) 358

2,2’,3,3’,5,5’,6-Heptachlorobiphenyl (PCB 178) 360

2,2’,3,4,4’,5,5’-Heptachlorobiphenyl (PCB 180) 362

2,2’,3,4,4’,5’,6-Heptachlorobiphenyl (PCB 183) 364

2,2’,3,4’,5,5’,6-Heptachlorobiphenyl (PCB 187) 366

2,2’,3,3’,4,4’,5,5’-Octachlorobiphenyl (PCB 194) 368

2,2’,3,3’,4,4’,5,6-Octachlorobiphenyl (PCB 195) 369

2,2’,3,3’,4,4’,5,6’ and 2,2’,3,4,4’,5,5’,6-Octachlorobiphenyl (PCB 196 & 203) 370

2,2’,3,3’,4,5,5’,6-Octachlorobiphenyl (PCB 199) 371

2,2’,3,3’,4,4’,5,5’,6-Nonachlorobiphenyl (PCB 206) 372

2,2’,3,3’,4,4’,5,5’,6,6’-Decachlorobiphenyl (PCB 209) 373

Dioxin-Like Chemicals 377

Polychlorinated Dibenzo-p-dioxins 377

1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) 378

1,2,3,4,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) 380

1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) 382

1,2,3,7,8,9-Hexachlorodibenzo-p-dioxin (HxCDD) 384

1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin (OCDD) 386

1,2,3,7,8-Pentachlorodibenzo-p-dioxin (PeCDD) 388

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) 390

Polychlorinated Dibenzofurans 392

1,2,3,4,6,7,8-Heptachlorodibenzofuran (HpCDF) 392

1,2,3,4,7,8,9-Heptachlorodibenzofuran (HpCDF) 394

1,2,3,4,7,8-Hexachlorodibenzofuran (HxCDF) 396
 vi Fourth National Report on Human Exposure to Environmental Chemicals 

Contents

1,2,3,6,7,8-Hexachlorodibenzofuran (HxCDF) 398

1,2,3,7,8,9-Hexachlorodibenzofuran (HxCDF) 400

2,3,4,6,7,8-Hexachlorodibenzofuran (HxCDF) 402

1,2,3,4,6,7,8,9-Octachlorodibenzofuran (OCDF) 404

1,2,3,7,8-Pentachlorodibenzofuran (PeCDF) 406

2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) 408

2,3,7,8-Tetrachlorodibenzofuran (TCDF) 410

Coplanar Polychlorinated Biphenyls 412

3,4,4’,5-Tetrachlorobiphenyl (PCB 81) 412

3,3’,4,4’,5-Pentachlorobiphenyl (PCB 126) 414

3,3’,4,4’,5,5’-Hexachlorobiphenyl (PCB 169) 416

Mono-ortho-substituted Polychlorinated Biphenyls 418

2,3,3’,4,4’-Pentachlorobiphenyl (PCB 105) 418

2,3’,4,4’,5-Pentachlorobiphenyl (PCB 118) 420

2,3,3’,4,4’,5-Hexachlorobiphenyl (PCB 156) 422

2,3,3’,4,4’,5’-Hexachlorobiphenyl (PCB 157) 424

2,3’,4,4’,5,5’-Hexachlorobiphenyl (PCB 167) 426

2,3,3’,4,4’,5,5’-Heptachlorobiphenyl (PCB 189) 428

Polycyclic Aromatic Hydrocarbons 434

Fluorene 436

2-Hydroxyfluorene 436

3-Hydroxyfluorene 438

9-Hydroxyfluorene 440

Naphthalene 442

1-Hydroxynaphthalene (1-Naphthol) 442

2-Hydroxynaphthalene (2-Naphthol) 444

Phenanthrene 447

1-Hydroxyphenanthrene 447

2-Hydroxyphenanthrene 449

3-Hydroxyphenanthrene 451

4-Hydroxyphenanthrene 453

Pyrene 455

1-Hydroxypyrene 456

Volatile Organic Compounds (VOCs) 458

Benzene 458

Chlorobenzene 461

Chlorobenzene (Monochlorobenzene) 461

1,2-Dichlorobenzene (o-Dichlorobenzene) 462

1,3-Dichlorobenzene (m-Dichlorobenzene) 464

1,4-Dichlorobenzene (Paradichlorobenzene) 464

1,2-Dibromo-3-chloropropane (DBCP) 466

2,5-Dimethylfuran 468

Ethylbenzene 470
Fourth National Report on Human Exposure to Environmental Chemicals vii

 Contents

Halogenated Solvents 473

Dichloromethane (Methylene chloride) 473

Trichloroethene (Trichloroethylene) 474

Tetrachloroethene (Perchloroethylene) 475

Other Halogenated Solvents 478

Dibromomethane 478

1,1-Dichloroethane 479

1,2-Dichloroethane (Ethylene dichloride) 480

1,1-Dichloroethene (Vinylidene chloride) 481

cis-1,2-Dichloroethene 481

trans-1,2-Dichloroethene 482

1,2-Dichloropropane 482

1,1,1-Trichloroethane (Methyl chloroform) 483

1,1,2-Trichloroethane 483

1,1,2,2-Tetrachloroethane 484

Tetrachloromethane (Carbon tetrachloride) 484

Hexachloroethane 487

Methyl tert-butyl ether (MTBE) 489

Nitrobenzene 492

Styrene 494

Toluene 497

Xylenes 500

o-Xylene 500

m- and p-Xylene 501

Appendices 503

Appendix A. Procedure to Estimate Percentiles 503

Appendix B. Changes and Edits to Results Released in the Third Report 506

Appendix C. References for Biomonitoring Analytical Methods 507

Appendix D. Limit of Detection Table 511

Appendix E. Abbreviations 519
Fourth National Report on Human Exposure to Environmental Chemicals 1

 Introduction

Introduction

The Fourth National Report on Human Exposure to 

Environmental Chemicals, 2009 (the Report) provides an 

ongoing assessment of the exposure of the U.S. population 

to environmental chemicals by the use of biomonitoring. 

The Report is cumulative (containing all the results from 

previous Reports) and provides new data for years 2003-

2004. Data for 75 new environmental chemicals are 

included for the survey period 2003-2004. The Report

website http://www.cdc.gov/exposurereport is also the best 

source for the most recent update of available data.

In each survey period, most chemicals or their metabolites 

were measured in blood, serum, and urine samples from 

random subsamples of about 2500 participants from 

the National Health and Nutrition Examination Survey 

(NHANES) conducted by the Centers for Disease Control 

and Prevention’s (CDC’s) National Center for Health 

Statistics. NHANES is a series of surveys designed to 

collect data related to the health and nutritional status of 

the U.S. population. The blood, serum, and urine exposure 

measurements presented in the Report were made by CDC’s 

Environmental Health Laboratory (Division of Laboratory 

Sciences, National Center for Environmental Health) using 

mass spectrometry methods.

The term environmental chemical refers to a chemical 

compound or chemical element present in air, water, food, 

soil, dust, or other environmental media (e.g., consumer 

products). Biomonitoring is the assessment of human 

exposure to chemicals by measuring the chemicals or their 

metabolites in such human specimens as blood or urine. A 

metabolite is a chemical alteration of the original compound 

produced by body tissues. Blood, serum, and urine levels 

reflect the amount of a chemical that actually gets into 

the body by all routes of exposure, including ingestion, 

inhalation, and dermal absorption. The measurement of 

an environmental chemical in a person’s blood or urine 

is an indication of exposure; it does not by itself mean 

that the chemical causes disease or an adverse effect. 

Research studies, separate from these data, are required to 

determine which blood or urine levels are safe and which 

are associated with disease or an adverse effect. For blood, 

serum, and urine levels, the Report provides geometric 

means and percentiles of environmental chemicals by age 

group, gender and race/ethnicity. More in-depth statistical 

analysis, including multivariate analysis incorporating 

health endpoints and other predictive variables, is beyond 

the scope of this document. We encourage scientists to 

examine the data further through analysis of the raw data 

available at http://www.cdc.gov/nchs/nhanes.htm.

Public Health Uses of the Report

The overall purpose of the Report is to provide unique 

exposure information to scientists, physicians, and health 

officials to help prevent exposure to some environmental 

chemicals. Specific public health uses of the exposure 

information in the Report are

•	 To determine which chemicals get into Americans and 

at what concentrations.

•	 For chemicals with a known toxicity level, to determine 

the prevalence of people with levels above those 

toxicity levels (e.g., a blood lead level greater than or 

equal to 10 micrograms per deciliter [≥ 10 μg/dL]).

•	 To establish reference values that can be used by 

physicians and scientists to determine whether a 

person or group has an unusually high exposure. This 

information is especially helpful to identify population 

groups that merit further assessment of exposure 

sources or health effects.

•	 To assess the effectiveness of public health efforts to 

reduce exposure of Americans to specific chemicals.

•	 To determine whether exposure levels are higher 

among such potentially vulnerable groups as minorities 

and children.

•	 To track, over time, trends in levels of exposure of the 

population.

•	 To set priorities for research on human health effects.
 2 Fourth National Report on Human Exposure to Environmental Chemicals 

What’s New in this Report

What’s New in this Report

In this Fourth Report, 75 new chemicals are added for the 2003-2004 survey period and are listed in Table 1. The 

process for selection is described at http://www.cdc.gov/exposurereport/chemical_selection.html.

Table 1. Chemicals reported for the first time in the Fourth National Report on Human Exposure to Environmental 

Chemicals, 2009 

Acrylamide Adducts Phthalate Metabolite

Acrylamide Mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) 

Glycidamide 

Polybrominated Diphenyl Ethers (PBDE) and

Total and Speciated Arsenic Polybrominated Biphenyl 

Arsenic, Total 2,2',4-Tribromodiphenyl ether (BDE 17) 

Arsenic (V) acid 2,4,4'-Tribromodiphenyl ether (BDE 28) 

Arsenobetaine 2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) 

Arsenocholine 2,3',4,4'-Tetrabromodiphenyl ether (BDE 66) 

Arsenous (III) acid 2,2',3,4,4'-Pentabromodiphenyl ether (BDE 85) 

Dimethylarsinic acid 2,2’,4,4’,5-Pentabromodiphenyl ether (BDE 99) 

Monomethylarsonic acid 2,2',4,4',6-Pentabromodiphenyl ether (BDE 100) 

Trimethylarsine oxide 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE 153) 

2,2',4,4',5,6'-Hexabromodiphenyl ether (BDE 154) 

Disinfection By-Products (Trihalomethanes) 2,2',3,4,4',5',6-Heptabromodiphenyl ether (BDE 183) 

Bromodichloromethane 2,2',4,4',5,5'-Hexabromobiphenyl (BB 153) 

Dibromochloromethane (Chlorodibromomethane) 

Bromoform (Tribromomethane) Volatile Organic Compounds (VOCs) 

Chloroform (Trichloromethane) Benzene 

Chlorobenzene (Monochlorobenzene) 

Environmental Phenols 1,2-Dibromo-3-chloropropane (DBCP) 

Benzophenone-3 (2-Hydroxy-4-methoxybenzophenone) Dibromomethane 

Bisphenol A (2,2-bis[4-Hydroxyphenyl] propane) 1,2-Dichlorobenzene (o-Dichlorobenzene) 

4-tert-Octyl phenol (4-[1,1,3,3-Tetramethylbutyl] phenol) 1,3-Dichlorobenzene (m-Dichlorobenzene) 

Triclosan (2,4,4’-Trichloro-2’-hydroxyphenyl ether) 1,4-Dichlorobenzene (p-Dichlorobenzene, 

Paradichlorobenzene) 

Non-dioxin-like Polychlorinated Biphenyls 1,1-Dichloroethane 

2,2'3,5'-Tetrachlorobiphenyl (PCB 44) 1,2-Dichloroethane (Ethylene dichloride) 

2,2'4,5'-Tetrachlorobiphenyl (PCB 49) 1,1-Dichloroethene (Vinylidene chloride) 

2,2',3,3’,4,4’,5,5’,6,6'-Decachlorobiphenyl (PCB 209) cis-1,2-Dichloroethene 

trans-1,2-Dichloroethene 

Perchlorate Dichloromethane (Methylene chloride) 

1,2-Dichloropropane 

Perfluorinated Compounds 2,5-Dimethylfuran 

Perfluorobutane sulfonic acid (PFBuS) Ethylbenzene 

Perfluorodecanoic acid (PFDeA) Hexachloroethane 

Perfluorododecanoic acid (PFDoA) Methyl-tert-butyl ether (MTBE) 

Perfluoroheptanoic acid (PFHpA) Nitrobenzene 

Perfluorohexane sulfonic acid (PFHxS) Styrene 

Perfluorononanoic acid (PFNA) 1,1,2,2-Tetrachloroethane 

Perfluorooctane sulfonamide (PFOSA) Tetrachloroethene 

Perfluorooctane sulfonic acid (PFOS) Tetrachloromethane (Carbon tetrachloride) 

2-(N-Ethyl-Perfluorooctane sulfonamido) acetic acid Toluene 

(Et-PFOSA-AcOH) 1,1,1-Trichloroethane (Methyl chloroform) 

2-(N-Methyl-perfluorooctane sulfonamido) acetic acid 1,1,2-Trichloroethane 

(Me-PFOSA-AcOH) Trichloroethene (Trichloroethylene) 

Perfluorooctanoic acid (PFOA) m- and p-Xylene 

Perfluoroundecanoic acid (PFUA) o-Xylene 
Fourth National Report on Human Exposure to Environmental Chemicals 3

 What’s Different in this Report

What’s Different in this Report

The Fourth Report uses a new procedure to estimate 

percentiles when the percentile estimate falls on a value 

that is repeated multiple times (e.g., five results that all 

have the value 90.1). Percentiles for all three NHANES 

survey periods (1999-2000, 2001-2002, 2003-2004) have 

been re-computed by use of this improved procedure. Only 

slight differences should be noted when one compares the 

recomputations to previous releases of the Report. Details 

of this procedure are provided in Appendix A.

2003-2004 data for the organochlorine pesticides and 

the dialkyl phosphate organophosphorus insecticides 

are included in the Report. Data for other pesticides are 

included only for 1999-2000 and 2001-2002. 2003-2004 

data for these other pesticides will be provided on this 

website as soon as they are available, and these data will be 

included in the next release of the Report.

Some results reported previously have been changed or 

removed due to improvements in analytical measurement 

or recognition of an analytical issue (e.g., the presence of 

an interference) that produced results of inadequate quality. 

Affected analytes were serum beta-hexachlorocyclohexane 

for the 2001-2002 survey period; urinary 2,4-dichlorophenol 

and 2,5-dichlorophenol for the 1999-2002 survey periods; 

and polycyclic aromatic hydrocarbons (PAHs) for one or 

more of the 1999-2002 survey periods. Explanations for 

each change are provided in Appendix B.
 4 Fourth National Report on Human Exposure to Environmental Chemicals 

Data Sources and Data Analysis

Data Sources and Data Analysis

Blood, serum, and urine samples from NHANES

Biomonitoring measurements for the Report were made in 

samples from participants in NHANES. NHANES is a series 

of surveys conducted by CDC’s National Center for Health 

Statistics (NCHS). NHANES is designed to collect data 

on the health and nutritional status of the U.S. population. 

NHANES collects information about a wide range of healthrelated behaviors, performs physical examinations, and 

collects samples for laboratory tests. NHANES is unique 

in its ability to examine public health issues in the U.S. 

population, such as risk factors for cardiovascular disease. 

Beginning in 1999, NHANES became a continuous survey, 

sampling the U.S. population annually and releasing the 

data in 2-year cycles. The sampling plan follows a complex, 

stratified, multistage, probability-cluster design to select a 

representative sample of the civilian, noninstitutionalized 

population in the United States based on age, gender, and 

race/ethnicity.

The NHANES protocol includes a home interview followed 

by a standardized physical examination in a mobile 

examination center. As part of the examination component, 

blood is obtained by venipuncture from participants aged 

1 year and older, and urine specimens are collected from 

participants aged 6 years and older. Additional detailed 

information on the design and conduct of the NHANES 

survey is available at http://www.cdc.gov/nchs/nhanes.htm.

Environmental chemicals were measured in blood, serum, 

or urine specimens collected as part of the examination 

component of NHANES. The participant ages for which 

a chemical was measured varied by chemical group. 

Most of the environmental chemicals were measured in 

randomly selected subsamples within specific age groups. 

Randomization of subsample selection is built into the 

NHANES design before sample collection begins. Different 

random subsamples include different participants. This 

subsampling was needed to ensure an adequate quantity of 

sample for analysis and to accommodate the throughput of 

the mass spectrometry analytical methods.

Age groups and sample sizes for each exposure measurement 

are provided in each of the data tables. Blood lead and 

blood cadmium were measured in all participants aged 1 

year and older for all survey periods. Total blood mercury 

was measured in children aged 1-5 years and in women 

aged 16-49 years in 1999-2002. Total blood mercury and 

inorganic blood mercury were measured in all participants 

aged 1 year and older in 2003-2004. Urinary mercury was 

measured in women aged 16-49 years in 1999-2002. For 

the 2003-2004 survey, urinary mercury was measured in a 

random one-third subsample of participants aged 6 years 

and older. Serum cotinine and acrylamide adducts were 

measured in the entire NHANES sample for ages 3 years 

and older. Cotinine is reported only in nonsmokers.

Though most chemicals in urine were measured in a 

random one-third subsample of participants aged 6 years 

and older, there have been some exceptions. Urinary 

levels of herbicides, selected pesticides, and metabolites 

of organophosphate pesticides were measured in a random 

one-half subsample of children aged 6-11 years in 1999 and 

2000; in a random one-quarter subsample of people aged 

12-59 years in 1999; and in a random one-third subsample 

of people aged 12 years and older in 2000. Otherwise in 

2001-2002 and 2003-2004, these chemicals were measured 

in a random one-third subsample of participants aged 6 

years and older.

Dioxins, furans, polychlorinated biphenyls (PCBs), and 

organochlorine pesticides were measured in serum from 

a random one-third subsample of participants aged 12 

years and older in 1999-2000 and 2003-2004. In 2001-

2002, dioxins, furans, and coplanar PCBs were measured 

in a random one-third subsample of participants aged 20 

years and older, while organochlorine pesticides and other 

PCBs were measured in a random one-third subsample of 

participants aged 12 years and older.

Chemicals in the Report were selected on the basis 

of scientific data that suggested exposure in the U.S. 

population; the seriousness of health effects known or 

suspected to result from some levels of exposure; the need 

to assess the effectiveness of public health actions to reduce 

exposure to a chemical; the availability of a biomonitoring 

analytical method with adequate accuracy, precision, 

sensitivity, specificity, and throughput; the availability 

of adequate blood or urine samples; and the incremental 

analytical cost to perform the biomonitoring analysis for 

the chemical. The availability of biomonitoring methods 

with adequate performance and acceptable cost was a major 

consideration. Details on the prioritization process for 

scoring nominated chemicals and the resulting scores are 

available at http://www.cdc.gov/exposurereport/chemical_

selection.html.

Laboratory Analysis

The blood, serum and urine exposure measurements in 

the Report were made by CDC’s Environmental Health 

Laboratory (Division of Laboratory Sciences, National 

Center for Environmental Health). The analytical methods 

used for measuring the environmental chemicals or their 
Fourth National Report on Human Exposure to Environmental Chemicals 5

Data Sources and Data Analysis

metabolites in blood, serum, and urine were based on isotope 

dilution mass spectrometry, inductively coupled plasma 

mass spectrometry, or graphite furnace atomic absorption 

spectrometry. Laboratory measurements underwent 

extensive quality control and quality assurance review, 

including tolerance limits for operational parameters, the 

measurement of quality control samples in each analytical 

run to detect unacceptable performance in accuracy or 

precision, and verification of traceable calibration materials. 

References for the analytical methods used to measure the 

different chemicals are provided in Appendix C.

Data Analysis

Because the NHANES is a complex, stratified, multistage, 

probability-cluster design, sample weights must be used 

to adjust for the unequal probability of selection into the 

survey. Sample weights also are used to adjust for possible 

bias resulting from nonresponse and are post-stratified 

to U.S. Census Bureau estimates of the U.S. population. 

Data were analyzed using the statistical software package 

Statistical Analysis System (SAS) (SAS Institute Inc., 

2002) and the statistical software package SUDAAN 

(SUDAAN Release 8.0, 2001). SUDAAN uses sample 

weights and calculates variance estimates that account for 

the complex survey design. This design does not permit 

straightforward analysis of exposure levels by non-targeted 

strata such as locality, state, or region; seasons of the year; 

proximity to sources of exposure; or by use of particular 

products. Guidelines for the analysis of NHANES data are 

provided by NCHS at http://www.cdc.gov/nchs/nhanes/

nhanes2003-2004/analytical_guidelines.htm.

The Report presents descriptive statistics on the blood, 

serum, or urine levels for each environmental chemical. 

Statistics include unadjusted geometric means and 

percentiles with confidence intervals. In each table, results 

are given for the total population as well as by age group, 

gender, and race/ethnicity as defined in NHANES. For these 

analyses, race/ethnicity is categorized based on the sample 

design as Mexican American, non-Hispanic black, and nonHispanic white. Other racial/ethnic groups are sampled, 

but the proportion of the total population represented by 

other racial/ethnic groups is not large enough to produce 

valid estimates. Other racial/ethnic groups are included in 

estimates that are based on the entire population sample. 

Age groups are as described for each chemical in each data 

table. Gender is coded as male or female.

Units: For chemicals measured in urine, levels are 

presented two ways: per volume of urine and per gram 

of creatinine. Urinary levels are expressed both ways in 

the literature and used for different purposes. Levels per 

gram of creatinine (i.e., creatinine corrected) adjust for 

urine dilution. For example, if one person has consumed 

more fluids than another person, his or her urine output is 

likely higher and the urine more dilute than that of the other 

person. Interpretation of creatinine corrected results should 

also recognize that creatinine correction can also partially 

adjust for differences in lean body mass or renal function 

among persons.

For dioxins, furans, PCBs, and organochlorine pesticides, 

serum levels are presented per gram of total lipid and per 

whole weight of serum. These compounds are lipophilic 

and concentrate in the body’s lipid stores, including the 

lipid in serum. Serum levels reported per gram of total lipid 

reflect the amount of these compounds that are stored in 

body fat. Serum levels per whole weight of serum are also 

included to facilitate comparison with studies investigating 

exposure to these chemicals and reported levels in these 

units. Other mostly non-lipophilic chemicals measured in 

serum are expressed per liter of serum (e.g., micrograms per 

liter). Acrylamide and glycidamide adducts are expressed 

as the picomoles per gram of blood hemoglobin to which 

the adduct is bound.

Units of measurement are important. Results are reported 

here using standard units, generally conforming to those 

most commonly used in biomonitoring measurements. 

Useful unit conversions are shown in Table 2.

Geometric means: A geometric mean provides a better 

estimate of central tendency for data that are distributed 

with a long tail at the upper end of the distribution. This 

type of distribution is common in the measurement of 

environmental chemicals in blood or urine. The geometric 

mean is influenced less by high values than is the arithmetic 

mean. Geometric means were calculated by taking the log of 

each concentration and then computing the weighted mean 

of those log-transformed values using SUDAAN software. 

Ninety-five percent confidence intervals around this 

Unit Abbreviation Value

liter L

deciliter dL 10-1 liters

milliliter mL 10-3 liters

gram g

milligram mg 10-3 grams

microgram μg 10-6 grams

nanogram ng 10-9 grams

picogram pg 10-12 grams

femtogram fg 10-15 grams

Table 2. Units of Measurements and Abbreviations
 6 Fourth National Report on Human Exposure to Environmental Chemicals 

Data Sources and Data Analysis

weighted mean were calculated by adding and subtracting an 

amount equal to the product of a Student’s t-statistic and the 

standard error of the weighted mean estimate. The degrees 

of freedom of the t-statistic were determined by subtracting 

the number of strata from the number of primary sampling 

units (PSUs) according to the data available from the 

complex survey design. The standard error was computed 

with SUDAAN’s Proc Descript (design=WR), which uses 

Taylor series linearization for variance estimation. The 

weighted geometric mean and its confidence limits were 

then obtained by taking the antilogs of this weighted mean 

and its upper and lower confidence limits.

Limit of detection: The limit of detection (LOD) is the 

level at which the measurement has a 95% probability of 

being greater than zero (Taylor, 1987). The LODs for each 

chemical and survey period are provided in each data table 

and collectively in Appendix D. Concentrations less than 

the LOD were assigned a value equal to the LOD divided 

by the square root of 2 for calculation of geometric means. 

Assigning a value of the LOD divided by 2 made little 

difference in geometric mean estimates. If the proportion 

of results below the LOD was greater than 40%, geometric 

means were not calculated. For the same chemical, LOD 

values may change over time as a result of improvements 

to analytical methods. One possible consequence is that 

results may be reported as “< LOD” in the 1999-2000 data 

but be reported as a concentration value above the LOD in 

2001-2002 or 2003-2004 because the analytical method had 

improved. Thus, for proper interpretation of LODs in the 

data tables, care must be taken to use the LOD that applies 

to the survey period. Percentile estimates (see below) that 

are less than the LOD for the chemical analysis are reported 

as “< LOD.”

For most chemicals, the LOD is constant for each 

individual specimen analyzed. For dioxins, furans, PCBs, 

organochlorine pesticides, and a few other pesticides, each 

individual sample has its own LOD. These analyses have 

an individual LOD for each sample, mostly because the 

sample volume used for analysis differed for each sample. 

A higher sample volume results in a lower LOD (i.e., a 

better ability to detect low levels). For these chemicals, the 

maximum LOD value is provided in each data table and 

in Appendix D. The maximum LOD was the highest LOD 

among all the individual samples analyzed — typically, 

the mean LOD was about 40-50% of the maximum 

LOD. The same procedure for imputing values below the 

LOD in calculations of geometric means was used for 

chemicals with individual LODs for each sample. That is, 

concentrations less than the individual LOD were assigned 

a value equal to the individual LOD divided by the square 

root of 2. For chemicals that had individual sample LODs, 

a conservative rule was used for reporting percentiles: if 

any individual sample LOD in the demographic group was 

above the percentile estimate, the percentile estimate was 

not reported.

For chemicals measured in urine, separate tables are 

presented for the chemical concentration expressed per 

volume of urine (uncorrected table) and the chemical 

concentration expressed per gram of creatinine (creatinine 

corrected table). Geometric mean and percentile calculations 

were performed separately for each of these concentrations. 

LOD calculations were performed using the chemical 

concentration expressed per volume of urine, because this 

concentration determines the analytical sensitivity. For this 

reason, LOD results for urine measurements in each data 

table and in Appendix D are in units of weight per volume 

of urine. In the creatinine corrected tables, a result for a 

geometric mean or percentile was reported as < LOD if the 

corresponding geometric mean or percentile was < LOD in 

the table using weight per volume of urine. For example, if 

the 50th percentile for males was < LOD in the table using 

weight per volume of urine, it would also be < LOD in the 

creatinine corrected table.

For chemicals measured in serum lipid, separate tables are 

presented for the chemical concentration expressed per 

volume of serum (lipid unadjusted table) and the chemical 

concentration expressed per amount of lipid (lipid adjusted 

table). Geometric mean and percentile calculations were 

performed separately for each of these concentrations. 

LOD calculations were performed using the chemical 

concentration expressed per amount of lipid, because this 

concentration determines the analytical sensitivity. For this 

reason, LOD results for chemicals measured in each data 

table and in Appendix D are in weight per amount of lipid. 

In the lipid unadjusted tables, a result for a geometric mean 

or percentile was reported as < LOD if the corresponding 

geometric mean or percentile was < LOD in the lipid 

adjusted table.

Percentiles: Percentiles (50th, 75th, 90th, and 95th) are given 

to provide additional information about the shape of the 

distribution. Percentile estimates and 95% confidence 

interval estimates that are less than the limit of detection are 

indicated as <LOD in the data tables. In the Third National 

Report on Human Exposure to Environmental Chemicals,

weighted percentile estimates for 1999-2000 and 2001-

2002 data were calculated using SAS Proc Univariate and 

a proportions estimation procedure. A percentile estimate 

may fall on a value that is repeated multiple times in a 

particular demographic group defined by age, sex and 

race (e.g., in non-Hispanic white males 12-19 years old, 

five results that all have a value of 90.1). Since the Third 
Fourth National Report on Human Exposure to Environmental Chemicals 7

Data Sources and Data Analysis

Report, we have improved the procedure for estimating 

percentiles to better handle this situation. This improved 

procedure makes each repeated value unique by adding a 

unique negligibly small number to each repeated value. 

All data from 1999-2004 have been reanalyzed using this 

new procedure to handle situations where the percentile 

falls on a repeating value. Therefore, occasional percentile 

estimates may differ slightly in the current Fourth Report

than in the Third Report. Appendix A gives the details of 

the new procedure for estimating percentiles.

Taylor JK. Quality Assurance of Chemical Measurements. Lewis 

Publishers, Boca Raton (FL), 1987.
 8 Fourth National Report on Human Exposure to Environmental Chemicals 

Interpretation of Report Data: Important Factors 

Interpretation of Report Data: Important 

Factors

Research studies, separate from the Report, are required 

for determining whether blood or urine levels are safe 

or are associated with disease or adverse effects.

The measurement of an environmental chemical in a 

person’s blood or urine does not by itself mean that the 

chemical causes disease. Advances in analytical methods 

allow us to measure low levels of environmental chemicals 

in people, but separate studies of varying exposure levels 

and health effects are needed to determine whether such 

blood or urine levels result in disease. These studies must 

also consider other factors such as duration of exposure. 

The Fourth Report does not present new data on health 

risks from different exposures.

For some environmental chemicals, such as lead, research 

studies have given us a good understanding of the health 

risks associated with different blood lead levels. However, 

for many environmental chemicals, we need more research 

to assess health risks from different blood or urine levels. 

The results shown in the Fourth Report should help 

prioritize and foster research on human health risks that 

result from exposure to environmental chemicals. For more 

information about exposure to environmental chemicals, 

see the section later in this Report titled “Chemical and 

Toxicological Information”, which includes Internet 

reference sites.

Persistent and nonpersistent chemicals; use of 

percentiles; comparison of levels between groups

In this Report, except for some metals, most measurements 

in urine quantify chemical metabolites of nonpersistent 

chemicals (those that do not stay in the body a long time). 

Persistent chemicals (those that stay in the body for a long 

time) are usually measured in serum as the parent chemical.

The higher percentiles (75th, 90th, 95th) provided for each 

chemical convey useful information about the upper 

distribution and range of levels in the population. The 

95th percentile is helpful for determining whether levels 

observed in separate public health investigations or other 

studies are unusual.

Levels of chemicals are provided for the demographic 

groups as stratified by age, gender, and race/ethnicity. 

Demographic groups may not be equal in their composition 

with respect to other variables. CDC scientists publish 

separate scientific papers that make detailed comparisons 

of levels of chemicals in different demographic groups. 

See http://www.cdc.gov/exposurereport/ for a list of these 

papers.

Not all the chemicals in the Report are measured in the 

same individuals. Therefore, it is not possible to determine 

the fraction of all measured chemicals that were found at 

detectable levels in a given person.

Blood, serum, and urine levels of a chemical should not 

be confused with levels of the chemical in air, water, 

food, soil, or dust.

Concentrations of environmental chemicals in blood or 

urine are not the same as those in air, water, food, soil, or 

dust. For example, a chemical concentration of 10 μg/L 

in water does not produce a level of 10 μg/L in blood or 

urine. Blood or urine levels may reflect exposure from one 

or more sources, including air, water, food, soil, and dust.

Levels of a chemical in blood, serum, and urine are 

determined by how much of the chemical has entered the 

body through all routes of exposure, including ingestion, 

inhalation, and dermal absorption, and how the chemical 

is distributed in body tissues, transformed into metabolites, 

and eliminated from the body. Although the levels in the 

blood, serum and urine are measures of the amount of a 

chemical that has entered the body by all routes of exposure, 

the blood or urine level alone does not determine which 

exposure source or which route of exposure has occurred.
Fourth National Report on Human Exposure to Environmental Chemicals 9

 Chemical and Toxicological Information 

Chemical and Toxicological Information

The Fourth Report presents biomonitoring data on 

the exposure of the U.S. population to environmental 

chemicals. The measurement of an environmental chemical 

in a person’s blood or urine does not by itself mean that 

the chemical causes disease or adverse effects. Advances in 

analytical methods allow us to measure increasingly lower 

levels of environmental chemicals in people. Separate 

studies of varying exposure levels and health effects 

associated with these levels are required to determine 

whether blood, serum, and urine levels result in disease 

or adverse effects. The data and information in the Fourth 

Report do not establish health effects, nor do they create 

guidelines.

The Fourth Report provides descriptive information about 

each chemical or chemical group including uses, sources, 

and pathways of human exposure; disposition within the 

body; effects in animals or humans; and comparative blood 

or urine levels from other studies. The information in the 

text is provided as an overview, and it is not intended as 

a comprehensive review of each chemical. Generally, 

the information was compiled from many publicly 

available sources, including documents from national and 

international agencies and organizations, peer-reviewed 

scientific papers obtained from electronic searches, and 

public government documents. Statements are based on 

common general information, consensus agreement among 

experts, or concordance among multiple scientific papers 

and sources. Examples of common institutional sources 

of information include the Agency for Toxic Substances 

and Disease Registry, the U.S. Environmental Protection 

Agency, and the agencies of the World Health Organization. 

If available, generally recognized guidelines for blood or 

urine levels are presented in the text. For most chemicals 

in this Report, such guidelines are not available. Some 

guidelines are from federal agencies. One exception is 

the American Conference of Governmental Industrial 

Hygienists (ACGIH), a private organization that publishes 

biological exposure indices (BEIs) that “generally indicate 

a concentration below which nearly all workers may 

be repeatedly exposed without adverse health effects” 

(ACGIH, 2007). BEIs can be the blood or urine levels of a 

chemical that correspond to air-exposure limits for workers 

set by ACGIH. This organization notes that these values are 

for workers and that it is not appropriate to apply them to 

the general population. Information about the BEI level is 

provided here for comparison, not to imply that the BEI is 

a safety level for general population exposure.

American Conference of Government Industrial Hygienists 

(ACGIH). 2007 TLVs and BEIs. Cincinnati (OH). Signature 

Publications. 2007.

Where can I find more information?

For more information about environmental chemicals, refer 

to the list of web links below and the references given in the 

text. Links to nonfederal organizations are provided solely 

as a service to our readers. These links do not constitute an 

endorsement of these organizations or their programs by 

CDC or the federal government. CDC is not responsible 

for the content of an individual organization’s Web pages 

found at these links.

U.S. Governmental Sources

Centers for Disease Control and Prevention (CDC) 

Resources:

•	 National Center for Health Statistics (NCHS)

(http://www.cdc.gov/nchs)

o National Health and Nutrition Examination 

Survey (NHANES)

(http://www.cdc.gov/nchs/nhanes.htm)

•	 National Institute for Occupational Safety and Health 

(NIOSH)

o Databases and Information Resources

(http://www.cdc.gov/niosh/database.html)

o Registry of Toxic Effects of Chemical 

Substances (RTECS)

(http://www.cdc.gov/niosh/rtecs)

Agency for Toxic Substances and Disease Registry 

(ATSDR)

•	 Toxicological Profiles and ToxFAQs

(http://www.atsdr.cdc.gov/toxpro2.html)

•	 Toxic Substances Portal

(http://www.atsdr.cdc.gov/substances/index.asp)

U.S. Food and Drug Administration (FDA)

•	 Center for Food Safety and Applied Nutrition

(http://www.cfsan.fda.gov)

•	 National Center for Toxicological Research 

(http://www.fda.gov/nctr)

U.S. Environmental Protection Agency (EPA)

•	 Integrated Risk-Information System (IRIS)

(http://www.epa.gov/iris)

•	 Office of Prevention, Pesticides, and Toxic Substances 

(OPPTS)

(http://www.epa.gov/opptsmnt/index.htm)

U.S. Geological Survey (USGS)

•	 (http://www/usgs.gov)
 10 Fourth National Report on Human Exposure to Environmental Chemicals 

Chemical and Toxicological Information

U.S. Department of Agriculture (USDA)

•	 Food Safety and Inspection Service

(http://www.fsis.usda.gov)

National Institutes of Health (NIH)

•	 National Institute for Environmental Health Sciences 

(NIEHS)

(http://www.niehs.nih.gov)

•	 National Toxicology Program (NTP)

(http://ntp.niehs.nih.gov)

•	 National Library of Medicine (NLM), Toxicology 

Data Network

(http://toxnet.nlm.nih.gov)

Professional and Academic Organizations

American Conference of Governmental Industrial 

Hygienists (http://www.acgih.org/home.htm)

Association of Public Health Laboratories

(http://www.aphl.org)

International Occupational Safety and Health 

Information Center

•	 International Chemical Safety Cards

(http://www.ilo.org/public/english/protection/

safework/cis/products/icsc/dtasht/index.htm)

The EXtension TOXicology NETwork (EXTOXNET)

•	 Pesticide Information Profiles

(http://extoxnet.orst.edu/pips/ghindex.html)

World Health Organization

International Programme on Chemical Safety (IPCS)

(http://www.who.int/pcs)

•	 Monographs of the Joint FAO/WHO Meeting on 

Pesticide Residues (http://www.inchem.org/pages/

jmpr.html)

International Agency for Research on Cancer (IARC)

(www.iarc.fr)

•	 Monographs on the Evaluation of Carcinogenic 

Risks to Humans

(http://monographs.iarc.fr/ENG/Monographs/

allmonos90.php)
Fourth National Report on Human Exposure to Environmental Chemicals 11

 Acrylamide

Acrylamide

CAS No. 79-06-1

General Information

Acrylamide is a small organic molecule existing as a 

white crystalline powder in its pure state. Commercially, 

acrylamide is synthesized and used in the production 

of polyacrylamide polymer, gels, and binding agents. 

Polyacrylamides are useful water-compatible polymers 

used in water treatment, mineral processing, pulp and paper 

production, and in the synthesis or compounding of dye 

materials, soil conditioners, and cosmetics (NTP-CERHR, 

2005). Smaller scale applications of polyacrylamides 

include additives to paperboard used for food packaging, 

in permanent press fabrics, in some sealing grouts, as an 

absorbent in disposable diapers, and in some cosmetics. 

In 1997, 217 million pounds of acrylamide were produced 

commercially in the U.S. (NTP-CERHR, 2005). Since 

acrylamide has limited volatility and high water solubility, 

environmental releases of acrylamide can enter aquatic 

systems and soils where it degrades within days and does 

not bioaccumulate (U.S. EPA, 1994). Recently, it was 

discovered that acrylamide is formed when starch-rich 

foods, such as potatoes and some grains, are heated at 

temperatures used for frying and baking. Natural substances 

in the food are converted to acrylamide. Foods such as 

french fries and potato chips can contain acrylamide at 

levels up to 100 times greater than levels found in cooked 

fish or poultry (DiNovi and Howard, 2004; FAO/WHO, 

2005; FDA, 2006; Tareke et al., 2002).

People may be exposed to acrylamide from foods, smoking, 

drinking water, and from dermal contact with products that 

contain residual acrylamide. In the general population, the 

main source of exposure is from the diet, and an average 

daily intake is estimated as 0.3-2.0 μg/kg for adults (FAO/

WHO, 2005), although additional exposures from cosmetic 

products could add a similar amount (NTP-CERHR, 2005). 

Estimated intakes in children are about twice that of adults 

(DiNovi and Howard, 2004). These estimated intakes are 

hundreds of times lower than occupational exposures, 

and well below doses known to cause nerve damage or 

carcinogenicity in animals, but are generally above the U.S. 

EPA reference dose of 0.2 μg/kg/day (U.S. EPA, 2006). 

Animal studies indicate that acrylamide is well absorbed, 

widely distributed in tissues, and is either metabolized 

to the reactive epoxide, glycidamide, or to glutathione 

conjugates (Calleman et al., 1990; Fennell et al., 2005). 

Elimination occurs mainly in the urine as mercapturic acid 

conjugates. Acrylamide is not thought to accumulate in the 

body at environmental doses, but can covalently bind to 

form adducts with proteins.

In humans, acrylamide has produced upper airway irritation 

following inhalation of high levels, ocular and dermal 

irritation from direct contact with acrylamide containing 

materials, and peripheral neuropathy following chronic 

Acrylamide 

Geometric mean and selected percentiles of hemoglobin adduct concentrations (in pmol/g hemoglobin) for the U.S. population 

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 61.2 (58.1-64.4) 54.8 (52.8-57.7) 79.1 (73.5-85.6) 141 (124-155) 192 (168-217) 7101 

Age group 

3-5 years 03-04 59.4 (53.6-65.7) 58.6 (51.7-64.9) 75.7 (63.4-83.6) 90.6 (81.9-105) 108 (86.2-118) 350

6-11 years 03-04 58.6 (56.1-61.2) 57.3 (55.2-59.7) 71.0 (67.4-76.3) 86.8 (81.2-91.4) 98.8 (91.0-104) 769

12-19 years 03-04 57.4 (54.4-60.5) 54.5 (52.1-57.4) 70.7 (65.6-75.7) 100 (89.2-114) 132 (115-151) 1889 

20-59 years 03-04 66.2 (62.2-70.6) 57.9 (54.6-61.1) 96.1 (83.6-108) 163 (147-191) 223 (194-243) 2570 

60 years and older 03-04 50.1 (47.9-52.3) 46.5 (44.0-49.2) 61.0 (57.6-66.0) 96.1 (88.0-108) 141 (120-152) 1523 

Gender 

Males 03-04 63.9 (60.2-67.9) 57.0 (53.7-60.1) 85.5 (79.2-93.7) 152 (139-175) 220 (189-237) 3509 

Females 03-04 58.7 (55.9-61.5) 53.4 (51.8-55.9) 73.9 (69.5-80.6) 126 (111-142) 164 (147-191) 3592 

Race/ethnicity 

Mexican Americans 03-04 61.7 (58.7-64.9) 57.4 (54.4-60.4) 73.0 (69.2-77.3) 101 (95.0-115) 149 (125-179) 1792 

Non-Hispanic blacks 03-04 63.8 (57.3-71.1) 57.1 (52.1-64.1) 86.5 (74.6-104) 156 (120-203) 218 (172-271) 1874 

Non-Hispanic whites 03-04 62.4 (59.0-66.0) 55.3 (53.0-58.6) 82.2 (75.4-89.1) 146 (129-163) 197 (172-223) 2994 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 3.0. 
 12 Fourth National Report on Human Exposure to Environmental Chemicals 

Acrylamide

occupational exposures. Axonal degeneration, presynaptic 

nerve terminal binding (LoPachin, 2005), and neuronal DNA 

reactivity (Doerge et al., 2005) have been demonstrated in 

animals. Animal studies have shown that acrylamide can 

cause nerve damage (neuropathy), reproductive effects 

(reduced litter size, fetal death, male germinal cell injury, 

dominant lethality), and cancer (mammary, adrenal, 

thyroid, scrotal, uterine, and other sites) (FAO/WHO, 

2005; NTP-CERHR, 2005, Rice, 2005; U.S. EPA, 2006). 

Glycidamide has been shown to react with DNA (Doerge et 

al., 2005; Klaunig et al., 2005; Maniere et al., 2005; Puppel 

et al., 2005), to increase the unscheduled synthesis of DNA 

in tumor susceptible tissues (Klaunig et al., 2005), and 

to increase DNA reactivity when glutathione availability 

is reduced (Klaunig et al., 2005; Puppel et al., 2005). In 

addition, altered gene expression in testicular tissues (Yang 

et al., 2005) and sperm DNA adducts (Xie et al., 2006) have 

been demonstrated after acrylamide dosing. Acrylamide is 

clastogenic and can produce dominant lethal mutations, 

probably through its epoxide metabolite, glycidamide 

(NTP-CERHR, 2005; U.S. EPA, 2006). IARC classifies 

acrylamide as probably carcinogenic to humans. Additional 

information is available from U.S. EPA at: http://www.epa.

gov/iris/ and from the Food and Agriculture Organization 

of the United Nations and WHO at: http://www.who.int/

ipcs/food/jecfa/summaries/summary_report_64_final.pdf.

Biomonitoring Information

Acrylamide and glycidamide hemoglobin adducts 

(AHA and GHA, respectively) are markers of integrated 

acrylamide exposure over the preceding few months. 

Adducts are formed when either acrylamide or glycidamide 

react to form a permanent covalent bond with hemoglobin 

in the blood. After exposure ceases, levels of AHA adducts 

decline but may remain detectable for several months 

(Hagmar et al., 2001). AHA levels have been shown to 

increase with dietary intake (Hagmar et al., 2005, Vesper 

2005) and smoking (Bergmark, 1997; Schettgen et al., 

2002, 2004).

Levels of AHA and GHA reported the NHANES 2003-

2004 sample are generally similar to those seen in several 

previous studies of non-occupationally exposed subjects 

(Bergmark et al., 1997; Hagmar et al., 2005; Schettgen et 

al., 2002, 2003, 2004; Vesper et al., 2006, 2008), although 

different analytic methods can affect results. Several of 

these studies have shown that smokers have adduct levels 

that are three to fourfold higher than non-smokers; most 

non-smokers had levels less than about 100 pmol/gram 

hemoglobin. The degree of formation of the more toxic 

glycidamide and levels of GHA can be influenced by 

polymorphisms in several of the enzymes that metabolize 

acrylamide (Duale et al., 2009). Younger children may have 

slightly higher levels possibly due to increased intake of 

acrylamide-containing foods relative to body size (Dybing 

et al., 2005, Mucci et al., 2008).

Glycidamide

Geometric mean and selected percentiles of hemoglobin adduct concentrations (in pmol/g hemoglobin) for the U.S. population 

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 59.3 (56.7-62.1) 59.9 (57.6-62.5) 85.9 (81.6-90.5) 130 (120-141) 167 (153-181) 7278 

Age group 

3-5 years 03-04 71.6 (66.9-76.7) 71.1 (66.9-78.9) 94.7 (87.3-101) 118 (103-126) 126 (119-135) 411

6-11 years 03-04 74.1 (70.3-78.2) 75.0 (70.9-77.9) 95.6 (90.4-103) 121 (112-134) 141 (126-157) 784

12-19 years 03-04 55.4 (51.1-60.1) 59.2 (56.1-62.1) 79.2 (72.7-86.7) 113 (94.9-138) 146 (123-169) 1931 

20-59 years 03-04 62.5 (59.4-65.8) 60.9 (58.7-64.4) 90.7 (84.4-98.2) 143 (130-159) 187 (169-204) 2623 

60 years and older 03-04 45.5 (42.8-48.3) 46.8 (44.8-49.3) 65.2 (63.5-66.9) 96.4 (90.0-103) 129 (111-141) 1529 

Gender 

Males 03-04 59.5 (56.9-62.3) 59.4 (56.8-61.8) 87.1 (82.5-92.3) 136 (123-148) 174 (157-197) 3604 

Females 03-04 59.1 (56.0-62.5) 60.4 (57.5-64.0) 85.0 (80.2-90.0) 125 (116-135) 159 (143-175) 3674 

Race/ethnicity 

Mexican Americans 03-04 64.7 (61.2-68.4) 65.4 (61.1-70.1) 87.4 (81.5-94.4) 118 (110-129) 152 (135-170) 1841 

Non-Hispanic blacks 03-04 53.8 (51.1-56.7) 56.0 (52.4-59.7) 83.0 (75.2-91.5) 121 (108-140) 159 (129-204) 1954 

Non-Hispanic whites 03-04 61.1 (57.6-64.9) 60.7 (57.9-64.2) 87.5 (83.0-93.5) 136 (124-149) 172 (157-194) 3044 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 4.0. 
Fourth National Report on Human Exposure to Environmental Chemicals 13

 Acrylamide

In occupational settings, AHA levels were several fold 

to several hundredfold higher than levels in non-exposed 

non-smokers (Bergmark et al., 1993; Hagmar et al., 2001; 

Perez et al., 1999). AHA levels correlated with a neurologic 

symptom index and specific physiologic measures in an 

occupational setting and correlated better with clinical signs 

and symptoms than urinary excretion of the mercapturic 

acid metabolite (Calleman et al., 1994). In another study, 

symptoms of numbness or tingling in the extremities did 

not occur in exposed workers whose AHA levels were 

below 510 pmol/gram hemoglobin, and 39% of workers 

with levels above 1000 pmol/gram hemoglobin had these 

symptoms (Hagmar et al., 2001).

Finding a measurable amount of acrylamide or glycidamide 

hemoglobin adducts in blood does not mean that these 

levels of acrylamide or glycidamide hemoglobin adducts 

cause adverse health effects. Biomonitoring studies of 

acrylamide or glycidamide hemoglobin adducts provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels of acrylamide than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Bergmark E, Calleman CJ, He F, Costa LG. Determination of 

hemoglobin adducts in humans occupationally exposed to 

acrylamide. Toxicol Appl Pharmacol 1993;120(1):45-54.

Bergmark E. Hemoglobin adducts of acrylamide and acrylonitrile 

in laboratory workers, smokers and nonsmokers. Chem Res 

Toxicol 1997 Jan;10(1):78-84.

Calleman CJ, Bergmark E, Costa LG. Acrylamide is metabolized 

to glycidamide in the rat: evidence from hemoglobin adduct 

formation. Chem Res Toxicol 1990;3:406-412.

Calleman CJ, Wu Y, He F, Tian G, Bergmark E, Zhang S, et al. 

Relationships between biomarkers of exposure and neurological 

effects in a group of workers exposed to acrylamide.Toxicol Appl 

Pharmacol 1994;126(2):361-371.

DiNovi M and Howard D. The Updated Exposure Assessment 

for Acrylamide. 2004 Acrylamide in Food Workshop: Update - 

Scientific Issues, Uncertainties, and Research Strategies. April 

13-15, 2004, Chicago, Illinois.

Doerge DR, da Costa GG, McDaniel LP, Churchwell MI, Twaddle 

NC, Beland FA. DNA adducts derived from administration 

of acrylamide and glycidamide to mice and rats. Mutat Res 

2005;580(1-2):131-141.

Duale N, Bjellaas T, Alexander J, Becher G, Haugen M, Paulsen 

JE, et al. Biomarkers of human exposure to acrylamide and 

relation to polymorphisms in metabolizing genes. Toxicol Sci. 

2009 Jan 8. [Epub ahead of print]

Dybing E, Farmer PB, Andersen M, Fennell TR, et al. Human 

exposure and internal dose assessments of acrylamide in food. 

Food Chem. Toxicol 2005;43:365–410.

Fennell TR, Summer SCJ, Snyder RW, Burgess J, Spicer R, 

Bridson WE, et al. Metabolism and hemoglobin adduct formation 

of acrylamide in humans. Toxicol Sci 2005;85:447-459.

Food and Drug Administration (FDA). Survey data on acrylamide 

in food: individual food products. CFSAN/Office of Plant and 

Dairy Foods. July, 2006. Available at URL: http://www.cfsan.fda.

gov/~dms/acrydata.html#u1004. 2/3/09

Hagmar L, Tornqvist M, Nordander C, Rosen I, Bruze M, 

Kautiainen A, Magnusson AL, Malmberg B, Aprea P, Granath F, 

Axmon A. Health effects of occupational exposure to acrylamide 

using hemoglobin adducts as biomarkers of internal dose. Scand 

J Work Environ Health 2001;27(4):219-226.

Hagmar L, Wirfalt E, Paulsson B, Tornqvist M. Differences in 

hemoglobin adduct levels of acrylamide in the general population 

with respect to dietary intake, smoking habits and gender. Mutat 

Res 2005;580(1-2):157-165.

Joint FAO/WHO Expert Committee on Food Additives, 64th

Meeting: Summary and Conclusions (FAO/WHO). Rome, Italy, 

8-17 February 2005. Available at URL: http://www.who.int/ipcs/

food/jecfa/summaries/summary_report_64_final.pdf. 2/3/09

Klaunig JE, Kamendulis LM. Mechanisms of acrylamide induced 

rodent carcinogenesis. Adv Exp Med Biol 2005;561:49-62.

LoPachin RM. Acrylamide neurotoxicity: neurological, 

morphological and molecular endpoints in animal models. Adv 

Exp Med Biol 2005;561:21-37.

Maniere I, Godard T, Doerge DR, Churchwell MI, Guffroy M, 

Laurentie M, et al. DNA damage and DNA adduct formation in 

rat tissues following oral administration of acrylamide. Mutat 

Res 2005;580(1-2):119-129.

Mucci LA, Wilson KM. Acrylamide intake through diet and 

human cancer risk. J Agric Food Chem 2008;56, 6013-6019.

National Toxicology Program, Center for the Evaluation of 

Risks to Human Reproduction (NTP-CERHR). Monograph on 

the Potential Human Reproductive and Developmental Effects 

of Acrylamide. February, 2005. NIH Publication No. 05-

4472. Available at URL: http://cerhr.niehs.nih.gov/chemicals/

acrylamide/Acrylamide_Monograph.pdf. 2/3/09

Perez HL, Cheong HK, Yang JS, Osterman-Golkar S. 

Simultaneous analysis of hemoglobin adducts of acrylamide and 
 14 Fourth National Report on Human Exposure to Environmental Chemicals 

Acrylamide

glycidamide by gas chromatography-mass spectrometry. Anal 

Biochem 1999;274(1):59-68.

Puppel N, Tjaden Z, Fueller F, Marko D. DNA strand breaking 

capacity of acrylamide and glycidamide in mammalian cells. 

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7;580(1-2):3-20.

Schettgen T, Broding HC, Angerer J, Drexler H. Hemoglobin 

adducts of ethylene oxide, propylene oxide, acrylonitrile and 

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Schettgen T, Rossbach B, Kutting B, Letzel S, Drexler H, Angerer 

J. Determination of haemoglobin adducts of acrylamide and 

glycidamide in smoking and non-smoking persons of the general 

population. Int J Hyg Environ Health 2004;207(6):531-9.

Schettgen T, Weiss T, Drexler H, Angerer J. A first approach to 

estimate the internal exposure to acrylamide in smoking and 

non-smoking adults from Germany. Int J Hyg Environ Health 

2003;206(1):9-14.

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Analysis of acrylamide, a carcinogen formed in heated foodstuffs. 

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2/3/09.

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Vesper HW, Ospina M, Meyers T, Ingham L, Smith A, Gray 

JG, et al. Automated method for measuring globin adducts 

of acrylamide and glycidamide at optimized Edman reaction 

conditions. Rapid Commun Mass Spectrom 2006;20(6):959-64.

Vesper HW, Licea-Perez H, Meyers T, Ospina M, Myers GL. Pilot 

study on the impact of potato chips consumption on biomarkers 

of acrylamide exposure. Adv Exp Med Biol 2005;561:89-96.

Vesper HW, Slimani N, Hallmans G, Tjønneland A, Agudo A, 

Benetou V, et al. Cross-sectional study on acrylamide hemoglobin 

adducts in subpopulations from the European Prospective 

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Food Chem 2008;56(15):6046-53.

Xie Q, Sun H, Liu Y, Ding X, Fu D, Liu K. Adduction 

of biomacromolecules with acrylamide (AA) in mice at 

environmental dose levels studied by accelerator mass 

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Fourth National Report on Human Exposure to Environmental Chemicals 15

 Cotinine

Cotinine

CAS No. 486-56-6

Metabolite of nicotine (a component of tobacco smoke)

General Information

Tobacco use is the most important preventable cause of 

premature morbidity and mortality in the United States. 

The consequences of smoking and of using smokeless 

tobacco products are well known and include an increased 

risk for several types of cancer, emphysema, acute 

respiratory illness, cardiovascular disease, stroke, and 

various other disorders (U.S. DHHS, 2006). Persons 

exposed to secondhand tobacco smoke (environmental 

tobacco smoke [ETS]) may have adverse health effects that 

include lung cancer and coronary heart disease; maternal 

exposure during pregnancy can result in lower birth weight. 

Children exposed to ETS are at increased risk for sudden 

infant death syndrome, acute respiratory infections, ear 

problems, and exacerbated asthma (U.S. DHHS, 2004). 

The smoke produced by burning tobacco contains at least 

250 chemicals that are toxic or carcinogenic, and more than 

50 compounds present in ETS are known or reasonably 

anticipated to be human carcinogens (NTP, 2004).

Cigarettes contain about 1.5% nicotine by weight 

(Kozlowski et al., 1998), producing roughly 1–2 mg of 

bioavailable nicotine per cigarette (Benowitz and Jacob, 

Serum Cotinine 

Metabolite of nicotine (component of tobacco smoke) 

Geometric mean and selected percentiles of serum concentrations (in ng/mL) for the non-smoking U.S. population from the 

National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * .060 (<LOD-.080) .240 (.190-.302) 1.02 (.770-1.28) 1.96 (1.60-2.62) 5999 

01-02** .062 (.050-.077) < LOD .160 (.120-.220) .930 (.740-1.17) 2.20 (1.83-2.44) 6819 

03-04 .071 (.057-.089) .050 (.040-.070) .210 (.140-.310) .990 (.740-1.30) 2.17 (1.81-2.54) 6320 

Age group 

3-11 years 99-00 .164 (.115-.234) .110 (.066-.188) .500 (.260-1.16) 1.88 (.997-3.44) 3.44 (1.42-4.79) 1174 

01-02** .110 (.076-.160) .070 (<LOD-.130) .570 (.310-1.00) 2.23 (1.63-2.78) 3.23 (2.53-4.01) 1415 

03-04 .137 (.088-.213) .120 (.060-.220) .620 (.310-1.20) 2.04 (1.38-2.94) 3.35 (2.12-4.68) 1252 

12-19 years 99-00 .163 (.142-.187) .110 (.080-.163) .540 (.428-.660) 1.66 (1.50-1.95) 2.62 (2.09-3.39) 1773 

01-02** .086 (.059-.126) .050 (<LOD-.110) .350 (.190-.580) 1.53 (1.09-2.12) 3.12 (2.47-3.99) 1902 

03-04 .110 (.087-.139) .080 (.060-.120) .510 (.350-.670) 1.55 (1.21-1.93) 2.68 (1.96-4.02) 1783 

20 years and older 99-00 * .050 (<LOD-.061) .167 (.140-.193) .630 (.533-.820) 1.50 (1.28-1.66) 3052 

01-02** .052 (<LOD-.063) < LOD .110 (.090-.150) .630 (.470-.790) 1.42 (1.14-1.89) 3502 

03-04 .058 (.047-.071) .040 (.030-.050) .140 (.100-.200) .630 (.480-.840) 1.54 (1.26-1.92) 3285 

Gender 

Males 99-00 .124 (.106-.145) .080 (.060-.110) .308 (.220-.410) 1.20 (.950-1.49) 2.39 (1.66-3.22) 2789 

01-02** .075 (.059-.094) .050 (<LOD-.070) .230 (.160-.320) 1.17 (.960-1.49) 2.44 (2.23-2.99) 3152 

03-04 .087 (.070-.108) .060 (.040-.080) .280 (.190-.360) 1.23 (.910-1.68) 2.63 (2.09-3.19) 2937 

Females 99-00 * < LOD .180 (.148-.230) .850 (.600-1.14) 1.85 (1.33-2.45) 3210 

01-02** .053 (<LOD-.066) < LOD .120 (.090-.180) .710 (.540-.990) 1.77 (1.32-2.20) 3667 

03-04 .060 (.047-.077) .040 (.030-.060) .160 (.110-.260) .860 (.580-1.15) 1.76 (1.32-2.22) 3383 

Race/ethnicity 

Mexican Americans 99-00 * < LOD .140 (.110-.180) .506 (.370-.726) 1.21 (.900-1.70) 2241 

01-02** .060 (<LOD-.084) < LOD .160 (.080-.310) .730 (.480-1.19) 2.12 (1.19-2.96) 1878 

03-04 .054 (.043-.068) .030 (.020-.050) .120 (.080-.180) .690 (.430-1.00) 2.65 (1.87-3.57) 1707 

Non-Hispanic blacks 99-00 .175 (.153-.201) .131 (.111-.150) .505 (.400-.625) 1.43 (1.21-1.75) 2.34 (1.84-3.50) 1333 

01-02** .164 (.137-.197) .130 (.110-.160) .580 (.450-.770) 1.77 (1.55-2.05) 3.15 (2.50-4.30) 1602 

03-04 .144 (.104-.198) .120 (.080-.180) .520 (.350-.770) 1.54 (1.20-2.14) 2.77 (2.18-3.54) 1704 

Non-Hispanic whites 99-00 * .050 (<LOD-.073) .216 (.154-.312) .950 (.621-1.40) 1.92 (1.48-3.02) 1950 

01-02** .052 (<LOD-.068) < LOD .120 (.090-.180) .800 (.570-1.11) 1.88 (1.48-2.30) 2847 

03-04 .066 (.050-.087) .040 (.030-.070) .180 (.120-.300) .920 (.620-1.32) 2.01 (1.70-2.49) 2500 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, and 03-04 are 0.05, and 0.015, respectively. 

** In the 2001-2002 survey period, 83% of measurements had an LOD of 0.015 ng/mL, and 17% had an LOD of 0.05 ng/mL. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 16 Fourth National Report on Human Exposure to Environmental Chemicals 

Cotinine

1994; Hukkanen et al., 2005). Inhaling tobacco smoke from 

either active or passive (ETS) smoking is the main source of 

nicotine exposure for the general population. Up to 90% of 

the nicotine delivered in tobacco smoke is absorbed rapidly 

from the lungs into the blood stream (Armitage et al., 1975; 

Iwase et al., 1991). Mean air concentrations of nicotine in 

public spaces where smoking is allowed range from 0.3 

to 30 μg/m3

, with higher levels measured in restaurants 

and bars. In homes with one or more smokers, mean air 

concentrations typically range from 2 to 14 μg/m3 (NTP, 

2004). For an adult, the primary sources for ETS exposure 

are in a workplace where smoking occurs and in a residence 

shared with one or more smokers. Children are primarily 

exposed to ETS by parents and caregivers who smoke.

Nicotine can also be absorbed from the gastrointestinal 

tract and skin by using snuff, chewing tobacco, or 

chewing gum, nasal sprays, or skin patches that contain 

nicotine. Workers who harvest tobacco can be exposed 

to nicotine and become intoxicated as a result of the 

transdermal absorption of nicotine contained in the plant. 

The tobacco plant, Nicotiana tabacum, contains nicotine 

in larger amounts than other nicotine-containing plants, 

which include potatoes, tomatoes, eggplants, and peppers. 

Nicotine is also used commercially as an insecticide in its 

sulfate and alkaloid forms.

Once absorbed, nicotine has a half-life in blood plasma 

of several hours (Benowitz, 1996). Cotinine, the primary 

metabolite of nicotine, is currently regarded as the best 

biomarker in active smokers and in nonsmokers exposed 

to ETS. Measuring cotinine is preferred over measuring 

nicotine because cotinine persists longer in the body with 

a plasma half-life of about 16 hours (Benowitz and Jacob, 

1994). However, non-Hispanic blacks metabolize cotinine 

more slowly than do non-Hispanic whites (Benowitz et al., 

1999; Perez-Stable et al., 1998). Cotinine can be measured 

in serum, urine, saliva, and hair. Nonsmokers exposed to 

typical levels of ETS have serum cotinine levels of less than 

1 ng/mL, with heavy exposure to ETS producing levels in 

the 1–10 ng/mL range. Active smokers almost always have 

levels higher than 10 ng/mL and sometimes higher than 500 

ng/mL (Hukkanen et al., 2005).

Nicotine stimulates preganglionic cholinergic receptors 

within peripheral sympathetic autonomic ganglia and at 

cholinergic sites within the central nervous system. Acute 

tobacco or nicotine intoxication can produce dizziness, 

nausea, vomiting, diaphoresis, salivation, diarrhea, variable 

changes in blood pressure and heart rate, seizures, and death. 

Nicotine also indirectly causes a release of dopamine in the 

brain regions that control pleasure and motivation, a process 

involved in the development of addiction. Symptoms of 

nicotine withdrawal include irritability, craving, cognitive 

and sleep disturbances, and increased appetite.

The IARC and the NTP consider tobacco smoke to be a 

human carcinogen. NIOSH guidelines consider ETS to be 

a potential occupational carcinogen and recommend that 

exposure be reduced to the lowest feasible concentration. 

The Federal Aviation Administration has banned the 

smoking of tobacco products on both domestic and foreign 

air carrier flights in the United States. More information 

about the effects of smoking and nicotine can be found at: 

http://www.nida.nih.gov/researchreports/nicotine/nicotine.

html.

Biomonitoring Information

Serum cotinine levels reflect recent exposure to nicotine in 

tobacco smoke. Nonsmoking is usually defined as a serum 

cotinine level of less than or equal to 10 ng/mL (Pirkle et 

al., 1996).

The serum cotinine levels seen in the NHANES 2003-

2004 appear approximately similar to levels seen in the 

previous survey period (NHANES 2001-2002) for the total 

population estimates. Serum cotinine has been measured 

in many studies of nonsmoking populations, with levels 

showing similar or slightly higher results (depending on the 

degree of ETS exposure) than those reported in the previous 

NHANES (CDC 2005; NCI, 1999). Over the previous 

decade, levels of exposure to ETS appeared to decrease 

since geometric mean cotinine serum concentrations in 

nonsmokers had fallen by approximately 70% and the rate 

of detectable cotinine in nonsmokers fell from 88% to 43% 

when NHANES 1988–1991 was compared to NHANES 

1999–2002, (CDC, 2005; Pirkle et al., 2006). The overall 

decline in population estimates of serum cotinine likely 

reflects decreased ETS exposure among nonsmokers 

in locations with smoke-free laws (Pickett et al., 2006; 

Soliman et al., 2004). During each previous NHANES 

survey, the adjusted geometric mean serum cotinine was 

higher in children (aged 4–11 years) than in adults among 

both non-Hispanic blacks and non-Hispanic whites (Pirkle 

et al., 2006). Non-Hispanic blacks had higher serum 

cotinine concentrations compared with either non-Hispanic 

whites or Mexican-Americans. Higher levels of cotinine 

have previously been reported for non-Hispanic black 

smokers (Caraballo et al., 1998). Differences in cotinine 

concentrations among race/ethnicity and age groups may 

be influenced by pharmacokinetic differences as well as 

by ETS exposure (Benowitz et al., 1999; Hukkanen et al., 

2005; Wilson et al., 2005).

Biomonitoring studies of serum cotinine will help physicians 
Fourth National Report on Human Exposure to Environmental Chemicals 17

 Cotinine

and public health officials determine whether people have 

been exposed to higher levels of ETS than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research about exposure to ETS 

and about its health effects.

References

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PJ, Turner DM. Absorption and metabolism of nicotine from 

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Benowitz NL. Cotinine as a biomarker of environmental tobacco 

smoke exposure. Epidemiol Rev 1996;18:188-204.

Benowitz NL, Jacob P. Metabolism of nicotine to cotinine 

studied by a dual stable isotope method. Clin Pharmacol Ther 

1994;56:483-493.

Benowitz NL, Perez-Stable EJ, Fong I, Modin G, Herrera B, 

Jacob P III. Ethnic differences in N-glucuronidation of nicotine 

and cotinine. J Pharmacol Exp Ther 1999;291(3):1196-1203.

Caraballo R, Giovino G, Pechacek TF, Mowery PD, Richter PA, 

Strauss WJ, et al. Racial/ethnic differences in serum cotinine 

levels among adult U.S. cigarette smokers: the Third National 

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(GA): 2005.

Hukkanen J, Jacob III P, Benowitz NL. Metabolism and 

disposition kinetics of nicotine. Pharmacol Rev 2005;57(1):79-

115.

International Agency for Research on Cancer. IARC Working 

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allmonos90.php. 4/13/09

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Carcinog Risks Hum. Vol 83. Summary of Data Reported and 

Evaluation [online] 2004. Available at URL: http://monographs.

iarc.fr/ENG/Monographs/allmonos90.php. 4/13/09

Iwase A, Aiba M, Kira S. Respiratory nicotine absorption in 

non-smoking females during passive smoking. Int Arch Occup 

Environ Health 1991;63:139-43.

Kozlowski LT, Mehta NY, Sweeney CT, Schwartz SS, Vogler GP, 

Jarvis MJ, et al. Filter ventilation and nicotine content of tobacco 

in cigarettes from Canada, the United Kingdom, and the United 

States. Tob Control 1998;7:369-375.

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Environmental Tobacco Smoke: The Report of the California 

Environmental Protection Agency. Smoking and Tobacco 

Control Monograph 10 [online]. 1999. Available at URL: http://

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Perez-Stable EJ, Herrera B, Jacob P III, Benowitz NL. Nicotine 

metabolism and intake in black and white smokers. JAMA 

1998;280:152-156.

Pickett MA, Schober SE, Brody DJ, Curtin LR, Giovino GA. 

Smoke-free laws and secondhand smoke exposure in US nonsmoking adults, 1999-2002. Tob Control 2006;15:302-307.

Pirkle JL, Bernert JT, Caudill SP, Sosnoff CS, Pechacek TF. 

Trends in the exposure of nonsmokers in the U.S. population 

to secondhand smoke: 1988-2002. Environ Health Perspect 

2006;114(6):853-858.

Pirkle JL, Flegal KM, Bernert JT, Brody DJ, Etzel RA, Maurer 

KR. Exposure of the U.S. population to environmental tobacco 

smoke: the Third National Health and Nutrition Examination 

Survey, 1988-1991. JAMA 1996;275:1233-1240.

Soliman S, Pollack HA, Warner K. Decrease in the prevalence 

of environmental tobacco smoke exposure in the home during 

the 1990s in families with children. Am J Public Health 

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Chronic Disease Prevention and Health Promotion, Office on 

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Fourth National Report on Human Exposure to Environmental Chemicals 19

 N,N-Diethyl-meta-toluamide (DEET) 

N,N-Diethyl-meta-toluamide (DEET)

CAS No. 134-62-3 

General Information

N,N-diethyl-meta-toluamide (DEET) is an insect repellent 

that was first marketed in 1957. DEET can be applied 

to clothing and the skin to repel biting insects. Its use is 

recommended for prevention of several vector-borne 

diseases. There are over 225 insect repellents brands 

containing DEET, and they range in concentration from 4% 

to 100%. DEET is also used in combination with dermal 

sun screens (U.S.EPA, 1998). DEET is not registered for 

use on agricultural commodities. One survey detected 

DEET in 74% of sampled streams in the U.S. (Kolpin et 

al., 2002).

General population exposure to DEET occurs from skin 

application and from inhalation of aerosol formulations. 

Exposure can also occur from consuming food contaminated 

by DEET on hands or that was sprayed nearby. About 3-8% 

of dermally applied DEET is absorbed, but higher DEET 

concentrations and different formulations may result in 

greater absorption (Sudakin and Trevathan, 2003). After 

absorption, DEET is metabolized via hydroxylation and 

dealkylation pathways and eliminated in the urine within 

approximately 24 hours (Selim et al., 1995; Sudakin and 

Trevathan, 2003). People in outdoor occupations may 

apply DEET more frequently or use higher concentration 

formulations resulting in higher levels of exposure.

Human health effects from DEET at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. DEET has low acute toxicity. 

Most reports of adverse effects from overexposure to DEET 

involve skin reactions (Bell et al., 2002). Neurological 

effects in humans, including seizures and encephalopathy, 

have been reported as result of self-poisoning by ingestion 

or excessive dermal application, (U.S. EPA, 1998). DEET 

is not a developmental or reproductive toxicant in animals 

(U.S.EPA, 2005). DEET is not genotoxic, and it has 

not been rated by IARC or NTP with respect to human 

carcinogenicity. Additional information is available from 

U.S.EPA at: http://www.epa.gov/pesticides/.

Urinary N,N-Diethyl-meta-toluamide (DEET) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1977 

01-02 * < LOD < LOD .110 (.100-.140) .180 (.140-.220) 2535 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 480 

01-02 * < LOD < LOD .130 (.100-.180) .210 (.120-.560) 580 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 672 

01-02 * < LOD < LOD .130 (.110-.160) .220 (.130-.520) 829 

20-59 years 99-00 * < LOD < LOD < LOD < LOD 825 

01-02 * < LOD < LOD .110 (<LOD-.130) .170 (.120-.210) 1126 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 964 

01-02 * < LOD < LOD .110 (.100-.150) .180 (.130-.250) 1191 

Females 99-00 * < LOD < LOD < LOD < LOD 1013 

01-02 * < LOD < LOD .110 (.100-.130) .170 (.130-.210) 1344 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 688 

01-02 * < LOD < LOD .110 (<LOD-.140) .130 (.110-.190) 678 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 518 

01-02 * < LOD < LOD .100 (<LOD-.140) .140 (.100-.240) 700 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 598 

01-02 * < LOD < LOD .110 (.100-.140) .180 (.130-.270) 956 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.449 and 0.1. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 20 Fourth National Report on Human Exposure to Environmental Chemicals 

N,N-Diethyl-meta-toluamide (DEET) 

Biomonitoring Information

Urinary levels of DEET reflect recent exposure. Urinary 

levels of DEET were characterized only at the 90th and 

95th percentiles of the U.S. representative subsamples from 

NHANES 2001-2002. In this survey period, the limit of 

detection was lower than for the NHANES 1999-2000 

survey period (CDC, 2005). DEET was detected in 10% of 

60 Latino children in eastern North Carolina farm worker 

households (Arcury et al., 2007). Urinary DEET levels as 

high as 5,690 μg/L were measured in eight park employees 

who applied 71% DEET once a day (Smallwood et al., 

1992).

Finding a measurable amount of DEET in urine does not 

mean that the level of DEET causes an adverse health 

effect. Biomonitoring studies on levels of DEET provide 

physicians and public health officials with reference 

values so that they can determine whether people have 

been exposed to higher levels of DEET than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Urinary N,N-Diethyl-meta-toluamide (DEET) (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1977 

01-02 * < LOD < LOD .270 (.240-.300) .410 (.350-.500) 2534 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 480 

01-02 * < LOD < LOD .330 (.230-.630) .640 (.280-1.93) 580 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 672 

01-02 * < LOD < LOD .190 (.150-.240) .250 (.190-.490) 828 

20-59 years 99-00 * < LOD < LOD < LOD < LOD 825 

01-02 * < LOD < LOD .270 (<LOD-.320) .410 (.370-.500) 1126 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 964 

01-02 * < LOD < LOD .200 (.170-.250) .320 (.250-.440) 1191 

Females 99-00 * < LOD < LOD < LOD < LOD 1013 

01-02 * < LOD < LOD .330 (.290-.370) .500 (.410-.580) 1343 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 688 

01-02 * < LOD < LOD .190 (<LOD-.230) .280 (.230-.350) 678 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 518 

01-02 * < LOD < LOD .130 (<LOD-.150) .190 (.140-.270) 699 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 598 

01-02 * < LOD < LOD .300 (.270-.350) .480 (.390-.550) 956 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 21

 N,N-Diethyl-meta-toluamide (DEET) 

References

Arcury TA, Grzywacz JG, Barr DB, Tapia J, Chen H, Quandt 

SA. Pesticide urinary metabolite levels of children in eastern 

North Carolina farmworker households. Environ Health Perspect 

2007;115(8):1254-1260.

Bell JW, Veltri JC, Page BC. Human exposures to N,N-diethyl-mtoluamide insect repellents reported to the American Association 

of Poison Control Centers, 1993-1997. Int J Toxicol 2002;2:341-

352.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005

Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, 

Barber LB, et al. Pharmaceuticals, hormones, and other organic 

wastewater contaminants in U.S. streams, 1999-2000: a national 

reconnaissance. Environ Sci Technol 2002;36(6):1202-1211.

Selim S, Hartnagel RE Jr, Osimitz TG, Gabriel KL, Schoenig 

GP. Absorption, metabolism, and excretion of N,N-diethyl-mtoluamide following dermal application to human volunteers. 

Fundam Appl Toxicol 1995;25:95-100.

Smallwood AW, DeBord KE, Lowry LK. N,N’-diethyl-mtoluamide (m-DET): analysis of an insect repellent in human 

urine and serum by high-performance liquid chromatography. J 

Anal Toxicol 1992;16(1):10-13.

Sudakin DL, Trevathan WR. DEET: a review and update of 

safety and risk in the general population. J Toxicol Clin Toxicol 

2003;41(6):831-839.

U.S. Environmental Protection Agency (U.S.EPA). 

Diethyltoluamide (DEET). Chemical Summary. U.S.EPA, 

Toxicity and Exposure Assessment in Children’s Health. 2005. 

Available at URL: http://www.epa.gov/teach/chem_summ/

DEET_summary.pdf. 4/9/09

U.S. Environmental Protection Agency (U.S.EPA). 

Reregistration Eligibility Decision (RED): DEET. EPA 738-R98-010. Washington (DC): U.S. EPA; September 1998. pp. 1-118. 

Available at URL: http://www.epa.gov/oppsrrd1/REDs/0002red.

pdf. 4/9/09
 22 Fourth National Report on Human Exposure to Environmental Chemicals 

Disinfection By-Products (Trihalomethanes)

Disinfection By-Products (Trihalomethanes)

Bromodichloromethane CAS No. 75-27-4

Dibromochloromethane (Chlorodibromomethane) 

CAS No. 124-48-1

Tribromomethane (Bromoform) CAS No. 75-25-2

Trichloromethane (Chloroform) CAS No. 57-57-8

General Information

Disinfection by-products (DBP) are a class of chemical 

by-products also referred to as trihalomethanes (THMs), 

formed when chlorine or bromine interacts with the natural 

organic materials found in water. DBPs also include other 

formed products, such as haloacetic acids, haloacetonitriles, 

haloketones, and chlorophenols. The composition and 

levels of specific DBPs are determined by water quality, 

water treatment conditions, and disinfectant type (IPCS, 

2000). Primary sources of DBPs are chlorinated drinking 

water and recreational water bodies, such as swimming 

pools.

In drinking water, trichloromethane is the predominant 

DBP, usually found at much higher levels than 

bromodichloromethane; tribromomethane is the least 

abundant (Krasner et al., 1989). DBPs are volatile at room 

temperature and can be detected in ambient air during 

activities such as showering, bathing, dishwashing, and 

swimming (Backer, et al., 2000; Gordon et al., 2006). 

Trichloromethane has industrial applications and is used 

to produce refrigerants and feedstock. It may be released 

into the environment where chlorine-based chemicals are 

used for bleaching and disinfecting processes or disposed at 

hazardous waste sites (IPCS, 2004; LaRegina, et al. 1986). 

Tribromomethane has limited industrial uses, mainly in 

geological assaying, electronics manufacturing, and as 

a solvent in laboratory analyses (ATSDR, 2005). DBPs 

tend not to bioaccumulate in aquatic organisms or persist 

in open or surface waters or soils, but they can remain in 

water within closed pipe systems. Workplace exposure 

may occur during the production of trichloromethane or 

tribromomethane, or in workplaces where DBPs may be 

generated, such as pulp or paper manufacturing, swimming 

pools, and water treatment plants (IPCS, 2004).

General population exposure to DBPs occurs primarily 

through ingesting chlorinated water and inhaling the water 

Blood Bromodichloromethane 

Geometric mean and selected percentiles of blood concentrations (in pg/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 2.21 (1.65-2.97) 2.30 (1.56-3.21) 4.63 (3.24-6.20) 8.45 (5.86-12.0) 12.0 (7.68-19.2) 785

03-04 1.50 (1.20-1.86) 1.40 (1.10-1.90) 3.40 (2.60-4.20) 6.20 (5.30-7.00) 9.50 (7.00-12.0) 1322

Age group 

20-59 years 01-02 2.21 (1.65-2.97) 2.30 (1.56-3.21) 4.63 (3.24-6.20) 8.45 (5.86-12.0) 12.0 (7.68-19.2) 785

03-04 1.50 (1.20-1.86) 1.40 (1.10-1.90) 3.40 (2.60-4.20) 6.20 (5.30-7.00) 9.50 (7.00-12.0) 1322

Gender 

Males 01-02 2.19 (1.60-3.00) 2.31 (1.63-3.21) 4.64 (3.21-6.08) 7.96 (5.74-15.3) 13.0 (6.93-20.5) 382

03-04 1.48 (1.18-1.85) 1.40 (.940-2.00) 3.40 (2.60-4.30) 6.60 (5.40-7.20) 11.0 (7.20-14.0) 650

Females 01-02 2.24 (1.66-3.01) 2.28 (1.49-3.24) 4.63 (3.09-7.01) 8.62 (5.26-12.9) 11.1 (7.68-25.0) 403

03-04 1.51 (1.21-1.90) 1.50 (1.10-1.90) 3.30 (2.50-4.20) 6.10 (4.69-7.30) 7.80 (6.40-12.0) 672

Race/ethnicity 

Mexican Americans 01-02 3.28 (2.29-4.68) 3.32 (2.19-4.70) 6.81 (3.71-10.4) 10.8 (8.24-14.7) 14.7 (11.1-20.5) 227

03-04 1.65 (1.15-2.38) 1.60 (.820-2.80) 3.50 (2.60-4.90) 7.30 (4.50-10.0) 10.0 (7.30-11.0) 244

Non-Hispanic blacks 01-02 2.32 (1.82-2.94) 2.50 (1.56-3.55) 4.57 (3.60-5.56) 8.69 (5.63-9.49) 10.0 (5.89-13.5) 130

03-04 1.56 (1.15-2.13) 1.70 (1.10-2.20) 2.90 (2.15-3.80) 5.10 (3.80-6.60) 6.60 (4.90-13.0) 290

Non-Hispanic whites 01-02 2.02 (1.42-2.87) 2.16 (1.36-3.09) 4.34 (2.92-6.01) 7.33 (4.72-15.3) 11.1 (6.01-26.1) 365

03-04 1.42 (1.11-1.81) 1.30 (.850-1.90) 3.30 (2.30-4.40) 6.20 (5.20-7.20) 9.80 (6.70-13.0) 684

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.233 and 0.62. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 
Fourth National Report on Human Exposure to Environmental Chemicals 23

 Disinfection By-Products (Trihalomethanes)

vapor. Dermal absorption also may occur during bathing 

and swimming (ATSDR, 1997, 2005; Dick, et al., 1995; 

Leavens et al., 2007). Each of the DBPs is rapidly absorbed 

and distributed widely throughout the body. In animals, 

these chemicals undergo hepatic metabolism to reactive 

chemicals, which can bind to cell macromolecules and be 

toxic in large amounts (IPCS, 2000). Ultimately, DBPs 

are metabolized to carbon dioxide, which is eliminated in 

exhaled air within a few hours. Only a small amount of each 

DBP is eliminated unchanged in urine. Elimination halflives for these chemicals are less than four hours (ATSDR, 

2005; Leavens et al., 2007).

Human health effects from DBPs at low environmental doses 

or at biomonitored levels from low environmental exposures 

are unclear or unknown. Humans exposed to massive levels 

of trichloromethane or tribromomethane develop central 

nervous system depression and hepatotoxicity (ATSDR, 

2005, 1997). Acute animal toxicity studies of each of these 

chemicals have found central nervous system depression, 

liver and renal damage or necrosis, and occasionally, 

cardiac depression and arrhythmias (IPCS, 2000). In 

studies of rodents chronically fed high doses of either 

trichloromethane or bromodichloromethane, carcinomas 

occurred in the liver and kidney; large intestine tumors and 

polyps were also noted with bromodichloromethane (NCI, 

1976; NTP, 1987). Chronic feeding studies in rodents with 

either dibromochloromethane or tribromomethane showed 

inconsistent evidence of carcinogenicity across species 

and genders. The DBPs did not produce reproductive or 

developmental effects in animals unless maternal toxicity 

was present, but bromodichloromethane altered sperm 

motility (IPCS, 2000). Numerous epidemiologic studies 

of the relationships between chlorinated water source 

and various cancers, adverse reproductive outcomes, 

and cardiovascular disease have been inconclusive 

(IPCS, 2000). IARC classified trichloromethane and 

bromodichloromethane as possible human carcinogens, 

and NTP determined that these chemicals are reasonably 

anticipated to be human carcinogens. However, IARC 

found dibromochloromethane and tribromomethane to be 

unclassifiable regarding human carcinogenicity. The U.S. 

EPA has established drinking water and environmental 

standards for “total THMs.” OSHA and ACGIH have 

established workplace standards and guidelines, 

respectively, for trichloromethane and tribromomethane. 

Information about external exposure (i.e., environmental 

levels) and health effects is available from ATSDR at: 

http://www.atsdr.cdc.gov/toxpro2.html.

Blood Dibromochloromethane 

Geometric mean and selected percentiles of blood concentrations (in pg/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 .867 (.521-1.44) .780 (.340-1.90) 2.61 (1.22-4.38) 5.46 (3.53-9.71) 8.96 (5.04-12.9) 781

03-04 * < LOD 1.30 (1.00-1.80) 3.60 (2.70-4.80) 7.20 (4.80-8.60) 1333

Age group 

20-59 years 01-02 .867 (.521-1.44) .780 (.340-1.90) 2.61 (1.22-4.38) 5.46 (3.53-9.71) 8.96 (5.04-12.9) 781

03-04 * < LOD 1.30 (1.00-1.80) 3.60 (2.70-4.80) 7.20 (4.80-8.60) 1333

Gender 

Males 01-02 .850 (.481-1.50) .730 (.300-2.25) 2.66 (.960-4.38) 4.77 (3.33-9.20) 8.06 (4.31-14.6) 371

03-04 * < LOD 1.30 (1.00-1.90) 3.70 (2.70-5.70) 7.20 (5.20-8.60) 657

Females 01-02 .884 (.550-1.42) .820 (.340-1.69) 2.54 (1.37-4.31) 6.30 (3.28-10.1) 9.91 (5.02-13.0) 410

03-04 * < LOD 1.30 (1.00-1.80) 3.60 (2.50-4.80) 6.60 (3.80-9.20) 676

Race/ethnicity 

Mexican Americans 01-02 1.61 (.843-3.06) 1.49 (.670-3.99) 4.59 (1.93-8.89) 9.26 (5.21-12.1) 12.0 (9.63-16.1) 233

03-04 1.20 (.963-1.50) 1.10 (.810-1.40) 2.30 (1.50-4.10) 5.20 (3.80-6.90) 7.70 (5.20-11.0) 256

Non-Hispanic blacks 01-02 1.03 (.505-2.09) .930 (.530-2.03) 2.03 (.770-7.06) 4.22 (2.01-10.5) 8.09 (2.80-16.5) 128

03-04 * < LOD .970 (.650-1.60) 1.90 (1.20-3.20) 3.20 (1.80-5.20) 288

Non-Hispanic whites 01-02 .736 (.413-1.31) .640 (<LOD-1.93) 2.49 (.870-4.27) 4.57 (3.00-7.12) 6.98 (4.27-11.1) 357

03-04 * < LOD 1.30 (.950-1.80) 3.30 (2.50-4.60) 6.60 (3.70-9.20) 685

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.271 and 0.62. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 24 Fourth National Report on Human Exposure to Environmental Chemicals 

Disinfection By-Products (Trihalomethanes)

Biomonitoring Information

Levels of blood DBPs reflect recent exposure. Geometric 

mean blood trichloromethane levels were 0.039 and 

0.043 ng/mL among non-smoking and smoking adults, 

respectively, in a subsample of NHANES 1999-2000 

participants (Lin et al., 2008), which were at least twice 

as high as comparable levels in NHANES 2001-2002 and 

2003-2004. In a non-representative sample of NHANES III 

(1988-1994) participants, the geometric mean and median 

blood trichloromethane levels, respectively, were 0.043 and 

0.023 mg/L (Churchill et al., 2001). Similar median blood 

trichloromethane levels were reported in smaller studies of 

U.S adults (Ashley et al., 2005; Backer et al., 2000; Buckley 

et al., 1997) and in this Report. Immediately following 

bathing or showering with chlorinated water, median blood 

levels of trichloromethane, dibromochloromethane, and 

bromodichloromethane can increase two to four times over 

baseline levels, and then return to baseline rapidly during 

the next one to two hours (Ashley et al., 2005; Backer et 

al., 2000).

Finding a measurable amount of one or more of these THMs 

in blood does not mean that the level of THMs causes an 

adverse health effect. Biomonitoring studies of blood 

THMs can provide physicians and public health officials 

with reference values so that they can determine whether 

or not people have been exposed to higher levels of THMs 

than levels found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

Blood Tribromomethane (Bromoform) 

Geometric mean and selected percentiles of blood concentrations (in pg/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 1.57 (1.07-2.31) 1.39 (.960-2.02) 2.78 (1.76-4.63) 6.05 (2.92-29.2) 15.5 (3.68-85.4) 774

03-04 * < LOD 1.80 (<LOD-2.80) 3.74 (2.30-7.10) 6.40 (3.60-14.0) 1310

Age group 

20-59 years 01-02 1.57 (1.07-2.31) 1.39 (.960-2.02) 2.78 (1.76-4.63) 6.05 (2.92-29.2) 15.5 (3.68-85.4) 774

03-04 * < LOD 1.80 (<LOD-2.80) 3.74 (2.30-7.10) 6.40 (3.60-14.0) 1310

Gender 

Males 01-02 1.49 (.944-2.34) 1.29 (.850-1.98) 2.65 (1.49-5.05) 6.12 (2.26-33.9) 14.9 (2.79-69.9) 374

03-04 * < LOD 1.90 (<LOD-2.87) 4.00 (2.40-6.80) 6.50 (4.00-13.0) 645

Females 01-02 1.67 (1.17-2.39) 1.46 (1.05-2.21) 2.86 (1.89-4.57) 5.69 (3.30-27.5) 22.2 (5.09-49.6) 400

03-04 * < LOD 1.72 (<LOD-2.65) 3.20 (1.93-7.70) 6.10 (3.10-31.0) 665

Race/ethnicity 

Mexican Americans 01-02 2.34 (1.15-4.77) 1.66 (.990-3.38) 4.03 (1.42-36.5) 28.3 (4.39-49.2) 40.8 (31.5-57.9) 234

03-04 * 1.60 (<LOD-3.10) 3.30 (<LOD-9.40) 7.60 (3.60-14.0) 11.0 (5.60-210) 242

Non-Hispanic blacks 01-02 1.51 (.857-2.67) 1.47 (.780-3.15) 2.58 (1.39-4.64) 4.34 (2.57-8.48) 6.27 (3.28-15.2) 121

03-04 * < LOD 1.60 (<LOD-2.30) 2.50 (1.80-3.20) 3.20 (2.40-6.10) 289

Non-Hispanic whites 01-02 1.47 (.980-2.22) 1.29 (.840-2.06) 2.58 (1.51-4.91) 5.69 (2.84-21.2) 11.0 (3.30-69.9) 362

03-04 * < LOD 1.70 (<LOD-2.90) 3.50 (2.00-7.70) 5.90 (3.30-21.0) 680

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.596 and 1.5. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 25

 Disinfection By-Products (Trihalomethanes)

Blood Trichloromethane (Chloroform) 

Geometric mean and selected percentiles of blood concentrations (in pg/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 16.6 (13.0-21.1) 16.1 (11.9-22.2) 31.7 (23.9-40.4) 55.5 (44.5-68.6) 72.1 (57.3-105) 744

03-04 10.2 (8.56-12.2) 10.0 (8.50-13.0) 20.0 (17.0-24.0) 35.0 (29.0-40.0) 50.0 (37.0-65.0) 1222

Age group 

20-59 years 01-02 16.6 (13.0-21.1) 16.1 (11.9-22.2) 31.7 (23.9-40.4) 55.5 (44.5-68.6) 72.1 (57.3-105) 744

03-04 10.2 (8.56-12.2) 10.0 (8.50-13.0) 20.0 (17.0-24.0) 35.0 (29.0-40.0) 50.0 (37.0-65.0) 1222

Gender 

Males 01-02 16.8 (12.0-23.5) 16.1 (11.0-24.8) 34.3 (22.4-48.7) 57.0 (39.9-76.4) 75.2 (54.5-156) 358

03-04 10.1 (8.43-12.1) 10.0 (7.90-14.0) 20.0 (17.0-25.0) 36.8 (29.0-49.0) 53.0 (36.8-69.0) 599

Females 01-02 16.4 (13.4-20.1) 16.6 (12.0-21.5) 29.2 (24.0-36.5) 53.5 (38.4-68.9) 69.5 (53.3-104) 386

03-04 10.4 (8.41-12.7) 10.0 (8.40-13.0) 20.0 (16.0-23.9) 33.0 (26.0-40.0) 46.0 (35.0-65.0) 623

Race/ethnicity 

Mexican Americans 01-02 17.0 (10.5-27.6) 14.5 (10.0-32.7) 35.1 (18.6-57.6) 60.7 (41.5-100) 93.0 (49.7-243) 223

03-04 9.17 (7.45-11.3) 9.30 (7.60-11.0) 19.0 (15.0-24.0) 34.0 (24.0-44.4) 44.4 (30.0-59.0) 225

Non-Hispanic blacks 01-02 19.1 (12.9-28.1) 20.9 (9.28-37.4) 38.4 (27.7-46.0) 55.9 (45.5-69.8) 68.9 (51.9-74.0) 116

03-04 11.8 (9.54-14.6) 12.0 (8.90-15.0) 20.0 (15.0-30.0) 35.0 (28.0-59.0) 61.0 (34.0-100) 272

Non-Hispanic whites 01-02 15.6 (12.0-20.2) 15.2 (11.2-20.5) 26.8 (20.4-39.5) 53.5 (35.3-72.1) 69.5 (53.5-105) 348

03-04 9.84 (8.09-12.0) 10.0 (8.10-13.0) 20.0 (16.0-23.0) 33.8 (27.0-40.0) 47.0 (35.0-67.0) 630

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 2.37 and 2.11. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 
 26 Fourth National Report on Human Exposure to Environmental Chemicals 

Disinfection By-Products (Trihalomethanes)

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for chloroform update. 1997 [online]. 

Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp6.html. 

4/26/09

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for bromoform and chlorodibromomethane. 

2005 [online]. Available at URL: http://www.atsdr.cdc.gov/

toxprofiles/tp130.html. 4/26/09

Ashley DL, Blount BC, Singer PC, Depaz E, Wilkes C, Gordon S, 

et al. Changes in blood trihalomethanes concentrations resulting 

from differences in water quality and water use activities. Arch 

Environ Occup Health 2005;60(1):7-15.

Backer LC, Ashley DL, Bonin MA, Cardinali FL, Kieszak SM, 

Wooten JV. Household exposures to drinking water disinfection 

by-products: whole blood trihalomethane levels. J Expo Anal 

Environ Epidemiol 2000;10(4):321-326.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, 

Needham LL. Environmental and biomarker measurements in 

nine homes in the lower Rio Grande Valley: multimedia results for 

pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-

732.

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures 

and blood volatile organic compound levels in a large populationbased sample. Arch Environ Health 2001;56(2):157-166.

Dick D, Ng KM, Sauder DN, Chu I. In vitro and in vivo

percutaneous absorption of 14C-chloroform in humans. Hum Exp 

Toxicol 1995;14: 260-265.

Gordon SM, Brinkman MC, Ashley DL, Blount BC, Lyu C, 

Masters J, Singer PC. Changes in breath trihalomethane levels 

resulting from household water-use activities. Environ Health 

Perspect 2006;114(4):514-521.

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 216. Disinfectants and Disinfectant 

By-Products. 2000 [online]. Available at URL: http://www.

inchem.org/documents/ehc/ehc/ehc216.htm.4/26/09

International Programme on Chemical Safety (IPCS). Concise 

International Chemical Assessment Document 58. Chloroform. 

2004 [online]. Available at URL: http://www.inchem.org/

documents/cicads/cicads/cicad58.htm. 4/26/09

Krasner SW, McGuire MJ, Jacaugelo JG, Patania NL, Reagan 

KM, Aieta EM. The occurrence of disinfection by-products in US 

drinking water. J Am Water Works Assoc 1989;81:41–53.

LaRegina J, Bozzelli JW, Harkov R, Gianti S. Volatility organic 

compounds at hazardous waste sites and a sanitary landfill in New 

Jersey. An up-to-date review of the present situation. Environ 

Prog 1986;5:18-27.

Leavens TL, Blount BC, De Marini DM, Madden MC, Valentine 

JL, Case MW, et al. Disposition of bromodichloromethane 

in humans following oral and dermal exposure. Toxicol Sci 

2007;99(2):432-445.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Expo Sci Environ Epidemiol 2008;18(4):421-9.

National Cancer Institute (NCI). Report on the carcinogenesis 

bioassay of chloroform (CAS No. 67-66-3). National Cancer 

Institute Carcinogenesis Technical Report Series March 1, 1976. 

[online]. Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/

LT_rpts/trChloroform.pdf. 4/26/09

National Toxicology Program (NTP). Carcinogenesis studies of 

bromodichloromethane (CAS No. 75-27-4) in F344/N rats and 

B6C31F mice (gavage studies). Technical Report Series No. 321. 

1987 [online]. Available at URL: http://ntp.niehs.nih.gov/ntp/

htdocs/LT_rpts/tr321.pdf. 4/26/09
Fourth National Report on Human Exposure to Environmental Chemicals 27

 Environmental Phenols

Benzophenone-3

CAS No. 131-57-7

General Information

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone) 

occurs naturally in some flowering plants. It is commercially 

synthesized as a sunscreen for use in lotions, conditioners, 

and cosmetics. It is also used as a UV stabilizer in plastic 

surface coatings and polymers. Benzophenone-3 is a 

common ingredient in sun-blocking agents.

People may be exposed through dermal application of 

sunscreens and cosmetic products. Small amounts of 

benzophenone-3 can be absorbed through human skin and 

excreted in the urine, mostly as a glucuronidated conjugate 

(Gonzalez et al., 2006; Gustavsson et al., 2002; Janjua et 

al., 2004; Ye et al., 2005). After dermal application of a 4% 

lotion over the entire body daily for 5 days, one study found 

that 1.2-8.7% of the applied benzophenone-3 amount was 

recovered in the urine (Gonzalez et al., 2006).

Human health effects from benzophenone-3 at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Following dermal 

application, some cases of photoallergy or allergy to 

benzophenone-3 have been reported. Male reproductive 

toxicity has been inconsistently reported in chronic high 

dose animal studies (Daston et al., 1993; French, 1992). 

Benzophenone-3 has weak estrogenic activity or weak 

anti-androgenic activity (French, 1992; Schlecht et al., 

2004; Schlumpf et al., 2001; Schreurs et al., 2005). No 

human hormonal changes were observed during four days 

of application of 10% benzophenone-3 lotion (Janjua et 

al., 2004). Benzophenone-3 is not considered mutagenic 

(Robison et al., 1994). IARC and NTP have no ratings as 

to human carcinogenicity of benzophenone-3.

Biomonitoring Information

Urinary benzophenone-3 levels include both conjugated 

and unconjugated forms and reflect recent exposure to 

the chemical. The NHANES 2003-2004 levels of urinary 

benzophenone-3 have been described by Calafat et al. 

(2008). The analysis showed that female participants had 

slightly higher urinary levels than males and that nonHispanic whites were more likely than non-Hispanic 

blacks to have levels above the 95th percentile of the overall 

population. In a study of 90 U.S. females aged 6-8 years, 

the median urinary benzophenone-3 level of 14.7 μg/L was 

comparable to the median level of children 6-11 years of age 

(17.2 μg/L) in the NHANES 2003-2004 subsample (Calafat 

et al., 2008; Wolff et al., 2007). Total benzophenone-3 

urinary concentrations were detectable in 90% of a small 

sample of adults in whom the values ranged up to 3000 

μg/L (Ye et al., 2005). Following short-term application of 

10% benzophenone-3 lotion, men and women had mean 

urinary levels of 140 and 60 μg/L, respectively (Janjua et 

al., 2004).

Finding a measurable amount of benzophenone-3 in urine 

does not mean that the levels of benzophenone-3 cause 

an adverse health effect. Biomonitoring studies on levels 

of benzophenone-3 provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels of 

benzophenone-3 than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.
 28 Fourth National Report on Human Exposure to Environmental Chemicals 

Environmental Phenols

Urinary Benzophenone-3 (2-Hydroxy-4-methoxybenzophenone) (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 22.2 (17.6-28.0) 16.2 (12.7-21.6) 82.0 (58.7-108) 415 (283-577) 1080 (686-1600) 2514 

Age group 

6-11 years 03-04 25.8 (19.5-34.1) 22.4 (14.4-33.7) 84.6 (41.0-131) 171 (132-365) 427 (171-710) 314

12-19 years 03-04 17.2 (13.7-21.5) 12.9 (10.4-16.5) 43.6 (29.5-57.7) 136 (91.7-239) 350 (173-646) 713

20 years and older 03-04 22.8 (17.8-29.1) 16.2 (12.7-21.9) 93.2 (66.0-130) 491 (361-700) 1330 (880-1880) 1487 

Gender 

Males 03-04 13.6 (10.8-17.1) 10.3 (8.36-12.9) 40.0 (24.9-62.5) 169 (93.3-316) 381 (229-685) 1228 

Females 03-04 35.5 (27.1-46.4) 28.2 (20.2-37.0) 144 (101-224) 686 (491-1130) 1850 (1220-2580) 1286 

Race/ethnicity 

Mexican Americans 03-04 15.1 (9.44-24.0) 11.1 (6.95-16.0) 40.7 (18.3-85.8) 158 (87.4-362) 595 (118-1860) 612

Non-Hispanic blacks 03-04 8.78 (6.49-11.9) 6.80 (5.27-9.00) 19.7 (13.5-33.4) 79.8 (46.8-139) 185 (79.8-536) 651

Non-Hispanic whites 03-04 28.3 (20.6-38.8) 22.0 (14.6-32.7) 116 (73.5-175) 510 (380-760) 1330 (852-2410) 1091 

Urinary Benzophenone-3 (2-Hydroxy-4-methoxybenzophenone) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 22.9 (18.1-28.9) 18.1 (15.5-23.2) 94.0 (67.5-123) 370 (225-570) 1040 (698-1390) 2517 

Age group 

6-11 years 03-04 21.2 (16.4-27.3) 17.2 (14.9-25.9) 66.7 (38.7-102) 158 (106-246) 246 (154-618) 314

12-19 years 03-04 22.9 (18.0-29.3) 20.1 (16.1-25.1) 67.1 (45.2-93.8) 170 (137-240) 407 (183-717) 715

20 years and older 03-04 23.1 (18.0-29.6) 18.1 (14.7-23.3) 109 (72.1-140) 450 (315-733) 1220 (769-1750) 1488 

Gender 

Males 03-04 16.8 (13.2-21.3) 13.7 (11.4-16.8) 55.3 (33.2-86.6) 178 (134-324) 567 (238-1350) 1229 

Females 03-04 30.7 (23.7-39.8) 26.0 (20.2-34.1) 137 (106-172) 596 (403-769) 1340 (776-1790) 1288 

Race/ethnicity 

Mexican Americans 03-04 16.5 (10.9-25.1) 11.9 (8.50-18.3) 45.5 (25.9-78.2) 178 (76.4-412) 412 (178-2180) 613

Non-Hispanic blacks 03-04 12.8 (9.38-17.4) 10.2 (7.40-14.4) 34.3 (22.8-50.6) 127 (90.8-176) 247 (143-499) 652

Non-Hispanic whites 03-04 27.7 (20.3-37.8) 24.4 (16.8-32.0) 121 (83.6-162) 507 (316-769) 1340 (733-2070) 1092 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.3. 
Fourth National Report on Human Exposure to Environmental Chemicals 29

 Environmental Phenols

References

Calafat AM, Wong LY, Ye X, Reidy JA, Needham LL. 

Concentrations of the sunscreen agent benzophenone-3 in 

residents of the United States: National Health and Nutrition 

Examination Survey 2003--2004. Environ Health Perspect 

2008;116(7):893-897.

Daston GP, Gettings SD, Carlton BD, Chudkowski M, Davis RA, 

Kraus AL, et al. Assessment of the reproductive toxic potential 

of dermally applied 2-hydroxy-4-methoxybenzophenone to male 

B6C3F1 mice. Fundam Appl Toxicol 1993;20(1):120-124.

French JE. NTP technical report on the toxicity studies of 

2-hydroxy-4-methoxybenzophenone (CAS No. 131-57-7) 

Adminstered topically and in dosed feed to F344/N Rats and 

B6C3F1 mice. National Institutes of Health Publication No. 92-

3344, October 1992 (also Toxic Rep Ser. 1992 Oct;21:1-E14).

Gonzalez H, Farbrot A, Larko O, Wennberg AM. Percutaneous 

absorption of the sunscreen benzophenone-3 after repeated 

whole-body applications, with and without ultraviolet irradiation. 

Br J Dermatol 2006;154(2):337-340.

Gustavsson Gonzalez H, Farbrot A, Larko O. Percutaneous 

absorption of benzophenone-3, a common component of topical 

sunscreens. Clin Exp Dermatol 2002;27(8):691-694.

Janjua NR, Mogensen B, Andersson AM, Petersen JH, Henriksen 

M, Skakkebaek NE, et al. Systemic absorption of the sunscreens 

benzophenone-3, octyl methoxycinnamate, and 3-(4-methylbenzylidene) camphor after whole-body topical application 

and reproductive hormone levels in humans. J Invest Dermatol 

2004;123(1):57-61.

Okereke CS, Barat SA, Abdel-Rahman MS. Safety evaluation of 

benzophenone-3 after dermal administration in rats. Toxicol Lett 

1995;80(1-3):61-67.

Robison SH, Odio MR, Thompson ED, Aardema MJ, Kraus 

AL. Assessment of the in vivo genotoxicity of 2-hydroxy 

4-methoxybenzophenone. Environ Mol Mutagen 1994;23(4):312-

317.

Schlecht C, Klammer H, Jarry H, Wuttke W. Effects of estradiol, 

benzophenone-2 and benzophenone-3 on the expression pattern of 

the estrogen receptors (ER) alpha and beta, the estrogen receptorrelated receptor 1 (ERR1) and the aryl hydrocarbon receptor 

(AhR) in adult ovariectomized rats. Toxicology 2004;205(1-

2):123-130.

Schlumpf M, Cotton B, Conscience M, Haller V, Steinmann 

B, Lichtensteiger W. In vitro and in vivo estrogenicity of UV 

screens. Environ Health Perspect 2001;109(3):239-244. Erratum 

in: Environ Health Perspect 2001;109(11):A517.

Schreurs RH, Sonneveld E, Jansen JH, Seinen W, van der Burg B. 

Interaction of polycyclic musks and UV filters with the estrogen 

receptor (ER), androgen receptor (AR), and progesterone receptor 

(PR) in reporter gene bioassays. Toxicol Sci 2005;83(2):264-272. 

Ye X, Kuklenyik Z, Needham LL, Calafat AM. Quantification 

of urinary conjugates of bisphenol A, 2,5-dichlorophenol, and 

2-hydroxy-4-methoxybenzophenone in humans by online solid 

phase extraction-high performance liquid chromatographytandem mass spectrometry. Anal Bioanal Chem 2005;383(4):638-

644.
 30 Fourth National Report on Human Exposure to Environmental Chemicals 

Environmental Phenols

Bisphenol A

CAS No. 80-05-7

General Information

Bisphenol A is a phenolic chemical which has been used for 

over 50 years in the manufacture of polycarbonate plastics 

and epoxy resins; in thermal paper production; and as a 

polymerization inhibitor in the formation of some polyvinyl 

chloride plastics. Polycarbonates are used to make products 

such as compact discs, automobile parts, baby bottles, plastic 

dinnerware, eyeglass lenses, toys, and impact-resistant 

safety equipment. Epoxy resins containing bisphenol A are 

used in protective linings of some canned food containers, 

wine vat linings, epoxy resin-based paints, floorings, and 

some dental composites. In recent years, about 5-6 billion 

pounds of bisphenol were produced annually worldwide. 

Bisphenol A may enter the environment from industrial 

sources or from product leaching, disposal, and use. In 

1999-2000, bisphenol A was detected in 41.2% of 139 U.S. 

streams in 30 states (Kolpin et al., 2002). Bisphenol A can 

be biodegraded and does not bioaccumulate significantly 

in aquatic organisms. Some invertebrates may be sensitive 

and show reproductive effects (European Commission, 

2003).

General population exposure to bisphenol A may occur 

through ingestion of foods in contact with bisphenol A 

containing materials. For small children, hand-to-mouth 

and direct oral contact with materials containing bisphenol 

A are possible. Exposure from indoor air is a small 

component of total exposure estimates (Wilson et al., 2007. 

In animal and human studies, bisphenol A is well absorbed 

orally. In humans, little free bisphenol A circulates after 

oral absorption due to the high degree of glucuronidation 

by the liver. The glucuronidated bisphenol A is excreted in 

the urine within 24 hours with no evidence of accumulation 

(Volkel et al., 2002).

Human health effects from bisphenol A at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Occupational exposure of epoxy 

workers to bisphenol A dust may produce eye irritation and 

skin sensitization. In animal studies, bisphenol A has low 

acute toxicity. It is not considered a teratogen (Kim et al., 

2001). Bisphenol A is rated as weakly estrogenic (Matthews 

et al., 2001). Some reproductive or developmental changes 

are observed at high doses in standard experimental 

animal studies (e.g., delayed vaginal opening and preputial 

separation) (Ema et al., 2001; Tyl et al., 2002; NTPCERHR, 2008). Reproductive and neurodevelopmental 

effects of bisphenol A at low doses in animals, including 

environmental doses potentially relevant to humans, have 

been the subject of ongoing scientific reviews and study 

(European Commission, 2002; Gray et al., 2004; NTP, 

2001; NTP-CERHR, 2007 and 2008; vom Saal and Hughes, 

2005 Welshons et al., 2006; Witorsch, 2002). Examples 

of recent animal studies which suggest possible low dose 

effects include altered development of the fetal prostate 

and mammary gland, inhibition of postnatal testosterone 

production, and changes in neurodevelopment (Akingbemi 

et al., 2004; Leranth et al., 2008; NTP-CERHR, 2007; 

Urinary Bisphenol A (2,2-bis[4-Hydroxyphenyl] propane) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 2.64 (2.38-2.94) 2.80 (2.50-3.10) 5.50 (5.00-6.20) 10.6 (9.40-12.0) 16.0 (14.4-17.2) 2517 

Age group 

6-11 years 03-04 3.55 (2.95-4.29) 3.80 (2.70-5.00) 6.90 (6.00-8.30) 12.6 (9.50-15.1) 16.0 (11.5-23.3) 314 

12-19 years 03-04 3.74 (3.31-4.22) 4.30 (3.60-4.60) 7.80 (6.50-9.00) 13.5 (11.8-15.2) 16.5 (15.2-20.9) 715 

20 years and older 03-04 2.41 (2.15-2.72) 2.60 (2.30-2.80) 5.10 (4.50-5.70) 9.50 (8.10-11.3) 15.2 (12.4-18.1) 1488 

Gender 

Males 03-04 2.92 (2.63-3.24) 3.20 (2.70-3.60) 6.10 (5.40-6.60) 10.4 (9.50-11.6) 16.0 (12.7-17.6) 1229 

Females 03-04 2.41 (2.11-2.75) 2.50 (2.20-2.80) 5.00 (4.20-6.20) 10.6 (8.70-12.5) 15.9 (13.5-20.1) 1288 

Race/ethnicity 

Mexican Americans 03-04 2.58 (2.15-3.08) 2.60 (2.10-3.20) 5.20 (4.40-6.50) 9.90 (7.30-13.9) 15.4 (10.2-19.7) 613 

Non-Hispanic blacks 03-04 4.24 (3.73-4.82) 4.30 (3.80-5.10) 8.20 (7.10-9.80) 14.2 (11.7-16.9) 20.6 (14.9-25.2) 652 

Non-Hispanic whites 03-04 2.51 (2.26-2.79) 2.70 (2.50-3.00) 5.20 (4.70-5.80) 9.60 (8.30-10.9) 15.1 (12.6-16.7) 1092 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.4. 
Fourth National Report on Human Exposure to Environmental Chemicals 31

 Environmental Phenols

Timms et al., 2005).

Bisphenol A is not considered mutagenic and is unlikely 

to be a carcinogen, although it may form DNA adducts in 

vitro and inhibit mitotic spindle activity (Haighton et al., 

2002). IARC and NTP do not have ratings for bisphenol 

A with respect to human carcinogenicity. The epoxy resin 

oligomer, bisphenol A diglycidyl ether, has limited evidence 

of animal carcinogenicity and is not classifiable as a human 

carcinogen by IARC.

Biomonitoring Information

Urinary levels of bisphenol A include both conjugated 

and unconjugated forms and reflect recent exposure to 

the chemical. In the participants of NHANES 2003-

2004, prevalent exposure to bisphenol A in the U.S. 

population was demonstrated with children, females, and 

lower income strata having slightly higher urinary levels 

(Calafat et al., 2008). This study confirmed levels seen in 

an earlier smaller sample of 394 U.S. residents (Calafat 

et al., 2005). Several previous small studies in Japanese 

pregnant women, Japanese university students, and Korean 

residents have found mean urinary bisphenol A levels 

to be similar or up to several times higher than those in 

the U.S. representative NHANES 2003-2004 subsample 

(Fujimaki et al., 2004; Kim et al., 2003; Ouchi and 

Watanabe, 2002), although one study of 73 Koreans found 

levels that averaged seven times higher than median levels 

in the NHANES 2003-2004 subsample (Yang et al., 2003; 

Calafat et al., 2008). Applications of certain dental sealants 

were shown to increase urinary levels of bisphenol A for 24 

hours (Joskow et al., 2006). Hanaoka et al. (2002) studied 

workers with exposure to bisphenol A diglycidyl ether and 

found mean urinary levels of bisphenol A about double that 

of unexposed workers.

Finding a measurable amount of bisphenol A in the urine 

does not mean that the levels of bisphenol A cause an 

adverse health effect. Biomonitoring studies on levels of 

bisphenol A provide physicians and public health officials 

with reference values so that they can determine whether 

people have been exposed to higher levels of bisphenol A 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

Urinary Bisphenol A (2,2-bis[4-Hydroxyphenyl] propane) (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 2.58 (2.36-2.82) 2.50 (2.31-2.80) 4.29 (3.88-4.75) 7.67 (6.62-8.66) 11.2 (9.78-12.4) 2514 

Age group 

6-11 years 03-04 4.32 (3.63-5.14) 4.29 (3.63-5.23) 7.14 (5.83-9.56) 12.2 (9.84-14.8) 15.7 (12.2-23.2) 314 

12-19 years 03-04 2.80 (2.52-3.11) 2.74 (2.35-3.22) 4.74 (4.21-5.09) 7.79 (6.41-8.87) 11.8 (8.05-14.2) 713 

20 years and older 03-04 2.39 (2.17-2.64) 2.36 (2.15-2.59) 3.93 (3.44-4.33) 6.64 (5.97-7.74) 10.0 (9.01-11.4) 1487 

Gender 

Males 03-04 2.38 (2.15-2.63) 2.31 (2.08-2.70) 4.19 (3.81-4.64) 7.10 (6.41-8.28) 9.94 (9.06-11.7) 1228 

Females 03-04 2.78 (2.50-3.08) 2.68 (2.40-2.94) 4.41 (3.81-5.15) 7.93 (6.48-10.2) 12.4 (9.29-18.2) 1286 

Race/ethnicity 

Mexican Americans 03-04 2.34 (2.02-2.71) 2.38 (2.00-2.65) 3.85 (3.24-4.55) 7.09 (5.00-9.04) 10.9 (8.50-14.3) 612 

Non-Hispanic blacks 03-04 2.92 (2.58-3.32) 2.95 (2.51-3.27) 4.90 (4.07-6.13) 8.64 (7.53-9.63) 11.9 (10.2-13.3) 651 

Non-Hispanic whites 03-04 2.58 (2.37-2.81) 2.55 (2.32-2.80) 4.30 (3.93-4.67) 7.58 (6.32-8.87) 11.0 (9.34-12.4) 1091 
 32 Fourth National Report on Human Exposure to Environmental Chemicals 

Environmental Phenols

References

Akingbemi BT, Sottas CM, Koulova AI, Klinefelter GR, and 

Hardy MP. Inhibition of testicular steroidogenesis by the 

xenoestrogen bisphenol A is associated with reduced pituitary 

luteinizing hormone secretion and decreased steroidogenic 

enzyme gene expression in rat Leydig cells. Endocrinology 

2004;145:592-603.

Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, 

Needham LL. Urinary concentrations of bisphenol A and 

4-nonylphenol in a human reference population. Environ Health 

Perspect 2005;113(4):391-395.

Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Exposure 

of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 

2003-2004. Environ Health Perspect 2008;116(1):39-44.

Ema M, Fujii S, Furukawa M, Kiguchi M, Ikka T, Harazono A. 

Rat two-generation reproductive toxicity study of bisphenol A. 

Reprod Toxicol 2001; 5: 505-523.

European Commission. Bisphenol A. Human Health. DirectorateGeneral Health and Consumer Protection.Scientific Committee 

on Toxicity, Ecotoxicity and the Environment (CSTEE). May 22, 

2002. Brussels, Belgium. Available at URL: http://ec.europa.eu/

health/ph_risk/committees/sct/documents/out156_en.pdf . 2/4/09

European Commission. 4,4’-Isopropylidenediphenol 

(Bisphenol-A) Summary Assessment Report. Joint Research 

Centre Institute of Health and Consumer Protection. 2003. 

Ispra, Italy. Available at URL: http://ecb.jrc.it/DOCUMENTS/

Existing-Chemicals/RISK_ASSESSMENT/SUMMARY/

bisphenolasum325.pdf. 2/4/09

Fujimaki K, Arakawa C, Yoshinaga J, Watanabe C, Serizawa S, 

Imai H, et al. Estimation of intake level of bisphenol A in Japanese 

pregnant women based on measurement of urinary excretion level 

of the metabolite. Nippon Eiseigaku Zasshi 2004;59(4):403-408. 

Gray GM, Cohen JT, Cunha G, Hughes C, McConnell EE, 

Rhomberg et al. Weight of the evidence evaluation of low-dose 

reproductive and developmental effects of bisphenol A. Hum 

Ecol Risk Assess 2004;10:875-921.

Haighton LA, Hlywka JJ, Doull J, Kroes R, Lynch BS, Munro 

IC. An evaluation of the possible carcinogenicity of bisphenol A 

to humans. Regul Toxicol Pharmacol 2002;35(2 Pt 1):238-254.

Hanaoka T, Kawamura N, Hara K, Tsugane S. Urinary bisphenol 

A and plasma hormone concentrations in male workers exposed 

to bisphenol A diglycidyl ether and mixed organic solvents. 

Occup Environ Med 2002;59(9):625-628.

Joskow R, Barr DB, Barr JR, Calafat AM, Needham LL, Rubin 

C. Exposure to bisphenol A from bis-glycidyl dimethacrylatebased dental sealants. J Am Dent Assoc 2006;137(3):353-362.

Kim JC, Shin HC, Cha SW, Koh WS, Chung MK, Han SS. 

Evaluation of developmental toxicity in rats exposed to the 

environmental estrogen bisphenol A during pregnancy. Life Sci 

2001;69(22):2611-2625.

Kim YH, Kim CS, Park S, Han SY, Pyo MY, Yang M. Gender 

differences in the levels of bisphenol A metabolites in urine. 

Biochem Biophys Res Commun 2003;312(2):441-448.

Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, 

Barber LB, et al. Pharmaceuticals, hormones, and other organic 

wastewater contaminants in U.S. streams, 1999-2000: a national 

reconnaissance. Environ Sci Technol 2002;36(6):1202-1211.

Leranth, C., Szigeti-Buck, K., MacLusky, N.J., and Hajszan, T. 

Bisphenol A prevents the synaptogenic response to testosterone 

in the brain of adult male rats. Endocrinology 2008;149:988-994.

Matthews JB, Twomey K, Zacharewski TR. In vitro and in 

vivo interactions of bisphenol A and its metabolite, bisphenol A 

glucuronide, with estrogen receptors alpha and beta. Chem Res 

Toxicol 2001;14(2):149-157.

National Toxicology Program Center for the Evaluation of 

Risks to Human Production (NTP-CERHR). NTP-CERHR 

Panel Report on Reproductive and Developmental Toxicity of 

Bisphenol A. November 26, 2007. Available at URL: http://cerhr.

niehs.nih.gov/chemicals/bisphenol/BPAFinalEPVF112607.pdf. 

2/4/09

National Toxicology Program Center for the Evaluation of 

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Panel Report on Reproductive and Developmental Toxicity of 

Bisphenol A. September, 2008. Available at URL: http://cerhr.

niehs.nih.gov/chemicals/bisphenol/bisphenol.pdf . 2/4/09

National Toxicology Program’s Report of the Endocrine 

Disruptors Low-Dose Peer Review (NTP). August 2001. 

National Toxicology Program, U.S. Department of Health and 

Human Services. National Institute of Environmental Health 

Sciences, National Institutes of Health. Research Triangle Park, 

NC. Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/liason/

LowDosePeerFinalRpt.pdf. 2/4/09

Ouchi K, Watanabe S. Measurement of bisphenol A in human 

urine using liquid chromatography with multi-channel 

coulometric electrochemical detection. J Chromatogr B Analyt 

Technol Biomed Life Sci 2002;780(2):365-370.

Timms BG, Howdeshell KL, Barton L, Bradley S, Richter 

CA, vom Saal FS. Estrogenic chemicals in plastic and oral 

contraceptives disrupt development of the fetal mouse prostate 

and urethra. Proc Natl Acad Sci USA 2005;102(19):7014-7019.

Tyl RW, Myers CB, Marr MC, Thomas BF, Keimowitz AR, 

Brine DR, et al. Three-generation reproductive toxicity study 

of dietary bisphenol A in CD Sprague-Dawley rats. Toxicol Sci 

2002;68(1):121-146.
Fourth National Report on Human Exposure to Environmental Chemicals 33

 Environmental Phenols

Volkel W, Colnot T, Csanady GA, Filser JG, Dekant W. 

Metabolism and kinetics of bisphenol A in humans at low doses 

following oral administration. Chem Res Toxicol 2002;15:1281-

1287.

Vom Saal FS, Hughes C. An extensive new literature concerning 

low-dose effects of bisphenol A shows the need for a new risk 

assessment. Environ Health Perspect 2005;113(8):926-33.

Welshons WV, Nagel SC, vom Saal FS. Large effects from 

small exposures. III. Endocrine mechanisms mediating effects 

of bisphenol A at levels of human exposure. Endocrinology 

2006;147(6 Suppl):S56-69.

Wilson NK, Chuang JC, Morgan MK, Lordo RA, Sheldon LS. 

An observational study of the potential exposures of preschool 

children to pentachlorophenol, bisphenol-A, and nonylphenol at 

home and daycare. Environ Res 2007;103(1):9-20.

Witorsch RJ. Low-dose in utero effects of xenoestrogens in 

mice and their relevance to humans: an analytical review of the 

literature. Food Chem Toxicol 2002;40(7):905-12. 

Yang M, Kim SY, Lee SM, Chang SS, Kawamoto T, Jang JY, et 

al. Biological monitoring of bisphenol a in a Korean population. 

Arch Environ Contam Toxicol 2003;44(4):546-51.
 34 Fourth National Report on Human Exposure to Environmental Chemicals 

Environmental Phenols

4-tert-Octylphenol

CAS No. 140-66-9

General Information

4-tert-Octyphenol, an alkylphenol, is used to manufacture 

alkylphenol ethoxylates, which are anionic surfactants 

used in detergents, industrial cleaners, and emulsifiers. 

Commercial formulations of alkylphenol ethoxylates 

usually contain a mixture of oligomers and isomers, and 

the polyethoxy chain may consist of up to 50 ethoxy units. 

Less frequently, the various alkylphenols have also been 

used as emulsifiers and modifiers in paints, pesticides, 

textiles, and some personal care products. Alkylphenols 

also have been used as plasticizers and antioxidants in 

plastics and resins. In the 1990s, over 500,000 tons of 

alkylphenol ethoxylates were produced annually worldwide. 

Nonylphenol ethoxylates are more commonly used than 

octylphenol ethoxylates. The alkylphenol ethoxylates enter 

the environment through human use of products containing 

them, through sewage, and through manufacturing waste 

streams (Warhurst, 1995; Ying et al., 2002). They are 

biodegraded to the corresponding alkylphenol (octylphenol 

or nonylphenol); to shorter chain alkylphenol ethoxylates; 

and to alkylphenoxycarboxylates. Octylphenols and 

nonylphenols can also enter the environment directly from 

manufacturing waste streams. During the 1980s and 1990s, 

several European nations banned the use of alkylphenol 

ethoxylates in domestic detergents and other uses. The 

alkylphenols can bioaccumulate in some fish, and some 

of their degradation products are toxic to aquatic life. In 

1999-2000, 4-octylphenol monoethoxylate was detected in 

43.5% of 139 U.S. streams in 30 states (Kolpin et al., 2002).

Human exposure to alkylphenols and alkylphenol 

ethoxylates may occur through ingestion of contaminated 

foods (e.g., fish) and drinking water, and from contact with 

some personal care products and detergents. Indoor and to 

a lesser extent, outdoor air may have detectable levels of 

4-tert-octylphenol and 4-tert-octylphenol monoethoxylates, 

leading to inhalation as another potential exposure route 

(Rudel et al., 2003; Saito et al., 2004). In rats, orally 

administered 4-tert-octylphenol was well absorbed, did not 

bioaccumulate, and was quickly eliminated from the blood 

(Certa et al., 1996). Disposition in humans has not been 

studied sufficiently.

Human health effects from 4-tert-octylphenol or the 

corresponding octylphenol ethoxylates at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Several alkylphenols, including 

4-tert-octylphenol, have demonstrated estrogenic effects 

particularly when injected at high doses in animals. These 

high dose parenteral effects of 4-tert-octylphenol have 

included altered sex hormone levels and hypothalamicpituitary suppression, impaired steroidogenesis, altered 

estrus cycles and reproductive outcomes, altered neonatal 

sexual development, testicular atrophy, and impaired 

spermatogenesis (e.g., Bian et al., 2006; Blake and 

Boockfor, 1997; Katsuda et al., 2000; Laws et al., 2000; 

Urinary 4-tert-Octylphenol (4-[1,1,3,3-Tetramethylbutyl] phenol) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * .300 (<LOD-.500) .900 (.600-1.30) 1.70 (1.20-2.40) 2.30 (1.60-3.20) 2517 

Age group 

6-11 years 03-04 .357 (.268-.477) .400 (.200-.500) .900 (.600-1.40) 1.70 (1.20-2.10) 2.10 (1.50-2.90) 314 

12-19 years 03-04 .369 (.274-.497) .400 (.200-.600) 1.10 (.600-1.60) 1.80 (1.20-2.50) 2.40 (1.60-3.20) 715 

20 years and older 03-04 * .300 (<LOD-.500) .900 (.500-1.30) 1.70 (1.10-2.40) 2.30 (1.60-3.20) 1488 

Gender 

Males 03-04 * .300 (<LOD-.500) 1.00 (.500-1.50) 1.80 (1.20-2.40) 2.20 (1.60-3.90) 1229 

Females 03-04 * .300 (<LOD-.400) .900 (.600-1.20) 1.70 (1.20-2.30) 2.30 (1.50-3.00) 1288 

Race/ethnicity 

Mexican Americans 03-04 * < LOD .500 (.300-.600) .900 (.600-1.40) 1.30 (.800-1.80) 613 

Non-Hispanic blacks 03-04 .389 (.299-.507) .400 (.300-.600) 1.10 (.700-1.50) 2.00 (1.30-2.60) 2.50 (1.60-3.10) 652 

Non-Hispanic whites 03-04 * .300 (<LOD-.600) 1.00 (.600-1.50) 1.80 (1.20-2.50) 2.30 (1.60-3.60) 1092 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 35

 Environmental Phenols

Myllymaki et al., 2005; Nagao et al., 2001; Sweeney et al., 

2000; Yoshida et al., 2001). It is unclear if estrogenic or 

other effects occur in animals through oral dosing, at lower 

or environmentally relevant doses (Blake et al., 2004; Tyl 

et al., 1999). 4-tert-Octylphenol is not considered directly 

genotoxic. IARC and NTP have not rated octylphenol, 

nonylphenol, or their corresponding ethoxylates with 

respect to human carcinogenicity.

Biomonitoring Information

Urinary levels of 4-tert-octyphenol reflect recent exposure. 

Calafat et al. (2008) showed that urinary levels of 4-tertoctyphenol were detectable in slightly greater than half of 

the participants of the U.S. representative subsample of 

NHANES 2003-2004. In a small number of adult Japanese 

volunteers, the urinary concentrations of 4-tert-octyphenol 

were near or below the detection limit (Inoue et al. 2003; 

Kawaguchi et al. 2004).

Finding measurable amounts of 4-tert-octylphenol in the 

urine does not mean that the levels of 4-tert-octylphenol 

cause an adverse health effect. Biomonitoring studies on 

levels of 4-tert-octylphenol provide physicians and public 

health officials with reference values so that they can 

determine whether people have been exposed to higher 

levels of 4-tert-octylphenol than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Urinary 4-tert-Octylphenol (4-[1,1,3,3-Tetramethylbutyl] phenol) (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * .320 (<LOD-.470) .860 (.550-1.25) 1.85 (1.31-2.54) 2.76 (2.02-4.00) 2514 

Age group 

6-11 years 03-04 .435 (.337-.560) .460 (.280-.610) 1.17 (.730-1.62) 2.03 (1.67-2.15) 2.50 (2.03-6.00) 314 

12-19 years 03-04 .276 (.199-.384) .270 (.160-.450) .740 (.470-1.22) 1.62 (1.11-2.59) 2.62 (1.53-3.68) 713 

20 years and older 03-04 * .300 (<LOD-.450) .850 (.540-1.25) 1.81 (1.25-2.71) 2.78 (1.96-4.14) 1487 

Gender 

Males 03-04 * .260 (<LOD-.420) .740 (.470-1.11) 1.59 (1.05-2.29) 2.40 (1.65-3.33) 1228 

Females 03-04 * .370 (<LOD-.530) 1.00 (.630-1.43) 2.20 (1.43-3.00) 3.33 (2.40-4.78) 1286 

Race/ethnicity 

Mexican Americans 03-04 * < LOD .410 (.270-.620) .910 (.640-1.43) 1.64 (.890-2.73) 612 

Non-Hispanic blacks 03-04 .269 (.207-.349) .270 (.170-.400) .770 (.500-1.08) 1.60 (1.10-2.11) 2.31 (1.68-2.78) 651 

Non-Hispanic whites 03-04 * .380 (<LOD-.570) 1.00 (.620-1.41) 2.03 (1.36-3.00) 3.06 (2.18-4.24) 1091 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 36 Fourth National Report on Human Exposure to Environmental Chemicals 

Environmental Phenols

References

Bian Q, Qian J, Xu L, Chen J, Song L, Wang X. The toxic effects 

of 4-tert-octylphenol on the reproductive system of male rats. 

Food Chem Toxicol 2006;44(8):1355-1361.

Blake CA, Boockfor FR, Nair-Menon JU, Millette CF, 

Raychoudhury SS, McCoy GL. Effects of 4-tert-octylphenol 

given in drinking water for 4 months on the male reproductive 

system of Fischer 344 rats. Reprod Toxicol 2004;18(1):43-51.

Blake CA, Boockfor FR. Chronic administration of the 

environmental pollutant 4-tert-octylphenol to adult male rats 

interferes with the secretion of luteinizing hormone,folliclestimulating hormone, prolactin, and testosterone. Biol Reprod 

1997;57(2):255-266.

Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Exposure 

of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 

2003-2004. Environ Health Perspect 2008;116(1):39-44.

Certa H, Fedtke N, Wiegand HJ, Muller AM, Bolt HM. 

Toxicokinetics of p-tert-octylphenol in male Wistar rats. Arch 

Toxicol 1996;71(1-2):112-122.

Inoue K, Kawaguchi M, Okada F, Takai N, Yoshimura Y, 

Horie M, et al. 2003. Measurement of 4-nonylphenol and 

4-tert-octylphenol in human urine by column-switching liquid 

chromatography-mass spectrometry. Anal Chim Acta 486:41-50.

Katsuda S, Yoshida M, Watanabe G, Taya K, Maekawa A. 

Irreversible effects of neonatal exposure to p-tert-octylphenol 

on the reproductive tract in female rats. Toxicol Appl Pharmacol 

2000;165(3):217-226.

Kawaguchi M, Inoue K, Sakui N, Ito R, Izumi S, Makino T, 

et al. Stir bar sorptive extraction and thermal desorption-gas 

chromatography-mass spectrometry for the measurement of 

4-nonylphenol and 4-tert-octylphenol in human biological 

samples. J Chromatogr B Analyt Technol Biomed Life Sci 

2004;799(1):119-125.

Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, 

Barber LB, et al. Pharmaceuticals, hormones, and other organic 

wastewater contaminants in U.S. streams, 1999-2000: a national 

reconnaissance. Environ Sci Technol 2002;36(6):1202-1211.

Laws SC, Carey SA, Ferrell JM, Bodman GJ, Cooper RL. 

Estrogenic activity of octylphenol, nonylphenol, bisphenol A and 

methoxychlor in rats. Toxicol Sci 2000;54(1):154-167.

Myllymaki SA, Karjalainen M, Haavisto TE, Toppari J, Paranko 

J. Infantile 4-tert-octylphenol exposure transiently inhibits rat 

ovarian steroidogenesis and steroidogenic acute regulatory protein 

(StAR) expression. Toxicol Appl Pharmacol 2005;207(1):59-68.

Nagao T, Yoshimura S, Saito Y, Nakagomi M, Usumi K, Ono 

H. Reproductive effects in male and female rats from neonatal 

exposure to p-octylphenol. Reprod Toxicol 2001;15(6):683-692.

Rudel RA, Camann DE, Spengler JD, Korn LR, Brody JG. 

Phthalates, alkylphenols, pesticides, polybrominated diphenyl 

ethers, and other endocrine-disrupting compounds in indoor air 

and dust. Environ Sci Technol 2003;37(20):4543-53.

Saito I, Onuki A, Seto H. Indoor air pollution by alkylphenols in 

Tokyo. Indoor Air 2004;14(5):325-332. 

Sweeney T, Nicol L, Roche JF, Brooks AN. Maternal exposure to 

octylphenol suppresses ovine fetal follicle-stimulating hormone 

secretion, testis size, and sertoli cell number. Endocrinology 

2000;141(7):2667-2673.

Tyl RW, Myers CB, Marr MC, Brine DR, Fail PA, Seely JC, et al. 

Two-generation reproduction study with para-tert-octylphenol in 

rats. Regul Toxicol Pharmacol 1999;30(2 Pt 1):81-95.

Warhurst AM. An environmental assessment of alkylphenol 

ethoxylates and alkylphenols. 1995. Available at URL: http://

www.foe.co.uk/resource/reports/ethoxylates_alkylphenols.pdf.

2/4/09

Ying GG, Williams B, Kookana R. Environmental fate of 

alkylphenols and alkylphenol ethoxylates--a review. Environ Int 

2002;28(3):215-226.

Yoshida M, Katsuda S, Takenaka A, Watanabe G, Taya K, 

Maekawa A. Effects of neonatal exposure to a high-dose p-tertoctylphenol on the male reproductive tract in rats. Toxicol Lett 

2001;121(1):21-33.
Fourth National Report on Human Exposure to Environmental Chemicals 37

 Environmental Phenols

Triclosan

CAS No. 3380-34-5

General Information

Triclosan is a phenolic diphenyl ether used for over 30 

years as a preservative and antiseptic agent. It acts by 

inhibiting bacterial fatty acid synthesis. Triclosan has 

been added to soaps, toothpastes, mouthwashes, acne 

medications, deodorants, and wound disinfection solutions, 

and has also been impregnated into some kitchen utensils, 

toys, and medical devices. Triclosan enters the aquatic 

environment mainly through residential wastewaters. 

It can be photochemically and biologically degraded, a 

process that can result in the formation of small amounts 

of 2,8-dichlorodibenzo-p-dioxin (Aranami et al., 2007; 

Mezcua et al., 2004). In 1999-2000, triclosan was found in 

57.6% of 139 U.S. streams sampled in 30 states (Kolpin et 

al., 2002). Triclosan has a low bioaccumulation potential in 

fish. There is some concern that widespread use of triclosan 

and other biocides can alter antibiotic resistance in bacteria 

(Aiello et al., 2007).

General population exposure results from dermal and oral 

use of products containing triclosan. Triclosan can remain 

present in the oral saliva for several hours after the use 

of toothpaste containing triclosan (Gilbert et al., 1987). 

Triclosan can be absorbed across skin into the blood stream. 

In the body it is conjugated to glucuronides and sulfates 

(Bodey et al., 1976; Moss et al., 2000). In animal and 

human studies, it is excreted over several days in the feces 

and urine as primarily as unchanged triclosan (Kanetoshi et 

al., 1988; (Sandborgh-Englund et al., 2006).

Human health effects from triclosan at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Triclosan formulations may rarely 

cause skin irritation. In animal studies, it has low acute 

toxicity. Some reports show endocrine effects are observed 

in amphibians and fish (Foran et al., 2000; Matsumura et 

al., 2005; Veldhoen et al., 2007). Triclosan is not considered 

teratogenic at maternally toxic doses, and has not been 

considered mutagenic or carcinogenic (Bhargava and 

Leonard, 1996; Lyman and Furia, 1969). IARC and NTP 

do not have ratings with respect to human carcinogenicity. 

Biomonitoring Information

Urinary triclosan levels reflect recent exposure. In a U.S. 

representative subsample of NHANES 2003-2004, Calafat 

et al., 2008 has shown higher levels during the third decade 

of life and among people with the highest household 

income, but not by race/ethnicity and sex. In a study of 

90 U.S. young girls, the median urinary triclosan level of 

7.2 μg/L was comparable to the median level (8.2 μg/L) of 

children 6-11 years of age who participated in NHANES 

2003-2004 (Wolff et al., 2007; Calafat et al., 2008).

Finding measurable amounts of triclosan in the urine does 

not mean that the levels of triclosan cause an adverse health 

effect. Biomonitoring studies on levels of triclosan provide 

physicians and public health officials with a reference 

values so that they can determine whether people have 

been exposed to higher levels of triclosan than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.
 38 Fourth National Report on Human Exposure to Environmental Chemicals 

Environmental Phenols

Urinary Triclosan (2,4,4’-Trichloro-2’-hydroxyphenyl ether) (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 12.7 (11.5-14.1) 9.48 (8.22-10.4) 43.9 (33.8-60.6) 212 (172-241) 368 (294-463) 2514 

Age group 

6-11 years 03-04 9.93 (7.43-13.3) 7.55 (4.72-13.4) 25.1 (15.3-35.6) 116 (39.9-236) 236 (115-336) 314

12-19 years 03-04 10.9 (8.32-14.2) 7.45 (5.48-10.7) 31.8 (21.9-61.1) 193 (90.7-318) 356 (169-580) 713

20 years and older 03-04 13.4 (12.0-15.1) 10.0 (8.89-11.4) 50.0 (36.0-73.8) 224 (186-272) 385 (308-506) 1487 

Gender 

Males 03-04 13.2 (11.3-15.6) 9.21 (6.86-12.1) 73.1 (45.8-85.9) 237 (175-294) 384 (294-506) 1228 

Females 03-04 12.2 (10.6-14.2) 9.54 (8.45-10.4) 32.3 (26.2-46.6) 182 (138-217) 336 (225-480) 1286 

Race/ethnicity 

Mexican Americans 03-04 13.3 (9.38-18.8) 9.18 (5.45-13.9) 66.7 (28.8-112) 292 (151-432) 453 (263-1150) 612

Non-Hispanic blacks 03-04 9.94 (7.92-12.5) 7.74 (5.50-10.0) 30.2 (25.6-37.3) 132 (78.0-213) 260 (127-513) 651

Non-Hispanic whites 03-04 13.3 (11.6-15.1) 9.82 (8.11-11.5) 47.0 (34.3-67.7) 213 (160-272) 358 (276-480) 1091 

Urinary Triclosan (2,4,4’-Trichloro-2’-hydroxyphenyl ether) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 13.0 (11.6-14.6) 9.20 (7.90-10.9) 47.4 (38.2-58.4) 249 (188-304) 461 (383-522) 2517 

Age group 

6-11 years 03-04 8.16 (6.20-10.8) 6.00 (4.00-8.50) 20.7 (14.3-31.6) 123 (36.4-163) 157 (113-380) 314

12-19 years 03-04 14.5 (11.0-19.1) 10.3 (8.20-13.1) 39.0 (26.5-86.4) 304 (134-566) 655 (310-890) 715

20 years and older 03-04 13.6 (12.0-15.3) 9.60 (8.20-11.5) 51.7 (39.6-65.7) 261 (198-317) 472 (406-522) 1488 

Gender 

Males 03-04 16.2 (13.4-19.6) 11.7 (9.30-14.8) 84.9 (50.6-111) 317 (231-433) 574 (461-716) 1229 

Females 03-04 10.6 (9.29-12.1) 7.60 (6.10-9.10) 33.2 (27.1-39.4) 144 (96.5-250) 380 (258-430) 1288 

Race/ethnicity 

Mexican Americans 03-04 14.6 (10.6-20.1) 8.80 (5.40-17.5) 65.4 (32.8-127) 357 (225-456) 597 (372-992) 613

Non-Hispanic blacks 03-04 14.4 (11.4-18.2) 11.1 (8.70-16.1) 37.6 (30.2-58.0) 203 (87.5-341) 450 (254-750) 652

Non-Hispanic whites 03-04 12.9 (11.2-14.9) 9.20 (7.40-11.0) 49.2 (37.8-63.4) 245 (163-334) 461 (383-527) 1092 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 2.3. 
Fourth National Report on Human Exposure to Environmental Chemicals 39

 Environmental Phenols

References

Aiello AE, Larson EL, Levy SB. Consumer antibacterial 

soaps: effective or just risky? Clin Infect Dis 2007;45 Suppl 

2:S137-S147.

Aranami K, Readman JW. Photolytic degradation of triclosan in 

freshwater and seawater. Chemosphere 2007;66:1052-1056.

Bhargava HN, Leonard PA.. Triclosan: applications and safety. 

Am J Infect Control 1996;24(3):209-218.

Bodey GP, Ebersole R, Hong HC. Randomized trial of a 

hexachlorophene preparation and P-300 bacteriostatic soaps. J 

Invest Dermatol 1976;67(4):532-537.

Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Urinary 

concentrations of triclosan in the U.S. population: 2003-2004. 

Environ Health Perspect 2008;116(3):303-307.

Foran CM, Bennett ER, Benson WH. Developmental evaluation 

of a potential non-steroidal estrogen: triclosan. Mar Environ Res 

2000;50(1-5):153-156.

Gilbert RJ, Williams PE. The oral retention and antiplaque 

efficacy of triclosan in human volunteers. Br J Clin Pharmacol 

1987;23(5):579-583.

Kanetoshi A, Ogawa H, Katsura E, Okui T, Kaneshima 

H. Disposition and excretion of Irgasan DP300 and its 

chlorinated derivatives in mice. Arch Environ Contam Toxicol 

1988;17(5):637-644.

Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, 

Barber LB, et al. Pharmaceuticals, hormones, and other organic 

wastewater contaminants in U.S. streams, 1999-2000: a national 

reconnaissance. Environ Sci Technol 2002;36(6):1202-1211.

Lyman FL, Furia T. Toxicology of 2, 4, 4’-trichloro-2’-hydroxydiphenyl ether. IMS Ind Med Surg 1969;38(2):64-71.

Matsumura N, Ishibashi H, Hirano M, Nagao Y, Watanabe 

N, Shiratsuchi H, et al. Effects of nonylphenol and triclosan 

on production of plasma vitellogenin and testosterone in male 

South African clawed frogs (Xenopus laevis). Biol Pharm Bull 

2005;28(9):1748-1751.

Mezcua M, Gomez MJ, Ferrer I, Aguera A, Hernando MD, 

Fernandez-Alba AR. Evidence of 2,7/2,8-dibenzodichloro-pdioxin as a photodegradation product of triclosan in water and 

wastewater samples. Anal Chim Acta 1004;524:241-247.

Moss T, Howes D, Williams FM. Percutaneous penetration 

and dermal metabolism of triclosan (2,4,4’-trichloro-2’-

hydroxydiphenyl ether). Food Chem Toxicol 2000;38(4):361-

370.

Sandborgh-Englund G, Adolfsson-Erici M, Odham G, Ekstrand 

J. Pharmacokinetics of triclosan following oral ingestion in 

humans. J Toxicol Environ Health A 2006;69(20):1861-1873.

Veldhoen N, Skirrow RC, Osachoff H, Wigmore H, Clapson 

DJ, Gunderson MP, et al. The bactericidal agent triclosan 

modulates thyroid hormone-associated gene expression and 

disrupts postembryonic anuran development. Aquat Toxicol 

2006;80(3):217-227. Erratum in: Aquat Toxicol 2007;83(1):84.

Wolff MS, Teitelbaum SL, Windham G, Pinney SM, Britton 

JA, Chelimo C, et al. Pilot study of urinary biomarkers of 

phytoestrogens, phthalates, and phenols in girls. Environ Health 

Perspect 2007;115:116-121.
 40 Fourth National Report on Human Exposure to Environmental Chemicals 

Fungicides

Pentachlorophenol 

CAS No. 87-86-5

Also a Metabolite of Several Organochlorine Insecticides

General Information

Pentachlorophenol (PCP) and its sodium salt were 

once widely used as a fungicide, bactericide, herbicide, 

mollusicide, algaecide and insecticide. Since 1984, PCP 

use in the U.S. has been restricted, and it is used primarily 

as a preservative for wood to be used outdoors (e.g., utility 

poles and fence posts). PCP cannot be used on wood in 

residential or agricultural buildings. PCP has been detected 

in soils, air, water and sediments because of the large 

amounts that were produced and used historically. In the 

environment, PCP is degraded by sunlight and metabolized 

rapidly by microorganisms, plants, and animals, so it is 

relatively non-persistent. General population exposure to 

PCP may occur by inhalation of contaminated air, ingestion 

of contaminated food or water, and dermal contact with 

PCP-treated products. Human exposure to PCP has become 

less common. Workers who manufacture or apply PCP may 

inhale it or absorb it through exposed skin.

PCP is absorbed rapidly and well by all exposure 

routes. After absorption, PCP is distributed to most 

tissues and is not extensively metabolized. The parent 

compound and conjugates, along with small amounts of 

tetrachlorohydroquinone and conjugates, are eliminated 

in the urine. After a single dose, PCP is eliminated over 

a few days (Braun et al., 1979); with repeated or chronic 

exposure, the elimination half-life may be a week or more 

(Uhl et al., 1986). PCP also may be eliminated in urine as 

a metabolite of hexachlorobenzene, other polychlorinated 

benzenes, and possibly of lindane (IPCS, 2002; Kohli et al., 

1976; To-Figueras et al., 1997).

Human health effects from PCP at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Acute, high dose exposure to 

PCP can induce a hypermetabolic state and excessive 

heat production as a result of uncoupling mitochondrial 

oxidative phosphorylation. Effects including hyperthermia, 

hypertension, and metabolic acidosis were observed in 

Urinary Pentachlorophenol 

Also a Metabolite of Several Organochlorine Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * .350 (.350-.350) .350 (.350-.350) .390 (.350-.960) 1.30 (.500-2.10) 1994 

01-02 * < LOD < LOD 1.23 (.590-1.76) 1.94 (1.58-2.53) 2528 

Age group 

6-11 years 99-00 * .350 (.350-.350) .350 (.350-.350) .770 (.350-1.51) 1.65 (.990-2.00) 482

01-02 * < LOD < LOD 1.37 (.890-1.70) 2.10 (1.58-2.75) 577

12-19 years 99-00 * .350 (.350-.350) .350 (.350-.350) .660 (.350-2.60) 2.00 (.510-5.90) 681

01-02 * < LOD < LOD 1.48 (.850-2.30) 2.30 (1.47-5.04) 826

20-59 years 99-00 * .350 (.350-.350) .350 (.350-.350) .350 (.350-.650) 1.10 (.350-2.00) 831

01-02 * < LOD < LOD 1.01 (<LOD-1.76) 1.90 (1.45-2.53) 1125 

Gender 

Males 99-00 * .350 (.350-.350) .350 (.350-.350) .630 (.350-1.30) 1.40 (.480-2.60) 973

01-02 * < LOD < LOD 1.32 (.680-1.80) 1.94 (1.47-3.09) 1190 

Females 99-00 * .350 (.350-.350) .350 (.350-.350) .350 (.350-.530) .890 (.350-2.00) 1021 

01-02 * < LOD < LOD 1.10 (<LOD-1.78) 1.98 (1.54-2.42) 1338 

Race/ethnicity 

Mexican Americans 99-00 * .350 (.350-.350) .350 (.350-.350) .350 (.350-.350) .650 (.350-1.90) 696

01-02 * < LOD < LOD .990 (<LOD-2.37) 1.62 (.510-3.64) 680

Non-Hispanic blacks 99-00 * .350 (.350-.350) .350 (.350-.350) .980 (.350-2.50) 1.65 (.860-2.70) 521

01-02 * < LOD < LOD 1.73 (1.33-2.33) 2.83 (2.08-3.67) 696

Non-Hispanic whites 99-00 * .350 (.350-.350) .350 (.350-.350) .390 (.350-1.10) 1.30 (.350-2.30) 603

01-02 * < LOD < LOD 1.18 (<LOD-1.76) 1.91 (1.48-2.42) 951

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.25 and 0.5. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 41

 Fungicides

adults and children severely exposed to PCP through 

ingestion, inhalation, or skin absorption. Death can 

result from seizures and cardiovascular collapse. In 

animals, chronically administered high doses of PCP 

were hepatotoxic, carcinogenic, and adversely affected 

thyroid function (U.S.EPA, 2004; van Raaij et al., 1991). 

Pentachlorophenol is not mutagenic or teratogenic. 

IARC has determined that pentachlorophenol is possibly 

carcinogenic to humans.

The U.S. EPA has developed standards for PCP in drinking 

water and the environment, and the FDA has established 

a standard for bottled water. OSHA has established an 

occupational standard. More information about external 

exposure (i.e., environmental levels) and health effects 

is available from the U.S. EPA at: http://www.epa.gov/

pesticides/ and from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html.

Biomonitoring Information

In NHANES 1999-2000 the median urinary PCP levels 

among children aged 6-11 and 12-19 years were as much 

as thirteen times lower compared to a sample of German 

children aged 6-14 years in 1990-1992 (4.6 and 14.9 mg/L, 

respectively) (Seifert et al., 2000). Among adults in the 

NHANES 1999-2000 subsample, the median and 95th

percentile urinary PCP levels were approximately three 

times lower than comparable values in German adults 

(2.08 and 5.0	mg/L, respectively) (Becker et al., 2003). In 

NHANES 2001-2002 subsamples, urinary PCP levels at the 

95th percentile were approximately fivefold lower than 95th

percentile values measured in a nonrandom subsample from 

NHANES III (1988-1994) participants (Hill et al., 1995). 

Urinary PCP levels at the 95th percentile in this Report are 

approximately half the corresponding 95th percentile values 

found in German adults evaluated in 1998 (Becker et al., 

2003). In a small sample of U.S. children in the 1980’s, 

the 95th percentile of urinary PCP levels was about fiftyfold 

higher than that for 6-11 year olds in NHANES 2001-2002

(Hill et al., 1989). Urinary levels of pentachlorophenol in 

the general population are far below (hundreds of times 

lower than) urine levels reported for workplace exposure 

to PCP or among people living in PCP-treated log homes 

(Cline et al., 1989).

Urinary Pentachlorophenol (creatinine corrected) 

Also a Metabolite of Several Organochlorine Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * .300 (.290-.320) .570 (.500-.650) 1.16 (.950-1.35) 1.67 (1.35-2.11) 1994 

01-02 * < LOD < LOD 1.52 (1.25-1.75) 2.26 (1.67-3.09) 2527 

Age group 

6-11 years 99-00 * .370 (.340-.420) .650 (.580-.780) .990 (.900-1.30) 1.83 (1.10-2.95) 482

01-02 * < LOD < LOD 1.84 (1.29-3.18) 3.18 (1.84-4.52) 577

12-19 years 99-00 * .250 (.220-.290) .400 (.330-.490) .760 (.500-1.40) 1.57 (.700-2.51) 681

01-02 * < LOD < LOD 1.21 (.910-1.56) 1.82 (1.25-2.82) 825

20-59 years 99-00 * .300 (.270-.320) .610 (.510-.730) 1.25 (1.00-1.40) 1.67 (1.30-2.19) 831

01-02 * < LOD < LOD 1.52 (<LOD-1.75) 2.19 (1.67-2.99) 1125 

Gender 

Males 99-00 * .260 (.240-.280) .470 (.380-.560) .920 (.780-1.25) 1.67 (1.16-1.84) 973

01-02 * < LOD < LOD 1.13 (.950-1.40) 1.73 (1.25-2.92) 1190 

Females 99-00 * .360 (.310-.430) .650 (.560-.830) 1.26 (1.09-1.35) 1.67 (1.35-2.19) 1021 

01-02 * < LOD < LOD 1.75 (<LOD-2.06) 2.69 (1.94-3.55) 1337 

Race/ethnicity 

Mexican Americans 99-00 * .300 (.270-.320) .500 (.430-.560) 1.06 (.710-1.40) 1.57 (1.21-2.00) 696

01-02 * < LOD < LOD 1.09 (<LOD-2.36) 1.94 (1.06-3.55) 680

Non-Hispanic blacks 99-00 * .250 (.220-.310) .440 (.360-.590) .850 (.590-1.30) 1.34 (.950-1.90) 521

01-02 * < LOD < LOD 1.30 (.800-1.78) 1.94 (1.48-2.79) 695

Non-Hispanic whites 99-00 * .320 (.290-.350) .630 (.510-.800) 1.25 (1.00-1.40) 1.67 (1.40-2.19) 603

01-02 * < LOD < LOD 1.52 (<LOD-1.78) 2.10 (1.67-3.08) 951

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 42 Fourth National Report on Human Exposure to Environmental Chemicals 

Fungicides

Finding a measurable amount of PCP in urine does not 

mean that the level of PCP causes an adverse health effect. 

Biomonitoring studies on levels of PCP provide physicians 

and public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of PCP than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research about PCP exposure and health effects.

References

Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German 

environmental survey 1998 (GerES III): environmental pollutants 

in the urine of the German population. Int J Hyg Environ Health 

2003; 206:15-24.

Braun WH, Blau GE, Chenoweth MB. The metabolism/ 

pharmacokinetics of pentachlorophenol in man and a comparison 

with the rat and monkey. Dev Toxicol Environ Sci 1979;4:289-

296.

Cline RE, Hill RH, Phillips DL, Needham LL. Pentachlorophenol 

measurements in body fluids of people in log homes and 

workplaces. Arch Environ Contam Toxicol 1989;18:475-481.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, 

et al. Pesticide residues in urine of adults living in the United 

States: reference range concentrations. Environ Res 1995;71:99-

108.

Hill RH Jr, To T, Holler JS, Fast DM, Smith SJ, Needham LL, et 

al. Residues of chlorinated phenols and phenoxy acid herbicides 

in the urine of Arkansas children. Arch Environ Contam Toxicol 

1989;18(4):469-474.

International Programme on Chemical Safety (IPCS). Pesticide 

residues in food-2002-Joint FAO/WHO meeting on pesticide 

residues. Lindane. 2002. available at URL:

http://www.inchem.org/documents/jmpr/jmpmono/2002pr08.

htm. 4/21/09

Kohli J, Jones D, Safe A. The metabolism of higher chlorinated 

benzene isomers. Can J Biochem 1976;54(3):203-208.

Seifert B, Becker K, Helm D, Krause C, Schulz C, Seiwert M. 

The German Environmental Survey 1990/1992 (GerES II): 

reference concentrations of selected environmental pollutants in 

blood, urine, hair, house dust, drinking water and indoor air. J 

Expo Anal Environ Epidemiol 2000;10:552-65.

To-Figueras J, Sala M, Otero R, Barrot C, Santiago-Silva 

M, Rodamilans M, et al. Metabolism of hexachlorobenzene 

in humans: association between serum levels and urinary 

metabolites in a highly exposed population. Environ Health 

Perspect 1997;105(1):78-83.

Uhl S, Schmid P, Schlatter C. Pharmacokinetics of 

pentachlorophenol in man. Arch Toxicol 1986;58:182-186.

U.S. Environmental Protection Agency (U.S. EPA). PCP: Human 

Risk Characterization [online]. 11/30/2004. Available at URL:

http://www.regulations.gov/fdmspublic/component/

main?main=DocketDetail&d=EPA-HQ-OPP-2004-0402. 

4/21/09

van Raaij JA, van den Berg KJ, Engel R, Bragt PC, Notten 

WR. Effects of hexachlorobenzene and its metabolites 

pentachlorophenol and tetrachlorohydroquinone on serum 

thyroid hormone levels in rats. Toxicology 1991: 67(1):107-16.
Fourth National Report on Human Exposure to Environmental Chemicals 43

 Fungicides

ortho-Phenylphenol

CAS No. 90-43-7

General Information

Ortho-phenylphenol (OPP, or 2-phenylphenol) and its 

water-soluble salt, sodium ortho-phenylphenate (SOPP), 

are antimicrobial agents used as bacteriostats, fungicides, 

and sanitizers. Both have been used in agriculture to control 

fungal and bacterial growth on stored crops, such as fruits 

and vegetables. SOPP is applied topically to the crop and 

then rinsed off, leaving the chemical residue OPP. Most 

agricultural food applications have been revoked, but OPP 

and SOPP are still used on pears and citrus (U.S.EPA, 

2006). OPP is still used as a disinfectant fungicide for 

industrial applications, on ornamental plants and turfs, in 

paints, and as a wood preservative. In the past, it was used 

in home sanitizers for surfaces. OPP is volatile, and it has 

limited water solubility, whereas SOPP is not volatile and is 

more water soluble. Both chemicals degrade within hours 

to weeks in the environment (U.S. EPA, 2006).

General population exposure can occur via dermal, 

inhalational, or oral routes from residential use and by 

ingesting treated food or food that was in contact with 

treated surfaces or equipment. OPP was detected in 40 

of 60 different canned beers at concentrations in the low 

parts per billion (Coelhan et al., 2006). Estimated human 

intakes have been below recommended intake limits 

(U.S.EPA, 2006). Workers who manufacture, formulate, 

or apply these chemicals may be more highly exposed 

than the general population. OPP is efficiently absorbed 

from the gastrointestinal tract and through the skin, and it 

is eliminated rapidly from the body as OPP glucuronide 

and sulfate conjugates (Bartels et al., 1998; Cnubben et al. 

2002; Timchalk et al., 1998). Available evidence suggests 

that OPP does not accumulate in the body; however, small 

amounts of OPP have been measured in human adipose 

tissue (Onstot and Stanley, 1989).

Human health effects from OPP at low environmental doses 

or at biomonitored levels from low environmental exposures 

are unknown. OPP is considered to be moderately toxic 

after acute oral doses in animal studies. Chronic dosing in 

animals resulted in such systemic effects as weight loss and 

Urinary ortho-Phenylphenol 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 .497 (.390-.632) .490 (<LOD-.600) .850 (.600-1.30) 1.50 (1.10-2.10) 2.00 (1.60-3.80) 1991 

01-02 * < LOD < LOD .570 (.370-.860) 1.27 (.710-2.85) 2529 

Age group 

6-11 years 99-00 .509 (.402-.645) .490 (<LOD-.630) .890 (.610-1.50) 1.90 (1.30-2.10) 2.20 (1.80-3.90) 480 

01-02 * < LOD < LOD 1.17 (.760-2.02) 2.30 (1.28-3.61) 577 

12-19 years 99-00 .508 (.370-.696) .490 (<LOD-.690) .890 (.570-1.50) 1.60 (1.20-3.50) 2.10 (1.40-7.20) 681 

01-02 * < LOD < LOD .740 (.480-1.34) 2.33 (.800-3.09) 827 

20-59 years 99-00 .493 (.389-.624) .490 (<LOD-.600) .820 (.600-1.20) 1.50 (1.10-1.90) 2.00 (1.50-2.90) 830 

01-02 * < LOD < LOD .450 (<LOD-.670) .930 (.540-2.23) 1125 

Gender 

Males 99-00 .498 (.389-.638) .470 (<LOD-.640) .830 (.600-1.30) 1.60 (1.20-2.00) 2.00 (1.50-3.90) 973 

01-02 * < LOD < LOD .610 (.350-1.03) 1.28 (.750-2.85) 1190 

Females 99-00 .496 (.386-.636) .490 (<LOD-.600) .860 (.580-1.30) 1.50 (1.00-2.10) 2.10 (1.50-4.50) 1018 

01-02 * < LOD < LOD .520 (.370-.790) 1.22 (.590-2.91) 1339 

Race/ethnicity 

Mexican Americans 99-00 .552 (.364-.836) .420 (<LOD-.950) 1.20 (.500-2.00) 2.20 (1.40-5.80) 3.80 (2.30-7.10) 695 

01-02 * < LOD < LOD 1.14 (<LOD-3.88) 2.92 (.560-8.22) 680 

Non-Hispanic blacks 99-00 .567 (.433-.742) .570 (.410-.780) .970 (.690-1.50) 1.60 (1.40-2.00) 2.00 (1.60-2.30) 520 

01-02 * < LOD < LOD .770 (.570-.890) 1.19 (.840-1.76) 695 

Non-Hispanic whites 99-00 .466 (.349-.621) .450 (<LOD-.600) .770 (.550-1.20) 1.40 (.880-2.10) 1.90 (1.40-5.10) 603 

01-02 * < LOD < LOD .450 (<LOD-.710) 1.07 (.570-2.23) 953 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.3 and 0.3. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 44 Fourth National Report on Human Exposure to Environmental Chemicals 

Fungicides

anemia, but no neurologic, reproductive, or developmental 

toxicity was observed (Bomhard et al., 2002; U.S.EPA 

2006). OPP was not found to be mutagenic. Dermally 

applied OPP was not carcinogenic in a 2-year experimental 

study in animals (NTP, 1986). In high dose animal studies, 

OPP or SOPP produced carcinomas of the bladder only after 

phase II detoxification pathways were saturated, leading to 

production of two metabolites, ortho-phenylhydroquinone 

and ortho-phenylbenzoquinone. These metabolites may 

induce carcinogenicity via nongenotoxic regenerative 

hyperplasia of the bladder (Appel, 2000; Bomhard et 

al., 2002; Brusick, 2005; Kwok et al., 1999; Nakagawa 

et al., 1992; Smith et al., 1998; U.S.EPA 2006), or, less 

likely, by possible genotoxic mechanisms (Hagiwara et 

al., 1984; Ito et al., 1984; Murata et al., 1999; Pathak and 

Roy, 1993; Zhao et al., 2002). IARC has classified SOPP 

as a possible human carcinogen, and it has classified OPP 

as not classifiable with respect to human carcinogenicity. 

Additional information is available from U.S.EPA at: http://

www.epa.gov/pesticides/.

Biomonitoring Information

Urinary OPP levels reflect recent exposure. Detectable 

levels were seen in over half the U.S. population in the 

subsamples from NHANES 1999-2000 and 2001-2002 

(CDC, 2005). Volunteers exposed to 0.4 mg dermally had 

urinary levels of OPP that were several hundred times 

higher than median levels found in NHANES 1999-2000 

and 2001-2002 (Bartels et al., 1997; CDC, 2005).

Finding a measurable amount of OPP in urine does not 

mean that the level of OPP causes an adverse health effect. 

Biomonitoring studies on levels of OPP provide physicians 

and public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of OPP than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

Urinary ortho-Phenylphenol (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 .444 (.353-.558) .410 (<LOD-.560) .840 (.620-1.11) 1.84 (1.24-2.33) 2.97 (2.04-4.29) 1991 

01-02 * < LOD < LOD .980 (.810-1.17) 1.75 (1.21-2.33) 2528 

Age group 

6-11 years 99-00 .550 (.455-.666) .510 (<LOD-.670) 1.02 (.800-1.27) 1.96 (1.43-2.59) 2.64 (2.09-3.58) 480 

01-02 * < LOD < LOD 1.91 (1.08-2.53) 2.69 (1.96-4.01) 577 

12-19 years 99-00 .343 (.248-.473) .320 (<LOD-.500) .690 (.460-.950) 1.17 (.880-1.93) 1.96 (1.09-6.32) 681 

01-02 * < LOD < LOD .780 (.640-1.21) 1.52 (.940-2.32) 826 

20-59 years 99-00 .453 (.361-.568) .420 (<LOD-.570) .860 (.620-1.12) 1.89 (1.24-2.47) 3.28 (2.06-4.93) 830 

01-02 * < LOD < LOD .910 (<LOD-1.07) 1.44 (1.05-2.30) 1125 

Gender 

Males 99-00 .382 (.301-.484) .360 (<LOD-.470) .750 (.550-.990) 1.43 (1.08-1.93) 2.09 (1.51-3.29) 973 

01-02 * < LOD < LOD .750 (.580-1.17) 1.61 (.750-2.43) 1190 

Females 99-00 .514 (.403-.656) .470 (<LOD-.580) .910 (.650-1.46) 2.06 (1.38-3.38) 3.78 (2.06-5.96) 1018 

01-02 * < LOD < LOD 1.11 (.910-1.38) 1.75 (1.33-2.38) 1338 

Race/ethnicity 

Mexican Americans 99-00 .496 (.311-.791) .420 (<LOD-.810) 1.11 (.560-2.31) 3.00 (1.25-6.08) 4.61 (2.40-13.4) 695 

01-02 * < LOD < LOD 1.28 (<LOD-4.26) 3.00 (.780-14.0) 680 

Non-Hispanic blacks 99-00 .385 (.291-.508) .380 (.270-.550) .670 (.510-.900) 1.21 (.900-1.62) 1.74 (1.43-2.13) 520 

01-02 * < LOD < LOD .670 (.480-.970) 1.17 (.770-2.18) 694 

Non-Hispanic whites 99-00 .440 (.329-.590) .410 (<LOD-.610) .860 (.600-1.20) 1.86 (1.12-2.59) 2.93 (1.88-4.81) 603 

01-02 * < LOD < LOD .980 (<LOD-1.11) 1.61 (1.11-1.91) 953 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 45

 Fungicides

References

Appel KE. The carcinogenicity of the biocide ortho-phenylphenol. 

Arch Toxicol 2000;74(2):61-71.

Brusick D. Analysis of genotoxicity and the carcinogenic 

mode of action for ortho-phenylphenol. Environ Mol Mutagen 

2005;45(5):460-481.

Bartels MJ, Brzak KA, Bormett GA. Determination of orthophenylphenol in human urine by gas chromatography-mass 

spectrometry. J Chromatogr B Biomed Sci Appl 1997;703(1-

2):97-104.

Bartels MJ, McNett DA, Timchalk C, Mendrala AL, Christenson 

WR, Sangha GK, et al.. Comparative metabolism of orthophenylphenol in mouse, rat and man. Xenobiotica 1998;28(6):579-

594.

Bomhard EM, Brendler-Schwaab SY, Freyberger A, Herbold 

BA, Leser KH, Richter M. O-phenylphenol and its sodium and 

potassium salts: a toxicological assessment. Crit Rev Toxicol 

2002;32(6):551-625.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Cnubben NH, Elliott GR, Hakkert BC, Meuling WJ, van de 

Sandt JJ. Comparative in vitro-in vivo percutaneous penetration 

of the fungicide ortho-phenylphenol. Regul Toxicol Pharmacol 

2002;35(2 Pt 1):198-208.

Coelhan M, Bromig KH, Glas K, Roberts AL. Determination and 

levels of the biocide ortho-phenylphenol in canned beers from 

different countries. J Agric Food Chem 2006;54(16):5731-5735. 

Hagiwara A, Shibata M, Hirose M, Fukushima S, Ito N. Long-term 

toxicity and carcinogenicity study of sodium o-phenylphenate in 

B6C3F1 mice. Food Chem Toxicol 1984;22(10):809-814.

Ito N, Fukushima S, Shirai T, Hagiwara A, Imaida K. Drugs, food 

additives and natural products as promoters in rat urinary bladder 

carcinogenesis. IARC Sci Publ 1984;(56):399-407.

Kwok ES, Buchholz BA, Vogel JS, Turteltaub KW, Eastmond 

DA. Dose-dependent binding of ortho-phenylphenol to protein 

but not DNA in the urinary bladder of male F344 rats. Toxicol 

Appl Pharmacol 1999;159(1):18-24.

Murata M, Moriya K, Inoue S, Kawanishi S. Oxidative damage 

to cellular and isolated DNA by metabolites of a fungicide orthophenylphenol. Carcinogenesis 1999;20(5):851-857.

Nakagawa Y, Tayama S, Moore GA, Moldeus P. Relationship 

between metabolism and cytotoxicity of ortho-phenylphenol in 

isolated rat hepatocytes. Biochem Pharmacol 1992;43(7):1431-

1437.

National Toxicology Program (NTP). NTP Technical report on 

the toxicology and carcinogenesis studies of ortho-phenylphenol 

(CAS No. 90-43-7) in Swiss CD-1 mice (dermal studies). March 

1986. Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/LT_

rpts/tr301.pdf. 4/13/09

Onstot JD, Stanley JS. Identification of SARA compounds in 

adipose tissue. U.S. Environmental Protection Agency (U.S. 

EPA), Office of Toxic Substances; 1989. EPA-560/5-89-003.

Pathak DN, Roy D. In vivo genotoxicity of sodium orthophenylphenol: phenylbenzoquinone is one of the DNA-binding 

metabolite(s) of sodium ortho-phenylphenol. Mutat Res 

1993;286(2):309-319.

Smith RA, Christenson WR, Bartels MJ, Arnold LL, St John 

MK, Cano M, et al. Urinary physiologic and chemical metabolic 

effects on the urothelial cytotoxicity and potential DNA adducts 

of o-phenylphenol in male rats. Toxicol Appl Pharmacol 

1998;150(2):402-413.

Timchalk C, Selim S, Sangha G, Bartels MJ. The pharmacokinetics 

and metabolism of 14C/13C-labeled ortho-phenylphenol 

formation following dermal application to human volunteers. 

Hum Exp Toxicol 1998;17(8):411-417.

U.S. Environmental Protection Agency (U.S.EPA). Reregistration 

Eligibility Decision (RED) for 2-phenylphenol and salts 

(Orthophenylphenol or OPP). July 28, 2006. EPA 739 R-06-

004. Available at URL: http://www.epa.gov/oppsrrd1/REDs/

phenylphenol_red.pdf. 4/9/09.

Zhao S, Narang A, Gierthy J, Eadon G. Detection and 

characterization of DNA adducts formed from metabolites 

of the fungicide ortho-phenylphenol. J Agric Food Chem 

2002;50(11):3351-3358.
 46 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

Herbicides

Herbicides are used to control undesirable weeds and plants 

in agricultural, residential, and aquatic environments. More 

herbicides are used annually than insecticides, with about 

553 million pounds of herbicides used in the U.S. during 

2001 (U.S.EPA, 2004). The herbicides discussed in this 

Report can be classified into the following categories: 

chlorophenoxy acids, chloroacetanilides, and atrazine.

General population exposure may result from herbicides 

used in residential, forestal, or agricultural applications, 

from residues on food, or from contamination of drinking 

water. Workers who manufacture, formulate, or apply these 

chemicals have greater exposure to herbicides than others. 

The FDA, U.S.EPA, and OSHA have developed criteria for 

the allowable levels for many of these chemicals in foods, 

drinking water and other environmental media, and the 

workplace, respectively.

Reference

U. S. Environmental Protection Agency (U.S.EPA). Office of 

Prevention Pesticides and Toxic Substances. Pesticide industry 

sales and usage - 2000 and 2001 market estimates. Washington 

(DC): U.S.EPA. May, 2004. Available at URL: http://www.epa.

gov/oppbead1/pestsales/01pestsales/market_estimates2001.pdf. 

3/17/09
Fourth National Report on Human Exposure to Environmental Chemicals 47

 Herbicides

Acetochlor

CAS No. 34256-82-1

General Information

Acetochlor is a chloroacetanilide type herbicide with 

restricted usage for preemergent control of grasses and 

broadleaf weeds on agricultural crop land, mainly corn. It 

is absorbed by plants and inhibits plant protein synthesis. 

Acetochlor is microbiologically degraded, remains in soils 

for up to 3 months, and has been detected in watersheds 

of agricultural lands (Battaglin et al., 2000; Hladik et al., 

2005; Kolpin et al., 2000). Acetochlor degrades in water 

to acetochlor sulfonic acid and acetochlor oxanilic acid. 

Plants can degrade acetochlor to 2-ethyl-6-methylaniline, 

2-hydroxyethyl-6-methylaniline, and hydroxymethyl ethyl 

aniline (U.S.EPA, 2006). Acetochlor is moderately toxic to 

fish and honey bees.

General population exposure to acetochlor may occur 

through diet or drinking water. Estimated human intakes of 

acetochlor have been below recommended limits (U.S.EPA, 

2006). In animals, a major pathway for acetochlor 

metabolism involves mercapturate conjugation, but other 

pathways occur, including one that produces 2-methyl-6-

ethylaniline and its reactive metabolite, the latter which 

may account for some observed effects (Coleman et 

al., 2000; Davison et al., 1994; Feng and Wratten, 1989; 

Jefferies et al., 1998). People exposed to acetochlor will 

excrete acetochlor mercapturate in their urine; however, 

this metabolite is not a marker of exposure to most plant 

metabolites or environmental degradates, which are often 

more prevalent in the environment.

Human health effects from acetochlor at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Acetochlor has low acute 

toxicity. Acetochlor has not shown developmental or fetal 

toxicity in chronic animal studies, but it has produced 

testicular atrophy, renal injury, and neurologic movement 

abnormalities (U.S.EPA 2000, 2006). Acetochlor is not 

mutagenic, and it is unlikely to be genotoxic at relevant 

doses (Ashby et al., 1996). However, in some species and 

at doses above maximum tolerated doses, animals have 

demonstrated tumors of the lung, nasal epithelia, and thyroid 

(U.S.EPA, 2000, 2006). U.S.EPA considers acetochlor 

likely to be carcinogenic in humans; NTP and IARC do not 

have ratings regarding human carcinogenicity. Additional 

information about external exposure (i.e., environmental 

levels) is available from U.S. EPA at: http://www.epa.gov/

pesticides/.

Biomonitoring Information

Urinary levels of acetochlor mercapturate reflect recent 

exposure. Urinary levels of acetochlor mercapturate were 

generally not detectable in the NHANES 2001-2002 

subsample (CDC, 2005). Acetochlor mercapturate was 

measured in the urine of farmers actively spraying the 

pesticide and the geometric mean was 8.0 μg/L (Curwin et 

al., 2005). Urinary acetochlor mercapturate levels of 0.5 to 

449 μg/L were measured in commercial applicators within 

24 hours following its application (Barr et al., 2007).

Finding measurable amounts of acetochlor mercapturate 

in the urine does not mean that the levels of acetochlor 

mercapturate cause an adverse health effect. Biomonitoring 

studies on levels of acetochlor mercapturate provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels of acetochlor than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.
 48 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

Urinary Acetochlor mercapturate 

Metabolite of Acetochlor 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2501 

Age group 

6-11 years 01-02 * < LOD < LOD < LOD < LOD 576

12-19 years 01-02 * < LOD < LOD < LOD < LOD 820

20-59 years 01-02 * < LOD < LOD < LOD < LOD 1105 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1178 

Females 01-02 * < LOD < LOD < LOD < LOD 1323 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 678

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 673

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 952

Limit of detection (LOD, see Data Analysis section) for Survey year 01-02 is 0.1. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary Acetochlor mercapturate (creatinine corrected) 

Metabolite of Acetochlor 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2500 

Age group 

6-11 years 01-02 * < LOD < LOD < LOD < LOD 576

12-19 years 01-02 * < LOD < LOD < LOD < LOD 819

20-59 years 01-02 * < LOD < LOD < LOD < LOD 1105 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1178 

Females 01-02 * < LOD < LOD < LOD < LOD 1322 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 678

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 672

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 952

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 49

 Herbicides

References

Ashby J, Kier L, Wilson AG, Green T, Lefevre PA, Tinwell H, 

et al. Evaluation of the potential carcinogenicity and genetic 

toxicity to humans of the herbicide acetochlor. Hum Exp Toxicol 

1996;15(9):702-735.

Barr DB, Hines CJ, Olsson AO, Deddens JA, Bravo R, Striley CA, 

et al. Identification of human urinary metabolites of acetochlor 

in exposed herbicide applicators by high performance liquid 

chromatography-tandem mass spectrometry. J Expo Sci Environ 

Epidemiol 2007;17(6):559-566.

Battaglin WA, Furlong ET, Burkhardt MR, Peter CJ. Occurrence 

of sulfonylurea, sulfonamide, imidazolinone, and other herbicides 

in rivers, reservoirs and ground water in the Midwestern United 

States, 1998. Sci Total Environ 2000;248(2-3):123-133.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Coleman S, Linderman R, Hodgson E, Rose RL. Comparative 

metabolism of chloroacetamide herbicides and selected 

metabolites in human and rat liver microsomes. Environ Health 

Perspect 2000;108(12):1151-1157.

Curwin BD, Hein MJ, Sanderson WT, Barr DB, Heederik D, 

Reynolds SJ, Ward EM, Alavanja MC. Urinary and hand wipe 

pesticide levels among farmers and nonfarmers in Iowa. J Expo 

Anal Environ Epidemiol 2005;15(6):500-508.

Davison KL, Larsen GL, Feil VJ. Comparative metabolism 

and elimination of acetanilide compounds by rat. Xenobiotica 

1994;24(10):1003-1012.

Feng PCC, Wratten SJ. In vitro transformation of chloroacetanilide 

herbicides by rat liver enzymes: A comparative study of 

metolachlor and alachlor. J Agri Food Chem 1989;37(4):1088-

1093.

Hladik ML, Hsiao JJ, Roberts AL. Are neutral chloroacetamide 

herbicide degradates of potential environmental concern? 

Analysis and occurrence in the upper Chesapeake Bay. Environ 

Sci Technol 2005;39(17):6561-6574.

Jefferies PR, Quistad GB, Casida JE. Dialkylquinonimines 

validated as in vivo metabolites of alachlor, acetochlor, and 

metolachlor herbicides in rats. Chem Res Toxicol 1998;11(4):353-

359.

Kolpin DW, Thurman EM, Linhart SM. Finding minimal 

herbicide concentrations in ground water? Try looking for their 

degradates. Sci Total Environ 2000;248(2-3):115-122.

U.S. Environmental Protection Agency (U.S. EPA). Acetochlor 

(Harness) Pesticide Petition Filing 1/00. Federal Register: January 

24, 2000, Volume 65, Number 15, pages 3682-3690. Available at 

URL(non U.S.EPA): http://pmep.cce.cornell.edu/profiles/herbgrowthreg/24-d-butylate/acetochlor/acetochlor_pet_100.html. 

5/30/06

U.S. Environmental Protection Agency (U.S. EPA). Report of 

the Food Quality Protection Act (FQPA) Tolerance Reassessment 

Progress and Risk Management Decision (TRED) for Acetochlor. 

March 2006. EPA 738-R-00-009. Available at URL: http://www.

epa.gov/oppsrrd1/reregistration/REDs/acetochlor_tred.pdf. 

5/30/06.

Whyatt RM, Barr DB, Camann DE, Kinney PL, Barr JR, 

Andrews HF, et al. Contemporary-use pesticides in personal air 

samples during pregnancy and blood samples at delivery among 

urban minority mothers and newborns. Environ Health Perspect 

2003;111(5):749-756.
 50 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

Alachlor

CAS No. 15972-60-8

General Information

Alachlor is a chloroacetanilide type herbicide with 

restricted usage for preemergent control of grasses and 

broadleaf weeds on agricultural cropland, including corn, 

soybeans, peanuts and other crops, and on non-crop land 

for general weed control. Since the late 1980s alachlor use 

has been declining. In 1993-1995, about 20-25% of the 

U.S. corn cropland was treated with alachlor. It is absorbed 

by plants and inhibits plant protein synthesis. Alachlor has 

a soil half-life of a few weeks. It is both metabolized in 

plants and degraded microbiologically in agricultural soils 

into as many as 19 metabolites and degradates. Alachlor 

and its degradates are leachable from agricultural soils 

and have been detected in watersheds of agricultural land 

including ground and surface waters (Battaglin et al., 2000; 

Hladik et al., 2005; Kolpin et al., 2000; USGS, 1999 and 

2007; WHO, 2003). Alachlor is highly toxic to freshwater 

fish and slightly toxic to birds and some invertebrates, but 

shows little bioaccumulation.

General population exposure to alachlor may occur through 

consumption of contaminated food or drinking water. 

Estimated human intakes have been below recommended 

limits (U.S.EPA, 1998). Because it can be absorbed through 

skin, the dermal exposure route is potentially significant 

for applicators, formulators, and field workers. In animal 

studies, alachlor is quickly absorbed after oral doses and 

mostly excreted as metabolites within a week (IPCS, 1996; 

U.S.EPA, 1998; WHO, 2003). In animals, mercapturate 

conjugates were predominant metabolites, but another 

metabolic pathway can produce 2,6-diethylaniline and 

its reactive metabolite; the latter may account for some 

observed effects (Davison et al., 1994; Feng and Wratten, 

1989; Jefferies et al., 1998). People exposed to alachlor will 

excrete alachlor mercapturate in their urine (Driskell et al., 

1996), but this metabolite is not a marker of exposure to 

most plant metabolites or environmental degradates which 

are often more prevalent in the environment.

Human health effects from alachlor at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Alachlor has low potential 

for acute toxicity. In chronic animal testing, alachlor 

has demonstrated hepatotoxicity, hemosiderosis, and 

uveal degeneration, but has not shown developmental or 

reproductive toxicity in mammalian systems (U.S.EPA, 

1998; WHO, 2003). Alachlor itself is not considered 

mutagenic, though positive genotoxic results are reported 

for several metabolites of alachlor (Brown et al., 1988; 

Hill et al., 1997; Tessier and Clark, 1995; U.S.EPA, 1998). 

Animal carcinogenicity studies have demonstrated tumors 

of the nasal turbinates, stomach, and thyroid only at either 

maximum tolerated doses or related to species-specific 

pathways (Heydens et al., 1999; IPCS, 1996; U.S.EPA, 

1998; WHO, 2003). U.S.EPA considers alachlor to be a 

probable human carcinogen at high doses, but not likely at 

low doses. NTP and IARC do not have ratings regarding 

human carcinogenicity. Additional information about is 

available from U.S. EPA at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of alachlor mercapturate reflect recent 

exposure. Urinary levels of alachlor mercapturate were 

generally not detectable in the NHANES 2001-2002 

subsample (CDC, 2005). In a study of applicators and 

workers exposed to alachlor, mean values of urinary 

concentrations of alachlor metabolites, as measured through 

conversion to deethylamine, ranged from 0.1 to 1.1 mg/L at 

various collection times (Sanderson et al., 1995). Hines et 

al. (2003) showed that 2.2% of a reference population had 

detectable alachlor equivalents by immunoassay in their 

urine, whereas 60% of applicators had detectable amounts. 

Finding measurable amounts of alachlor mercapturate in the 

urine does not mean that the levels of alachlor mercapturate 

cause an adverse health effect. Biomonitoring studies on 

levels of alachlor mercapturate provide physicians and 

public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of alachlor than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.
Fourth National Report on Human Exposure to Environmental Chemicals 51

 Herbicides

Urinary Alachlor mercapturate 

Metabolite of Alachlor 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1942 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 463

12-19 years 99-00 * < LOD < LOD < LOD < LOD 662

20-59 years 99-00 * < LOD < LOD < LOD < LOD 817

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 950

Females 99-00 * < LOD < LOD < LOD < LOD 992

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 679

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 507

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 586

Limit of detection (LOD, see Data Analysis section) for Survey year 99-00 is 1.18. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary Alachlor mercapturate (creatinine corrected) 

Metabolite of Alachlor 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1942 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 463

12-19 years 99-00 * < LOD < LOD < LOD < LOD 662

20-59 years 99-00 * < LOD < LOD < LOD < LOD 817

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 950

Females 99-00 * < LOD < LOD < LOD < LOD 992

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 679

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 507

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 586

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 52 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

References

Battaglin WA, Furlong ET, Burkhardt MR, Peter CJ. Occurrence 

of sulfonylurea, sulfonamide, imidazolinone, and other herbicides 

in rivers, reservoirs and ground water in the Midwestern United 

States, 1998. Sci Total Environ 2000;248(2-3):123-133.

Brown MA, Kimmel EC, Casida JE. DNA adduct formation by 

alachlor metabolites. Life Sci 1988;43(25):2087-94. Erratum in: 

Life Sci 1989;44(18):1325.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Davison KL, Larsen GL, Feil VJ. Comparative metabolism 

and elimination of acetanilide compounds by rat. Xenobiotica 

1994;24(10):1003-1012.

Driskell WJ, Hill RH Jr, Shealy DB, Hull RD, Hines CJ. 

Identification of a major human urinary metabolite of alachlor by 

LC-MS/MS. Bull Environ Contam Toxicol 1996;56(6):853-859. 

Feng PCC, Wratten SJ. In vitro transformation of chloroacetanilide 

herbicides by rat liver enzymes: A comparative study of 

metolachlor and alachlor. J Agri Food Chem 1989;37(4):1088-

1093.

Heydens WF, Wilson AG, Kier LD, Lau H, Thake DC, Martens 

MA. An evaluation of the carcinogenic potential of the herbicide 

alachlor to man. Hum Exp Toxicol. 1999;18(6):363-391.

Hill AB, Jefferies PR, Quistad GB, Casida JE. Dialkylquinoneimine 

metabolites of chloroacetanilide herbicides induce sister 

chromatid exchanges in cultured human lymphocytes. Mutat Res. 

1997;395(2-3):159-171.

Hines CJ, Deddens JA, Striley CA, Biagini RE, Shoemaker DA, 

Brown KK, et al. Biological monitoring for selected herbicide 

biomarkers in the urine of exposed custom applicators: application 

of mixed-effect models. Ann Occup Hyg 2003;47(6):503-517.

Hladik ML, Hsiao JJ, Roberts AL. Are neutral chloroacetamide 

herbicide degradates of potential environmental concern? 

Analysis and occurrence in the upper Chesapeake Bay. Environ 

Sci Technol 2005;39(17):6561-6574.

International Programme on Chemical Safety (IPCS). WHO/

FAO Data Sheets on Pesticides. No. 86. ALACHLOR. World 

Health Organization, Geneva, 1996. Available at URL: http://

www.inchem.org/documents/pds/pds/pest86_e.htm. 2/27/09

Jefferies PR, Quistad GB, Casida JE. Dialkylquinonimines 

validated as in vivo metabolites of alachlor, acetochlor, and 

metolachlor herbicides in rats. Chem Res Toxicol 1998;11(4):353-

359.

Kolpin DW, Thurman EM, Linhart SM. Finding minimal 

herbicide concentrations in ground water? Try looking for their 

degradates. Sci Total Environ 2000;248(2-3):115-122.

Sanderson WT, Biagini R, Tolos W, Henningsen G, MacKenzie 

B. Biological monitoring of commercial pesticide applicators for 

urine metabolites of the herbicide alachlor. Am Ind Hyg Assoc J 

1995;56(9):883-889.

Tessier DM, Clark JM. Quantitative assessment of the mutagenic 

potential of environmental degradative products of alachlor. J Ag 

Food Chem 1995;43(9):2504-2512.

U.S. Environmental Protection Agency (U.S. EPA). Reregistration 

Eligibility Decision (RED) Alachlor. December 1998. EPA 738-

R-98-020. Available at URL: http://www.epa.gov/oppsrrd1/

REDs/0063.pdf. 2/27/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s Waters

Pesticides in the Nation’s Streams and Ground Water, 1992-2001. 

Circular 1291. Supplemental Technical Information (available 

on-line only). March 2006, revised February 15, 2007. Available 

at URL: http://water.usgs.gov/nawqa/pnsp/pubs/circ1291/

supporting_info.php. 4/2/09

U.S. Geological Survey (USGS). Water-Resources Investigations 

Report: Distribution of Major Herbicides in Ground Water of the 

United States Water Resource Investigations Report No. 98-4245 

(by Barbash JE, Thelin GP, Kolpin DW, Gilliom RJ). Sacramento, 

California, 1999.

Whyatt RM, Barr DB, Camann DE, Kinney PL, Barr JR, 

Andrews HF, et al. Contemporary-use pesticides in personal air 

samples during pregnancy and blood samples at delivery among 

urban minority mothers and newborns. Environ Health Perspect 

2003;111(5):749-756.

World Health Organization (WHO). Alachlor in Drinking-water. 

Background document for development of WHO Guidelines for 

Drinking-water Quality. 2003. Available at URL: http://www.

who.int/water_sanitation_health/dwq/chemicals/en/alachlor.pdf. 

2/27/00
Fourth National Report on Human Exposure to Environmental Chemicals 53

 Herbicides

Atrazine

CAS No. 1912-24-9

General Information

Atrazine is a widely used chlorotriazine herbicide that acts 

against broadleaf and grassy weeds. Related chlorotriazine 

herbicides include simazine, propazine, and cyanazine, all 

of which act by inhibiting plant photosynthesis. Atrazine 

is applied pre- and post-emergence to agricultural land 

for crops such as corn and sorghum. It is also used as a 

non-selective herbicide. Atrazine was first registered as an 

herbicide in 1958. More than 70 million pounds have been 

applied annually in recent years, with about 75% of corn 

cropland receiving treatment. Atrazine has limited water 

solubility and is not tightly bound to soil, but it is leachable 

into ground and surface waters. In regions where atrazine 

is used, it is one of the more commonly detected pesticides 

in surface and ground waters (USGS, 2007). In soils, 

atrazine is slowly degraded to dealkylated products, which 

have half-lives of several months. Bacteria and plants can 

metabolize atrazine to hydroxyatrazine. Atrazine does not 

bioaccumulate. It has little toxicity in birds and moderate 

toxicity in some fish and aquatic invertebrates. Atrazine 

may alter the sexual development of frogs at environmental 

levels (Gammon et al., 2005; Hayes et al., 2002; U.S.EPA, 

2003a).

For the general population, drinking water is an infrequent 

source of atrazine exposure, but estimates of seasonal intakes 

from drinking water in a small number of communities 

have exceeded the recommended limits (U.S.EPA, 2003b). 

As a result, atrazine use has progressively been restricted in 

an effort to reduce surface and ground water contamination. 

Applicators of atrazine may be exposed dermally and by 

inhalation. Atrazine is well absorbed orally, metabolized, 

and then eliminated in the urine over a few days (Bradway 

et al., 1982; Catenacci et al., 1993; Timchalk et al., 1990). In 

animals and humans, glutathione conjugation appeared to be 

the major route of biotransformation, resulting in atrazine 

mercapturate and N-dealkylation products (IPCS, 1996; 

U.S.EPA, 2003b). Atrazine mercapturate products accounted 

for a major proportion of human urinary metabolites (Lucas 

et al., 1993). The dealkylated chloroatrazine metabolites, 

Urinary Atrazine mercapturate 

Metabolite of Atrazine 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1878 

01-02 * < LOD < LOD < LOD < LOD 2477 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 449

01-02 * < LOD < LOD < LOD < LOD 568

12-19 years 99-00 * < LOD < LOD < LOD < LOD 639

01-02 * < LOD < LOD < LOD < LOD 809

20-59 years 99-00 * < LOD < LOD < LOD < LOD 790

01-02 * < LOD < LOD < LOD < LOD 1100 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1162 

Females 99-00 * < LOD < LOD < LOD < LOD 959

01-02 * < LOD < LOD < LOD < LOD 1315 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 676

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 498

01-02 * < LOD < LOD < LOD < LOD 684

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 550

01-02 * < LOD < LOD < LOD < LOD 918

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.791 and 0.3. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 54 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

particularly diaminochloroatrazine (the main dealkylated 

product), may mediate some effects of atrazine (Laws et 

al., 2003). Dealkylated metabolites from atrazine can also 

result from metabolism of other chlorotriazine pesticides, 

including simazine, propazine, and cyanazine. In addition 

to being human metabolites of atrazine, the dealkylated 

atrazine metabolites and hydroxyatrazine can occur in the 

environment from the breakdown of the parent chemical. 

Thus, detection of these dealkylated metabolites in a 

person’s urine may also reflect exposure to these degradates 

in the environment.

Human health effects of atrazine at environmental doses 

or at biomonitored levels from environmental exposure 

are unknown. In mammalian studies, atrazine is rated as 

having low acute toxicity. Atrazine product formulations 

can be mild skin sensitizers and irritants. Chronic high 

dose toxicity observed in animals includes decreased 

body weight, myocardial muscle degeneration, liver 

toxicity, developmental ossification defects, impaired 

fertility, altered estrus cycles, increased pituitary weight, 

delayed onset of puberty, and reduced levels of luteinizing 

hormone, prolactin, and testosterone (Gillis et al., 1994; 

Laws et al., 2000 and 2003; Rayner et al., 2004; Stoker 

et al., 2000 and 2002; U.S.EPA, 2003b). Atrazine and the 

dealkylated chlorinated metabolites did not have estrogen 

receptor activity, but they reduced the pituitary secretion 

of luteinizing hormone and prolactin and also inhibited 

aromatase at high doses in some mammalian species 

(Cooper et al., 2000; Eldridge et al., 1994 and 1999; 

Gammon et al., 2005; Sanderson et al., 2002; Stevens et al., 

1999). Estimated human exposures are thousands of times 

lower than doses that caused effects in animals (Gammon et 

al., 2005). Some human ecologic and epidemiologic studies 

of reproductive and cancer outcomes have shown either 

positive or no associations, but the effects are difficult to 

attribute due to lack of exposure markers or due to mixed 

chemical or pesticide exposures (ATSDR, 2003; Gammon 

et al., 2005; Sathiakumar and Delzell, 1997). Atrazine 

is not considered genotoxic. IARC considers atrazine 

not classifiable with respect to human carcinogenicity, 

and U.S.EPA considers atrazine unlikely to be a human 

carcinogen. Additional information is available from U.S. 

EPA at: http://www.epa.gov/pesticides/ and from ATSDR 

at: http://www.atsdr.cdc.gov/toxpro2.html.

Urinary Atrazine mercapturate (creatinine corrected) 

Metabolite of Atrazine 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1878 

01-02 * < LOD < LOD < LOD < LOD 2476 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 449

01-02 * < LOD < LOD < LOD < LOD 568

12-19 years 99-00 * < LOD < LOD < LOD < LOD 639

01-02 * < LOD < LOD < LOD < LOD 808

20-59 years 99-00 * < LOD < LOD < LOD < LOD 790

01-02 * < LOD < LOD < LOD < LOD 1100 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1162 

Females 99-00 * < LOD < LOD < LOD < LOD 959

01-02 * < LOD < LOD < LOD < LOD 1314 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 676

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 498

01-02 * < LOD < LOD < LOD < LOD 683

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 550

01-02 * < LOD < LOD < LOD < LOD 918

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 55

 Herbicides

Biomonitoring Information

Urinary levels of atrazine mercapturate reflect recent 

exposure. In the NHANES 2001-2002 subsample, levels of 

atrazine mercapturate were generally not detectable (CDC, 

2005). In small studies of Maryland residents in 1995-

1996 (MacIntosh et al., 1999) and 83 Minnesota children 

with multiple urine collections during 1997 (Adgate et al., 

2001), atrazine mercapturate was infrequently detected 

at the detection limit of < 1 μg/L. In a study of 60 farm 

worker children, atrazine was detected in only four children 

(Arcury et al., 2007). Through immunoassay atrazine 

equivalents (detected mostly as atrazine mercapturate), the 

urinary geometric mean levels for herbicide applicators in 

Ohio and Wisconsin were about 6 μg/L (Hines et al., 2003; 

Perry et al., 2000). The geometric mean of urinary atrazine 

mercapturate was 1.2 μg/L in 15 farmers studied several 

days after spraying the pesticide (Curwin et al., 2005). In 

a small number of field workers, urinary concentrations 

ranged from 5-1756 μg/L (Lucas et al., 1993).

Finding measurable amounts of atrazine mercapturate in 

urine does not mean that the levels of atrazine mercapturate 

cause an adverse health effect. Biomonitoring studies on 

levels of atrazine mercapturate provide physicians and 

public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of atrazine than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

References

Adgate JL, Barr DB, Clayton CA, Eberly LE, Freeman NC, 

Lioy PJ, et al. Measurement of children’s exposure to pesticides: 

analysis of urinary metabolite levels in a probability-based 

sample. Environ Health Perspect 2001;109(6):583-590.

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for atrazine. 2001 [online]. Available at 

URL: http://www.atsdr.cdc.gov/toxprofiles/tp153.html. 3/11/09

Arcury TA, Grzywacz JG, Barr DB, Tapia J, Chen H, Quandt 

SA. Pesticide urinary metabolite levels of children in eastern 

North Carolina farmworker households. Environ Health Perspect 

2007;115(8):1254-1260.

Bradway DE, Moseman RF. Determination of urinary residue 

levels of the N-dealkyl metabolites of triazine herbicides. J Agric 

Food Chem 1982;30(2):244-247.

Catenacci G, Barbieri F, Bersani M, Ferioli A, Cottica D, Maroni 

M. Biological monitoring of human exposure to atrazine. Toxicol 

Lett 1993;69(2):217-222.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Cooper RL, Stoker TE, Tyrey L, Goldman JM, McElroy WK. 

Atrazine disrupts the hypothalamic control of pituitary-ovarian 

function. Toxicol Sci 2000;53(2):297-307.

Curwin BD, Hein MJ, Sanderson WT, Barr DB, Heederik D, 

Reynolds SJ, et al. Urinary and hand wipe pesticide levels among 

farmers and nonfarmers in Iowa. J Expo Anal Environ Epidemiol 

2005;15(6):500-508.

Eldridge JC, Wetzel LT, Stevens JT, Simpkins JW. The mammary 

tumor response in triazine-treated female rats: a thresholdmediated interaction with strain and species-specific reproductive 

senescence. Steroids 1999;64(9):672-678.

Eldridge JC, Fleenor-Heyser DG, Extrom PC, Wetzel LT, 

Breckenridge CB, Gillis JH, et al. Short-term effects of 

chlorotriazines on estrus in female Sprague-Dawley and Fischer 

344 rats. J Toxicol Environ Health 1994;43(2):155-167.

Gammon DW, Aldous CN, Carr WC Jr, Sanborn JR, Pfeifer KF. 

A risk assessment of atrazine use in California: human health and 

ecological aspects. Pest Manag Sci 2005;61(4):331-355.

Gillis JH, et al. Short-term effects of chlorotriazines on estrus in 

female Sprague-Dawley and Fischer 344 rats. J Toxicol Environ 

Health 1994;43(2):155-167.

Hayes TB, Collins A, Lee M, Mendoza M, Noriega N, Stuart AA, 

Vonk A. Hermaphroditic, demasculinized frogs after exposure to 

the herbicide atrazine at low ecologically relevant doses. Proc 

Natl Acad Sci USA 2002;99(8):5476-5480.

Hines CJ, Deddens JA, Striley CA, Biagini RE, Shoemaker DA, 

Brown KK, et al. Biological monitoring for selected herbicide 

biomarkers in the urine of exposed custom applicators: application 

of mixed-effect models. Ann Occup Hyg 2003;47(6):503-517.

International Programme on Chemical Safety (IPCS). WHO/

FAO Data Sheets on Pesticides. No. 82. ATRAZINE. World 

Health Organization, Geneva, 1996. Available at URL: http://

www.inchem.org/documents/pds/pds/pest82_e.htm. 3/11/09

Laws SC, Ferrell JM, Stoker TE, Cooper RL. Pubertal development 

in female Wistar rats following exposure to propazine and atrazine 

biotransformation by-products, diamino-S-chlorotriazine and 

hydroxyatrazine. Toxicol Sci 2003;76(1):190-200.

Laws SC, Ferrell JM, Stoker TE, Schmid J, Cooper RL. The 

effects of atrazine on female wistar rats: an evaluation of the 

protocol for assessing pubertal development and thyroid function. 

Toxicol Sci 2000;58(2):366-376.

Lucas AD, Jones AD, Goodrow MH, Saiz SG, Blewett C, Seiber 

JN, et al. Determination of atrazine metabolites in human urine: 
 56 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

development of a biomarker of exposure. Chem Res Toxicol 

1993;6(1):107-116.

MacIntosh DL, Needham LL, Hammerstrom KA, Ryan PB. A 

longitudinal investigation of selected pesticide metabolites in 

urine. J Expo Anal Environ Epidemiol 1999;9(5):494-501.

Perry M, Christiani D, Dagenhart D, Tortorelli J, Singzoni B. 

Urinary biomarkers of atrazine exposure among farm pesticide 

applicators. Ann Epidemiol 2000;10(7):479.

Rayner JL, Wood C, Fenton SE. Exposure parameters necessary 

for delayed puberty and mammary gland development in LongEvans rats exposed in utero to atrazine. Toxicol Appl Pharmacol 

2004;195(1):23-34.

Sanderson JT, Boerma J, Lansbergen GW, van den Berg M. 

Induction and inhibition of aromatase (CYP19) activity by 

various classes of pesticides in H295R human adrenocortical 

carcinoma cells. Toxicol Appl Pharmacol 2002;182(1):44-54.

Sathiakumar N, Delzell E. A review of epidemiologic studies of 

triazine herbicides and cancer. Crit Rev Toxicol 1997;27(6):599-

612.

Stevens JT, Breckenridge CB, Wetzel L. A risk characterization 

for atrazine: oncogenicity profile. J Toxicol Environ Health A 

1999;56(2):69-109.

Stoker TE, Laws SC, Guidici DL, Cooper RL. The effect of 

atrazine on puberty in male Wistar rats: an evaluation in the 

protocol for the assessment of pubertal development and thyroid 

function. Toxicol Sci 2000;58(1):50-59.

Stoker TE, Guidici DL, Laws SC, Cooper RL. The effects of 

atrazine metabolites on puberty and thyroid function in the male 

Wistar rat. Toxicol Sci 2002;67(2):198-206.

Timchalk C, Dryzga MD, Langvardt PW, Kastl PE, Osborne DW. 

Determination of the effect of tridiphane on the pharmacokinetics 

of [14C]-atrazine following oral administration to male Fischer 

344 rats. Toxicology 1990;61(1):27-40.

U.S. Environmental Protection Agency (U.S. EPA). Office of 

Prevention, Pesticides and Toxic Substances, EPA Office of 

Pesticide Programs, Environmental Fate and Effects Division. 

White paper on potential developmental effects of atrazine 

on amphibians. Washington (DC). May 2003a. Available at 

URL: http://www.epa.gov/scipoly/sap/meetings/2003/june/

finaljune2002telconfreport.pdf. 6/1/09

U.S. Environmental Protection Agency (U.S. EPA). Interim 

Reregistration Eligibility Decision For Atrazine. Case No. 0062. 

2003b. Available at URL: http://www.epa.gov/oppsrrd1/REDs/

atrazine_ired.pdf. 3/11/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s 

Waters. Pesticides in the Nation’s Streams and Ground Water, 

1992-2001. Circular 1291. Supplemental Technical Information 

(available on-line only). March 2006, revised February 15, 

2007. Available at URL: http://water.usgs.gov/nawqa/pnsp/pubs/

circ1291/supporting_info.php. 4/2/09
Fourth National Report on Human Exposure to Environmental Chemicals 57

 Herbicides

2,4-Dichlorophenoxyacetic Acid

CAS No. 94-75-7

General Information

Widely used throughout the United States, the chlorophenoxy 

herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) controls 

broadleaf weeds in residential, agricultural, and aquatic 

environments. It was first registered with U.S.EPA in 

1948. Similar to other chlorophenoxy herbicides, it acts 

as a plant growth hormone. At low levels, these herbicides 

can enhance plant growth, but at higher levels they are 

herbicidal. 2,4-D can be applied either as an aqueous salt 

or as oil-soluble esters, and it is often mixed with other 

chlorophenoxy acid herbicides (such as dicamba, MCPA, 

and mecoprop). As much as 62 million pounds of 2,4-D 

were used in the U.S. in 2001 (U.S.EPA, 2004). It is poorly 

bound in soils, with a half-life of several days to several 

weeks. It is rarely detected in ground waters (USGS, 2007). 

Acid and salt forms are much less toxic to fish and aquatic 

invertebrates than the ester forms.

General population exposure to 2,4-D may occur during 

residential applications, by direct contact with agricultural 

and residential areas after applications, and by consuming 

food or drinking water contaminated with 2, 4-D. Recent 

estimates of chronic intakes of 2,4-D have been below 

recommended intake limits (U.S.EPA, 2005). 2,4-D is 

rapidly absorbed via oral and inhalation routes. It is not well 

absorbed through the skin, although dermal exposure may 

be significant for herbicide manufacturing plant workers 

exposed to high concentrations of 2,4-D or exposed for 

prolonged periods. Once absorbed, 2,4-D is eliminated 

mostly unchanged in the urine with an elimination half-life 

ranging from 10 to 33 hours (Arnold et al., 1989; Kohli et 

al., 1974; Sauerhoff et al., 1977).

Human health effects from 2,4-D at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. 2,4-D has low acute toxicity. 

Intentional overdoses and unintentional high dose 

exposures to chlorophenoxy acid herbicides have resulted 

in weakness, headache, dizziness, nausea, abdominal pain, 

myotonia, hypotension, renal and hepatic injury, and delayed 

Urinary 2,4-Dichlorophenoxyacetic acid 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1977 

01-02 * < LOD .230 (<LOD-.320) .690 (.560-.910) 1.27 (1.02-1.37) 2413 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD 1.30 (<LOD-2.40) 477

01-02 * < LOD .310 (.210-.400) .740 (.550-1.13) 1.55 (1.00-2.21) 546

12-19 years 99-00 * < LOD < LOD < LOD 1.10 (<LOD-1.60) 677

01-02 * < LOD .250 (<LOD-.420) .690 (.440-1.16) 1.24 (.690-1.66) 797

20-59 years 99-00 * < LOD < LOD < LOD < LOD 823

01-02 * < LOD .210 (<LOD-.310) .690 (.540-.910) 1.27 (.930-1.49) 1070 

Gender 

Males 99-00 * < LOD < LOD < LOD 1.10 (<LOD-1.80) 962

01-02 * < LOD .330 (.230-.490) .930 (.680-1.22) 1.51 (1.27-2.08) 1135 

Females 99-00 * < LOD < LOD < LOD < LOD 1015 

01-02 * < LOD < LOD .490 (.370-.660) .890 (.670-1.22) 1278 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 695

01-02 * < LOD .260 (<LOD-.350) .730 (.610-.910) 1.20 (.960-1.43) 659

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 1.20 (<LOD-1.70) 520

01-02 * < LOD < LOD .610 (.420-.890) 1.07 (.810-1.48) 668

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 589

01-02 * < LOD .250 (<LOD-.410) .760 (.560-1.10) 1.32 (1.05-2.03) 892

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.952 and 0.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 58 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

neuropathy (Bradberry et al., 2004). The acid and salt forms 

of 2,4-D are eye irritants. Acute high doses administered to 

laboratory animals produced ataxia, myotonia, and evidence 

of histological injury to the kidneys, liver, thyroid, eyes, 

adrenals and gonads (NTP, 2006; U.S.EPA, 2005). 2,4-D 

does not have significant reproductive, developmental, or 

teratogenic effects in chronic rodent studies (Charles et al., 

2001; IPCS, 1996; U.S.EPA 2005). Epidemiological studies 

have reported associations of several types of cancer, such 

as soft tissue sarcoma and non-Hodgkin’s lymphoma, with 

the exposure to chlorophenoxy herbicides as defoliants 

or contaminated herbicides. It is unclear whether these 

associations are related to the chlorophenoxy herbicides, 

other exposures, or to contaminants in the herbicide 

formulations (specifically 2,3,7,8-tetrachlorodibenzo-pdioxin) (Garabrant and Philbert, 2002; IOM, 2003; IPCS, 

1996; Pearce and McLean; 2005; U.S.EPA, 2005). 2,4-D 

was not found to be genotoxic or carcinogenic in animal 

studies (Garabrant and Philbert, 2002; IPCS, 1996; 

U.S.EPA, 2005). IARC considers the chlorophenoxyacetic 

acids group of chemicals as possibly carcinogenic to 

humans. Additional information is available from U.S.EPA 

at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of 2,4-D reflect recent exposure. The 95th

percentiles of the NHANES 1999-2000 and 2001-2002 

subsamples were roughly similar to the 95th percentile 

values reported in a nonrandom subsample from NHANES 

III (1988-1994) (CDC, 2005; Hill et al., 1995). In previous 

samples of the U.S. population (Hill et al., 1995; Kutz et 

al., 1992), in small samples of children (Hill et al., 1989), 

and of adults and children (Baker et al., 2000), urinary 

2,4-D levels were detectable in less than a quarter of the 

individuals studied.

2,4-D production plant workers and a few forestry workers 

spraying 2,4-D had urinary levels several hundred to 

several thousand times higher than the 95th percentiles of 

the NHANES subsamples (CDC, 2005; Frank et al., 1985; 

Kolmodin-Hedman and Erne, 1980; Knopp et al., 1994).

Average post-application urinary levels of 2,4-D in farmers 

were more than 25-fold higher than the 95th percentiles 

in the NHANES 1999-2000 and 2001-2002 subsamples 

(Arbuckle et al., 2005; CDC, 2005). Post-application 

levels in farmers and home gardeners were dependent on 

Urinary 2,4-Dichlorophenoxyacetic acid (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1977 

01-02 * < LOD .380 (<LOD-.410) .670 (.610-.780) 1.08 (.930-1.26) 2412 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD 1.32 (<LOD-2.24) 477

01-02 * < LOD .490 (.380-.680) 1.13 (.820-1.35) 1.41 (1.27-1.73) 546

12-19 years 99-00 * < LOD < LOD < LOD .590 (<LOD-1.05) 677

01-02 * < LOD .270 (<LOD-.380) .480 (.330-.660) .660 (.520-.920) 796

20-59 years 99-00 * < LOD < LOD < LOD < LOD 823

01-02 * < LOD .380 (<LOD-.410) .670 (.580-.790) 1.08 (.810-1.29) 1070 

Gender 

Males 99-00 * < LOD < LOD < LOD .670 (<LOD-1.16) 962

01-02 * < LOD .340 (.270-.410) .640 (.560-.790) 1.14 (.890-1.39) 1135 

Females 99-00 * < LOD < LOD < LOD < LOD 1015 

01-02 * < LOD < LOD .700 (.610-.780) 1.08 (.810-1.26) 1277 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 695

01-02 * < LOD .350 (<LOD-.390) .720 (.560-.850) 1.13 (.780-1.56) 659

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD .590 (<LOD-1.19) 520

01-02 * < LOD < LOD .440 (.340-.570) .780 (.550-.980) 667

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 589

01-02 * < LOD .410 (<LOD-.470) .740 (.620-.890) 1.17 (.990-1.40) 892

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 59

 Herbicides

the time since application, the amount of pesticide applied, 

the number of acres to which it was applied (Curwin et 

al., 2005), and the use of protective clothing or equipment 

(Arbuckle et al., 2005; Harris et al., 1992). In farm families, 

geometric mean urinary levels of 2,4-D were highest in the 

farmers who applied the 2,4-D; other family members had 

levels ranging only slightly higher than the 95th percentile 

levels in NHANES 1999-2000 and 2001-2002 subsamples 

(CDC, 2005; Mandel et al., 2005). 

Finding a measurable amount of 2,4-D in urine does not 

mean that the level of the 2,4-D will result in an adverse 

health effect. Biomonitoring studies of 2,4-D in urine 

provide physicians and public health officials with reference 

values so that they can determine whether other people have 

been exposed to higher levels of 2,4-D than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Arbuckle TE, Cole DC, Ritter L, Ripley BD. Biomonitoring of 

herbicides in Ontario farm applicators. Scand J Work Environ 

Health 2005;31 Suppl 1:90-97.

Arnold EK, Beasley VR. The pharmacokinetics of chlorinated 

phenoxy acid herbicides: a literature. Vet Hum Toxicol 

1989;31(2):121-125.

Baker SE, Barr DB, Driskell WJ, Beeson MD, Needham LL. 

Quantification of selected pesticide metabolites in human urine 

using isotope dilution high-performance liquid chromatography/

tandem mass spectrometry. J Expo Anal Environ Epidemiol 

2000;10(6 Pt 2):789-798.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005

Charles JM, Hanley TR Jr, Wilson RD, van Ravenzwaay B, 

Bus JS. Developmental toxicity studies in rats and rabbits on 

2,4-dichlorophenoxyacetic acid and its forms. Toxicol Sci 

2001;60(1):121-131.

Curwin BD, Hein MJ, Sanderson WT, Barr DB, Heederik D, 

Reynolds SJ, et al. Urinary and hand wipe pesticide levels among 

farmers and nonfarmers in Iowa. J Expo Anal Environ Epidemiol 

2005 Nov;15(6):500-508.

Frank R, Campbell RA, Sirons G J. Forestry workers involved 

in aerial application of 2,4-dichlorophenoxyacetic acid (2,4-D): 

exposure and urinary excretion. Arch Environ Contam Toxicol 

1985;4:427-435.

Garabrant DH, Philbert MA. Review of 2,4-dichlorophenoxyacetic 

acid (2,4-D) epidemiology and toxicology. Crit Rev Toxicol 

2002;32(4):233-257.

Harris SA, Solomon KR, Stephenson GR. Exposure of 

homeowners and bystanders to 2,4 dichlorophenoxyacetic acid 

(2,4-D). J Environ Sci Health B 1992;27(1):23-38.

Hill RH Jr, To T, Holler JS, Fast DM, Smith SJ, Needham LL, et 

al. Residues of chlorinated phenols and phenoxy acid herbicides 

in the urine of Arkansas children. Arch Environ Contam Toxicol 

1989;18(4):469-474.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, et 

al. Pesticide residues in urine of adults living in the United States: 

reference range concentrations. Environ Res 1995;71(2):99-108. 

International Programme on Chemical Safety-INCHEM (IPCS). 

Pesticides residues in food: 1996 evaluations Part II Toxicology. 

914. Dichlorophenoxyacetic acid, 2,4-. Available at URL: http://

www.inchem.org/documents/jmpr/jmpmono/v96pr04.htm. 

3/17/09

Institute of Medicine (IOM). Board on Health Promotion and 

Disease Prevention. Committee to Review the Health Effects in 

Vietnam Veterans of Exposure to Herbicides (Fourth Biennial 

Update. Veterans and Agent Orange: update 2002. Washington 

(DC): National Academies Press; 2003. Available at URL: http://

www.nap.edu/catalog.php?record_id=10603. 3/17/09

Knopp D. Assessment of exposure to 2,4-dichlorophenoxyacetic 

acid in the chemical industry: results of a five year biological 

monitoring study. Occup Environ Med 1994;51(3):152-159.

Kohli JD, Khanna RN, Gupta BN, Dhar MM, Tandon JS, Sircar 

KP. Absorption and excretion of 2,4-dichlorophenoxyacetic acid 

in man. Xenobiotica 1974;4:97-100.

Kolmodin-Hedman B, Erne K. Estimation of occupational 

exposure to phenoxy acids (2,4-D and 2,4,5-T). Arch Toxicol 

Suppl 1980;4:318-321.

Kutz FW, Cook BT, Carter-Pokras OD, Brody D, Murphy RS. 

Selected pesticide residues and metabolites in urine from a 

survey of the U.S. general population. J Toxicol Environ Health 

1992;37(2):277-291.

Mandel JS, Alexander BH, Baker BA, Acquavella JF, Chapman 

P, Honeycutt R. Biomonitoring for farm families in the farm 

family exposure study. Scand J Work Environ Health 2005;31 

Suppl 1:98-104.

National Toxicology Program (NTP). TOX-63: TOXICITY 

REPORT CURVES. Tables, Survival and Growth Curves 

from NTP Toxicity Studies. TOX-63 Peroxisone Project 

(2,4-Dichlorophenoxyacetic Acid). Updated March 7, 

2006. Available at URL: http://ntp.niehs.nih.gov/index.

cfm?objectid=06FF8DA6-E5A1-90CD-3F26562CEC5CDDE5. 

3/17/09
 60 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

Sauerhoff MW, Braun WH, Blau GE, Gehring PJ. The fate 

of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral 

administration to man. Toxicology 1977;8:3-1U.S. Environmental 

Protection Agency (U.S.EPA). 2,4-D RED Facts. June 2005. EPA 

738 F-05-002. Available at URL: http://www.epa.gov/oppsrrd1/

REDs/factsheets/24d_fs.htm. 3/17/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s 

Waters. Pesticides in the Nation’s Streams and Ground Water, 

1992-2001. Circular 1291. Supplemental Technical Information 

(available on-line only). March 2006, revised February 15, 

2007. Available at URL: http://water.usgs.gov/nawqa/pnsp/pubs/

circ1291/supporting_info.php. 4/2/09

U. S. Environmental Protection Agency (U.S.EPA). Office of 

Prevention Pesticides and Toxic Substances. Pesticide industry 

sales and usage - 2000 and 2001 market estimates. Washington 

(DC): U.S.EPA. May, 2004. Available at URL: http://www.epa.

gov/oppbead1/pestsales/01pestsales/market_estimates2001.pdf.

3/17/09.
Fourth National Report on Human Exposure to Environmental Chemicals 61

 Herbicides

Metolachlor

CAS No. 51218-45-2

General Information

Metolachlor is a chloroacetanilide type herbicide that is 

applied for preemergent control of grasses and broadleaf 

weeds on agricultural crop land, including corn, soybeans, 

sorghum and other crops, and on non-crop land for general 

weed control. It is absorbed by plants and inhibits plant 

protein synthesis. Metolachlor has a soil half-life of a few 

weeks to three months and is degraded microbiologically 

and photochemically to at least five different products. 

Metolachlor or its degradates can leach from soils and have 

been detected in watersheds of agricultural land, in both 

ground and surface waters (Battaglin et al., 1999; Gilliom, 

2007; Hladik et al., 2005; Kolpin et al., 2000; USGS, 2007; 

WHO, 2003). Occasionally in the past, metolachlor levels 

in water have exceeded lifetime human health advisory 

levels (U.S.EPA, 1995). Metolachlor shows little potential 

to bioaccumulate but is moderately toxic to fish.

General population exposure may occur through the 

consumption of contaminated food or drinking water. 

Estimated human intakes have been below recommended 

limits (U.S.EPA, 1995). Metolachlor is well absorbed 

dermally, so applicators, formulators, and field workers 

may have significant exposures via this route. In animal 

studies, metolachlor was quickly absorbed after dermal 

or oral doses, and eliminated in urine and feces over two 

to three days (WHO, 2003). In animals, mercapturate 

conjugates were the predominant metabolites, but another 

metabolic pathway can produce 2-methyl-6-ethylaniline 

and its reactive metabolite which may account for observed 

effects (Coleman et al., 2000; Davison et al., 1994; Feng 

and Wratten, 1989; Jefferies et al., 1998). People exposed 

to metolachlor will excrete metolachlor mercapturate in 

their urine. This metabolite is not a marker of exposure 

to either plant metabolites or environmental degradates of 

metolachlor which can be present in the environment.

Human health effects from metolachlor at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Metolachlor has low potential for 

acute toxicity (U.S. EPA, 1995). Salivation, lacrimation, 

and convulsions were observed at lethal doses in animal 

studies. Metolachlor did not show developmental or 

reproductive toxicity in chronic animal studies, and it was 

not mutagenic in mammalian cells (U.S.EPA, 1995; WHO, 

2003). U.S.EPA considers metolachlor to be a possible 

human carcinogen; NTP and IARC do not have ratings 

regarding human carcinogenicity. Additional information is 

available from U.S. EPA at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of metolachlor mercapturate reflect recent 

exposure. Urinary levels of metolachlor mercapturate 

were generally not detectable in the NHANES 2001-2002 

subsample, though the 95th percentile for males was 0.200 

μg/L (CDC, 2005). The geometric mean metolachlor 

mercapturate was 4.7 μg/L in the urine of farmers after they 

had sprayed metolachlor (Curwin et al., 2005). Hines et al. 

(2003) showed that 2.2% of a small reference population 

had detectable metolachlor equivalents by immunoassay 

in their urine, whereas 60% of applicators had detectable 

amounts.

Finding measurable amounts of metolachlor mercapturate 

in the urine does not mean that the levels of metolachlor 

mercapturate cause an adverse health effect. Biomonitoring 

studies on levels of metolachlor mercapturate provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels metolachlor than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.
 62 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

Urinary Metolachlor mercapturate 

Metabolite of Metolachlor 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2538 

Age group 

6-11 years 01-02 * < LOD < LOD < LOD < LOD 580

12-19 years 01-02 * < LOD < LOD < LOD < LOD 831

20-59 years 01-02 * < LOD < LOD < LOD < LOD 1127 

Gender 

Males 01-02 * < LOD < LOD < LOD .200 (<LOD-.220) 1192 

Females 01-02 * < LOD < LOD < LOD < LOD 1346 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 679

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 701

Non-Hispanic whites 01-02 * < LOD < LOD < LOD .200 (<LOD-.240) 957

Limit of detection (LOD, see Data Analysis section) for Survey year 01-02 is 0.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary Metolachlor mercapturate (creatinine corrected) 

Metabolite of Metolachlor 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2537 

Age group 

6-11 years 01-02 * < LOD < LOD < LOD < LOD 580

12-19 years 01-02 * < LOD < LOD < LOD < LOD 830

20-59 years 01-02 * < LOD < LOD < LOD < LOD 1127 

Gender 

Males 01-02 * < LOD < LOD < LOD .440 (<LOD-.500) 1192 

Females 01-02 * < LOD < LOD < LOD < LOD 1345 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 679

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 700

Non-Hispanic whites 01-02 * < LOD < LOD < LOD .670 (<LOD-.740) 957

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 63

 Herbicides

References

Battaglin WA, Furlong ET, Burkhardt MR, Peter CJ. Occurrence 

of sulfonylurea, sulfonamide, imidazolinone, and other herbicides 

in rivers, reservoirs and ground water in the Midwestern United 

States, 1998. Sci Total Environ 2000;248(2-3):123-133.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Coleman S, Linderman R, Hodgson E, Rose RL. Comparative 

metabolism of chloroacetamide herbicides and selected 

metabolites in human and rat liver microsomes. Environ Health 

Perspect 2000;108(12):1151-1157.

Curwin BD, Hein MJ, Sanderson WT, Barr DB, Heederik D, 

Reynolds SJ, Ward EM, Alavanja MC. Urinary and hand wipe 

pesticide levels among farmers and nonfarmers in Iowa. J Expo 

Anal Environ Epidemiol 2005;15(6):500-508.

Davison KL, Larsen GL, Feil VJ. Comparative metabolism 

and elimination of acetanilide compounds by rat. Xenobiotica 

1994;24(10):1003-1012.

Feng PCC, Wratten SJ. In vitro transformation of chloroacetanilide 

herbicides by rat liver enzymes: A comparative study of 

metolachlor and alachlor. J Agri Food Chem 1989;37(4):1088-

1093.

Gillion, R. Pesticides in U.S. streams and groundwater. Environ 

Sci Technol 2007;41:3409-3414. Available at URL: http://water.

usgs.gov/nawqa/pnsp/pubs/files/051507.ESTfeature_gilliom.pdf 

3/30/09

Hines CJ, Deddens JA, Striley CA, Biagini RE, Shoemaker DA, 

Brown KK, et al. Biological monitoring for selected herbicide 

biomarkers in the urine of exposed custom applicators: application 

of mixed-effect models. Ann Occup Hyg 2003;47(6):503-517.

Hladik ML, Hsiao JJ, Roberts AL. Are neutral chloroacetamide 

herbicide degradates of potential environmental concern? 

Analysis and occurrence in the upper Chesapeake Bay. Environ 

Sci Technol 2005;39(17):6561-6574.

Jefferies PR, Quistad GB, Casida JE. Dialkylquinonimines 

validated as in vivo metabolites of alachlor, acetochlor, and 

metolachlor herbicides in rats. Chem Res Toxicol 1998;11(4):353-

359.

Kolpin DW, Thurman EM, Linhart SM. Finding minimal 

herbicide concentrations in ground water? Try looking for their 

degradates. Sci Total Environ 2000;248(2-3):115-122.

U.S. Environmental Protection Agency (U.S. EPA). Reregistration 

Eligibility Decision (RED) Metolachlor. April 1995. EPA 738-

R-95-006. Available at URL: http://www.epa.gov/oppsrrd1/

REDs/0001.pdf. 3/26/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s Waters

Pesticides in the Nation’s Streams and Ground Water, 1992-2001. 

Circular 1291. Supplemental Technical Information (available 

on-line only). March 2006, revised February 15, 2007. Available 

at URL: http://water.usgs.gov/nawqa/pnsp/pubs/circ1291/

supporting_info.php. 4/2/09

U.S. Geological Survey (USGS). Water-Resources Investigations 

Report: Distribution of Major Herbicides in Ground Water of the 

United States Water Resource Investigations Report No. 98-4245 

(by Barbash JE, Thelin GP, Kolpin DW, Gilliom RJ). Sacramento, 

California, 1999. Available at URL: http://water.usgs.gov/nawqa/

pnsp/pubs/wrir984245/text.html. 6/1/09

Whyatt RM, Barr DB, Camann DE, Kinney PL, Barr JR, 

Andrews HF, et al. Contemporary-use pesticides in personal air 

samples during pregnancy and blood samples at delivery among 

urban minority mothers and newborns. Environ Health Perspect 

2003;111(5):749-756.

World Health Organization (WHO). Metolachlor in Drinkingwater. Background document for development of WHO 

Guidelines for Drinking-water Quality. 2003. Available at URL: 

http://www.who.int/water_sanitation_health/dwq/chemicals/

metolachlor.pdf. 3/27/09
 64 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

2,4,5-Trichlorophenoxyacetic Acid

CAS No. 93-76-5

General Information

2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) is a 

chlorophenoxy acid herbicide that is no longer registered 

for use in the United States. Chlorophenoxy herbicides 

act as plant growth hormones. At low levels, these 

herbicides can enhance plant growth, but higher levels are 

herbicidal. 2,4,5-T was once applied as either an aqueous 

salt or as an oil-soluble ester. Ester forms of 2,4,5-T and 

2,4-D were used as defoliants in the Vietnam War (e.g., 

Agent Orange), and concern about contamination with 

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) led to the 

discontinuation of 2,4,5-T use as a herbicide in 1985. The 

half-life of 2,4,5-T in soil varies with conditions, ranging 

from several weeks to many months. 2,4,5-T degrades to 

2,4,5-trichlorophenol and other degradates. 2,4,5-T has 

been rarely detected in ground waters (USGS, 2007).

Given the commercial unavailability of 2,4,5-T, the general 

population is unlikely to be exposed to it. Although 2,4,5-

T is rapidly absorbed via oral and inhalation routes, it is 

not well absorbed through the skin. Once absorbed into the 

body, 2,4,5-T is eliminated mostly unchanged in the urine, 

with an elimination half-life of approximately 19 hours 

(Arnold et al., 1989; Kohli et al., 1974).

Human health effects from 2,4,5-T at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Intentional overdoses and 

unintentional high dose occupational exposures to 

chlorophenoxy acid herbicides have resulted in weakness, 

headache, dizziness, nausea, abdominal pain, myotonia, 

hypotension, renal and hepatic injury, and delayed 

neuropathy (Bradberry et al., 2004). Teratogenic and 

developmental effects have been reported in studies of 

multiple rodent strains treated with high doses of technical 

grade 2,4,5-T (Holson et al., 1992; Mohammad and St. 

Omer, 1986; Nelson et al., 1992). Epidemiological studies 

have reported associations of several types of cancer, such 

as soft tissue sarcoma and non-Hodgkin’s lymphoma, with 

the exposure to chlorophenoxy herbicides as defoliants 

Urinary 2,4,5-Trichlorophenoxyacetic acid 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1814 

01-02 * < LOD < LOD < LOD < LOD 2538 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 430

01-02 * < LOD < LOD < LOD < LOD 580

12-19 years 99-00 * < LOD < LOD < LOD < LOD 618

01-02 * < LOD < LOD < LOD < LOD 831

20-59 years 99-00 * < LOD < LOD < LOD < LOD 766

01-02 * < LOD < LOD < LOD < LOD 1127 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 891

01-02 * < LOD < LOD < LOD < LOD 1192 

Females 99-00 * < LOD < LOD < LOD < LOD 923

01-02 * < LOD < LOD < LOD < LOD 1346 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 652

01-02 * < LOD < LOD < LOD < LOD 679

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 483

01-02 * < LOD < LOD < LOD < LOD 701

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 531

01-02 * < LOD < LOD < LOD < LOD 957

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 1.2 and 0.1. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 65

 Herbicides

or contaminated herbicides. It is unclear whether these 

associations are related to the chlorophenoxy herbicides, 

other exposures, or to contaminants in the herbicide 

formulations (specifically 2,3,7,8-tetrachlorodibenzop-dioxin) (Garabrant and Philbert, 2002; IOM, 2003; 

IPCS, 1996; Pearce and McLean, 2005; U.S.EPA, 2004). 

2,4,5-T itself is not mutagenic. IARC considers the 

chlorophenoxyacetic acids group of chemicals as possibly 

carcinogenic to humans. Additional information is available 

from U.S.EPA at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of 2,4,5-T reflect recent exposure. In the 

NHANES 1999-2000 and 2001-2002 subsamples (CDC, 

2005), urinary levels of 2,4,5-T were generally below the 

limit of detection, similar to results of NHANES II (1976-

1980), in which urinary levels of 2,4,5-T also were below 

the limit of detection (Kutz et al., 1992). Mean urinary 

levels of 2,4,5-T measured after a day of exposure in a 

few asymptomatic herbicide applicators were 35,000 times 

higher than the detection limit for the NHANES 2001-2002 

data (Kolmodin-Hedman and Erne, 1980).

Finding a measurable amount of 2,4,5-T does not mean 

that the level will result in an adverse health effect. 

Biomonitoring studies on 2,4,5-T in urine also provide 

physicians and public health officials with reference values 

so that they can determine whether other people have been 

exposed to higher levels of 2,4,5-T than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Urinary 2,4,5-Trichlorophenoxyacetic acid (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1814 

01-02 * < LOD < LOD < LOD < LOD 2537 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 430

01-02 * < LOD < LOD < LOD < LOD 580

12-19 years 99-00 * < LOD < LOD < LOD < LOD 618

01-02 * < LOD < LOD < LOD < LOD 830

20-59 years 99-00 * < LOD < LOD < LOD < LOD 766

01-02 * < LOD < LOD < LOD < LOD 1127 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 891

01-02 * < LOD < LOD < LOD < LOD 1192 

Females 99-00 * < LOD < LOD < LOD < LOD 923

01-02 * < LOD < LOD < LOD < LOD 1345 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 652

01-02 * < LOD < LOD < LOD < LOD 679

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 483

01-02 * < LOD < LOD < LOD < LOD 700

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 531

01-02 * < LOD < LOD < LOD < LOD 957

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 66 Fourth National Report on Human Exposure to Environmental Chemicals 

Herbicides

References

Arnold EK, Beasley VR. The pharmacokinetics of chlorinated 

phenoxy acid herbicides: a literature. Vet Hum Toxicol 

1989;31(2):121-125.

Bradberry SM, Proudfoot AT, Vale JA. Poisoning due to 

chlorophenoxy herbicides. Toxicol Rev 2004;23(2):65-73.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Garabrant DH, Philbert MA. Review of 2,4-dichlorophenoxyacetic 

acid (2,4-D) epidemiology and toxicology. Crit Rev Toxicol 

2002;32(4):233-257.

Holson JF, Gaines TB, Nelson CJ, LaBorde JB, Gaylor 

DW, Sheehan DM, et al. Developmental toxicity of 

2,4,5-trichlorophenoxyacetic acid (2,4,5-T). I. Multireplicated 

dose-response studies in four inbred strains and one outbred stock 

of mice. Fundam Appl Toxicol 1992;19(2):286-297.

International Programme on Chemical Safety-INCHEM (IPCS). 

Pesticides residues in food: 1996 evaluations Part II Toxicology. 

914. Dichlorophenoxyacetic acid, 2,4-. Available at URL: http://

www.inchem.org/documents/jmpr/jmpmono/v96pr04.htm. 

3/17/09

Institute of Medicine (IOM). Board on Health Promotion and 

Disease Prevention. Committee to Review the Health Effects in 

Vietnam Veterans of Exposure to Herbicides (Fourth Biennial 

Update. Veterans and Agent Orange: update 2002. Washington 

(DC): National Academies Press; 2003. Available at URL: http://

www.nap.edu/catalog.php?record_id=10603. 3/17/09

Kohli JD, Khanna RN, Gupta BN, Dhar MM, Tandon JS, Sircar 

KP. Absorption and excretion of 2,4,5-trichlorophenoxy acetic 

acid in man. Arch Int Pharmacodyn Ther 1974; 210:250-255.

Kolmodin-Hedman B, Erne K. Estimation of occupational 

exposure to phenoxy acids (2,4-D and 2,4,5-T). Arch Toxicol 

Suppl 1980;4:318-21.

Kutz FW, Cook BT, Carter-Pokras OD, Brody D, Murphy RS. 

Selected pesticide residues and metabolites in urine from a 

survey of the U.S. general population. J Toxicol Environ Health 

1992;37(2):277-91.

Mohammad FK, St Omer VE. Behavioral and developmental 

effects in rats following in utero exposure to 2,4-D/2,4,5-t 

mixture. Neurobehav Toxicol Teratol 1986;8(5):551-60.

Nelson CJ, Holson JF, Gaines TB, LaBorde JB, 

McCallum WF, Wolff GL, et al. Developmental toxicity of 

2,4,5-trichlorophenoxyacetic acid (2,4,5-T). II. Multireplicated 

dose-response studies with technical and analytical grades 

of 2,4,5-T in four-way outcross mice. Fundam Appl Toxicol 

1992;19(2):298-306.

Pearce N, McLean D. Agricultural exposures and non-Hodgkin’s 

lymphoma. Scand J Work Environ Health 2005;31 Suppl 1:18-

25; discussion 5-7.

U. S. Environmental Protection Agency (U.S.EPA). Office of 

Prevention Pesticides and Toxic Substances. Pesticide industry 

sales and usage - 2000 and 2001 market estimates. Washington 

(DC): U.S.EPA. May, 2004. Available at URL: http://www.epa.

gov/oppbead1/pestsales/01pestsales/market_estimates2001.pdf.

3/17/09
Fourth National Report on Human Exposure to Environmental Chemicals 67

 Carbamate Insecticides 

Carbamate Insecticides

General Information

N-methyl carbamate insecticides (carbamates) have 

been widely used in the U.S. and throughout the world. 

In agricultural applications, the use of the carbamate 

insecticides has decreased, being replaced by pyrethroid 

and other insecticides. Carbamates have been used on 

residential lawns, ornamentals, in nurseries, and on golf 

courses. Carbamates do not persist in the environment 

and have a low potential for bioaccumulation. Some 

other chemical types of carbamates, thiocarbamates and 

dithiocarbamates, are used as herbicides and fungicides.

General population exposure to carbamates occurs during 

contact with residential uses and, less commonly, from 

ingesting contaminated foods. Agricultural workers 

can be exposed when they re-enter areas recently 

treated. Exposures of workers also can occur during 

the manufacture, formulation, or application of these 

chemicals. Carbamates can be absorbed through the skin, 

via inhalation, or by ingestion. Criteria for allowable levels 

of specific carbamates in food, the environment, and the 

workplace have been developed by the U.S. FDA, U.S. 

EPA, and OSHA, respectively.

Carbamate insecticides act by inhibiting acetylcholinesterase enzymes, leading to an increase of acetylcholine in 

the nervous system. At high doses, toxic symptoms include 

nausea, vomiting, cholinergic signs, weakness, paralysis, 

and seizures. The mechanism of toxicity of carbamate 

insecticides is similar to that of organophosphate pesticides; 

however, carbamate insecticides generally are reversible 

inhibitors of acetylcholinesterase activity, acting for a 

shorter time than organophosphate pesticides. Carbamate 

insecticides are rapidly eliminated from the body. Only 

two metabolites are measured in this Report (metabolites 

of carbofuran and propoxur), of the carbamate insecticides 

still used in the U.S.
 68 Fourth National Report on Human Exposure to Environmental Chemicals 

Carbamate Insecticides

Carbofuran

CAS No. 1563-66-2

General Information

Carbofuranphenol is a metabolite of four different carbamate 

insecticides: benfuracarb; carbofuran; carbosulfan; and 

furathiocarb. Only carbofuran is registered in the U.S. 

Carbofuran is a broad spectrum, restricted-use insecticide 

and nematicide applied to a variety of field, fruit, and 

vegetable crops for control of beetles, borers, nematodes, 

weevils, and similar pests. Recently, registered uses of 

carbofuran were cancelled except for the following: field 

corn; potatoes; pumpkins; sunflowers; pine seedlings; 

and spinach grown for seed (U.S.EPA, 2009). About 1 

million pounds have been used annually (U.S.EPA, 2007). 

Carbofuran is not registered for use in residential settings 

or food-handling establishments. In soils of varying 

composition, carbofuran has a half-life ranging from one 

to three months. It can leach into ground waters, but it 

has been detected only infrequently in either surface or 

ground waters (Gilliom, 2007; USGS, 2007). Carbofuran 

is very highly toxic to fish and aquatic invertebrates, and 

it is highly toxic to birds where granular applications are 

used, but such applications have been restricted since 1991 

(U.S.EPA, 2007).

General population exposure can occur through 

consumption of food contaminated with carbofuran. 

Because estimated acute intakes from some dietary 

components in young children may exceed recommended 

intake limits, the U.S.EPA is in the process of revoking 

current regulations that allow carbofuran residues in food 

(U.S.EPA, 2009). Pesticide handlers and applicators are 

at greater risk for exposure and a number of incidents of 

systemic poisoning have been reported. After absorption, 

carbofuran is metabolized to phenolic metabolites and 

3-hydroxycarbofuran, which are quickly eliminated in the 

urine.

Human health effects from carbofuran at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Carbofuran was very highly 

acutely toxic in animal studies, causing effects related 

Urinary Carbofuranphenol 

Metabolite of Benfuracarb, Carbofuran, Carbosulfan, and Furathiocarb 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD .770 (<LOD-1.30) 1994 

01-02 * < LOD < LOD < LOD < LOD 2530 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD .450 (<LOD-2.20) 482

01-02 * < LOD < LOD < LOD < LOD 578

12-19 years 99-00 * < LOD < LOD < LOD .570 (<LOD-1.20) 681

01-02 * < LOD < LOD < LOD < LOD 827

20-59 years 99-00 * < LOD < LOD < LOD .840 (<LOD-1.50) 831

01-02 * < LOD < LOD < LOD < LOD 1125 

Gender 

Males 99-00 * < LOD < LOD < LOD .740 (<LOD-1.50) 973

01-02 * < LOD < LOD < LOD < LOD 1190 

Females 99-00 * < LOD < LOD < LOD .840 (<LOD-1.50) 1021 

01-02 * < LOD < LOD < LOD < LOD 1340 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD .590 (<LOD-2.00) 1.90 (<LOD-5.10) 696

01-02 * < LOD < LOD < LOD < LOD 680

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD .550 (<LOD-1.60) 521

01-02 * < LOD < LOD < LOD < LOD 696

Non-Hispanic whites 99-00 * < LOD < LOD < LOD .740 (<LOD-1.50) 603

01-02 * < LOD < LOD < LOD < LOD 953

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.4 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 69

 Carbamate Insecticides 

to acetylcholinesterase enzyme inhibition. In contrast, 

carbofuranphenol is not an inhibitor of acetylcholinesterase 

enzymes. Carbofuran was not teratogenic, but high chronic 

doses in animals produced nonspecific developmental 

effects, such as reduced weight gain and pup survival 

(WHO, 2004). Testicular toxicity at subacute doses was 

reported in adult rats, rat pups, and dogs (Pant et al., 

1995, 1997; WHO, 2004). Carbofuran was found not to be 

mutagenic or carcinogenic in animals (U.S.EPA, 2007). It 

is not rated by IARC with regard to human carcinogenicity. 

Additional information is available from U.S.EPA at: http://

www.epa.gov/pesticides/.

Biomonitoring Information

Urinary carbofuranphenol levels reflect recent exposure. 

The level of this metabolite in urine may reflect exposure to 

carbofuran or to carbofuranphenol as a degradation product 

in the environment or food. In representative subsamples 

from NHANES 1999-2000 and 2001-2002, most urinary 

levels of carbofuranphenol were below the limit of detection 

(CDC, 2005). In a nonrandom subsample from NHANES III 

(1988-1994), the 99th percentile level of carbofuranphenol 

was 2.1μg/L (Hill et al., 1995). In a previous study of U.S. 

farmers and their families, carbofuranphenol was detected 

in 6.7% of urine samples (Shealy et al., 1997); the 95th 

percentile value in that study was 0.73 μg/L. Urinary levels 

of carbofuranphenol in two applicators were three and 

sixfold higher than the detection limit for the NHANES 

2003-2004 subsample (Petropoulou et al., 2006).

Finding a measurable amount of carbofuranphenol in 

urine does not mean that the level of carbofuranphenol 

causes an adverse health effect. Biomonitoring studies on 

levels of carbofuranphenol provide physicians and public 

health officials with reference values so that they can 

determine whether people have been exposed to higher 

levels of carbofuran or related carbamates than are found 

in the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Urinary Carbofuranphenol (creatinine corrected) 

Metabolite of Benfuracarb, Carbofuran, Carbosulfan, and Furathiocarb 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD .780 (<LOD-1.00) 1994 

01-02 * < LOD < LOD < LOD < LOD 2529 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD .990 (<LOD-2.80) 482

01-02 * < LOD < LOD < LOD < LOD 578

12-19 years 99-00 * < LOD < LOD < LOD .480 (<LOD-.850) 681

01-02 * < LOD < LOD < LOD < LOD 826

20-59 years 99-00 * < LOD < LOD < LOD .880 (<LOD-1.06) 831

01-02 * < LOD < LOD < LOD < LOD 1125 

Gender 

Males 99-00 * < LOD < LOD < LOD .670 (<LOD-1.08) 973

01-02 * < LOD < LOD < LOD < LOD 1190 

Females 99-00 * < LOD < LOD < LOD .880 (<LOD-1.13) 1021 

01-02 * < LOD < LOD < LOD < LOD 1339 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD .780 (<LOD-1.94) 1.83 (<LOD-4.16) 696

01-02 * < LOD < LOD < LOD < LOD 680

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD .700 (<LOD-1.08) 521

01-02 * < LOD < LOD < LOD < LOD 695

Non-Hispanic whites 99-00 * < LOD < LOD < LOD .740 (<LOD-.930) 603

01-02 * < LOD < LOD < LOD < LOD 953

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 70 Fourth National Report on Human Exposure to Environmental Chemicals 

Carbamate Insecticides

References

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Gillion, R. Pesticides in U.S. streams and groundwater. Environ 

Sci Technol 2007;41:3409-3414. Available at URL: http://water.

usgs.gov/nawqa/pnsp/pubs/files/051507.ESTfeature_gilliom.

pdf. 4/9/09

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, et 

al. Pesticide residues in urine of adults living in the United States: 

reference range concentrations. Environ Res 1995;71(2):99-108.

Pant N, Prasad AK, Srivastava SC, Shankar R, Srivastava SP. 

Effect of oral administration of carbofuran on male reproductive 

system of rat. Hum Exp Toxicol 1995;14(11):889-894.

Pant N, Shankar R, Srivastava SP. In utero and lactational 

exposure of carbofuran to rats: effect on testes and sperm. Hum 

Exp Toxicol 1997;16(5):267-272.

Petropoulou SS, Gikas E, Tsarbopoulos A, Siskos PA. Gas 

chromatographic-tandem mass spectrometric method for the 

quantitation of carbofuran, carbaryl and their main metabolites in 

applicators’ urine. J Chromatogr A 2006;1108(1):99-110.

Shealy DB, Barr JR., Ashley DL, Patterson DG Jr, Camann DE, 

Bond AE. Correlation of environmental carbaryl measurements 

with serum and urinary 1-naphthol measurements in a farmer 

applicator and his family. Environ Health Perspect 1997;105:510-

513.

U.S. Environmental Protection Agency (U.S.EPA) Carbofuran 

cancellation process. March 28, 2009. Available at URL: http://

www.epa.gov/pesticides/reregistration/carbofuran/carbofuran_

noic.htm. 4/10/09

U.S. Environmental Protection Agency (U.S.EPA). Reregistration 

Eligibility Decision for Carbofuran. September 2007. Available 

at URL: http://www.epa.gov/pesticides/reregistration/REDs/

carbofuran_red.pdf. 4/10/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s Waters:

Pesticides in the Nation’s Streams and Ground Water, 1992-2001. 

Circular 1291. Supplemental Technical Information (available 

on-line only). March 2006, revised February 15, 2007. Available 

at URL: http://water.usgs.gov/nawqa/pnsp/pubs/circ1291/

supporting_info.php. 4/2/09

World Health Organization (WHO). Carbofuran in DrinkingWater. Background document for development of WHO 

Guidelines for Drinking-water Quality. 2004. Available at URL: 

http://www.who.int/water_sanitation_health/dwq/chemicals/

carbofuran.pdf. 4/9/09
Fourth National Report on Human Exposure to Environmental Chemicals 71

 Carbamate Insecticides 

Propoxur

CAS No. 114-26-1

General Information

2-Isopropoxyphenol is a metabolite of propoxur, a carbamate 

used to control ants, roaches, hornets, and similar pests in 

residential areas and around commercial food-handling 

establishments. Propoxur has also been used in pest strips 

and pet flea collars. Like several other pesticides, propoxur 

has been used outside the U.S. as a replacement for DDT 

in malaria vector control. Propoxur may remain in the 

environment for weeks to several months, longer than most 

carbamates (U.S.EPA, 1997b). Despite its mobility in soil 

and its potential for leaching into groundwater, propoxur 

has been rarely detected in U.S. surface or ground waters 

(Gilliom, 2007; USGS, 2007). Although propoxur is toxic 

to birds and aquatic life, ecologic exposures are unlikely 

due to current outdoor use restrictions.

General population exposure to propoxur through the diet 

is likely to be limited because of usage restrictions (U.S. 

EPA, 1997a). Estimated human intakes have been below 

recommended intake limits (U.S.EPA, 1997b). Pesticide 

applicators are likely to have the highest exposures. 

Propoxur can be absorbed through the skin, lungs, and 

gastrointestinal tract. Propoxur does not accumulate in 

blood or tissues and is eliminated rapidly from the body 

(Leenheers et al., 1992; WHO, 2003). In animal and human 

studies, 2-isopropoxyphenol was one of several urine 

metabolites (U.S.EPA, 1997b).

Human health effects from propoxur at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. In animal studies, propoxur has 

moderate acute toxicity consisting of anticholinesterase 

effects (U.S.EPA, 1997b). 2-Isopropoxyphenol does not 

inhibit acetylcholinesterase enzymes. Propoxur is not 

considered mutagenic, embryotoxic, or teratogenic (WHO, 

2003). U.S. EPA considers propoxur to be a probable 

human carcinogen, based on bladder tumors in male rats 

(U.S. EPA, 1997b). The human carcinogenic potential 

of propoxur has not been evaluated by IARC or NTP. 

Additional information is available from U.S.EPA at: http://

www.epa.gov/pesticides/.

Biomonitoring Information

Urinary 2-isopropoxyphenol levels reflect recent exposure. 

The level of this metabolite in urine may reflect exposure to 

propoxur or to 2-isopropoxyphenol as a degradation product 

in the environment or food (U.S.EPA, 1997b). In the U.S. 

representative subsamples from NHANES 1999-2000 and 

2001-2002, most 2-isopropoxyphenol levels in urine were 

below the limit of detection (CDC, 2005). In a nonrandom 

subsample from NHANES III (1988-1994), the 95th 

percentile level of 2-isopropoxyphenol was 1.7 μg/L (Hill 

et al., 1995). Higher urinary levels of 2-isopropoxyphenol 

have been measured in a few pesticide applicators, with a 

range of 45-306 μg/g creatinine (Hardt and Angerer, 1999).

Finding a measurable amount of 2-isopropoxyphenol in 

urine does not mean that the level of 2-isopropoxyphenol 

causes an adverse health effect. Biomonitoring studies 

on levels of 2-isopropoxyphenol provide physicians and 

public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of propoxur than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.
 72 Fourth National Report on Human Exposure to Environmental Chemicals 

Carbamate Insecticides

Urinary 2-Isopropoxyphenol 

Metabolite of Propoxur 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1917 

01-02 * < LOD < LOD < LOD < LOD 2503 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 456

01-02 * < LOD < LOD < LOD < LOD 574

12-19 years 99-00 * < LOD < LOD < LOD < LOD 655

01-02 * < LOD < LOD < LOD < LOD 820

20-59 years 99-00 * < LOD < LOD < LOD < LOD 806

01-02 * < LOD < LOD < LOD < LOD 1109 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 936

01-02 * < LOD < LOD < LOD < LOD 1178 

Females 99-00 * < LOD < LOD < LOD < LOD 981

01-02 * < LOD < LOD < LOD < LOD 1325 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 664

01-02 * < LOD < LOD < LOD < LOD 677

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 500

01-02 * < LOD < LOD < LOD < LOD 696

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 585

01-02 * < LOD < LOD < LOD < LOD 931

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 1.1 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 73

 Carbamate Insecticides 

Urinary 2-Isopropoxyphenol (creatinine corrected) 

Metabolite of Propoxur 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1917 

01-02 * < LOD < LOD < LOD < LOD 2502 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 456

01-02 * < LOD < LOD < LOD < LOD 574

12-19 years 99-00 * < LOD < LOD < LOD < LOD 655

01-02 * < LOD < LOD < LOD < LOD 819

20-59 years 99-00 * < LOD < LOD < LOD < LOD 806

01-02 * < LOD < LOD < LOD < LOD 1109 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 936

01-02 * < LOD < LOD < LOD < LOD 1178 

Females 99-00 * < LOD < LOD < LOD < LOD 981

01-02 * < LOD < LOD < LOD < LOD 1324 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 664

01-02 * < LOD < LOD < LOD < LOD 677

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 500

01-02 * < LOD < LOD < LOD < LOD 695

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 585

01-02 * < LOD < LOD < LOD < LOD 931

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 74 Fourth National Report on Human Exposure to Environmental Chemicals 

Carbamate Insecticides

References

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Gillion, R. Pesticides in U.S. streams and groundwater. Environ 

Sci Technol 2007;41:3409-3414. Available at URL: http://water.

usgs.gov/nawqa/pnsp/pubs/files/051507.ESTfeature_gilliom.

pdf. 4/9/09

Hardt J, Angerer J. Gas chromatographic method with massselective detection for the determination of 2-isopropoxyphenol 

in human urine. J Chromatogr B Biomed Sci Appl 1999;723(1-

2):139-145.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, et 

al. Pesticide residues in urine of adults living in the United States: 

reference range concentrations. Environ Res 1995;71(2):99-108.

Leenheers LH, van Breugel DC, Ravensberg JC, Meuling WJ, 

Jongen MJ. Determination of 2-isopropoxyphenol in urine by 

capillary gas chromatography and mass-selective detection. J 

Chromatogr 1992;578(2):189-194.

U.S. Environmental Protection Agency (U.S.EPA). RED Facts. 

Propoxur. August 1997a. EPA 738 F-97-009. Available at URL: 

http://www.epa.gov/oppsrrd1/REDs/factsheets/2555fact.pdf. 

4/9/09

U.S. Environmental Protection Agency (U.S.EPA). Reregistration 

Eligibility Decision (RED) Propoxur. August 1997b. EPA 738-

R-97-009. Available at URL: http://www.epa.gov/pesticides/

reregistration/REDs/2555red.pdf. 4/9/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s 

Waters. Pesticides in the Nation’s Streams and Ground Water, 

1992-2001. Circular 1291. Supplemental Technical Information 

(available on-line only). March 2006, revised February 15, 

2007. Available at URL: http://water.usgs.gov/nawqa/pnsp/pubs/

circ1291/supporting_info.php. 4/2/09

World Health Organization (WHO). WHO Specifications and 

Evaluations for Public Health Pesticides. Propoxur. FAO/WHO 

Evaluation Report 80/2003. 2003. Available at URL: http://

www.who.int/whopes/quality/en/propoxur_eval_spec_WHO_

October_2005.pdf. 4/9/09
Fourth National Report on Human Exposure to Environmental Chemicals 75

 Organochlorine Pesticides

Organochlorine Pesticides

General Information

Organochlorine pesticides, an older class of pesticides, are 

effective against a variety of insects. These chemicals were 

introduced in the 1940s, and many of their uses have been 

cancelled or restricted by the U.S. EPA because of their 

environmental persistence and potential adverse effects on 

wildlife and human health. Many organochlorines are no 

longer used widely in the U.S., but other countries continue 

to use them. Hexachlorobenzene has been used primarily as 

a fungicide or biocide.

Organochlorine pesticides can enter the environment after 

pesticide applications, disposal of contaminated wastes 

into landfills, and releases from manufacturing plants 

that produce these chemicals. Some organochlorines are 

volatile, and some can adhere to soil or particles in the 

air. In aquatic systems, sediments adsorb organochlorines, 

which can then bioaccumulate in fish and other aquatic 

mammals. These chemicals are fat soluble, so they are 

found at higher concentrations in fatty foods. In the general 

population, diet is the main source of exposure, primarily 

through the ingestion of fatty foods such as dairy products 

and fish. Usage restrictions have been associated with 

a general decrease in serum organochlorine levels in the 

U.S. population and other developed countries (Hagmar 

et al., 2006; Kutz et al., 1991). Contaminated drinking 

water and air are usually minor exposure sources. Infants 

can be exposed through breast milk, and the fetus can be 

exposed in utero via the placenta. Workers can be exposed 

to organochlorines in the manufacture, formulation, or 

application of these chemicals. The FDA, U.S. EPA, and 

OSHA have developed standards for allowable levels of 

certain organochlorines in foods, the environment, and the 

workplace, respectively. Attributing human health effects 

to specific organochlorine chemicals is difficult because 

exposure to multiple organochlorine chemicals occurs 

often and these chemicals may have similar actions.

The table shows selected parent organochlorines and 

their metabolites that can be measured in serum or urine. 

Measurements of these chemicals can reflect either recent 

or cumulative exposures, or both. Some of the metabolites 

can be produced from more than one pesticide. The level 

of a metabolite in a person’s blood or urine may indicate 

exposure to the parent pesticide as well as to the metabolite 

itself.

Organochlorine Pesticides and Metabolites in this Report

Organochlorine Pesticide 

(CAS number)

Serum pesticide or metabolite(s) 

(CAS number)

Urinary pesticide or metabolite(s) 

(CAS number) 

Aldrin (309-00-02) Aldrin (309-00-02) 

Dieldrin (60-57-1) 

Chlordane (12789-03-6) Oxychlordane (27304-13-8) 

trans-Nonachlor (3734-49-4) 

Dichlorodiphenyltrichloroethanes 

p,p’-DDT (50-29-3) 

p,p’-DDE (72-55-9) 

o,p’-DDT (789-02-6)

Dieldrin (60-57-1) Dieldrin (60-57-1) 

Endrin (72-20-8) Endrin (72-20-8) 

Heptachlor (76-44-8) Heptachlor epoxide (1024-57-3) 

Hexachlorobenzene (118-74-1) Hexachlorobenzene (118-74-1) 

Pentachlorophenol (87-86-5) 

2,4,6-Trichlorophenol (88-06-2) 

2,4,5-Trichlorophenol (95-95-4) 

Hexachlorocyclohexanes beta-Hexachlorocyclohexane (319-85-7) 

gamma-Hexachlorocyclohexane (58-89-9)

Pentachlorophenol (87-86-5) 

2,4,6-Trichlorophenol (88-06-2) 

2,4,5-Trichlorophenol (95-95-4) 

Mirex (2385-85-5) Mirex (2385-85-5) 

2,4,5-Trichlorophenol (95-95-4) 

2,4,6-Trichlorophenol (88-06-2) 

2,4,5-Trichlorophenol (95-95-4) 

2,4,6-Trichlorophenol (88-06-2) 
 76 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

References

Hagmar L, Wallin E, Vessby B, Jonsson BA, Bergman A, 

Rylander L. Intra-individual variations and time trends 1991-2001 

in human serum levels of PCB, DDE and hexachlorobenzene. 

Chemosphere 2006;64(9):507-513.

Kutz FW, Wood PH, Bottimore DP. Organochlorine pesticides 

and polychlorinated biphenyls in human adipose tissue. Rev 

Environ Contam Toxicol 1991;120:1-82.
Fourth National Report on Human Exposure to Environmental Chemicals 77

 Organochlorine Pesticides

Aldrin

CAS No. 309-00-02 

Dieldrin

CAS No. 60-57-1

Also a Metabolite of Aldrin

General Information

Aldrin and dieldrin are no longer produced or used in the 

U.S. From the 1950s to 1970, both chemicals were applied 

mainly as a soil insecticide or seed dressing for food and 

commodity crops. Dieldrin was also used for mothproofing 

clothes and carpets. In tropical countries, dieldrin was used 

as a residual spray in residential dwellings to control vectorborne diseases such as malaria. The U.S. EPA cancelled 

agricultural uses of both pesticides in 1970; termiticide 

uses were cancelled in 1987. Aldrin is readily converted 

to dieldrin in the environment and in plants that take up 

the chemical. Aldrin volatilizes after agricultural soil 

applications or is converted to dieldrin, which volatilizes 

more slowly. These chemicals persist in the environment 

and bioaccumulate in foods (Jorgenson 2001; USGS, 

2007). Aldrin is rarely detected in plants or animal tissues, 

but dieldrin has been detected in meats, dairy products, 

and in crops grown in soils that have been contaminated, 

usually by application, manufacturing, or disposal.

General population exposure to these chemicals occurs 

through the diet, and detection of dieldrin residue in foods 

has decreased over time (FDA, 2008). Inhalation exposure 

may occur among people living in residences where aldrin 

was applied historically as a pesticide. Aldrin and dieldrin 

are absorbed following ingestion, inhalation, and dermal 

application. After absorption, aldrin is metabolized to 

dieldrin so rapidly that aldrin is rarely detected. Dieldrin 

accumulates in fatty tissues, and its metabolites are excreted 

in bile and feces (ATSDR, 2002). It is also excreted in breast 

milk and can cross the placenta. The elimination half-life of 

dieldrin is approximately 1 year (IPCS, 1989; Jorgenson 

2001).

Human health effects from aldrin and dieldrin at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. At high doses, 

aldrin and dieldrin block inhibitory neurotransmitters in 

the central nervous system (Narahashi et al., 1992). This 

blocking action can cause abnormal excitation of the brain, 

leading to symptoms such as headache, confusion, muscle 

Serum Aldrin (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2275 

03-04 * < LOD < LOD < LOD < LOD 1946 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 756

03-04 * < LOD < LOD < LOD < LOD 588

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1519 

03-04 * < LOD < LOD < LOD < LOD 1358 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1057 

03-04 * < LOD < LOD < LOD < LOD 946

Females 01-02 * < LOD < LOD < LOD < LOD 1218 

03-04 * < LOD < LOD < LOD < LOD 1000 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 559

03-04 * < LOD < LOD < LOD < LOD 456

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 512

03-04 * < LOD < LOD < LOD < LOD 485

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1045 

03-04 * < LOD < LOD < LOD < LOD 881

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 5.94 and 7.8. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 78 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

twitching, nausea, vomiting, and seizures. When fed to 

experimental animals, both aldrin and dieldrin caused liver 

enlargement and liver tumors; dieldrin at higher doses 

caused irritability, tremors, and occasionally, seizures 

(Smith, 1991). When dieldrin was fed to pregnant rodents, 

the offspring had altered CNS neurotransmitter levels 

(Sanchez-Ramos et al., 1998) and behavioral changes 

(Carlson and Rosellini, 1987). Studies done in vitro showed 

that dieldrin binds to estrogen receptors (Soto et al., 1995), 

but no estrogenic effect was noted in a study that used 

cultured cells (Tully et al., 2000). Epidemiologic and animal 

studies have not conclusively associated dieldrin exposure 

with risk for developing Parkinson’s disease (Corrigan et 

al., 2000; Kanthasamy et al., 2005; Li et al., 2005).

The U.S. EPA has established environmental standards for 

aldrin and dieldrin, and the FDA monitors foods for pesticide 

residues. OSHA has established workplace exposure 

standards for aldrin and dieldrin. IARC has determined that 

aldrin and dieldrin are not classifiable with regard to human 

carcinogenicity. Information about external exposure (i.e., 

environmental levels) and health effects is available from 

ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

In the NHANES 2001-2002 and 2003-2004 subsamples, 

serum aldrin levels were below the limit of detection, 

similar to results in a subsample of NHANES II (1976-

1980) (Stehr-Green, 1989). Levels of aldrin also were not 

detectable in 1996-1997 pooled samples from New Zealand 

adults (Bates et al., 2004).

Serum dieldrin levels at the 95th percentile in NHANES 

2001-2002 and 2003-2004 subsamples were approximately 

ten times lower than the corresponding percentile measured 

in NHANES II (1976-1980), in which only 10.6% of the 

subsample had dieldrin levels above the limit of detection 

(Stehr-Green 1989). The median level in pooled samples 

from New Zealand adults obtained in 1996-1997 was 

generally similar to the 90th percentile for adults in this 

Report (Bates et al., 2004). In samples obtained between 

1973 and 1991 from Norwegian women, the median serum 

dieldrin level was generally similar to the 90th percentile for 

females in this Report (Ward et al., 2000). Danish women 

whose serum was collected in 1976 had a median dieldrin 

level near the 95th percentile for females in this Report

(Hoyer et al., 1998). In a study of pesticide applicators with 

occupational exposure to aldrin, median levels of dieldrin 

were more than thirtyfold higher than the 95th percentile 

Serum Aldrin (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2275 

03-04 * < LOD < LOD < LOD < LOD 1946 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 756

03-04 * < LOD < LOD < LOD < LOD 588

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1519 

03-04 * < LOD < LOD < LOD < LOD 1358 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1057 

03-04 * < LOD < LOD < LOD < LOD 946

Females 01-02 * < LOD < LOD < LOD < LOD 1218 

03-04 * < LOD < LOD < LOD < LOD 1000 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 559

03-04 * < LOD < LOD < LOD < LOD 456

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 512

03-04 * < LOD < LOD < LOD < LOD 485

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1045 

03-04 * < LOD < LOD < LOD < LOD 881

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 79

 Organochlorine Pesticides

Serum Dieldrin (lipid adjusted) 

Also a Metabolite of Aldrin 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD < LOD 15.3 (14.5-17.4) 20.3 (18.7-22.4) 2159

03-04 * < LOD 9.00 (8.40-9.90) 14.4 (12.1-16.4) 19.0 (15.8-24.2) 1952

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 716

03-04 * < LOD < LOD < LOD 9.10 (<LOD-16.4) 587

20 years and older 01-02 * < LOD 10.5 (<LOD-11.6) 16.6 (15.1-18.2) 21.3 (19.1-24.0) 1443

03-04 * < LOD 9.50 (8.80-10.4) 14.9 (12.8-17.0) 19.5 (16.0-25.7) 1365

Gender 

Males 01-02 * < LOD < LOD 15.7 (14.4-18.7) 20.3 (18.6-24.0) 1007

03-04 * < LOD 9.30 (8.40-10.8) 15.1 (13.1-19.1) 21.9 (14.9-38.5) 954

Females 01-02 * < LOD < LOD 15.3 (13.4-17.2) 19.8 (18.0-21.6) 1152

03-04 * < LOD 8.70 (7.80-9.50) 12.8 (11.2-15.4) 16.9 (13.9-22.4) 998

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD 11.7 (<LOD-15.1) 15.4 (12.7-19.1) 539

03-04 * < LOD < LOD 10.8 (9.00-14.1) 14.0 (10.6-24.1) 456

Non-Hispanic blacks 01-02 * < LOD < LOD 15.0 (11.8-19.1) 20.6 (15.8-25.2) 484

03-04 * < LOD 8.80 (<LOD-10.1) 13.0 (10.5-15.8) 15.9 (13.3-21.5) 487

Non-Hispanic whites 01-02 * < LOD < LOD 15.6 (14.8-17.8) 21.1 (18.9-23.6) 980

03-04 * < LOD 9.30 (8.60-10.2) 14.9 (12.5-17.5) 19.7 (15.6-33.4) 885

Limits of detection (LOD, see Data Analysis section) for survey years 01-02 and 03-04 are 10.5 and 7.8. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum Dieldrin (whole weight) 

Also a Metabolite of Aldrin 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD < LOD .110 (.100-.120) .150 (.130-.170) 2159

03-04 * < LOD .059 (.054-.064) .098 (.083-.112) .138 (.109-.177) 1952

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 716

03-04 * < LOD < LOD < LOD .048 (<LOD-.093) 587

20 years and older 01-02 * < LOD .070 (<LOD-.080) .120 (.110-.130) .160 (.140-.180) 1443

03-04 * < LOD .062 (.056-.069) .102 (.088-.117) .139 (.112-.182) 1365

Gender 

Males 01-02 * < LOD < LOD .120 (.100-.130) .160 (.130-.190) 1007

03-04 * < LOD .064 (.054-.075) .109 (.084-.138) .147 (.108-.242) 954

Females 01-02 * < LOD < LOD .100 (.090-.110) .140 (.120-.160) 1152

03-04 * < LOD .055 (.049-.060) .089 (.077-.100) .110 (.096-.147) 998

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD .090 (<LOD-.100) .120 (.090-.140) 539

03-04 * < LOD < LOD .077 (.062-.116) .113 (.073-.158) 456

Non-Hispanic blacks 01-02 * < LOD < LOD .090 (.070-.110) .130 (.090-.190) 484

03-04 * < LOD .053 (<LOD-.058) .080 (.063-.101) .103 (.080-.149) 487

Non-Hispanic whites 01-02 * < LOD < LOD .110 (.100-.130) .150 (.130-.180) 980

03-04 * < LOD .062 (.054-.070) .103 (.086-.124) .139 (.109-.202) 885

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 80 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

in the NHANES 2001-2002 and 2003-2004 subsamples 

(Edwards and Priestly 1994).

Finding a measurable amount of aldrin or dieldrin in serum 

does not mean that the level of aldrin or dieldrin causes 

an adverse health effect. Biomonitoring studies on levels 

of aldrin and dieldrin provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels of 

aldrin or dieldrin than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for aldrin/dieldrin [online]. September 

2002. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp1.html. 4/21/09

Bates MN, Buckland SJ, Garrett N, Ellis H, Needham LL, 

Patterson DG Jr, et al. Persistent organochlorines in the serum 

of the non-occupationally exposed New Zealand population. 

Chemosphere 2004;54:1431-1443.

Carlson JN, Rosellini RA. Exposure to low doses of the 

environmental chemical dieldrin causes behavioral deficits in 

animals prevented from coping with stress. Psychopharmacology 

(Berl) 1987;91(1):122-126.

Corrigan FM, Wienburg CL, Shore RF, Daniel SE, Mann D. 

Organochlorine insecticides in substantia nigra in Parkinson’s 

disease. J Toxicol Environ Health, Part A 2000;59:229-234.

Edwards JW, Priestly BG. Effect of occupational exposure 

to aldrin on urinary D-glucaric acid, plasma dieldrin, and 

lymphocyte sister chromatid exchange. Int Arch Occup Environ 

Health 1994;66(4):229-234.

Food and Drug Administration (FDA). Center for Food Safety 

and Applied Nutrition/Office of Plant and Dairy Foods. FDA 

Pesticide Program Residue Monitoring 1993-2006 [online]. 

August 2008. Available at URL: http://www.cfsan.fda.gov/~dms/

pesrpts.html. 4/21/09

Hoyer AP, Grandjean P, Jorgensen T, Brock JW, Hartvig HB. 

Organochlorine exposure and risk of breast cancer. Lancet 

1998;352:1816-1820.

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 91. Aldrin and Dieldrin [online]. 

1989. Available at URL: http://www.inchem.org/documents/ehc/

ehc/ehc91.htm. 4/21/09

Jorgenson JL. Aldrin and dieldrin: A review of research on their 

production environmental deposition and fate, bioaccumulation, 

toxicology, and epidemiology in the United States. Environ 

Health Perspect 2001;109(Supp1):113-139.

Kanthasamy AG, Kitzazwa M, Kanthasamy A, Anantharam V. 

Dieldrin-induced neurotoxicity: relevance to Parkinson’s disease 

pathogenesis. Neurotoxicol 2005;26:701-719.

Li AA, Mink PJ, McIntosh LJ, Teta MJ, Finley B. Evaluation 

of epidemiologic and animal data associating pesticides with 

Parkinson’s disease. J Occup Environ Med 2005;47:1059-1087.

Narahashi T, Frey JM, Ginsburg KS, Roy ML. Sodium and 

GABA-activated channels as the targets of pyrethroids and 

cyclodienes. Toxicol Lett 1992;64-65 Spec. No:429-436.

Sanchez-Ramos J, Facca A, Basit A, Song S. Toxicity of dieldrin 

for dopaminergic neurons in mesencephalic cultures. Exp Neurol 

1998;150:263-271.

Smith AG. Chlorinated Hydrocarbon Insecticides. In Hayes WJ, 

Jr and Laws ER, Jr, Eds. Handbook of Pesticide Toxicology, Vol. 

2 Classes of Pesticides. New York, Academic Press, Inc. 1991, 

pp. 731-915.

Soto AM, Sonnenschein C, Chung KL, Fernandez MG, Olea N, 

Serrano FO. The E-SCREEN assay as a tool to identify estrogens: 

an update on estrogenic environmental pollutants. Environ Health 

Perspect 1995;103(Suppl 7):113-122.

Stehr-Green, PA. Demographic and seasonal influences on 

human serum pesticide residue levels. J Toxicol Environ Health 

1989;27:405-421.

Tully DB, Cox, VT, Mumtaz MM, David VL, Chapin RE. Six 

high-priority organochlorine pesticides, either singly or in 

combination, are nonestrogenic in transfected HeLa cells. Reprod 

Toxicol 2000;14:95-102.

United States Geological Survey (USGS). Pesticides in the 

Nation’s Stream and Ground Water, 1992-2001. Revised Feb. 

15, 2007 [online]. Available at URL: http://pubs.usgs.gov/

circ/2005/1291/. 6/1/09

Ward EM, Schulte P, Grajewski B, Andersen A, Patterson DG 

Jr, Turner W, et al. Serum organochlorine levels and breast 

cancer: a nested case-control study of Norwegian women. Cancer 

Epidemiol Biomarkers Prev 2000;9:1357-1367.
Fourth National Report on Human Exposure to Environmental Chemicals 81

 Organochlorine Pesticides

Chlordane

CAS No. 57-74-9

Heptachlor

CAS No. 76-44-8

General Information

Chlordane and heptachlor are structurally related 

organochlorine pesticides and were used in the U.S. from 

the early 1950’s until the mid-1980’s. As a result of the 

manufacturing process, the technical grade product of 

each chemical contains 10%-20% of the other chemical, 

in addition to trace amounts of numerous other related 

compounds (ATSDR, 2007). Technical grade chlordane had 

contained 7% trans-nonachlor. Chlordane is not currently 

produced or used in the U.S. Since 1992, heptachlor use 

has been limited to treatment of fire ants near power 

transformers. Until 1988, chlordane was used to kill termites 

and other insects on agricultural crops, lawns, buildings, 

and in soil. Heptachlor was used as a soil and seed treatment 

and for termite control in and around buildings until 1988. 

Both pesticides are persistent in soils and sediments and 

have been detected in water from agricultural run-off and 

near production and disposal facilities (ATSDR, 1994, 

2007). Heptachlor and chlordane are somewhat volatile and 

may be detected in the air and dust of buildings long after 

treatment for termite or insect control (Whitemore et al., 

1994).

Heptachlor and chlordane and their metabolites 

bioaccumulate in fatty animal tissues. Consequently, foods 

high in fat such as meat, fish, and dairy products are the 

usual sources of exposure to these chemicals in the general 

population. Both of these chemicals and their metabolites 

can cross the placenta and are excreted into breast milk, 

which results in exposure to the fetus and nursing infant 

Serum Oxychlordane (lipid adjusted) 

Metabolite of Chlordane 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 20.8 (17.8-23.0) 34.4 (30.5-38.6) 44.8 (40.2-49.6) 1661 

01-02 11.4 (<LOD-12.5) 11.1 (<LOD-12.5) 21.7 (19.3-24.4) 36.4 (31.5-41.4) 49.7 (42.0-61.2) 2249 

03-04 9.37 (8.69-10.1) 10.3 (9.20-11.0) 18.0 (16.8-20.1) 29.0 (26.8-32.1) 37.7 (34.8-43.8) 1978 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 663

01-02 * < LOD < LOD < LOD 11.5 (<LOD-12.6) 752

03-04 * < LOD < LOD 9.20 (<LOD-11.5) 11.5 (8.10-18.9) 595

20 years and older 99-00 * < LOD 23.3 (21.0-25.9) 37.7 (32.3-43.5) 47.7 (43.1-50.8) 998

01-02 12.9 (11.7-14.3) 13.3 (11.4-14.9) 23.9 (21.2-26.7) 38.5 (33.4-45.9) 53.1 (44.1-65.9) 1497 

03-04 10.6 (9.82-11.5) 11.4 (10.6-12.4) 19.9 (17.9-21.5) 31.3 (28.8-33.2) 39.2 (36.5-44.8) 1383 

Gender 

Males 99-00 * < LOD 18.1 (16.1-19.6) 31.3 (25.9-38.2) 42.4 (35.3-49.6) 793

01-02 11.1 (<LOD-12.6) 11.1 (<LOD-12.6) 20.6 (16.6-24.9) 33.1 (27.5-43.8) 48.1 (40.2-56.9) 1049 

03-04 9.10 (8.20-10.1) 9.90 (8.30-11.2) 17.1 (15.6-18.4) 27.6 (25.3-32.2) 36.0 (32.7-39.2) 963

Females 99-00 * < LOD 22.3 (20.1-25.9) 36.9 (31.5-40.3) 46.2 (39.1-51.8) 868

01-02 11.7 (10.7-12.7) 11.0 (<LOD-12.9) 23.1 (20.7-25.0) 37.5 (34.5-42.1) 52.8 (42.7-70.0) 1200 

03-04 9.63 (8.89-10.4) 10.6 (9.10-11.3) 20.1 (17.4-21.7) 30.3 (27.5-32.7) 41.9 (36.3-45.5) 1015 

Race/ethnicity 

Mexican Americans 99-00 * < LOD 16.3 (<LOD-19.9) 28.9 (18.8-42.0) 39.9 (26.8-61.0) 628

01-02 * < LOD 13.9 (11.0-18.4) 27.2 (21.0-33.1) 37.9 (29.9-42.0) 557

03-04 * < LOD 12.8 (10.1-15.8) 22.9 (15.8-31.4) 31.4 (22.4-51.6) 462

Non-Hispanic blacks 99-00 * < LOD 18.7 (<LOD-32.2) 39.9 (26.5-47.3) 48.6 (43.5-65.5) 350

01-02 11.7 (<LOD-13.6) < LOD 22.8 (17.2-28.3) 41.4 (30.6-53.7) 56.5 (41.8-73.5) 501

03-04 8.74 (<LOD-10.2) 8.70 (<LOD-10.6) 18.9 (15.9-21.5) 35.1 (25.4-40.2) 44.2 (37.7-56.8) 493

Non-Hispanic whites 99-00 * < LOD 21.8 (18.6-24.6) 34.2 (28.9-40.9) 44.0 (37.2-49.8) 559

01-02 12.1 (11.0-13.3) 11.8 (10.5-13.9) 23.0 (20.1-25.7) 37.5 (31.6-45.1) 52.2 (41.0-67.4) 1031 

03-04 10.2 (9.36-11.1) 11.2 (10.0-12.1) 19.7 (17.2-21.7) 30.3 (26.8-33.6) 37.7 (34.3-45.5) 898

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 14.5, 10.5, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 82 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

(Dallaire et al., 2002; Rogan, 1996; Takahashi et al., 1981). 

Chlordane and heptachlor are absorbed after oral, dermal, 

and inhalation exposure. Chlordane is metabolized primarily 

to oxychlordane and to a lesser extent, to heptachlor. The 

major metabolite of heptachlor is heptachlor epoxide, which 

is also persistent in the body (ATSDR, 2007). Elimination 

of all these chemicals from the body occurs over months to 

years, and breast milk is a major excretion route in lactating 

women.

Human health effects from either chlordane or heptachlor 

at low environmental doses or at biomonitored levels from 

low environmental exposures are unknown. Acute, high 

doses of either chlordane or heptachlor block inhibitory 

neurotransmitters and result in central nervous system 

toxicity, characterized by seizures and paralysis. In 

laboratory animal studies, chronic doses of heptachlor have 

produced liver enlargement and injury; both chlordane and 

heptachlor induced hepatic cytochrome P450 enzymes 

and increased the incidence of liver tumors (NTP, 1977a, 

1977b; Smith, 1991). Chronic feeding studies with either 

chlordane or heptachlor have demonstrated reduced 

fertility, neonatal mortality, and alterations in immune 

function of offspring. Subtle neurodevelopmental effects 

have been observed rodents after prenatal exposure to 

heptachlor (IPCS, 2006). Epidemiologic studies have 

not demonstrated teratogenic or developmental effects 

(Baker et al., 1991; Le Marchand et al., 1986). No clear 

evidence of excessive cancer rates was demonstrated in 

human epidemiologic studies (ATSDR, 2007; IARC, 2001; 

Shindell and Ulrich, 1986). IARC considers chlordane and 

heptachlor as possibly carcinogenic to humans. OSHA has 

established occupational exposure criteria, and NIOSH and 

ACGIH have recommended workplace exposure levels for 

each pesticide. The U.S. EPA has established environmental 

criteria for chlordane and heptachlor, and the U.S. FDA 

established allowable residues of chlordane, heptachlor, and 

heptachlor epoxide in foods and bottled water. Information 

Serum Oxychlordane (whole weight) 

Metabolite of Chlordane 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD .140 (.120-.150) .260 (.200-.290) .310 (.290-.340) 1661 

01-02 .070 (<LOD-.077) .070 (<LOD-.080) .140 (.130-.160) .250 (.220-.300) .350 (.290-.440) 2249 

03-04 .057 (.053-.062) .063 (.058-.068) .119 (.106-.133) .204 (.189-.213) .269 (.246-.291) 1978 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 663

01-02 * < LOD < LOD < LOD .060 (<LOD-.070) 752

03-04 * < LOD < LOD .047 (<LOD-.063) .066 (.048-.092) 595

20 years and older 99-00 * < LOD .150 (.140-.180) .280 (.230-.300) .330 (.300-.400) 998

01-02 .082 (.074-.091) .080 (.070-.090) .160 (.140-.180) .270 (.230-.320) .370 (.310-.450) 1497 

03-04 .067 (.061-.073) .073 (.066-.079) .130 (.115-.146) .210 (.203-.227) .286 (.258-.320) 1383 

Gender 

Males 99-00 * < LOD .120 (.100-.140) .220 (.180-.280) .300 (.260-.340) 793

01-02 .069 (<LOD-.079) .070 (<LOD-.080) .130 (.120-.160) .230 (.190-.300) .320 (.250-.430) 1049 

03-04 .056 (.050-.063) .063 (.055-.076) .115 (.100-.126) .189 (.168-.207) .258 (.216-.302) 963

Females 99-00 * < LOD .140 (.130-.170) .270 (.200-.310) .320 (.290-.400) 868

01-02 .071 (.065-.077) .070 (<LOD-.080) .150 (.130-.160) .260 (.230-.310) .370 (.280-.510) 1200 

03-04 .058 (.053-.064) .063 (.057-.068) .126 (.104-.146) .208 (.199-.231) .286 (.245-.331) 1015 

Race/ethnicity 

Mexican Americans 99-00 * < LOD .100 (<LOD-.130) .210 (.130-.320) .290 (.190-.410) 628

01-02 * < LOD .100 (.070-.130) .200 (.150-.240) .280 (.210-.360) 557

03-04 * < LOD .083 (.066-.104) .149 (.108-.230) .230 (.148-.373) 462

Non-Hispanic blacks 99-00 * < LOD .110 (<LOD-.170) .240 (.170-.290) .320 (.240-.430) 350

01-02 .066 (<LOD-.077) < LOD .130 (.090-.170) .260 (.180-.350) .350 (.240-.560) 501

03-04 .049 (<LOD-.057) .050 (<LOD-.062) .112 (.087-.136) .225 (.165-.287) .315 (.253-.348) 493

Non-Hispanic whites 99-00 * < LOD .140 (.120-.170) .270 (.200-.300) .320 (.280-.380) 559

01-02 .075 (.068-.083) .080 (.070-.090) .150 (.130-.170) .250 (.220-.310) .370 (.280-.450) 1031 

03-04 .063 (.058-.070) .070 (.063-.077) .128 (.110-.148) .207 (.190-.223) .271 (.242-.315) 898

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 83

 Organochlorine Pesticides

about external exposure (i.e., environmental levels) and 

health effects of chlordane and heptachlor is available 

from ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html. A 

recent assessment of heptachlor is available at: http://www.

inchem.org/documents/cicads/cicads/cicad70.htm#ref.

Biomonitoring Information

Serum oxychlordane and trans-nonachlor levels in 

NHANES 1999-2000, 2001-2002, and 2003-2004 

subsamples were comparable to levels measured in 

Swedish women from 1996-1997 (Glynn et al., 2003). In 

serum samples obtained in between 1994 and1997 from 

Inuit women in different Arctic countries, the reported 

oxychlordane and trans-nonachlor geometric mean levels 

from Canada and Greenland groups were about threefold 

to fivefold higher than among females in this Report (van 

Oostdam et al., 2004). A small sample of Polish women had 

mean levels of oxychlordane and trans-nonachlor that were 

about fivefold lower than in females in the NHANES 2001-

2002 subsample (Jaraczweska et al., 2006). Serum transnonachlor levels among females in the NHANES 1999-

2001 subsample were about one half the levels obtained 

between 1994 and 1996 from women in New York (Wolff 

et al., 2000). 

Levels of heptachlor epoxide among females in this Report

were approximately one tenth of the corresponding 90th

percentile for a cohort of pregnant women in California 

studied from 1963 to 1967 (James et al., 2002). Two 

episodes (one each in Arkansas and Hawaii) of inadvertent 

heptachlor contamination of dairy cattle feed occurred in 

the early-to-mid 1980’s, resulting in human exposure to 

heptachlor epoxide that was excreted into the milk. For the 

exposed persons drinking milk in the Arkansas episode, 

mean serum heptachlor epoxide and oxychlordane levels 

were about sevenfold and threefold higher, respectively, 

than the 90th percentile values of NHANES 1999-2000 

(Stehr-Green et al., 1988). In the Hawaii episode, the 

mean serum heptachlor epoxide and oxychlordane levels 

were more than twice as high, respectively, than the 90th

percentile values of NHANES 1999-2000 (Baker, 1993).

Finding a measurable amount of oxychlordane, transnonachlor, or heptachlor epoxide in serum does not 

mean that the level of oxychlordane, trans-nonachlor, 

or heptachlor epoxide causes an adverse health effect. 

Biomonitoring studies on levels of oxychlordane, transnonachlor, and heptachlor epoxide provide physicians 

and public health officials with reference ranges so that 

they can determine whether people have been exposed to 

higher levels of heptachlor and chlordane than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.
 84 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

Serum Heptachlor epoxide (lipid adjusted) 

Metabolite of Heptachlor 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 15.4 (<LOD-19.8) 24.0 (15.1-38.8) 1589 

01-02 * < LOD < LOD 14.8 (13.0-17.8) 21.8 (18.2-27.3) 2259 

03-04 * < LOD < LOD 13.4 (11.1-15.9) 18.9 (15.9-23.0) 1963 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 638

01-02 * < LOD < LOD < LOD < LOD 741

03-04 * < LOD < LOD < LOD < LOD 592

20 years and older 99-00 * < LOD < LOD 17.8 (<LOD-23.9) 27.1 (16.8-46.1) 951

01-02 * < LOD < LOD 15.7 (13.7-18.8) 23.1 (19.1-29.1) 1518 

03-04 * < LOD 8.20 (<LOD-9.50) 14.5 (11.6-17.6) 20.6 (16.8-24.0) 1371 

Gender 

Males 99-00 * < LOD < LOD < LOD 19.6 (<LOD-27.2) 760

01-02 * < LOD < LOD 13.9 (12.0-17.8) 20.8 (15.9-25.3) 1047 

03-04 * < LOD < LOD 13.4 (11.2-16.4) 18.6 (16.6-21.3) 956

Females 99-00 * < LOD < LOD 18.2 (<LOD-25.2) 27.7 (16.0-54.3) 829

01-02 * < LOD < LOD 15.6 (13.3-18.2) 23.2 (18.9-29.8) 1212 

03-04 * < LOD < LOD 13.5 (11.0-16.8) 19.6 (14.8-24.5) 1007 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD 15.3 (<LOD-25.6) 22.2 (<LOD-62.3) 598

01-02 * < LOD < LOD 13.2 (<LOD-16.3) 16.8 (13.8-23.1) 553

03-04 * < LOD < LOD 10.6 (8.10-13.5) 13.7 (10.9-16.5) 460

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 19.5 (<LOD-32.4) 336

01-02 * < LOD < LOD 14.6 (11.7-19.0) 21.5 (18.2-27.3) 503

03-04 * < LOD < LOD 13.5 (10.1-16.8) 18.6 (12.7-25.2) 490

Non-Hispanic whites 99-00 * < LOD < LOD 16.5 (<LOD-21.8) 26.4 (<LOD-54.3) 539

01-02 * < LOD < LOD 15.3 (13.0-19.6) 22.8 (18.9-29.8) 1041 

03-04 * < LOD 7.90 (<LOD-9.40) 14.0 (11.2-17.6) 20.4 (15.8-24.5) 888

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 14.6, 10.5, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 85

 Organochlorine Pesticides

Serum Heptachlor epoxide (whole weight) 

Metabolite of Heptachlor 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .110 (<LOD-.140) .180 (.110-.220) 1589 

01-02 * < LOD < LOD .100 (.090-.120) .150 (.130-.180) 2259 

03-04 * < LOD < LOD .094 (.076-.108) .128 (.108-.161) 1963 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 638

01-02 * < LOD < LOD < LOD < LOD 741

03-04 * < LOD < LOD < LOD < LOD 592

20 years and older 99-00 * < LOD < LOD .130 (<LOD-.170) .190 (.130-.270) 951

01-02 * < LOD < LOD .110 (.090-.140) .170 (.140-.190) 1518 

03-04 * < LOD .057 (<LOD-.063) .101 (.082-.116) .135 (.113-.173) 1371 

Gender 

Males 99-00 * < LOD < LOD < LOD .150 (<LOD-.180) 760

01-02 * < LOD < LOD .100 (.090-.120) .150 (.110-.180) 1047 

03-04 * < LOD < LOD .094 (.077-.111) .126 (.106-.149) 956

Females 99-00 * < LOD < LOD .120 (<LOD-.190) .200 (.120-.310) 829

01-02 * < LOD < LOD .100 (.090-.130) .170 (.130-.200) 1212 

03-04 * < LOD < LOD .096 (.071-.108) .133 (.107-.173) 1007 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD .100 (<LOD-.170) .170 (<LOD-.380) 598

01-02 * < LOD < LOD .090 (<LOD-.110) .120 (.100-.240) 553

03-04 * < LOD < LOD .069 (.053-.097) .098 (.074-.113) 460

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD .110 (<LOD-.200) 336

01-02 * < LOD < LOD .090 (.070-.110) .130 (.100-.180) 503

03-04 * < LOD < LOD .087 (.067-.104) .110 (.090-.157) 490

Non-Hispanic whites 99-00 * < LOD < LOD .120 (<LOD-.170) .180 (<LOD-.310) 539

01-02 * < LOD < LOD .100 (.090-.130) .170 (.130-.190) 1041 

03-04 * < LOD .055 (<LOD-.063) .101 (.077-.117) .135 (.111-.180) 888

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 86 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

Serum trans-Nonachlor (lipid adjusted) 

Metabolite of Chlordane 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 18.3 (16.7-20.0) 17.9 (16.1-20.1) 31.9 (28.9-36.0) 55.1 (48.4-62.6) 79.4 (67.6-88.1) 1933 

01-02 17.0 (15.2-18.9) 17.9 (15.5-20.5) 33.7 (30.2-37.2) 56.3 (49.6-66.0) 78.2 (64.0-113) 2286 

03-04 14.7 (13.1-16.5) 14.8 (13.5-17.0) 30.2 (26.7-32.5) 49.0 (42.6-54.7) 68.3 (58.6-82.3) 1955 

Age group 

12-19 years 99-00 * < LOD < LOD 18.8 (<LOD-20.6) 25.2 (19.1-28.4) 664 

01-02 * < LOD < LOD 13.4 (11.8-16.4) 19.2 (15.2-23.5) 758 

03-04 * < LOD 8.70 (<LOD-12.5) 16.1 (10.7-23.7) 22.6 (16.1-34.6) 589 

20 years and older 99-00 20.8 (19.0-22.8) 20.7 (18.0-23.5) 35.4 (30.9-40.3) 59.9 (51.8-67.6) 82.7 (74.9-89.6) 1269 

01-02 19.8 (17.6-22.3) 20.9 (19.0-23.1) 36.6 (32.8-41.1) 60.6 (52.5-69.9) 84.9 (66.0-123) 1528 

03-04 16.9 (15.1-18.9) 17.3 (14.6-20.0) 31.8 (28.9-35.3) 51.4 (45.9-58.6) 74.7 (59.8-90.0) 1366 

Gender 

Males 99-00 17.7 (16.5-19.1) 17.2 (14.9-20.1) 30.2 (27.7-34.2) 51.1 (47.3-58.6) 78.2 (60.2-88.1) 922 

01-02 17.0 (14.8-19.5) 18.3 (14.8-21.1) 34.4 (28.3-39.3) 54.8 (45.0-68.9) 78.2 (59.7-113) 1062 

03-04 14.8 (12.7-17.3) 14.6 (12.2-18.0) 30.8 (26.7-35.3) 51.0 (42.0-59.4) 68.6 (56.0-93.8) 955 

Females 99-00 18.8 (16.7-21.1) 18.4 (16.1-22.2) 32.9 (29.0-38.3) 59.0 (48.4-67.6) 80.8 (71.5-95.5) 1011 

01-02 17.0 (15.4-18.7) 17.6 (15.0-20.3) 32.8 (30.4-36.7) 56.9 (51.9-65.5) 78.1 (65.5-111) 1224 

03-04 14.5 (13.1-16.1) 15.0 (13.8-16.3) 28.2 (25.3-32.8) 48.1 (41.4-52.7) 68.3 (56.8-79.9) 1000 

Race/ethnicity 

Mexican Americans 99-00 * < LOD 25.1 (22.7-29.5) 40.7 (35.1-51.8) 56.3 (45.8-77.2) 650 

01-02 11.9 (<LOD-14.6) 10.6 (<LOD-14.5) 26.0 (19.3-30.4) 47.9 (36.3-57.2) 59.8 (49.3-74.1) 558 

03-04 10.2 (7.86-13.2) 9.10 (<LOD-11.1) 20.7 (11.1-34.7) 39.5 (25.9-65.5) 62.2 (36.0-93.4) 457 

Non-Hispanic blacks 99-00 20.3 (17.0-24.1) 17.5 (15.4-23.5) 35.7 (28.9-45.5) 77.0 (60.8-90.7) 107 (84.0-143) 404 

01-02 18.8 (15.4-22.9) 19.2 (14.7-22.0) 36.8 (28.3-50.5) 73.6 (50.8-110) 112 (68.7-160) 514 

03-04 14.4 (12.2-17.0) 13.8 (11.2-16.3) 30.8 (26.5-36.1) 59.9 (47.7-77.7) 86.6 (56.8-129) 486 

Non-Hispanic whites 99-00 19.1 (17.2-21.1) 19.0 (16.9-22.2) 32.8 (28.0-37.6) 52.5 (44.9-64.4) 74.0 (62.3-86.7) 722 

01-02 17.5 (15.6-19.7) 19.0 (16.3-21.1) 34.0 (29.7-38.1) 55.5 (45.9-69.4) 78.7 (59.1-126) 1052 

03-04 15.8 (13.7-18.2) 16.0 (13.8-19.3) 30.8 (26.4-35.0) 48.8 (42.1-55.7) 67.6 (57.5-87.3) 889 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 14.5, 10.5, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 87

 Organochlorine Pesticides

Serum trans-Nonachlor (whole weight) 

Metabolite of Chlordane 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 .109 (.099-.119) .110 (.090-.120) .210 (.190-.240) .370 (.330-.420) .550 (.470-.630) 1933 

01-02 .104 (.093-.116) .110 (.100-.120) .220 (.190-.250) .390 (.330-.480) .590 (.430-.800) 2286 

03-04 .089 (.080-.100) .094 (.084-.108) .191 (.171-.211) .324 (.290-.371) .470 (.410-.558) 1955 

Age group 

12-19 years 99-00 * < LOD < LOD .090 (<LOD-.110) .120 (.100-.130) 664 

01-02 * < LOD < LOD .070 (.060-.080) .090 (.080-.130) 758 

03-04 * < LOD .041 (<LOD-.060) .081 (.054-.117) .109 (.081-.161) 589 

20 years and older 99-00 .128 (.116-.141) .130 (.110-.150) .230 (.210-.260) .400 (.360-.460) .580 (.490-.690) 1269 

01-02 .125 (.111-.141) .130 (.120-.150) .240 (.210-.280) .420 (.350-.540) .640 (.470-.840) 1528 

03-04 .106 (.095-.119) .112 (.096-.127) .210 (.186-.237) .355 (.301-.405) .520 (.430-.594) 1366 

Gender 

Males 99-00 .106 (.098-.114) .100 (.090-.120) .210 (.180-.220) .350 (.310-.400) .520 (.400-.630) 922 

01-02 .105 (.091-.122) .110 (.090-.130) .220 (.190-.260) .380 (.310-.500) .580 (.390-.830) 1062 

03-04 .092 (.079-.108) .098 (.085-.126) .202 (.177-.232) .343 (.285-.395) .458 (.395-.594) 955 

Females 99-00 .111 (.099-.125) .110 (.090-.130) .220 (.190-.250) .390 (.310-.460) .580 (.460-.690) 1011 

01-02 .103 (.093-.113) .110 (.090-.120) .220 (.180-.240) .400 (.340-.450) .590 (.430-.830) 1224 

03-04 .087 (.078-.097) .092 (.079-.098) .183 (.161-.210) .317 (.286-.367) .470 (.409-.565) 1000 

Race/ethnicity 

Mexican Americans 99-00 * < LOD .170 (.120-.210) .310 (.240-.340) .390 (.320-.520) 650 

01-02 .071 (<LOD-.091) .060 (<LOD-.090) .160 (.120-.210) .330 (.270-.390) .470 (.360-.590) 558 

03-04 .062 (.047-.082) .055 (<LOD-.069) .135 (.069-.237) .288 (.158-.559) .414 (.279-.651) 457 

Non-Hispanic blacks 99-00 .112 (.093-.134) .100 (.080-.130) .220 (.180-.300) .490 (.340-.600) .760 (.510-.960) 404 

01-02 .106 (.085-.131) .110 (.080-.130) .220 (.160-.310) .490 (.320-.680) .680 (.410-1.20) 514 

03-04 .080 (.068-.096) .078 (.061-.093) .186 (.145-.242) .417 (.272-.565) .573 (.497-.684) 486 

Non-Hispanic whites 99-00 .116 (.104-.129) .120 (.100-.140) .220 (.190-.240) .370 (.300-.440) .510 (.440-.630) 722 

01-02 .108 (.096-.122) .120 (.100-.130) .220 (.190-.250) .390 (.310-.490) .600 (.400-.930) 1052 

03-04 .098 (.085-.113) .103 (.090-.124) .205 (.173-.234) .327 (.288-.390) .461 (.397-.576) 889 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 88 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for chlordane [online]. May 1994. Available 

at URL: http://www.atsdr.cdc.gov/toxprofiles/tp31.html. 4/21/09 

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for heptachlor and heptachlor epoxide 

[online]. August 2007. Available at URL: http://www.atsdr.cdc.

gov/toxprofiles/tp12.html. 4/21/09 

Baker DB, Loo S, Barker J. Evaluation of human exposure to 

the heptachlor epoxide contamination of milk in Hawaii. Hawaii 

Med J 1991;50(3):108-118.

Baker DB. Estimation of Human Exposure to Heptachlor 

Epoxide and Related Pesticides in Hawaii. A Report to the 

Hawaii Heptachlor Research and Education Foundation. 1993. 

Available at URL: http://www.heptachlor.org/site/foundation/

research/projects2.htm. 4/21/09

Dallaire F, Dewailly E, Laliberte C, Muckle G, Ayotte P. 

Temporal trends of organochlorine concentrations in umbilical 

cord blood of newborns from the lower north shore of the St. 

Lawrence River (Quebec, Canada). Environ Health Perspect 

2002;110(8):835-838.

Glynn AW, Granath F, Aune M, Atuma S, Darnerud PO, Bjerselius 

R, et al. Organochlorines in Swedish women: determinants of 

serum concentrations. Environ Health Perspect 2003;111:349-

355.

International Agency for Research on Cancer (IARC). 

International Agency for Research on Cancer (IARC) - Summaries 

& Evaluations. Chlordane and heptachlor [online]. Vol. 79, 2001. 

Available at URL: http://www.inchem.org/documents/iarc/

vol79/79-12.html. 9/25/07

International Programme in Chemical Safety (IPCS). Concise 

International Chemical Assessment Document 70 Heptachlor 

[online]. 2006. Available at URL: http://www.inchem.org/

documents/cicads/cicads/cicad70.htm. 4/21/09

James RA, Hertz-Picciotto I, Willman E, Keller JA, Charles 

MJ. Determinants of serum polychlorinated biphenyls and 

organochlorine pesticides measured in women from the child 

health and development study cohort, 1963-1967. Environ Health 

Perspect 2002;110:617-624.

Jaraczewska K, Lulek J, Covaci A, Voorspoels S, KalubaSkotarczak A, Drews K, et al. Distribution of polychlorinated 

biphenyls, organochlorine pesticides and polybrominated 

diphenyl ethers in human umbilical cord serum, maternal serum 

and milk from Wielkopolska region, Poland. Sci Tot Environ 

2006;372:20-31.

LeMarchand L, Kolonel LN, Siegel BZ, Dendle WH. Trends in 

birth defects for a Hawaiian population exposed to heptachlor and 

for the United States. Arch Environ Health, 1986;41:145–148.

National Toxicology Program (NTP). Bioassay of chlordane for 

possible carcinogenicity. Natl Cancer Inst Carcinog Tech Rep Ser 

1977a;8:1-123. Available at URL: http://ntp.niehs.nih.gov/ntp/

htdocs/LT_rpts/tr008.pdf. 6/1/09

National Toxicology Program (NTP). Bioassay of heptachlor for 

possible carcinogenicity. Natl Cancer Inst Carcinog Tech Rep Ser 

1977b;9:1-109. Available at URL: http://ntp.niehs.nih.gov/ntp/

htdocs/LT_rpts/tr009.pdf. 6/1/09

Rogan WJ. Pollutants in breast milk. Arch Pediatr Adolesc Med 

1996;150:981-990.

Shindell S and Ulrich S. Mortality of workers employed in the 

manufacture of chlordane: an update. J Occup Med 1986;28:497-

501.

Smith AG. Chlorinated Hydrocarbon Insecticides. In Hayes WJ, 

Jr and Laws ER, Jr, Eds. Handbook of Pesticide Toxicology, Vol. 

2 Classes of Pesticides. New York, Academic Press, Inc. 1991 

pp. 731-915.

Stehr-Green P, Wohlleb JC, Royce W, Head SL. An evaluation 

of serum pesticide residue levels and liver function in persons 

exposed to dairy products contaminated with heptachlor. JAMA 

1988;259(3):374-377.

Takahashi W, Saidein D, Takei G, Wong L. Organochloride 

pesticide residues in human milk in Hawaii, 1979-1980. Bull 

Environ Contam Toxicol 1981:27:506-511.

Van Oostdam JC, Dewailly E, Gilman A, Hansen JC, Odland 

JO, Chashchin V, et al. Circumpolar maternal blood contaminant 

survey, 1994-1997 organochlorine compounds. Sci Total Environ 

2004;330:55-70.

Wolff MS, Berkowitz GS, Brower S, Senie R, Bleiweiss IJ, 

Tartter P, et al. Organochlorine exposures and breast cancer risk 

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Fourth National Report on Human Exposure to Environmental Chemicals 89

 Organochlorine Pesticides

Dichlorodiphenyltrichloroethane (DDT)

CAS No. 50-29-3

General Information

Dichlorodiphenyltrichloroethane (DDT) has been used 

widely as a broad spectrum insecticide in agriculture and for 

control of vector-borne diseases. It was produced and used 

in the U.S. after World War II until 1972, when virtually 

all use of it was banned. It is still used in some countries, 

particularly for endemic vector and malaria control. DDT 

was used at one time as a treatment for head and body 

lice. DDT usually refers to the technical product, which 

is a mixture containing p,p’-DDT (65%-80%), o,p’-DDT 

(15%-21%), p,p’-DDD (4% or less), and trace amounts 

of several related compounds. DDT is converted in the 

environment to other more stable chemical forms, including 

1,1’-(2,2-dichloroethenylidene)-bis[4-chlorobenzene] 

(DDE) and 1,1’-dichloro-(2,2-bis(p-chlorophenyl) ethane 

(DDD). These chemicals are highly persistent in soil, 

sediments, air, and water, as well as in plant and animal 

tissues. The biodegradation half-life of DDT in soil varies 

from 2 to 15 years, depending on conditions.

In the general U.S. population, food, particularly meat, 

fish, and dairy products, continues to be the primary source 

of DDT exposure, although DDT and DDE intakes have 

decreased over time (FDA, 2008; Gunderson, 1988). Food 

imported from countries that still use DDT may contain 

the chemical or its residues. DDT can be absorbed after 

ingestion, inhalation, or dermal exposure. In the body, 

DDT is converted to DDE and several other metabolites. 

DDT and DDE are distributed to all body tissues with the 

highest concentrations found in adipose tissues (ATSDR, 

2002; Smith, 1991). Only a small proportion of DDT is 

metabolized and excreted (Smith, 1991). DDT and DDE 

can cross the placenta, resulting in fetal exposure. Both 

Serum p,p'-Dichlorodiphenyltrichloroethane (DDT) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 28.0 (21.9-34.0) 1679 

01-02 * < LOD < LOD < LOD 26.6 (22.5-36.0) 2305 

03-04 * < LOD < LOD 11.9 (10.0-15.1) 19.5 (15.1-27.5) 1965 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 677 

01-02 * < LOD < LOD < LOD < LOD 756 

03-04 * < LOD < LOD < LOD 9.10 (<LOD-12.2) 595 

20 years and older 99-00 * < LOD < LOD < LOD 30.5 (23.0-37.3) 1002 

01-02 * < LOD < LOD < LOD 28.1 (23.8-39.0) 1549 

03-04 * < LOD < LOD 12.9 (10.3-16.5) 20.7 (15.9-28.7) 1370 

Gender 

Males 99-00 * < LOD < LOD < LOD 25.1 (<LOD-39.3) 799 

01-02 * < LOD < LOD < LOD 21.6 (<LOD-25.8) 1073 

03-04 * < LOD < LOD 10.6 (9.10-13.7) 15.2 (11.8-26.9) 959 

Females 99-00 * < LOD < LOD < LOD 29.4 (23.0-35.8) 880 

01-02 * < LOD < LOD 18.3 (<LOD-21.9) 36.6 (25.5-54.3) 1232 

03-04 * < LOD < LOD 14.0 (10.8-17.5) 21.0 (18.0-27.8) 1006 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD 61.3 (27.0-155) 155 (59.3-590) 635 

01-02 * < LOD < LOD 83.1 (33.3-236) 293 (104-541) 566 

03-04 * < LOD 8.90 (<LOD-12.9) 24.0 (18.6-33.3) 48.6 (31.1-71.1) 461 

Non-Hispanic blacks 99-00 * < LOD < LOD 22.3 (<LOD-31.5) 31.5 (23.2-65.0) 356 

01-02 * < LOD < LOD 23.2 (<LOD-40.9) 40.9 (21.2-95.8) 514 

03-04 * < LOD 9.00 (<LOD-10.4) 17.5 (14.8-23.2) 30.7 (19.0-53.4) 490 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 564 

01-02 * < LOD < LOD < LOD 17.9 (<LOD-20.7) 1061 

03-04 * < LOD < LOD 9.70 (8.50-11.2) 12.9 (10.7-16.6) 890 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 20.7, 17.4, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 90 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

chemicals are excreted in breast milk, resulting in exposure 

to nursing infants (Rogan, 1996).

Human health effects from DDT at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. In high dose, accidental exposures, 

overt signs of acute human toxicity include vomiting, 

tremor, and seizures. Experimental human dosing studies 

conducted over an 18 month period and during which 

doses well above environmental levels were given did not 

demonstrate overt clinical abnormalities (ATSDR, 2002; 

Hayes et al., 1956). In laboratory animals, both DDT and 

DDE may induce specific cytochrome P450 isozymes 

(Nims et al., 1998). DDT may bind to estrogen receptors 

(Chen et al., 1997); and o,p’-DDD and p,p’-DDE can 

produce anti-androgenic effects (Gray et al., 2001). Animal 

studies reported reduced fertility, premature delivery, 

reproductive organ abnormalities, and altered behavior 

after neonatal exposure (Eriksson and Talts, 2000; Gray 

et al., 2001). Reproductive effects in humans affecting 

birth weight, fertility, and duration of lactation, have not 

been consistently demonstrated (Beard, 2006; Gladen and 

Rogan, 1995; Jusko et al., 2006), although the risk for 

preterm delivery may be related to maternal DDE levels 

(Longnecker et al., 2001). Epidemiologic studies of children 

with environmental exposure to DDT and DDE have not 

demonstrated neurologic or developmental abnormalities 

(Gladen et al., 2004; Jusko et al., 2006; Longnecker et al., 

2002; Mariussen and Fonnum, 2006). Several reviews of 

cancer epidemiologic studies have concluded that a link 

between DDT and breast cancer is inconclusive (Beard, 

2006; Calle et al., 2002; Snedeker, 2001). Studies of DDT 

exposure and pancreatic cancer, lung cancer, and leukemia 

have also been inconclusive (ADSDR. 2002; Beard, 2006). 

It is difficult to attribute outcomes in human studies solely 

to DDT because of potential co-exposure to other persistent 

organohalogen chemicals (e.g., polychlorinated biphenyls, 

other organochlorines, dioxins and furans).

A workplace standard for DDT has been established by 

Serum p,p'-Dichlorodiphenyltrichloroethane (DDT) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD .170 (.130-.220) 1679 

01-02 * < LOD < LOD < LOD .180 (.160-.220) 2305 

03-04 * < LOD < LOD .078 (.065-.097) .128 (.098-.167) 1965 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 677 

01-02 * < LOD < LOD < LOD < LOD 756 

03-04 * < LOD < LOD < LOD .048 (<LOD-.069) 595 

20 years and older 99-00 * < LOD < LOD < LOD .190 (.150-.230) 1002 

01-02 * < LOD < LOD < LOD .200 (.170-.260) 1549 

03-04 * < LOD < LOD .084 (.068-.106) .142 (.105-.189) 1370 

Gender 

Males 99-00 * < LOD < LOD < LOD .150 (<LOD-.240) 799 

01-02 * < LOD < LOD < LOD .150 (<LOD-.180) 1073 

03-04 * < LOD < LOD .071 (.059-.095) .108 (.078-.180) 959 

Females 99-00 * < LOD < LOD < LOD .190 (.150-.230) 880 

01-02 * < LOD < LOD .130 (<LOD-.150) .240 (.180-.400) 1232 

03-04 * < LOD < LOD .087 (.071-.106) .146 (.106-.207) 1006 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD .400 (.190-1.00) 1.00 (.330-4.26) 635 

01-02 * < LOD < LOD .530 (.250-1.34) 1.62 (.570-4.01) 566 

03-04 * < LOD .063 (<LOD-.079) .146 (.114-.203) .313 (.189-.627) 461 

Non-Hispanic blacks 99-00 * < LOD < LOD .120 (<LOD-.170) .180 (.140-.420) 356 

01-02 * < LOD < LOD .130 (<LOD-.290) .250 (.120-.530) 514 

03-04 * < LOD .051 (<LOD-.061) .112 (.080-.143) .201 (.132-.343) 490 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 564 

01-02 * < LOD < LOD < LOD .130 (<LOD-.140) 1061 

03-04 * < LOD < LOD .064 (.054-.075) .086 (.074-.107) 890 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 91

 Organochlorine Pesticides

OSHA and a guidance established by ACGIH. IARC 

classifies DDT (p,p’-DDT) as a possible human carcinogen. 

NTP considers DDT as being reasonably anticipated to 

be a human carcinogen. More information about external 

exposure (i.e., environmental levels) and health effects 

is available from the U.S. EPA at: http://www.epa.gov/

pestcides/ and from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html.

Biomonitoring Information

DDE persists in the body longer than DDT, so serum DDE 

levels may be an indicator of historic exposure and may be 

higher than DDT levels in the same person. In general, levels 

of DDT and DDE increase as a person ages as a result of 

cumulative exposure (ATSDR, 2002; Smith, 1991). Since 

the 1970’s, mean serum levels of DDT and DDE in the U.S. 

population declined by about fivefold to tenfold, compared 

to levels observed in this Report (Anderson et al., 1998; 

Stehr-Green, 1989). Declining DDE levels over time have 

also been observed in the German population, and the most 

recent median levels for German adults and children are 

similar to levels in this Report (Becker et al., 2002; Heudorf 

et al., 2003; Link et al., 2005). Median DDE levels among 

a population-based sample of Swedish women in 1996-

1997 were similar to females in the NHANES 1999-2000 

subsample (Glynn et al., 2003). A study of New Zealand 

adults sampled in 1996-1997 reported median DDE levels 

that were about threefold higher than the median for adults 

in the NHANES 1999-2000 subsample (Bates et al., 

2004). In a population-based sample of men and women 

from eastern Slovakia, the lipid-adjusted geometric mean 

levels of DDT and DDE were each fivefold to tenfold 

higher than the 95th percentile and geometric mean levels, 

respectively, for males and females in the NHANES 1999-

2000 subsample (Pavuk et al., 2004).

Compared to females in the NHANES 1999-2000 

subsample, mean DDE levels were about fivefold higher 

among women of southern Spain exposed by virtue of 

Serum p,p'-Dichlorodiphenyldichloroethene (DDE) (lipid adjusted) 

Metabolite of Dichlorodiphenyltrichloroethane 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 260 (226-298) 226 (184-278) 537 (476-631) 1150 (976-1350) 1830 (1410-2300) 1964 

01-02 295 (267-327) 251 (228-278) 598 (521-699) 1410 (1210-1500) 2320 (1830-2780) 2298 

03-04 238 (195-292) 203 (163-275) 509 (376-655) 1170 (836-1570) 1860 (1400-2380) 1956 

Age group 

12-19 years 99-00 118 (102-135) 108 (97.7-119) 185 (141-237) 339 (243-479) 528 (339-812) 686 

01-02 124 (106-146) 113 (100-140) 213 (172-253) 319 (282-389) 456 (343-722) 758 

03-04 105 (84.7-129) 93.6 (81.0-114) 167 (123-240) 341 (211-586) 522 (313-1430) 588 

20 years and older 99-00 297 (256-344) 269 (213-323) 608 (530-693) 1260 (1030-1550) 2020 (1520-2730) 1278 

01-02 338 (303-376) 285 (249-337) 695 (595-798) 1480 (1310-1700) 2550 (1980-3080) 1540 

03-04 268 (217-332) 233 (175-314) 557 (420-734) 1270 (877-1800) 1990 (1500-2470) 1368 

Gender 

Males 99-00 249 (220-283) 223 (182-262) 494 (380-578) 1010 (789-1130) 1430 (1080-2160) 937 

01-02 285 (252-323) 248 (222-285) 520 (441-627) 1160 (937-1360) 1900 (1580-2490) 1069 

03-04 235 (193-288) 200 (164-262) 466 (331-653) 1000 (763-1400) 1610 (1210-2320) 955 

Females 99-00 270 (226-322) 234 (184-302) 601 (492-711) 1350 (1040-1720) 2210 (1570-2810) 1027 

01-02 305 (273-341) 256 (219-297) 708 (567-844) 1480 (1410-1710) 2670 (1940-3300) 1229 

03-04 241 (193-301) 207 (161-281) 539 (386-735) 1250 (813-1900) 2010 (1500-2450) 1001 

Race/ethnicity 

Mexican Americans 99-00 674 (574-792) 624 (545-701) 1350 (1090-1660) 3090 (2040-4950) 4950 (3070-9350) 657 

01-02 652 (569-747) 561 (455-690) 1400 (1050-1950) 4110 (2520-6550) 7080 (3080-15600) 566 

03-04 444 (362-545) 373 (283-522) 875 (608-1170) 2150 (1520-2470) 3290 (2380-9240) 457 

Non-Hispanic blacks 99-00 295 (241-362) 251 (199-313) 668 (492-874) 1850 (1040-2220) 2300 (1560-5680) 416 

01-02 324 (262-400) 248 (223-296) 762 (583-999) 1620 (1180-2980) 3260 (1270-6900) 515 

03-04 262 (233-295) 216 (173-267) 589 (453-747) 1620 (1130-2310) 2860 (1880-3440) 487 

Non-Hispanic whites 99-00 217 (189-249) 194 (162-238) 438 (355-507) 825 (647-1010) 1160 (1010-1350) 732 

01-02 253 (226-284) 225 (203-254) 463 (402-558) 1150 (878-1340) 1640 (1410-1940) 1053 

03-04 208 (165-263) 177 (148-238) 417 (302-564) 907 (574-1480) 1490 (909-2300) 888 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 18.6, 8.3, and 7.8, respectively. 
 92 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

nearby agriculture (Botella et al., 2004). A small study of 

Indian men with background exposure reported mean serum 

DDT and DDE levels that were around fiftyfold higher 

than the 95th percentile for DDT and tenfold to twentyfold 

higher than the geometric mean DDE levels among males 

in this Report (Bhatnagar et al., 2004). Consumers of Great 

Lakes sport fish had mean serum DDE levels that were 

only slightly higher than nonconsumers, 309 versus 268 

ng/g lipid, which is similar to the overall geometric mean 

of 260 ng/g lipid in the NHANES 1999-2000 subsample 

(Bloom et al., 2005). High mean levels of whole blood 

DDT (about 3,860 ng/L) and DDE (about 14,490 ng/L) 

were found many years ago in a study of pesticide workers 

in Argentina (Radomski et al., 1971). Workers involved in 

production or application of DDT developed neurologic 

abnormalities associated with blood levels around 100-300

mg/L, considerably higher than levels in this Report (Smith, 

1991).

In the NHANES 1999-2000, 2001-2002 and 2003-2004 

subsamples, serum levels of o,p’-DDT were below the 

limits of detection. In a subsample of NHANES II (1976-

1980) participants, less than one percent had detectable 

serum levels of o,p’-DDT (Stehr-Green, 1989).

Finding a measurable amount of p,p’-DDT, o,p’-DDT, or 

p,p’-DDE in serum does not mean that the level of the 

chemical causes an adverse health effect. Biomonitoring 

studies on levels of DDT and DDE provide physicians 

and public health officials with reference values so that 

they can determine whether people have been exposed to 

higher levels of DDT or DDE than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Serum p,p'-Dichlorodiphenyldichloroethene (DDE) (whole weight) 

Metabolite of Dichlorodiphenyltrichloroethane 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 1.54 (1.33-1.79) 1.31 (1.09-1.66) 3.50 (2.97-4.27) 7.49 (6.14-9.25) 11.6 (9.25-14.8) 1964 

01-02 1.81 (1.64-2.01) 1.57 (1.37-1.72) 3.97 (3.43-4.59) 8.81 (7.85-10.1) 15.4 (12.9-17.6) 2298 

03-04 1.45 (1.18-1.79) 1.26 (1.00-1.58) 3.16 (2.40-4.21) 7.07 (5.55-9.80) 12.1 (8.37-16.0) 1956 

Age group 

12-19 years 99-00 .561 (.488-.646) .520 (.430-.600) .870 (.680-1.18) 1.52 (1.13-2.25) 2.32 (1.76-3.56) 686 

01-02 .623 (.534-.726) .590 (.500-.730) 1.00 (.820-1.22) 1.65 (1.39-2.07) 2.30 (1.91-3.14) 758 

03-04 .516 (.419-.635) .456 (.385-.557) .796 (.611-1.19) 1.69 (.994-2.69) 2.51 (1.56-6.71) 588 

20 years and older 99-00 1.83 (1.56-2.14) 1.61 (1.26-2.07) 4.17 (3.48-4.66) 8.12 (6.37-10.6) 12.3 (9.87-16.7) 1278 

01-02 2.14 (1.91-2.39) 1.77 (1.61-2.05) 4.59 (4.10-5.26) 9.75 (8.34-11.5) 16.8 (13.7-19.1) 1540 

03-04 1.69 (1.36-2.10) 1.46 (1.12-1.96) 3.68 (2.66-4.96) 7.91 (6.01-11.0) 12.8 (9.25-16.8) 1368 

Gender 

Males 99-00 1.49 (1.30-1.70) 1.25 (1.10-1.44) 3.02 (2.57-3.80) 6.43 (5.40-8.00) 9.63 (6.63-15.6) 937 

01-02 1.77 (1.57-2.01) 1.59 (1.36-1.76) 3.40 (3.03-4.10) 7.48 (6.43-8.75) 13.1 (9.66-17.6) 1069 

03-04 1.46 (1.18-1.80) 1.30 (1.04-1.58) 2.80 (2.18-4.13) 6.71 (5.51-8.54) 9.93 (7.51-15.4) 955 

Females 99-00 1.59 (1.32-1.92) 1.38 (1.03-1.99) 4.05 (3.15-4.79) 8.18 (6.36-11.5) 13.2 (9.81-18.5) 1027 

01-02 1.85 (1.66-2.06) 1.49 (1.32-1.75) 4.57 (3.81-5.47) 10.2 (9.01-11.9) 16.8 (13.4-19.7) 1229 

03-04 1.45 (1.16-1.82) 1.25 (.965-1.66) 3.55 (2.43-4.59) 7.87 (5.41-12.6) 13.7 (8.50-17.3) 1001 

Race/ethnicity 

Mexican Americans 99-00 3.92 (3.40-4.51) 3.52 (3.17-3.91) 8.22 (7.26-10.4) 22.0 (12.2-32.2) 32.2 (19.7-48.1) 657 

01-02 3.92 (3.37-4.57) 3.53 (2.68-4.34) 9.34 (7.31-12.5) 26.6 (17.9-38.3) 40.9 (26.8-90.5) 566 

03-04 2.69 (2.18-3.32) 2.24 (1.70-3.24) 5.78 (4.54-7.21) 13.0 (9.53-15.6) 22.9 (15.3-43.4) 457 

Non-Hispanic blacks 99-00 1.63 (1.31-2.02) 1.37 (1.11-1.66) 3.84 (3.01-5.69) 11.2 (6.57-13.3) 14.6 (8.88-35.2) 416 

01-02 1.82 (1.46-2.28) 1.38 (1.22-1.72) 4.39 (3.52-6.06) 10.6 (7.24-17.6) 19.4 (8.51-49.3) 515 

03-04 1.47 (1.30-1.65) 1.20 (.963-1.51) 3.76 (2.85-4.75) 9.23 (7.19-14.9) 16.8 (14.7-20.6) 487 

Non-Hispanic whites 99-00 1.32 (1.14-1.53) 1.13 (1.01-1.35) 2.88 (2.34-3.36) 5.75 (4.62-6.53) 8.04 (6.32-9.81) 732 

01-02 1.57 (1.39-1.76) 1.41 (1.27-1.58) 3.11 (2.56-3.68) 7.00 (6.02-8.34) 11.3 (8.60-13.7) 1053 

03-04 1.29 (1.01-1.64) 1.12 (.890-1.49) 2.63 (1.84-3.90) 6.36 (3.90-8.71) 9.71 (6.01-15.0) 888 
Fourth National Report on Human Exposure to Environmental Chemicals 93

 Organochlorine Pesticides

Serum o,p'-Dichlorodiphenyltrichloroethane (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1669 

01-02 * < LOD < LOD < LOD < LOD 2279 

03-04 * < LOD < LOD < LOD < LOD 1946 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667 

01-02 * < LOD < LOD < LOD < LOD 756 

03-04 * < LOD < LOD < LOD < LOD 588 

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1002 

01-02 * < LOD < LOD < LOD < LOD 1523 

03-04 * < LOD < LOD < LOD < LOD 1358 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 796 

01-02 * < LOD < LOD < LOD < LOD 1059 

03-04 * < LOD < LOD < LOD < LOD 949 

Females 99-00 * < LOD < LOD < LOD < LOD 873 

01-02 * < LOD < LOD < LOD < LOD 1220 

03-04 * < LOD < LOD < LOD < LOD 997 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 632 

01-02 * < LOD < LOD < LOD < LOD 565 

03-04 * < LOD < LOD < LOD < LOD 458 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 354 

01-02 * < LOD < LOD < LOD < LOD 507 

03-04 * < LOD < LOD < LOD < LOD 486 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 560 

01-02 * < LOD < LOD < LOD < LOD 1045 

03-04 * < LOD < LOD < LOD < LOD 880 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 20.7, 17.4, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 94 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

Serum o,p'-Dichlorodiphenyltrichloroethane (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1669 

01-02 * < LOD < LOD < LOD < LOD 2279 

03-04 * < LOD < LOD < LOD < LOD 1946 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667 

01-02 * < LOD < LOD < LOD < LOD 756 

03-04 * < LOD < LOD < LOD < LOD 588 

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1002 

01-02 * < LOD < LOD < LOD < LOD 1523 

03-04 * < LOD < LOD < LOD < LOD 1358 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 796 

01-02 * < LOD < LOD < LOD < LOD 1059 

03-04 * < LOD < LOD < LOD < LOD 949 

Females 99-00 * < LOD < LOD < LOD < LOD 873 

01-02 * < LOD < LOD < LOD < LOD 1220 

03-04 * < LOD < LOD < LOD < LOD 997 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 632 

01-02 * < LOD < LOD < LOD < LOD 565 

03-04 * < LOD < LOD < LOD < LOD 458 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 354 

01-02 * < LOD < LOD < LOD < LOD 507 

03-04 * < LOD < LOD < LOD < LOD 486 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 560 

01-02 * < LOD < LOD < LOD < LOD 1045 

03-04 * < LOD < LOD < LOD < LOD 880 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 95

 Organochlorine Pesticides

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Transcriptional activation of the human estrogen receptor by 

DDT isomers and metabolites in yeast and MCF-7 cells. Biochem 

Pharmacol 1997;53(8):1161-1172.

Eriksson P, Talts U. Neonatal exposure to neurotoxic pesticides 

increases adult susceptibility: a review of current findings. 

Neurotoxicol 2000;21(1-2)37-48.

Food and Drug Administration (FDA). Center for Food Safety 

and Applied Nutrition/Office of Plant and Dairy Foods. FDA 

Pesticide Program Residue Monitoring 1993-2006 [online]. 

August 2008. Available at URL: http://www.cfsan.fda.gov/~dms/

pesrpts.html. 4/21/09

Gladen BC, Rogan WJ. DDE and shortened duration of lactation 

in a northern Mexican town. Am J Public Health 1995;85:504-

508.

Gladen BC, Klebanoff MA, Hediger ML, Katz SH, Barr DB, Davis 

MD, et al. Prenatal DDT exposure in relation to anthropometric 

and pubertal measures in adolescent males. Environ Health 

Perspect 2004;112(17):1761-1767.

Glynn AW, Granath F, Aune M, Atuma S, Darnerud PO, Bjerselius 

R, et al. Organochlorines in Swedish women: determinants of 

serum concentrations. Environ Health Perspect 2003;111:349-

355.

Gray LE Jr, Ostby J, Furr J, Wolf CJ, Lambright C, Parks L, 

et al. Effects of environmental antiandrogens on reproductive 

development in experimental animals. Hum Reprod Updat 

2001;7(3):248-264.

Gunderson EL. FDA total diet study, April 1982 to 1984, dietary 

intakes of pesticides, selected elements, and other chemicals. J 

Assoc Off Anal Chem 1988;71(6):1200-1209.

Hayes WJ, Jr., Durham WF, Cueto C, Jr. The effect of known 

repeated oral doses of chlorophenothane (DDT) in man. JAMA 

1956;162:890-897.

Heudorf U, Angerer J, Drexler H. Current internal exposure 

to pesticides in children and adolescents in Germany: blood 

plasma levels of pentachlorophenol (PCP), lindane (g-HCH), 

and dichloro(diphenyl)ethylene (DDE), a biostable metabolite 

of dichloro(diphenyl)trichloroethane (DDT). Int J Hyg Environ 

Health 2003;206:485-491.

Jusko TA, Koepsell TD, Baker RJ, Greenfield TA, Willman EJ, 

Charles MJ, et al. Maternal DDT exposures in relation to fetal 

and 5-year growth. Epidemiology 2006;17(6):692-700.

Link B, Gabrio T, Zoellner I, Piechotowski I, Paepke O, Herrman 

T, et al. Biomonitoring of persistent organochlorine pesticides, 

PCD/PCDFs and dioxin-like PCBs in blood of children from 

South West Germany (Baden-Wuerttemberg) from 1993-2003. 

Chemosphere 2005;58:1185-1201.

Longnecker MP, Klebanoff MA, Zhou H, Brock JW. Association 

between maternal serum concentration of the DDT metabolite 

DDE and preterm and small-for-gestational-age babies at birth. 

Lancet 2001;358:110-114.

Longnecker MP, Klebanoff MA, Brock JW, Zhou H, Gray 

KA, Needham LL, et al. Maternal serum level of 1,1-dichloro2,2-bi(p-chlorophenyl)ethylene and risk of cryptorchidism, 

hypospadias, and polythelia among male offspring. Am J 

Epidemiol 2002;155(4):313-322.
 96 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

Mariussen E, Fonnum F. Neurochemical targets and behavioral 

effects of organohalogen compounds: an update. Crit Rev Toxicol 

2006;36:253-589.

Nims R, Lubet R, Fox S, Jones CR, Thomas PE, Reddy AB, et al. 

Comparative pharmacodynamics of CYP2B induction by DDT, 

DDE, and DDD in male rat liver and cultured rat hepatocytes. J 

Toxicol Environ Health Part A 1998;53:455-477.

Pavuk M, Cerhan JR, Lynch CF, Schecter A, Petrik J, Chovancova 

J, et al. Environmental exposure to PCBs and cancer incidence in 

eastern Slovakia. Chemosphere 2004;54:1509-520.

Radomski JL, Astolfi E, Deichmann WB, Rey AA. Blood levels 

of organochlorine pesticides in Argentina: occupationally and 

nonoccupationally exposed adults, children and newborn infants. 

Toxicol Appl Pharmacol 1971;20(2):186-193.

Rogan WJ. Pollutants in breast milk. Arch Pediatr Adolesc Med 

1996;150:981-990.

Smith AG. Chlorinated Hydrocarbon Insecticides. In Hayes WJ, 

Jr and Laws ER, Jr, Eds. Handbook of Pesticide Toxicology, Vol. 

2 Classes of Pesticides. New York, Academic Press, Inc. 1991 

pp. 731-915.

Snedeker SM. Pesticides and breast cancer risk: a review of DDT, 

DDE, and dieldrin. Environ Health Perspect 2001;109:35-47.

Stehr-Green, PA. Demographic and seasonal influences on 

human serum pesticide residue levels. J Toxicol Environ Health 

1989;27:405-421.
Fourth National Report on Human Exposure to Environmental Chemicals 97

 Organochlorine Pesticides

Endrin

CAS No. 72-20-8

General Information

Endrin, a stereoisomer of dieldrin, is no longer manufactured 

in the U.S. All uses of the pesticide in the U.S. have 

been cancelled by the U.S. EPA. Endrin was used as an 

insecticide, rodenticide and avicide. Endrin was not widely 

used as a termiticide, unlike aldrin and dieldrin. Depending 

on soil conditions, endrin can persist for years. Ketoendrin 

is a major photodegradation product (IPCS, 1992). Endrin 

has been detected in soils, and occasionally at low levels in 

sediment and surface waters, largely the result of historical 

agricultural application or run off from contaminated soils 

(ATSDR, 1996; IPCS, 1992).

General population exposure can occur after ingestion of 

endrin residues on food items imported from countries 

where endrin is still used, or from contact with contaminated 

soils and sediments in areas where endrin was applied, 

manufactured, or discarded. Over time, endrin has been 

detected with declining frequency in U.S. total diet surveys 

(FDA, 2008). Endrin is absorbed rapidly after ingestion, 

inhalation or dermal exposure routes. In the body, endrin 

is converted rapidly to its major metabolite, anti-12-

hydroxyendrin. Further conversion occurs to 12-ketoendrin 

and various conjugated metabolites which are excreted in 

urine and feces. Because it is metabolized so rapidly, endrin 

usually is not detected in serum of exposed individuals, 

unless the dose is high and the exposure is very recent. 

Endrin does not accumulate in body tissues (IPCS, 1992; 

Smith, 1991).

Human health effects from endrin at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. At high doses, endrin blocks 

inhibitory neurotransmitters in the central nervous system 

resulting in excitation and seizures (Narahashi et al., 1992). 

An epidemic of acute endrin poisoning, characterized 

by generalized seizures in previously healthy persons 

occurred in Pakistan when sugar contaminated with endrin 

was ingested (Rowley et al., 1987). High doses produced 

renal tubular necrosis and diffuse kidney degeneration in 

animals. Hepatic effects of endrin exposure have included 

necrosis, fatty infiltration, and inflammation (Smith, 1991). 

Skeletal abnormalities and cleft palate in the offspring 

were associated with endrin when it was fed to pregnant 

laboratory rodents (Chernoff et al., 1979; Kavlock et al., 

1981).

Serum Endrin (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD 5.10 (<LOD-5.40) 2187 

03-04 * < LOD < LOD < LOD < LOD 1825 

Age group 

12-19 years 01-02 * < LOD < LOD 5.20 (<LOD-5.50) 5.60 (5.40-5.70) 730

03-04 * < LOD < LOD < LOD < LOD 539

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1457 

03-04 * < LOD < LOD < LOD < LOD 1286 

Gender 

Males 01-02 * < LOD < LOD < LOD 5.20 (<LOD-5.40) 1022 

03-04 * < LOD < LOD < LOD < LOD 885

Females 01-02 * < LOD < LOD < LOD < LOD 1165 

03-04 * < LOD < LOD < LOD < LOD 940

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD 5.30 (<LOD-6.50) 547

03-04 * < LOD < LOD < LOD < LOD 433

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD 5.40 (<LOD-6.30) 487

03-04 * < LOD < LOD < LOD < LOD 446

Non-Hispanic whites 01-02 * < LOD < LOD < LOD 5.10 (<LOD-5.40) 1000 

03-04 * < LOD < LOD < LOD < LOD 831

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 5.09 and 7.8. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 98 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

The U.S. EPA has established environmental standards for 

endrin, and the FDA monitors foods for pesticide residues. 

Workplace exposure standards for endrin have been 

established by OSHA. IARC has determined that endrin 

is not classifiable with regard to human carcinogenicity. 

Information about external exposure (i.e., environmental 

levels) and health effects of endrin is available from ATSDR 

at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

In the NHANES 2001-2002 and 2003-2004 subsamples, 

serum levels of endrin were below the limit of detection. 

This finding is consistent with other general population 

studies (Bates et al., 2004; Ward et al., 2000). In a small 

study of Spanish women hospitalized for elective surgery, 

endrin was detected in 9% of serum samples, with the 

highest value 6.24 ng/mL (about 6.24 ng/g of serum) 

(Botella et al., 2004).

Finding a measurable amount of endrin in serum does 

not mean that the level of endrin causes an adverse health 

effect. Biomonitoring studies on levels of endrin provide 

physicians and public health officials with reference 

values so that they can determine whether people have 

been exposed to higher levels of endrin than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Serum Endrin (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD .020 (<LOD-.020) 2187 

03-04 * < LOD < LOD < LOD < LOD 1825 

Age group 

12-19 years 01-02 * < LOD < LOD .020 (<LOD-.020) .020 (.020-.020) 730

03-04 * < LOD < LOD < LOD < LOD 539

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1457 

03-04 * < LOD < LOD < LOD < LOD 1286 

Gender 

Males 01-02 * < LOD < LOD < LOD .020 (<LOD-.020) 1022 

03-04 * < LOD < LOD < LOD < LOD 885

Females 01-02 * < LOD < LOD < LOD < LOD 1165 

03-04 * < LOD < LOD < LOD < LOD 940

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD .020 (<LOD-.020) 547

03-04 * < LOD < LOD < LOD < LOD 433

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD .020 (<LOD-.020) 487

03-04 * < LOD < LOD < LOD < LOD 446

Non-Hispanic whites 01-02 * < LOD < LOD < LOD .020 (<LOD-.020) 1000 

03-04 * < LOD < LOD < LOD < LOD 831

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 99

 Organochlorine Pesticides

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for endrin [online]. August 1996. Available 

at URL: http://www.atsdr.cdc.gov/toxprofiles/tp89.html. 4/21/09

Bates MN, Buckland SJ, Garrett N, Ellis H, Needham LL, 

Patterson DG Jr, et al. Persistent organochlorines in the serum 

of the non-occupationally exposed New Zealand population. 

Chemosphere 2004;54:1431-1443.

Botella B, Crespo J, Rivas A, Cerrillo I, Olea-Serrano MF, Olea 

N. Exposure of women to organochlorine pesticides in Southern 

Spain. Environ Res 2004;96:34-40.

Chernoff N, Kavlock RJ, Hanisch RC, Whitehouse DA, Gray 

JA, Gray LE, et al. Perinatal toxicity of endrin in rodents. I. 

Fetotoxic effects of prenatal exposure in hamsters. Toxicology 

1979;13:155-165.

Food and Drug Administration (FDA). Center for Food Safety 

and Applied Nutrition/Office of Plant and Dairy Foods. FDA 

Pesticide Program Residue Monitoring 1993-2006 [online]. 

August 2008. Available at URL: http://www.cfsan.fda.gov/~dms/

pesrpts.html. 4/21/09

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 130. Endrin [online]. 1992. 

Available at URL: http://www.inchem.org/documents/ehc/ehc/

ehc130.htm. 4/21/09

Kavlock RJ, Chernoff H, Hanisch RC, Gray J, Rogers E, Gray 

LE. Perinatal toxicity of endrin in rodents. II. Fetotoxic effects of 

prenatal exposure in rats and mice. Toxicology 1981;21:141-150.

Narahashi T, Frey JM, Ginsburg KS, Roy ML. Sodium and 

GABA-activated channels as the targets of pyrethroids and 

cyclodienes. Toxicol Lett 1992;64-65 Spec. No:429-436.

Rowley DL, Rab MA, Hardjotanojo W, Liddle J, Burse VW, 

Saleem M, Sokal D, et al. Convulsions caused by endrin poisoning 

in Pakistan. Pediatrics 1987;79(6):928-934.

Smith AG. Chlorinated Hydrocarbon Insecticides. In Hayes WJ, 

Jr and Laws ER, Jr, Eds. Handbook of Pesticide Toxicology, Vol. 

2 Classes of Pesticides. New York, Academic Press, Inc. 1991, 

pp. 731-915.

Ward EM, Schulte P, Grajewski B, Andersen A, Patterson DG 

Jr, Turner W, et al. Serum organochlorine levels and breast 

cancer: a nested case-control study of Norwegian women. Cancer 

Epidemiol Biomarkers Prev 2000;9:1357-136.
 100 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

Hexachlorobenzene

CAS No. 118-74-1

General Information

Hexachlorobenzene (HCB) was used from the 1930’s to 

the 1970’s in the U.S. primarily as a fungicide and seed 

treatment until the U.S. EPA cancelled its use in 1984. 

Although it is not manufactured as an end-product in the 

U.S., HCB may be created as either a byproduct or an 

impurity in the manufacturing process for certain chemicals 

and pesticides.

Hexachlorobenzene has entered the environment as a result 

of industrial activities and pesticide applications, and has 

been detected in soil, air, water, and sediment (Barber et 

al., 2005). It is a persistent chemical and bioaccumulates 

in both aquatic and terrestrial food chains (ATSDR, 2002). 

The general population may be exposed to HCB through 

diet, particularly by consuming fish, wildfowl, or game 

taken from areas with HCB contamination, and foods with 

a high fat content. The FDA dietary surveys have shown 

that over time, HCB has been detected in fewer foods 

since the 1980s (FDA, 2008; Gunderson, 1988). Workers 

in chemical manufacturing industries may be exposed to 

HCB via inhalation or dermal pathways.

HCB is well absorbed after oral administration, distributes 

widely throughout the body, and accumulates in fatty tissues 

where it persists for years. HCB is slowly metabolized, and 

elimination occurs by renal and fecal routes; breast milk 

is an additional route of elimination in nursing women. 

Urinary metabolites include pentachlorophenol (PCP), 

2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6-trichlorophenol 

(2,4,6-TCP) (To-Figueras et al., 1997); these metabolites 

can also be produced after exposure to other chlorinated 

compounds (Kohli et al., 1976). Therefore, measuring HCB 

in serum is a specific indicator of exposure to the parent 

Serum Hexachlorobenzene (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1702 

01-02 * < LOD < LOD < LOD < LOD 2277 

03-04 15.2 (14.5-15.9) 14.9 (14.2-15.7) 19.0 (18.1-20.3) 24.4 (22.6-26.4) 28.9 (25.6-32.8) 1961 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 591

01-02 * < LOD < LOD < LOD < LOD 747

03-04 13.3 (12.5-14.1) 13.4 (11.5-14.9) 16.7 (15.5-18.4) 20.7 (19.7-22.7) 25.3 (22.7-30.2) 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1111 

01-02 * < LOD < LOD < LOD < LOD 1530 

03-04 15.5 (14.7-16.2) 15.1 (14.5-15.9) 19.4 (18.3-20.9) 24.8 (22.7-26.6) 29.0 (25.6-33.6) 1373 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 807

01-02 * < LOD < LOD < LOD < LOD 1058 

03-04 14.5 (13.8-15.3) 14.2 (13.4-15.0) 18.1 (17.0-19.3) 23.6 (21.0-25.6) 26.9 (25.2-31.3) 957

Females 99-00 * < LOD < LOD < LOD < LOD 895

01-02 * < LOD < LOD < LOD < LOD 1219 

03-04 15.8 (15.0-16.6) 15.7 (15.1-16.4) 20.0 (18.7-21.4) 24.9 (23.0-28.6) 29.8 (26.5-33.7) 1004 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 583

01-02 * < LOD < LOD < LOD < LOD 554

03-04 16.2 (14.9-17.7) 15.3 (14.7-16.4) 20.4 (18.3-22.5) 27.6 (24.7-29.4) 33.7 (27.6-44.6) 460

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 350

01-02 * < LOD < LOD < LOD < LOD 511

03-04 14.5 (13.9-15.0) 14.1 (13.7-15.1) 18.3 (16.6-19.9) 22.3 (20.9-24.0) 26.6 (23.9-30.9) 488

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD < LOD < LOD < LOD 1052 

03-04 15.1 (14.4-16.0) 15.0 (14.2-15.9) 19.2 (17.9-20.8) 24.3 (22.3-26.4) 28.2 (24.9-32.8) 888

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 118.0, 31.4, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 101

 Organochlorine Pesticides

chemical.

Human health effects from HCB at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Chronic feeding studies in 

animals have demonstrated kidney injury, immunologic 

abnormalities, reproductive and developmental toxicities, 

and liver and thyroid cancers (ATSDR, 2002). In humans, 

very high, acute doses produce central nervous system 

depression and seizures. HCB interferes with normal 

heme synthesis, which is manifested by increased deltaaminolevulinic acid synthase activity and decreased 

uroporphyrinogen decarboxylase activity. With chronic 

exposure, a consequence of these heme abnormalities is a 

condition known as acquired porphyria cutanea tarda. This 

condition, as well as hypertrichosis, arthritis, thyromegaly, 

anorexia, and weakness, were seen in an epidemic of 

poisoning in Turkey that occurred from 1955 to 1959 when 

HCB-treated seed grain was diverted for bread production. 

Infants were exposed transplacentally and through breast 

milk, and many died before 2 years of age (Peters et al., 

1982; Schmid, 1960).

IARC classifies hexachlorobenzene as possibly carcinogenic 

to humans, and NTP classifies hexachlorobenzene as 

reasonably anticipated to be a human carcinogen. ACGIH 

has developed workplace exposure limits for HCB. The 

U.S. EPA has established a drinking water standard, and 

the FDA has established a bottled water standard for 

HCB. More information about external exposure (i.e., 

environmental levels) and health effects is available from 

the U.S. EPA at: http://www.epa.gov/pesticides/ and from 

ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Serum concentrations reflect the body burden of HCB. 

HCB levels were generally below the limits of detection 

Serum Hexachlorobenzene (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1702 

01-02 * < LOD < LOD < LOD < LOD 2277 

03-04 .092 (.088-.097) .090 (.086-.095) .120 (.113-.126) .157 (.145-.167) .186 (.169-.212) 1961 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 591

01-02 * < LOD < LOD < LOD < LOD 747

03-04 .065 (.062-.069) .064 (.060-.069) .079 (.072-.086) .102 (.091-.111) .123 (.111-.141) 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1111 

01-02 * < LOD < LOD < LOD < LOD 1530 

03-04 .097 (.092-.102) .095 (.090-.099) .123 (.118-.130) .160 (.147-.175) .191 (.174-.223) 1373 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 807

01-02 * < LOD < LOD < LOD < LOD 1058 

03-04 .090 (.085-.095) .087 (.082-.094) .115 (.107-.122) .147 (.135-.163) .179 (.159-.203) 957

Females 99-00 * < LOD < LOD < LOD < LOD 895

01-02 * < LOD < LOD < LOD < LOD 1219 

03-04 .095 (.089-.100) .092 (.088-.099) .123 (.118-.132) .163 (.148-.176) .190 (.176-.226) 1004 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 583

01-02 * < LOD < LOD < LOD < LOD 554

03-04 .098 (.089-.109) .090 (.081-.107) .125 (.114-.152) .171 (.157-.203) .225 (.178-.258) 460

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 350

01-02 * < LOD < LOD < LOD < LOD 511

03-04 .081 (.077-.085) .078 (.073-.083) .104 (.095-.118) .140 (.127-.155) .167 (.145-.196) 488

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD < LOD < LOD < LOD 1052 

03-04 .094 (.088-.099) .092 (.086-.097) .121 (.114-.129) .156 (.143-.173) .182 (.163-.218) 888

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 102 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

in the NHANES 1999-2000 and 2001-2002 subsamples. 

As a result of the lower limit of detection in NHANES 

2003-2004, more HCB levels were quantified. Agerelated increases of HCB in body fat and serum have 

been consistently noted in general population studies 

(Becker et al., 2002; Bertram et al., 1986; Glynn et al., 

2003). In a representative sample of the 1998 German 

adult population, HCB levels were directly related to age, 

and the geometric mean concentration of HCB in whole 

blood was 0.44 mg/L, lower than the limit of detection (on 

a lipid adjusted basis) in NHANES 1999-2000 and 2001-

2002, but approximately five times higher than the overall 

geometric mean level in 2003-2004 (Becker et al., 2002). 

In the 1976-1980 NHANES subsample, HCB detection in 

serum also was proportional to age, but overall, only 4.9% 

of participants had quantifiable levels (Stehr-Green, 1989). 

In Spain, factory workers chronically exposed to HCB 

and residents near the factory had serum HCB levels that 

were 150 to 50 times higher, respectively, than the limits 

of detection (on a whole weight basis) in NHANES 1999-

2000 and 2001-2002 (Herrero et al., 1999). Residency near 

industrial or agricultural areas has been associated with 

higher serum HCB levels (Barber et al., 2005; Bradman et 

al., 2006). Over the past two decades, however, declines 

in background HCB levels ranging from around 50%-

90% have been documented in studies using cord blood 

(Dallaire et al., 2002; Lackman, 2002) and among children 

(Link et al., 2005); the more recent values in these studies 

were similar to the lipid adjusted limit of detection in 

NHANES 1999-2000 and 2001-2002 (Dallaire et al., 2002; 

Lackmann, 2002; Link et al., 2005).

Finding a measurable amount of hexachlorobenzene in 

serum does not mean that the level of the hexachlorobenzene 

causes an adverse health effect. Biomonitoring studies 

on levels of HCB provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels 

of hexachlorobenzene than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for hexachlorobenzene update [online]. 

September 2002. Available at URL: http://www.atsdr.cdc.gov/

toxprofiles/tp90.html. 4/21/09

Barber JL, Sweetman AJ, van Wijk D, Jones KC. 

Hexachlorobenzene in the global environment: emissions, levels, 

distribution, trends and processes. Sci Tot Environ 2005;349:1-

44.

Becker K, Kaus S, Krause C, Lepom P, Schulz C, Seiwert M, et al. 

German Environmental Survey 1998 (GerES III): environmental 

pollutants in blood of the German population. Int J Hyg Environ 

Health 2002;205:297-308.

Bertram HP, Kemper FH, Muller C. Hexachlorobenzene content 

in human whole blood and adipose tissue: experiences in 

environmental specimen banking. IARC Sci Publ 1986;77:173-

182.

Bradman A, Schwartz JM. Fenster L, Barr DB, Holland NT, 

Eskenazi B. Factors predicting organochlorine pesticide levels 

in pregnant Latina women living in a United States agricultural 

area. J Exp Sci Environ Epidemiol 2007;17:388–399.

Dallaire F, Dewailly E, Laliberte C, Muckle G, Ayotte P. 

Temporal trends of organochlorine concentrations in umbilical 

cord blood of newborns from the lower north shore of the St. 

Lawrence River (Quebec, Canada). Environ Health Perspect 

2002;110(8):835-838.

Food and Drug Administration (FDA). Center for Food Safety 

and Applied Nutrition/Office of Plant and Dairy Foods. FDA 

Pesticide Program Residue Monitoring 1993-2006 [online]. 

August 2008. Available at URL: http://www.cfsan.fda.gov/~dms/

pesrpts.html. 4/21/09

Glynn AW, Granath F, Aune M, Atuma S, Darnerud PO, Bjerselius 

R, et al. Organochlorines in Swedish women: determinants of 

serum concentrations. Environ Health Perspect 2003;111:349-

355.

Gunderson EL. FDA total diet study, April 1982 to 1984, dietary 

intakes of pesticides, selected elements, and other chemicals. J 

Assoc Off Anal Chem 1988;71(6):1200-1209.

Herrero C, Ozalla D, Sala M, Otero R, Santiago-Silva M, Lecha 

M, et al. Urinary porphyrin excretion in a human population highly 

exposed to hexachlorobenzene. Arch Dermatol 1999;135(4):400-

404.

Kohli J, Jones D, Safe A. The metabolism of higher chlorinated 

benzene isomers. Can J Biochem 1976;54(3):203-208.

Lackmann GM. Polychlorinated biphenyls and hexachlorobenzene 

in full-term neonates. Reference values updated. Biol Neonate 

2002;81(2):82-85.

Link B, Gabrio T, Zoellner I, Piechotowski I, Paepke O, Herrman 

T, et al. Biomonitoring of persistent organochlorine pesticides, 

PCD/PCDFs and dioxin-like PCBs in blood of children from 

South West Germany (Baden-Wuerttemberg) from 1993-2003. 

Chemosphere 2005;58:1185-1201.

Peters HA, Gocmen A, Cripps DJ, Bryan GT, Dogramaci I. 

Epidemiology of hexachlorobenzene-induced porphyria in 

Turkey: clinical and laboratory follow-up after 25 years. Arch 

Neurol 1982;39(12):744-749.
Fourth National Report on Human Exposure to Environmental Chemicals 103

 Organochlorine Pesticides

Schmid R. Cutaneous porphyria in Turkey. N Engl J Med 

1960;263:397-398.

Stehr-Green, PA. Demographic and seasonal influences on 

human serum pesticide residue levels. J Toxicol Environ Health 

1989;27:405-421.

To-Figueras J, Sala M, Otero R, Barrot C, Santiago-Silva 

M, Rodamilans M, et al. Metabolism of hexachlorobenzene 

in humans: association between serum levels and urinary 

metabolites in a highly exposed population. Environ Health 

Perspect 1997;105(1):78-83.
 104 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

Hexachlorocyclohexane

CAS No. 608-73-1

beta-Hexachlorocyclohexane

CAS No. 319-85-7

gamma-Hexachlorocyclohexane

CAS No. 58-89-9

General Information

Hexachlorocyclohexane (HCH), formerly referred to as 

benzene hexachloride, exists in several isomeric forms, 

including alpha, beta, gamma, and delta. The gamma

isomer, commonly known as lindane, can be used as an 

insecticide and has been used to kill soil-dwelling and 

plant-eating insects. The other isomers can be formed 

during the synthesis of lindane, and have been used either 

as fungicides or to synthesize other chemicals. Technical 

grade HCH is a mixture of all four isomers, containing about 

64% alpha and 10%-15% gamma isomers. It is no longer 

produced or sold in the U.S. In 2006, the U.S. EPA cancelled 

agricultural uses of lindane (ATSDR, 2005). Lindane (1%) 

lotion and shampoo are available by prescription for singleuse application to treat human scabies and head lice.

HCH isomers, particularly alpha and gamma have been 

detected widely in air, soil, water, and sediment as a result 

of historic production and use. As pesticide applications 

of HCH were increasingly restricted or eliminated, 

environmental levels declined. Lindane has a half-life 

of about two weeks in soils and water. HCH does not 

bioaccumulate to an appreciable extent in plants (ATSDR, 

2005). However, HCH isomers are lipophilic, so they can 

accumulate in fatty tissues of animals. General population 

Serum beta-Hexachlorocyclohexane (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 9.68 (<LOD-10.9) < LOD 19.1 (16.0-21.6) 42.0 (33.4-50.6) 68.9 (50.6-89.5) 1893

01-02** * < LOD 16.0 (14.2-17.3) 36.7 (30.4-45.7) 67.2 (50.3-85.7) 2291

03-04 * < LOD 14.1 (12.1-16.5) 32.1 (27.1-37.8) 56.5 (43.7-69.4) 1959

Age group 

12-19 years 99-00 * < LOD < LOD < LOD 11.7 (<LOD-16.1) 653

01-02** * < LOD < LOD < LOD 13.1 (9.70-19.0) 758

03-04 * < LOD < LOD < LOD 8.80 (<LOD-14.7) 589

20 years and older 99-00 10.9 (9.61-12.4) < LOD 21.1 (18.9-24.0) 46.0 (35.9-56.8) 73.4 (52.7-96.0) 1240

01-02** 9.87 (9.04-10.8) 7.80 (6.90-8.90) 17.4 (16.0-20.5) 39.6 (33.2-52.0) 71.7 (53.7-96.2) 1533

03-04 7.89 (<LOD-9.09) < LOD 16.3 (13.6-18.4) 35.2 (29.6-42.5) 62.2 (48.2-87.6) 1370

Gender 

Males 99-00 * < LOD 14.6 (10.8-19.1) 29.8 (23.3-38.7) 44.9 (32.8-68.9) 901

01-02** * < LOD 12.9 (11.1-15.7) 27.5 (24.0-34.4) 45.7 (35.2-55.6) 1067

03-04 * < LOD 10.4 (8.70-12.5) 21.6 (17.7-26.4) 35.3 (26.1-49.9) 952

Females 99-00 11.1 (9.56-12.8) < LOD 22.0 (19.1-27.6) 51.3 (42.2-67.6) 81.8 (64.4-111) 992

01-02** 10.2 (9.46-11.0) 7.70 (6.90-8.50) 18.5 (16.2-22.7) 47.5 (37.6-62.0) 84.7 (62.0-111) 1224

03-04 8.43 (<LOD-9.45) < LOD 18.6 (16.9-21.5) 41.8 (33.9-51.4) 70.3 (62.2-98.4) 1007

Race/ethnicity 

Mexican Americans 99-00 16.7 (13.7-20.2) 15.5 (11.6-20.4) 37.7 (29.6-47.3) 97.9 (62.6-135) 142 (99.8-199) 632

01-02** 13.1 (11.6-14.7) 11.8 (9.60-13.4) 25.8 (21.1-32.7) 69.4 (50.8-87.6) 134 (85.7-166) 563

03-04 10.5 (8.66-12.8) 10.0 (<LOD-12.7) 23.8 (17.5-29.9) 50.1 (30.0-70.3) 70.3 (42.5-123) 460

Non-Hispanic blacks 99-00 * < LOD 15.4 (12.0-23.1) 37.9 (30.2-42.2) 49.9 (40.9-81.1) 403

01-02** * < LOD 12.0 (8.20-16.2) 36.2 (18.4-73.4) 71.2 (31.9-178) 513

03-04 * < LOD 9.70 (8.30-11.9) 27.1 (21.1-36.3) 48.2 (34.8-54.3) 487

Non-Hispanic whites 99-00 * < LOD 17.5 (14.2-20.5) 34.7 (25.2-46.1) 51.6 (40.0-70.8) 702

01-02** * < LOD 14.4 (11.8-16.8) 31.9 (26.6-37.8) 52.0 (37.7-69.5) 1051

03-04 * < LOD 12.8 (10.9-14.7) 27.6 (22.1-32.2) 40.8 (32.3-56.5) 887

Limits of detection (LOD, see Data Analysis section) for survey years 99-00, 01-02, and 03-04 are 9.36, 6.76, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

**In survey period 2001-2002, each result has been multiplied by 1.5528. See the section “What’s New” at the beginning of this Report for details. 
Fourth National Report on Human Exposure to Environmental Chemicals 105

 Organochlorine Pesticides

exposure to HCH is through the diet. The U.S. FDA pesticide 

monitoring program has shown a temporal decline in the 

detection of lindane, from 6% of samples in 1982-1984 

to 2% in 1994 (FDA, 2008; Gunderson 1988). Pesticide 

applicators or agricultural workers could be exposed to 

HCH by inhalation and dermal pathways.

HCH isomers are absorbed after inhalation, ingestion, or 

dermal exposure. Distribution is mainly to fatty tissues. 

After dermal application of lindane 1% lotion, the serum 

half-life was about 20 hours among children (Ginsburg et 

al., 1977). The beta isomer accumulates in fatty tissues and 

is metabolized more slowly, resulting in a half-life of about 

seven years. HCH isomers are metabolized to chlorophenol 

metabolites that are excreted in the urine (Angerer et al., 

1983). HCH crosses the placenta and is also excreted in 

breast milk (Radomski et al., 1971; Rogan, 1996; Saxena 

et al., 1981).

Human health effects from HCH isomers at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Acute high dose 

toxicity in rodents affects the central nervous system 

producing decreased activity, ataxia, and seizures. When 

animals were chronically fed lindane at high doses, 

enlarged livers, hepatic enzyme induction, and nephropathy 

developed (IPCS, 2002). Acute high doses of lindane after 

ingestion or excessive skin application of the 1% lotion 

have produced seizures in humans, probably by blocking 

inhibitory neurotransmitters in the central nervous system. 

Workers who directly handled HCH have complained 

of headache, paresthesias, tremors, and memory loss 

(Nigam et al., 1986). OSHA and ACGIH have established 

workplace standards and guidelines, respectively, for 

lindane. U.S. EPA has established a drinking water 

standard, and FDA has established a bottled water standard 

and food residue tolerances for lindane. IARC classifies 

Serum beta-Hexachlorocyclohexane (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .058 (<LOD-.066) < LOD .120 (.100-.150) .290 (.220-.360) .450 (.360-.560) 1893

01-02** * < LOD .100 (.090-.120) .250 (.210-.310) .460 (.340-.600) 2291

03-04 * < LOD .092 (.081-.103) .216 (.173-.254) .372 (.294-.442) 1959

Age group 

12-19 years 99-00 * < LOD < LOD < LOD .050 (<LOD-.070) 653

01-02** * < LOD < LOD < LOD .080 (.050-.100) 758

03-04 * < LOD < LOD < LOD .048 (<LOD-.064) 589

20 years and older 99-00 .067 (.059-.077) < LOD .140 (.120-.160) .330 (.240-.410) .480 (.410-.620) 1240

01-02** .062 (.057-.069) .050 (.050-.060) .120 (.100-.140) .270 (.230-.350) .480 (.370-.690) 1533

03-04 .050 (<LOD-.058) < LOD .103 (.089-.125) .234 (.191-.290) .412 (.308-.587) 1370

Gender 

Males 99-00 * < LOD .090 (.080-.120) .210 (.160-.250) .290 (.220-.470) 901

01-02** * < LOD .080 (.070-.100) .200 (.150-.260) .310 (.250-.400) 1067

03-04 * < LOD .072 (.056-.089) .144 (.118-.174) .222 (.170-.305) 952

Females 99-00 .065 (.056-.077) < LOD .150 (.120-.190) .380 (.300-.450) .560 (.420-.680) 992

01-02** .062 (.057-.067) .050 (.040-.050) .130 (.110-.150) .320 (.260-.400) .570 (.450-.710) 1224

03-04 .051 (<LOD-.057) < LOD .118 (.103-.130) .290 (.244-.319) .442 (.382-.661) 1007

Race/ethnicity 

Mexican Americans 99-00 .098 (.080-.119) .090 (.070-.110) .240 (.200-.310) .580 (.390-.840) .910 (.580-1.37) 632

01-02** .078 (.068-.091) .070 (.050-.080) .160 (.130-.210) .470 (.330-.700) 1.01 (.620-1.32) 563

03-04 .064 (.051-.080) .057 (<LOD-.086) .139 (.124-.190) .331 (.191-.501) .521 (.297-.814) 460

Non-Hispanic blacks 99-00 * < LOD .100 (.070-.140) .250 (.190-.290) .360 (.280-.460) 403

01-02** * < LOD .070 (.050-.110) .220 (.120-.410) .410 (.190-1.05) 513

03-04 * < LOD .065 (.047-.083) .167 (.131-.214) .281 (.200-.404) 487

Non-Hispanic whites 99-00 * < LOD .120 (.100-.140) .250 (.170-.340) .390 (.280-.510) 702

01-02** * < LOD .090 (.080-.110) .210 (.180-.260) .350 (.250-.480) 1051

03-04 * < LOD .083 (.073-.096) .175 (.146-.220) .287 (.221-.372) 887

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

**In survey period 2001-2002, each result has been multiplied by 1.5528. See the section “What’s New” at the beginning of this Report for details. 
 106 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

hexachlorocyclohexane isomers as possibly carcinogenic to 

humans, and NTP classifies hexachlorocyclohexane isomers 

as reasonably anticipated to be human carcinogens. More 

information about external exposure (i.e., environmental 

levels) and health effects is available from the U.S. EPA at: 

http://www.epa.gov/pesticides/ and from ATSDR at: http://

www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Because of its longer half-life, beta-HCH may be detected 

in a higher percentage of the general population than are the 

other HCH isomers. Studies of general populations have 

shown declining beta-HCH levels since the 1970s (ATSDR, 

2005; Kutz et al., 1991; Link et al., 2005; Radomski et al., 

1971; Stehr-Green, 1989; Sturgeon et al., 1998). Additional 

factors associated with higher beta-HCH levels include 

rural residence, older age, male sex, and a diet that includes 

meat (Becker et al., 2002; Kutz et al., 1991; Stehr-Green, 

1989).

In NHANES 1999-2000, 2001-2002, and 2003-2004, 

serum levels of lindane were generally below the limits 

of detection, which were considerably lower (as much as 

twentyfold) than mean levels reported in small studies of 

adults in Spain (Botella et al., 2004) and India (Bhatnagar 

et al., 2004). In recent years, studies in populations with 

environmental exposure have reported lindane levels below 

the limit of detection in most persons (Anderson et al., 

1998; Bates et al., 2004; Becker et al., 2002). In populationbased studies of New Zealand adults and German adults 

and children, the maximum and 95th percentile beta-HCH 

values, respectively, were similar to the 95th percentiles in 

this Report. In an earlier (1996-1997) sample of German 

children, aged 9-11 years, the 95th percentile of betaHCH levels was twofold to threefold higher than the 95th

percentile of 12-19 year olds in the comparable NHANES 

Serum gamma-Hexachlorocyclohexane (Lindane) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1799 

01-02 * < LOD < LOD < LOD < LOD 2280 

03-04 * < LOD < LOD < LOD < LOD 1960 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660 

01-02 * < LOD < LOD < LOD < LOD 758 

03-04 * < LOD < LOD < LOD < LOD 593 

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1139 

01-02 * < LOD < LOD < LOD < LOD 1522 

03-04 * < LOD < LOD < LOD < LOD 1367 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 863 

01-02 * < LOD < LOD < LOD < LOD 1060 

03-04 * < LOD < LOD < LOD < LOD 952 

Females 99-00 * < LOD < LOD < LOD < LOD 936 

01-02 * < LOD < LOD < LOD < LOD 1220 

03-04 * < LOD < LOD < LOD < LOD 1008 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631 

01-02 * < LOD < LOD < LOD < LOD 563 

03-04 * < LOD < LOD < LOD < LOD 461 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 380 

01-02 * < LOD < LOD < LOD < LOD 509 

03-04 * < LOD < LOD < LOD < LOD 490 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 646 

01-02 * < LOD < LOD < LOD < LOD 1045 

03-04 * < LOD < LOD < LOD < LOD 884 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 14.5, 10.5, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 107

 Organochlorine Pesticides

2001-2002 survey period (Link et al., 2005). In a small 

study of adults who consumed sport fish from the Great 

Lakes, the median beta-HCH levels were similar or slightly 

higher than the 95th percentile in this Report (Anderson et 

al., 1998). A study of Swedish women aged 54 years and 

older reported a median beta-HCH level that was slightly 

higher than the geometric mean for women reported in the 

NHANES 1999-2000 survey period (Glynn et al., 2003). 

Beta-HCH and lindane levels in workers involved in HCH 

production have been more than 1000-fold higher than 

the 95th percentile and limit of detection (lipid adjusted), 

respectively, in this Report (Nigam et al., 1986; Radomski 

et al., 1971).

Finding a measurable amount of HCH isomers in serum 

does not mean that the level of HCH isomers causes an 

adverse health effect. Biomonitoring studies on levels of 

HCH isomers provide physicians and public health officials 

with reference values so that they can determine whether 

people have been exposed to higher levels of HCH isomers 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

Serum gamma-Hexachlorocyclohexane (Lindane) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1799 

01-02 * < LOD < LOD < LOD < LOD 2280 

03-04 * < LOD < LOD < LOD < LOD 1960 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660 

01-02 * < LOD < LOD < LOD < LOD 758 

03-04 * < LOD < LOD < LOD < LOD 593 

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1139 

01-02 * < LOD < LOD < LOD < LOD 1522 

03-04 * < LOD < LOD < LOD < LOD 1367 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 863 

01-02 * < LOD < LOD < LOD < LOD 1060 

03-04 * < LOD < LOD < LOD < LOD 952 

Females 99-00 * < LOD < LOD < LOD < LOD 936 

01-02 * < LOD < LOD < LOD < LOD 1220 

03-04 * < LOD < LOD < LOD < LOD 1008 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631 

01-02 * < LOD < LOD < LOD < LOD 563 

03-04 * < LOD < LOD < LOD < LOD 461 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 380 

01-02 * < LOD < LOD < LOD < LOD 509 

03-04 * < LOD < LOD < LOD < LOD 490 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 646 

01-02 * < LOD < LOD < LOD < LOD 1045 

03-04 * < LOD < LOD < LOD < LOD 884 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 108 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

References

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Toxicological profile for hexachlorocyclohexanes update 

[online]. August 2005. Available at URL: http://www.atsdr.cdc.

gov/toxprofiles/tp43.html. 4/21/09

Anderson HA, Falk C, Hanrahan L, Olson J, Burse VW, Needham 

LL, et al. Profiles of Great Lakes critical pollutants: a sentinel 

analysis of human blood and urine. The Great Lakes Consortium. 

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Angerer J, Maass R, Heinrich R. Occupational exposure 

to hexachlorocyclohexane. VI. Metabolism of gammahexachlorocyclohexane in man. Int Arch Occup Environ Health 

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Bates MN, Buckland SJ, Garrett N, Ellis H, Needham LL, 

Patterson DG Jr, et al. Persistent organochlorines in the serum 

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Becker K, Kaus S, Krause C, Lepom P, Schulz C, Seiwert M, et al. 

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Health 2002;205:297-308.

Bhatnagar VK, Kashyap R, Zaidi SS, Kulkarni PK, Saiyed HN. 

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Ahmedabad, India. Bull Environ Contam Toxicol 2004;72:261-

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Botella B, Crespo J, Rivas A, Cerrillo I, Olea-Serrano MF, Olea 

N. Exposure of women to organochlorine pesticides in Southern 

Spain. Environ Res 2004;96:34-4Food and Drug Administration 

(FDA). Center for Food Safety and Applied Nutrition/Office 

of Plant and Dairy Foods. FDA Pesticide Program Residue 

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Ginsburg CM, Lowry W, Reisch JS. Absorption of lindane 

(g benzene hexachloride) in infants and children. J Pediatr 

1977;91:998-1000.

Glynn AW, Granath F, Aune M, Atuma S, Darnerud PO, Bjerselius 

R, et al. Organochlorines in Swedish women: determinants of 

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355.

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residues in food-2002-Joint FAO/WHO meeting on pesticide 

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and polychlorinated biphenyls in human adipose tissue. Rev 

Environ Contam Toxicol 1991;120:1-82.

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T, et al. Biomonitoring of persistent organochlorine pesticides, 

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South West Germany (Baden-Wuerttemberg) from 1993-2003. 

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GS, Bai KM, et al. Serum hexachlorocyclohexane residues in 

workers engaged at a HCH manufacturing plant. Int Arch Occup 

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Fourth National Report on Human Exposure to Environmental Chemicals 109

 Organochlorine Pesticides

Mirex

CAS No. 2385-85-5

General Information

Mirex has not been produced or used in the U.S. since 1977. 

Formerly, its major uses were as a flame retardant additive 

and as a pesticide to kill fire ants and yellow jackets in 

the southeastern U.S., where it was applied directly to 

soil and by aerial spraying. Mirex binds strongly to soil, 

where it has a half-life of 12 years; it is a highly persistent 

chemical in the environment. Mirex has been detected in 

air, soil, sediments, water, aquatic organisms, animals, and 

foods. Mirex contamination of Lake Ontario and adjacent 

waterways has been well documented (ATSDR, 1995). The 

most likely sources of human exposure to mirex are eating 

fish from contaminated water or living in areas with soil 

contaminated by historic mirex manufacturing, disposal, 

or pesticide application. Some states and the U.S. EPA 

have issued public health advisories or warnings that fish 

from contaminated lakes and rivers may contain mirex. 

Occupational exposure is limited to workers at sites where 

mirex contamination is present.

Mirex is absorbed through the skin and from the 

gastrointestinal tract, after which it is widely distributed 

in the body and stored in fat. Ingested mirex that is not 

absorbed is eliminated in the feces within about 48 hours. 

Mirex is not metabolized in the body. In studies conducted 

in the 1970’s and 1980’s, mirex was detected in human 

adipose samples, especially those from persons living in 

the southeastern U.S. (Kutz et al., 1985, 1991). Mirex can 

cross the placenta and be excreted in breast milk, resulting 

in exposure to newborns and nursing infants.

Human health effects from mirex at low environmental 

doses or at biomonitored levels from low environmental 

Serum Mirex (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1853 

01-02 * < LOD < LOD 15.8 (<LOD-73.7) 57.1 (13.2-230) 2257 

03-04 * < LOD < LOD 8.40 (<LOD-13.0) 13.2 (7.90-29.6) 1951 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 659

01-02 * < LOD < LOD < LOD < LOD 728

03-04 * < LOD < LOD < LOD < LOD 592

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1194 

01-02 * < LOD < LOD 19.6 (<LOD-108) 71.0 (14.6-305) 1529 

03-04 * < LOD < LOD 9.10 (<LOD-15.6) 15.4 (8.10-37.1) 1359 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 887

01-02 * < LOD < LOD 16.1 (<LOD-65.6) 50.8 (12.3-225) 1052 

03-04 * < LOD < LOD 9.70 (<LOD-15.4) 15.5 (9.70-24.4) 949

Females 99-00 * < LOD < LOD < LOD < LOD 966

01-02 * < LOD < LOD 15.0 (<LOD-108) 63.0 (12.0-374) 1205 

03-04 * < LOD < LOD < LOD 11.6 (<LOD-31.3) 1002 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 617

01-02 * < LOD < LOD < LOD < LOD 548

03-04 * < LOD < LOD < LOD < LOD 459

Non-Hispanic blacks 99-00 * < LOD < LOD 15.5 (<LOD-42.2) 39.5 (<LOD-115) 398

01-02 * < LOD 13.7 (<LOD-47.3) 51.3 (15.4-230) 153 (30.5-425) 500

03-04 * < LOD < LOD 18.1 (8.70-40.8) 40.3 (15.5-82.7) 484

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 688

01-02 * < LOD < LOD 15.1 (<LOD-104) 66.7 (12.5-291) 1049 

03-04 * < LOD < LOD < LOD 11.6 (<LOD-23.4) 884

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 14.6, 10.5, and 7.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 110 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

exposures are unknown. Laboratory animals fed high doses 

developed liver enlargement and liver tumors; reproductive 

toxicity included decreased fertility and testicular damage. 

In addition, developmental abnormalities including 

cataracts and edema in the offspring have been reported 

(ATSDR, 1995; Smith, 1991). The U.S. EPA has established 

environmental standards for mirex, and the FDA monitors 

foods for pesticide residue and has established an action 

level for mirex in fish tissue. IARC classifies mirex as 

possibly carcinogenic to humans, and NTP classifies mirex 

as reasonably anticipated to be a human carcinogen. More 

information about external exposure (i.e., environmental 

levels) and health effects is available from the ATSDR at: 

http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

In the NHANES 1999-2000, 2001-2002, and 2003-2004 

subsamples, as well as in a subsample of NHANES 

II (1976-1980) participants, serum mirex levels were 

generally below the limits of detection (Stehr-Green, 1989). 

Fishermen in New York who consumed Great Lakes sport 

fish had median levels of lipid-adjusted serum mirex that 

were lower than the 95th percentile value among males the 

NHANES 2001-2002 subsample (Bloom et al., 2005). In 

samples obtained between 1994 and 1997, Inuit mothers 

from three Arctic areas had geometric mean serum mirex 

levels that were threefold to sevenfold higher than nonInuit mother from other Arctic regions. The geometric mean 

mirex levels of the Inuit mothers were 8, 7.8, and 4.7 ng/g 

of lipid, which is approximately twofold to threefold lower 

than the 90th percentile for females in the NHANES 2001-

2002 subsample but similar to 95th percentile for females in 

the NHANES 2003-2004 subsample (Van Oostdam et al., 

2004).

Finding a measurable amount of mirex in serum does 

not mean that the level of mirex causes an adverse health 

Serum Mirex (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1853 

01-02 * < LOD < LOD .100 (<LOD-.470) .410 (.080-1.73) 2257 

03-04 * < LOD < LOD .054 (<LOD-.084) .093 (.052-.170) 1951 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 659

01-02 * < LOD < LOD < LOD < LOD 728

03-04 * < LOD < LOD < LOD < LOD 592

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1194 

01-02 * < LOD < LOD .140 (<LOD-.690) .470 (.090-1.92) 1529 

03-04 * < LOD < LOD .059 (<LOD-.102) .106 (.053-.215) 1359 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 887

01-02 * < LOD < LOD .110 (<LOD-.470) .370 (.090-1.37) 1052 

03-04 * < LOD < LOD .064 (<LOD-.106) .108 (.062-.170) 949

Females 99-00 * < LOD < LOD < LOD < LOD 966

01-02 * < LOD < LOD .090 (<LOD-.510) .430 (.070-1.79) 1205 

03-04 * < LOD < LOD < LOD .077 (<LOD-.170) 1002 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 617

01-02 * < LOD < LOD < LOD < LOD 548

03-04 * < LOD < LOD < LOD < LOD 459

Non-Hispanic blacks 99-00 * < LOD < LOD .090 (<LOD-.220) .220 (<LOD-.450) 398

01-02 * < LOD .090 (<LOD-.240) .310 (.090-1.41) 1.08 (.170-3.02) 500

03-04 * < LOD < LOD .112 (.055-.268) .256 (.089-.635) 484

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 688

01-02 * < LOD < LOD .100 (<LOD-.610) .450 (.080-1.79) 1049 

03-04 * < LOD < LOD < LOD .079 (<LOD-.174) 884

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 111

 Organochlorine Pesticides

effect. Biomonitoring studies on levels of mirex provide 

physicians and public health officials with reference 

values so that they can determine whether people have 

been exposed to higher levels of mirex than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for mirex and chlordecone [online]. August 

1995. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp66.html. 4/21/09

Bloom MS, Vena JE, Swanson MK, Moysich KB, Olson 

JR. Profiles of ortho-polychlorinated biphenyl congeners, 

dichlorodiphenyldichloroethylene, hexachlorobenzene, and 

Mirex among male Lake Ontario sportfish consumers: the New 

York State Angler cohort study. Environ Res 2005;97(2):178-

192.

Kutz FW, Strassman SC, Stroup CR, Carra JS, Leininger CC, Watts 

DL, et al. The human body burden of mirex in the southeastern 

United States. J Toxicol Environ Health 1985;15:385-394.

Kutz FW, Wood PH, Bottimore DP. Organochlorine pesticides 

and polychlorinated biphenyls in human adipose tissue. Rev 

Environ Contam Toxicol 1991;120:1-82.

Smith AG. Chlorinated Hydrocarbon Insecticides. In Hayes WJ, 

Jr and Laws ER, Jr, Eds. Handbook of Pesticide Toxicology, Vol. 

2 Classes of Pesticides. New York, Academic Press, Inc. 1991 

pp. 731-915.

Stehr-Green, PA. Demographic and seasonal influences on 

human serum pesticide residue levels. J Toxicol Environ Health 

1989;27:405-421.

Van Oostdam JC, Dewailly E, Gilman A, Hansen JC, Odland 

JO, Chashchin V, et al. Circumpolar maternal blood contaminant 

survey, 1994-1997 organochlorine compounds. Sci Total Environ 

2004;330:55-70.
 112 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

2,4,5-Trichlorophenol

CAS No. 95-95-4

2,4,6-Trichlorophenol

CAS No. 88-06-2

Metabolites of Organochlorine Pesticides and Other 

Environmental Chemicals

General Information

The chlorophenols, 2,4,5-trichlorophenol (2,4,5-TCP) 

and 2,4,6-trichlorophenol (2,4,6-TCP), are metabolites of 

several organochlorine chemicals, including hexachlorobenzene and hexachlorocyclohexanes. Historically, 2,4,5-

TCP and 2,4,6-TCP were used as intermediates in the 

production of certain pesticides; 2,4,6-TCP was also used 

as a wood preservative and may still be used in production 

of some fungicides (ATSDR, 1999). Trichlorophenols 

are no longer manufactured commercially, but they may 

be produced as by-products during manufacturing of 

other chlorinated aromatic compounds. Formation of 

2,3,7,8-tetrachlorodibenzo-p-dioxin occurs during the 

synthesis of 2,4,5-trichlorophenol. Small amounts of 

trichlorophenols also can be produced during combustion 

of natural materials and the chlorination of drinking water 

or waste water that contains phenols. Environmental 

sources of these compounds include industrial discharges 

or run off from pesticide facilities or disposal sites. Both 

chemicals have been detected in air, surface water, soils, 

and sediments; however, recent sampling of U.S. public 

drinking water systems did not detect 2,4,6-TCP in any 

of the samples (U.S. EPA, 2006). Trichlorophenols have 

been detected in fish taken from waters near waste water 

treatment and industrial discharges (ATSDR, 1999).

General population exposure may occur by ingesting 

contaminated food or water and by inhaling contaminated 

air. Exposure to trichlorophenols also may result from 

metabolism of lindane, hexachlorobenzene, other 

organochlorines, and polychlorinated benzenes (Kohil et 

al., 1976). Occupational exposures, usually at herbicide 

production or waste incineration facilities, may occur by 

inhalation or dermal routes. Such workers would probably 

Urinary 2,4,5-Trichlorophenol 

Metabolite of Several Organochlorine Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 1.40 (1.00-3.20) 5.40 (2.50-16.0) 16.0 (4.30-40.0) 1994 

01-02 * < LOD < LOD < LOD 2.42 (<LOD-8.27) 2497 

Age group 

6-11 years 99-00 * < LOD 1.40 (1.10-3.40) 4.80 (2.30-11.0) 11.0 (4.20-36.0) 482

01-02 * < LOD < LOD < LOD 2.42 (<LOD-12.7) 570

12-19 years 99-00 * < LOD 1.60 (.940-3.72) 5.40 (2.50-25.0) 24.0 (3.80-41.0) 681

01-02 * < LOD < LOD < LOD 2.19 (<LOD-6.63) 815

20-59 years 99-00 * < LOD 1.40 (.980-3.30) 5.40 (2.40-18.0) 18.0 (4.30-44.0) 831

01-02 * < LOD < LOD < LOD 2.71 (<LOD-8.27) 1112 

Gender 

Males 99-00 * < LOD 1.40 (.980-3.80) 5.40 (2.60-8.40) 11.0 (5.30-27.0) 973

01-02 * < LOD < LOD < LOD 5.57 (<LOD-15.8) 1178 

Females 99-00 * < LOD 1.50 (1.00-3.20) 6.50 (2.30-27.0) 21.0 (3.20-71.0) 1021 

01-02 * < LOD < LOD < LOD < LOD 1319 

Race/ethnicity 

Mexican Americans 99-00 * .950 (<LOD-1.30) 1.80 (1.30-3.50) 8.60 (4.60-18.0) 21.0 (8.90-33.0) 696

01-02 * < LOD < LOD < LOD 14.9 (<LOD-121) 661

Non-Hispanic blacks 99-00 * < LOD 1.30 (.900-2.20) 5.00 (2.00-8.40) 9.00 (3.50-63.0) 521

01-02 * < LOD < LOD < LOD 2.31 (<LOD-9.03) 696

Non-Hispanic whites 99-00 * < LOD 1.50 (.920-3.60) 4.60 (2.40-11.0) 9.20 (4.30-27.0) 603

01-02 * < LOD < LOD < LOD 2.71 (<LOD-8.27) 939

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.9 and 0.9. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 113

 Organochlorine Pesticides

be exposed to mixtures of chlorophenols, in addition 

to dioxins, furans, and other chlorinated compounds. 

However, recent small studies have not demonstrated 

increased exposure to trichlorophenols in workers who 

dredged contaminated soils or incinerated waste materials 

(Agramunt et al., 2003; Radon et al., 2004).

Human health effects from 2,4,5-TCP or 2,4,6-TCP at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Laboratory animals 

chronically fed high doses of 2,4,6-TCP had increased 

rates of hepatic tumors, leukemias, and lymphomas. At 

lower doses, animals showed hepatocellular abnormalities. 

Neither 2,4,5-TCP nor 2,4,6-TCP were developmental or 

reproductive toxicants in animals (ATSDR 1999). IARC 

classifies combined exposures to polychlorophenols, which 

includes trichlorophenols, as being possibly carcinogenic 

to humans. IARC considers the experimental evidence 

for animal carcinogenicity inadequate for 2,4,5-TCP 

and limited for 2,4,6-TCP. NTP classifies 2,4,6-TCP as 

reasonably anticipated to be a human carcinogen. More 

information about external exposure (i.e., environmental 

levels) and health effects is available from ATSDR at: 

http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

In the NHANES 1999-2000 and 2001-2002 subsamples, 

urinary 2,4,6-TCP levels at the 95th percentile were up to 

eight times higher than 3.3 mg/L in a nonrandom subsample 

from NHANES III (Hill et al., 1995) and up to 19 times 

higher than the 95th percentile value of 1.3 mg/L reported 

in German adults aged 18-69 years (Becker et al., 2003). 

Among 6-11 year old children in NHANES 1999-2000, the 

95th percentile urinary 2,4,6-TCP level was approximately 

eight times higher than the corresponding percentile in a 

small group of 2-6 year old children living near an herbicide 

manufacturing facility: 33 versus 4 mg/L (Hill et al., 1989). 

In the same 2-6 year old children, the 95th percentile urinary 

2,4,5-TCP, 7.0 mg/L, was similar to the corresponding 

percentile for 6-11 year olds in NHANES 1999-2000 (Hill 

et al., 1989). The 95th percentiles for 2,4,5-TCP among 

adults in this Report and in a nonrandom subsample from 

NHANES III (Hill et al., 1995) were similar, but almost 

twenty times higher than 95th percentile values reported 

in German adults aged 18-69 years (Becker et al., 2003). 

Urinary 2,4,5-Trichlorophenol (creatinine corrected) 

Metabolite of Several Organochlorine Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 2.36 (1.53-3.16) 5.57 (3.24-11.2) 11.9 (5.00-19.6) 1994 

01-02 * < LOD < LOD < LOD 4.57 (<LOD-7.11) 2496 

Age group 

6-11 years 99-00 * < LOD 2.29 (1.19-4.78) 5.86 (3.83-12.4) 12.8 (5.28-25.4) 482

01-02 * < LOD < LOD < LOD 5.82 (<LOD-32.5) 570

12-19 years 99-00 * < LOD 1.44 (.920-2.50) 3.80 (1.93-11.2) 11.2 (2.62-20.1) 681

01-02 * < LOD < LOD < LOD 2.75 (<LOD-6.74) 814

20-59 years 99-00 * < LOD 2.46 (1.60-3.24) 5.75 (3.37-11.5) 11.7 (4.78-19.6) 831

01-02 * < LOD < LOD < LOD 4.57 (<LOD-7.11) 1112 

Gender 

Males 99-00 * < LOD 1.67 (1.02-3.15) 4.24 (3.05-8.02) 9.55 (4.13-13.6) 973

01-02 * < LOD < LOD < LOD 4.68 (<LOD-8.37) 1178 

Females 99-00 * < LOD 2.67 (1.79-4.00) 7.95 (3.05-17.8) 16.3 (5.00-29.3) 1021 

01-02 * < LOD < LOD < LOD < LOD 1318 

Race/ethnicity 

Mexican Americans 99-00 * .980 (<LOD-1.33) 2.49 (1.68-4.24) 6.90 (4.19-12.4) 12.4 (6.88-16.9) 696

01-02 * < LOD < LOD < LOD 12.1 (<LOD-58.0) 661

Non-Hispanic blacks 99-00 * < LOD 1.16 (.820-2.31) 3.43 (2.20-6.32) 7.69 (2.69-18.2) 521

01-02 * < LOD < LOD < LOD 2.81 (<LOD-9.17) 695

Non-Hispanic whites 99-00 * < LOD 2.44 (1.53-3.24) 4.78 (3.47-8.43) 9.64 (4.27-17.8) 603

01-02 * < LOD < LOD < LOD 4.73 (<LOD-8.37) 939

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 114 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

A small study of adults who ate Great Lakes sport fish 

reported a mean urine 2,4,5-TCP level of 0.7 mg/L, similar 

to the limit of detection for this Report (Anderson et al., 

1998). Urinary 2,4,5-TCP and 2,4,6-TCP were monitored in 

a group of hazardous waste incinerator workers from 1999-

2002. Mean values of 2,4,5-TCP (0.2-0.6 mg/g creatinine) 

and 2,4,6-TCP (0.7-3.5 mg/g creatinine) were similar to the 

limit of detection for 2,4,5-TCP and to the median 2,4,6-

TCP values, respectively, for males in NHANES 1999-

2002 (Agramunt et al., 2003). In harbor workers exposed 

to chlorophenol-contaminated river silt, the median urinary 

2,4,6-TCP level, 0.36 mg/g creatinine, was about six times 

lower than the median urinary levels for males in this 

Report (Radon et al., 2004). Sawmill workers exposed to 

chlorophenol wood preservatives had urinary 2,4,6-TCP 

levels that were as much as 450 times higher than the 

median level among adults in the NHANES 1999-2000 

subsample (Pekari et al., 1991).

Finding a measurable amount of 2,4,5-TCP or 2,4,6-TCP in 

urine does not mean that the level of 2,4,5-TCP or 2,4,6-

TCP causes an adverse health effect. Biomonitoring studies 

on levels of 2,4,5-TCP and 2,4,6-TCP provide physicians 

and public health officials with reference values so that 

they can determine whether people have been exposed to 

higher levels of 2,4,5-TCP or 2,4,6-TCP than are found in 

the general population. Biomonitoring data will also help 

scientists plan and conduct research about 2,4,5-TCP or 

2,4,6-TCP exposure and health effects.

Urinary 2,4,6-Trichlorophenol 

Metabolite of Several Organochlorine Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 2.85 (2.55-3.18) 2.50 (2.40-2.70) 4.90 (3.80-7.70) 15.0 (7.80-25.0) 25.0 (15.0-44.0) 1989 

01-02 * 1.68 (<LOD-2.44) 5.95 (4.89-6.63) 10.8 (9.98-11.7) 14.9 (13.4-17.9) 2503 

Age group 

6-11 years 99-00 4.47 (3.36-5.95) 3.80 (2.70-6.40) 11.0 (4.80-20.0) 24.0 (14.0-38.0) 33.0 (20.5-46.0) 481

01-02 3.08 (2.52-3.76) 3.00 (1.91-4.32) 7.79 (5.73-9.99) 13.4 (10.6-17.3) 19.2 (14.1-25.3) 574

12-19 years 99-00 3.56 (3.00-4.23) 3.00 (2.60-3.70) 6.00 (4.30-11.0) 20.4 (9.60-37.0) 37.0 (20.0-54.0) 678

01-02 3.24 (2.74-3.84) 3.26 (2.33-4.40) 7.49 (6.45-9.40) 13.6 (11.0-18.2) 19.4 (17.3-26.6) 820

20-59 years 99-00 2.52 (2.23-2.85) 2.40 (2.10-2.45) 4.20 (3.50-5.30) 12.0 (6.00-21.0) 21.0 (11.0-41.0) 830

01-02 * < LOD 4.89 (3.70-6.28) 9.66 (8.72-10.7) 13.3 (11.8-15.2) 1109 

Gender 

Males 99-00 2.92 (2.58-3.31) 2.60 (2.40-2.90) 5.20 (3.90-8.10) 15.0 (8.48-26.0) 26.0 (15.0-38.0) 970

01-02 * 2.36 (1.70-3.04) 6.65 (5.98-7.53) 12.1 (10.8-13.1) 17.0 (13.6-22.2) 1178 

Females 99-00 2.78 (2.35-3.28) 2.40 (2.30-2.60) 4.80 (3.40-7.59) 16.0 (6.40-32.0) 25.0 (14.0-50.0) 1019 

01-02 * < LOD 4.69 (3.59-6.09) 9.75 (8.25-11.6) 13.3 (11.7-16.6) 1325 

Race/ethnicity 

Mexican Americans 99-00 2.70 (2.20-3.32) 2.70 (2.10-3.10) 4.90 (4.20-6.70) 15.0 (8.20-23.0) 23.0 (14.0-43.0) 694

01-02 * 2.07 (<LOD-3.23) 5.31 (3.95-6.54) 11.4 (8.51-12.8) 15.6 (12.6-19.8) 677

Non-Hispanic blacks 99-00 3.14 (2.40-4.12) 2.80 (2.10-3.40) 6.60 (3.40-14.0) 18.0 (9.30-33.0) 32.0 (16.0-68.0) 519

01-02 2.78 (2.18-3.53) 2.58 (1.32-4.02) 6.45 (5.09-7.67) 11.1 (8.87-14.9) 17.9 (11.8-24.7) 696

Non-Hispanic whites 99-00 2.74 (2.46-3.06) 2.45 (2.30-2.80) 4.60 (3.80-6.60) 13.0 (6.60-21.0) 21.0 (12.0-37.0) 602

01-02 * 1.57 (<LOD-2.20) 6.10 (5.01-6.65) 10.7 (9.67-12.3) 14.7 (13.3-17.9) 931

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 1.0 and 1.3. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 115

 Organochlorine Pesticides

Urinary 2,4,6-Trichlorophenol (creatinine corrected) 

Metabolite of Several Organochlorine Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 2.54 (2.30-2.81) 2.38 (2.14-2.68) 4.91 (3.83-6.49) 12.1 (8.67-17.0) 21.2 (13.6-31.5) 1989 

01-02 * 2.43 (<LOD-2.75) 4.38 (4.18-4.78) 8.33 (7.10-9.26) 11.6 (9.25-15.6) 2502 

Age group 

6-11 years 99-00 4.82 (3.87-6.00) 4.71 (3.41-6.53) 11.5 (7.63-15.3) 22.7 (14.1-32.6) 32.6 (22.7-36.8) 481

01-02 4.00 (3.28-4.87) 4.01 (3.29-4.81) 8.26 (6.16-10.4) 13.9 (9.51-21.5) 21.2 (12.9-64.1) 574

12-19 years 99-00 2.40 (2.08-2.78) 2.33 (1.95-2.68) 4.35 (3.13-6.00) 11.6 (6.94-13.6) 14.4 (11.3-23.6) 678

01-02 2.51 (2.18-2.90) 2.78 (2.09-3.17) 4.52 (3.83-5.92) 8.29 (6.81-9.89) 12.5 (8.73-22.8) 819

20-59 years 99-00 2.32 (2.04-2.63) 2.22 (1.89-2.56) 4.25 (3.38-5.63) 10.0 (6.72-16.9) 19.6 (10.9-34.4) 830

01-02 * < LOD 4.05 (3.66-4.38) 7.10 (6.43-7.72) 9.82 (8.53-11.9) 1109 

Gender 

Males 99-00 2.24 (1.99-2.53) 2.15 (1.82-2.42) 4.41 (3.56-5.88) 10.8 (7.04-16.4) 18.0 (11.5-28.5) 970

01-02 * 2.23 (1.91-2.65) 4.22 (3.77-4.73) 8.05 (6.70-9.17) 12.2 (8.79-17.7) 1178 

Females 99-00 2.88 (2.49-3.33) 2.63 (2.25-2.96) 5.53 (3.88-7.23) 13.3 (9.65-21.9) 25.1 (13.3-37.0) 1019 

01-02 * < LOD 4.58 (4.19-5.11) 8.40 (7.27-9.51) 10.9 (9.26-13.6) 1324 

Race/ethnicity 

Mexican Americans 99-00 2.43 (2.06-2.87) 2.50 (2.22-2.82) 5.44 (3.87-7.10) 10.8 (8.46-14.9) 18.4 (12.1-21.8) 694

01-02 * 2.22 (<LOD-2.88) 4.25 (3.47-5.76) 8.15 (6.21-11.1) 11.6 (9.63-13.9) 677

Non-Hispanic blacks 99-00 2.13 (1.65-2.76) 1.90 (1.60-2.52) 4.00 (2.76-8.02) 11.6 (5.32-19.7) 19.5 (10.9-29.5) 519

01-02 1.98 (1.55-2.52) 2.02 (1.48-2.76) 3.83 (3.17-4.88) 6.52 (5.50-8.06) 9.91 (7.14-13.2) 695

Non-Hispanic whites 99-00 2.59 (2.33-2.88) 2.42 (2.20-2.77) 4.87 (3.83-6.06) 11.2 (7.62-15.5) 19.6 (12.9-32.8) 602

01-02 * 2.63 (<LOD-2.88) 4.60 (4.29-4.98) 8.56 (7.22-9.65) 12.0 (9.25-17.1) 931

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 116 Fourth National Report on Human Exposure to Environmental Chemicals 

Organochlorine Pesticides 

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for chlorophenols [online]. July 1999. 

Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp107.

html. 4/21/09

Agramunt MC, Domingo A, Domingo JL, Corbella J. Monitoring 

internal exposure to metals and organic substances in workers at 

a hazardous waste incinerator after 3 years of operation. Toxicol 

Lett 2003;146:83-91.

Anderson HA, Falk C, Hanrahan L, Olson J, Burse VW, Needham 

LL, et al. Profiles of Great Lakes critical pollutants: a sentinel 

analysis of human blood and urine. The Great Lakes Consortium. 

Environ Health Perspect 1998;106(5):279-289.

Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German 

environmental survey 1998 (GerES III): environmental pollutants 

in the urine of the German population. Int J Hyg Environ Health 

2003; 206:15-24.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, 

et al. Pesticide residues in urine of adults living in the United 

States: reference range concentrations. Environ Res 1995;71:99-

108.

Hill RH Jr, To T, Holler JS, Fast DM, Smith SJ, Needham LL, et 

al. Residues of chlorinated phenols and phenoxy acid herbicides 

in the urine of Arkansas children. Arch Environ Contam Toxicol 

1989;18(4):469-474.

Kohli J, Jones D, Safe A. The metabolism of higher chlorinated 

benzene isomers. Can J Biochem 1976;54(3):203-208.

Pekari K, Luotamo M, Jarvisalo J, Lindroos L, Aitio A. Urinary 

excretion of chlorinated phenols in saw-mill workers. Int Arch 

Occup Environ Health 1991;63:57-62.

Radon K, Wegner R, Heinrich-Ramm R, Baur X, Poschadel 

B, Szadkowski D. Chlorophenol exposure in harbor workers 

exposed to river silt aerosols. Am J Ind Med 2004;45:440-445.

U. S. Environmental Protection Agency (U.S.EPA). The analysis 

of occurrence data from the first unregulated contaminant 

monitoring regulation (UCMR 1) in support of regulatory 

determinations for the second drinking water contaminant 

candidate list [online]. December 2006 Draft. Available at URL: 

http://www.epa.gov/safewater/ccl/pdfs/reg_determine2/report_

ccl2-reg2_ucmr1_occurrencereport.pdf. 5/19/09
Fourth National Report on Human Exposure to Environmental Chemicals 117

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

Organophosphorus Insecticides: Dialkyl 

Phosphate Metabolites

General Information

Organophosphorus insecticides, which are active against 

a broad spectrum of insects, have accounted for a large 

share of all insecticides used in the United States. 

Although organophosphorus insecticides are still used for 

insect control on many food crops, most residential uses 

have been phased out in the United States as a result of 

implementation of the Food Quality Protection Act of 1996. 

Certain organophosphorus insecticides (e.g., malathion, 

naled) are also registered for public health applications 

(e.g., mosquito control) in the United States. An estimated 

73 million pounds of organophosphorus insecticides (70% 

of all insecticides) were used in the United States in 2001, 

with usage declining 45% since 1980 (U.S. EPA, 2004). 

Approximately 40 organophosphorus insecticides in a 

wide variety of formulations are registered for use in the 

United States by the U.S. EPA. In general, the various 

organophosphorus insecticides demonstrate low vapor 

pressures (with some exceptions), slight to moderate water 

solubility, moderate to high soil binding, widely varying 

degrees of soil leaching or runoff potential, and a low 

persistence in the environment.

General population exposure to organophosphorus 

insecticides may occur by ingesting contaminated food 

and from hand-to-mouth contact with surfaces containing 

organophosphorus insecticides; less common routes 

include inhalation and dermal contact. In general, the 

organophosphorus insecticides have better gastrointestinal 

than dermal absorption. Mammalian elimination halflives can range from hours to weeks. The thiophosphate 

type organophosphorus insecticides (e.g., chlorpyriphos) 

are initially metabolized to the more toxic “oxon” form. 

Most organophosphorus insecticides undergo hydrolysis 

with excretion of major hydrolytic metabolites in the 

urine. Estimated intakes by the general population are 

usually considered below regulatory thresholds though 

concerns have been raised about some organophosphrus 

insecticides because of unique routes of exposures and 

intakes in infants and children (NRC, 1993). Farm workers, 

gardeners, florists, pesticide applicators, and manufacturers 

of these insecticides may have greater exposure than the 

general population. Many states have programs to monitor 

Pesticide

(CAS number)

Dimethylphosphate 

(813-79-5)

Dimethylthiophosphate 

(1112-38-5)

Dimethyldithiophosphate

(756-80-9) 

Diethylphosphate 

(598-02-7)

Diethylthiophosphate

(2465-65-8) 

Diethyldithiophosphate

(298-06-6)

Azinphos methyl • • •

Chlorethoxyphos • •

Chlorpyrifos • •

Chlorpyrifos methyl • •

Coumaphos • •

Dichlorvos (DDVP) •

Diazinon • •

Dicrotophos •

Dimethoate • • •

Disulfoton • • •

Ethion • • •

Fenitrothion • •

Fenthion • •

Isazaphos-methyl • •

Malathion • • •

Methidathion • • •

Methyl parathion • •

Naled •

Oxydemeton-methyl • •

Parathion • •

Phorate • • •

Phosmet • • •

Pirimiphos-methyl • •

Sulfotepp • •

Temephos • •

Terbufos • • •

Tetrachlorvinphos •
 118 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

cholinesterase activity in the blood of pesticide applicators 

as part of monitoring exposure to organophosphorus 

insecticides. The U.S. FDA, USDA, U.S. EPA, and OSHA 

have developed criteria on allowable levels of these 

chemicals in foods, the environment, and the workplace.

The acute high dose effects of the organophosphorus 

insecticides from intentional and unintentional overdoses 

or from high-dose worker exposures are well known and 

include neurological dysfunction that results from the 

inhibition of the enzyme acetylcholinesterase leading to 

excess acetylcholine in the central and peripheral nervous 

systems. Acute symptoms include nausea, vomiting, 

cholinergic effects, weakness, paralysis, and seizures. 

Mild to severe peripheral neuropathies and residual 

deficits in neurocognitive functioning can persist following 

acute poisonings (London et al., 1998; Rosenstock et al., 

1991; Savage et al., 1988). Chronic exposures studied in 

farmers and insecticide applicators, who have neither 

past acute poisoning or significant reduction in blood 

cholinesterase activity, have shown possible subtle or 

subclinical neurological effects, though various study 

results are inconsistent (Albers et al., 2004; Daniell et al., 

1992.; Engel et al., 1998; Farahat et al., 2003; Fiedler et 

al., 1997; Jamal et al., 2002; Maizlish et al., 1987; PeirisJohn et al., 2002; Pilkington et al., 2001; Rodnitzky et al., 

1975; Rothlein et al., 2006; Stephens et al., 1995; Stokes 

et al., 1995; Young et al., 2005). Animal studies at high 

doses generally demonstrate the effects of inhibition 

of acetylcholinesterase mentioned above for acute 

poisoning in humans, as well as mechanistically-related 

neurodevelopmental and reproductive effects (Astroff et 

al., 1998a and 1998b; Prendergast et al., 1998). Few animal 

studies have addressed the potential for low environmental 

doses to produce non-cholinergic effects (i.e., without 

inhibition of acetylcholinesterase). Additional information 

about insecticides is available from U.S. EPA at: http://

www.epa.gov/pesticides/ and from ATSDR at: http://www.

atsdr.cdc.gov/toxpro2.html.

About 75% of registered organophosphorus insecticides are 

metabolized in the body to measurable dialkyl phosphate 

metabolites. The dialkyl phosphate metabolites do not 

inhibit acetylcholinesterase and are not considered toxic, but 

are regarded as markers of exposure to organophosphorus 

insecticides. Dialkyl phosphate metabolites can be present 

in urine after low level exposures to organophosphorus 

insecticides that do not cause clinical symptoms or inhibition 

of cholinesterase activity (Davies and Peterson, 1997; 

Franklin et al., 1981). Measurement of these metabolites 

reflects recent exposure, predominantly in the previous few 

days. Dialkyl phosphates may also occur in the environment 

as a result of degradation of organophosphorus insecticides 

(Lu et al., 2005), and therefore, the presence in a person’s 

urine may reflect exposure to the metabolite itself.

Generally, six urinary dialkyl phosphate metabolites of 

organophosphorus insecticides are measured in this Report

and other research studies: dimethylphosphate (DMP); 

dimethylthiophosphate (DMTP); dimethyldithiophosphate 

(DMDTP); diethylphosphate (DEP); diethylthiophosphate 

(DETP); and diethyldithiophosphate (DEDTP). The 

table shows the six urinary metabolites and the parent 

organophosphorus insecticides responsible for these 

metabolites. For example, chlorpyrifos is metabolized to 

both diethylphosphate and diethythiophosphate. Each of the 

six urinary dialkyl phosphate metabolites can be produced 

from the metabolism of more than one organophosphorus 

insecticide. Therefore, the presence of one or more dialkyl 

phosphate metabolites without additional information 

cannot be linked to exposure to a specific organophosphorus 

insecticide.

Biomonitoring Information

Urinary dialkyl phosphate levels reflect recent exposure. In 

nationally representative subsamples of the U.S. population 

from NHANES 1999-2000 and 2001-2002 (CDC, 2005), 

geometric mean urinary dialkyl phosphate levels were 

generally lower than levels reported in smaller studies of 

children and adults in Italy and Germany (Aprea et al., 

2000; Aprea et al., 1996; Heudorf and Angerer, 2001; 

Saieva et al., 2004). In these studies and the NHANES 

subsamples, children have slightly higher levels than adults. 

Diet influences the measured levels of urinary dialkyl 

phosphates. For example, subjects ingesting “organicallygrown” foods were shown to have lower levels of urinary 

dialkyl phosphates than subjects eating a conventional 

diet (Curl et al., 2003). Also, urinary levels in children of 

farm workers and non-farm workers have been reported 

to correlate weakly with environmental dust levels of 

particular insecticides in some, but not all, studies (Bouvier 

et al., 2006; Curl et al., 2003; Rothlein et al., 2006).

Measurements of dialkyl phosphates in urine have been 

used to document exposure of farmers, agricultural workers, 

pest-control workers, and others to organophosphorus 

insecticides (Davies and Peterson, 1997; Franklin et al., 

1981; Krieger and Dinoff, 2000; Takamiya, 1994). In 

some of these occupational studies, reported levels of 

urinary dialkyl phosphates may exceed levels seen in the 

general population by up to fiftyfold, though in general, 

worker levels are only moderately higher. Urinary levels 

of dialkyl phosphate metabolites vary with the type of 

field application, seasonal use of the parent insecticide, 

and demonstrate substantial variability when measured 
Fourth National Report on Human Exposure to Environmental Chemicals 119

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

over multiple times of day and over multiple days, which 

may reflect changes in exposure, collection timing, and 

elimination kinetics (Kissel et al., 2005; Koch et al., 2002; 

Lambert et al., 2005; Petchuay et al., 2006).

Children and pregnant family members of farm workers 

were reported to have median levels of many urinary 

dialkyl phosphates that were either similar or slightly 

higher (Arcury et al., 2006; Bradman et al., 2005) than 

those presented in U.S. representative subsamples from 

NHANES 1999-2000 and 2001-2002 (CDC, 2005), 

except for one study in which DMTP levels were up to 

fourteenfold higher depending on the season and the type 

of crop application (Lambert et al., 2005). Also, estimates 

of dose or intake calculated from urinary dialkyl phosphate 

levels in studies of pregnant women in one agricultural 

community (Castorina et al., 2003) and in another study 

of workers exposed on reentry to treated orchards (Fenske 

et al., 2003) generally did not exceed doses considered to 

be safe. Estimates of dose or intake for the general U.S. 

population as calculated from urinary dialkyl phosphate 

measurements were below environmental dose estimates 

based on multiple routes of exposure (Duggan et al., 2003).

Information is limited with regard to associations between 

levels of urinary dialkyl phosphates and any health effects. 

Summed levels of urinary dialkyl phosphates in prenatal 

samples from mothers of neonates living in an agricultural 

community were associated with subtle changes in one of 

seven domains of neurophysiologic neonatal testing during 

one restricted postnatal period of time (Young et al., 2005). 

In a study of farm workers, median urinary levels of DMTP 

and DMDTP were more than twentyfold higher than median 

levels in the U.S. population (CDC, 2005), and these higher 

levels were associated with a few subtle neurobehavioral 

test results (Rothlein et al., 2006).

Finding a measurable amount of dialkyl phosphate 

metabolites in urine does not mean that the level of dialkyl 

phosphate metabolites causes an adverse health effect. 

Biomonitoring studies of dialkyl phosphate metabolites 

provide physicians and public health officials with reference 

values so that they can determine whether or not people 

have been exposed to higher levels of organophosphorus 

pesticides than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.
 120 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

Urinary Diethylphosphate (DEP) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 1.03 (.670-1.58) 1.20 (.750-1.70) 3.20 (2.30-4.80) 7.60 (5.00-12.0) 13.0 (7.70-23.0) 1949 

01-02 * < LOD 2.76 (2.42-3.16) 6.33 (5.68-7.46) 11.4 (9.15-12.5) 2520 

03-04 * < LOD 4.54 (3.38-5.97) 10.2 (9.00-12.1) 15.7 (14.1-17.2) 1931 

Age group 

6-11 years 99-00 1.32 (.757-2.29) 1.50 (.860-2.60) 4.50 (2.10-7.90) 11.0 (4.80-24.0) 16.0 (8.50-36.0) 471

01-02 * .290 (<LOD-1.04) 3.45 (2.36-4.47) 9.56 (6.33-18.0) 20.0 (9.44-38.2) 576

03-04 * < LOD 5.13 (2.48-7.94) 10.9 (8.08-15.9) 16.1 (10.9-18.5) 308

12-19 years 99-00 1.21 (.758-1.94) 1.40 (.970-2.10) 3.70 (2.40-5.50) 8.00 (4.70-19.0) 20.0 (8.00-27.0) 664

01-02 * < LOD 2.86 (1.96-3.95) 7.58 (5.71-9.15) 11.0 (9.35-12.4) 822

03-04 * .530 (<LOD-2.32) 5.80 (4.34-7.67) 14.8 (9.12-19.8) 20.8 (14.8-32.7) 701

20-59 years 99-00 .955 (.623-1.47) 1.10 (.700-1.60) 3.00 (1.80-4.80) 7.30 (4.70-11.0) 11.0 (6.80-22.0) 814

01-02 * < LOD 2.71 (2.34-3.12) 5.79 (5.05-7.21) 10.4 (7.43-12.3) 1122 

03-04 * < LOD 4.37 (3.02-5.81) 9.74 (8.35-11.3) 14.2 (11.5-16.2) 922

Gender 

Males 99-00 1.11 (.717-1.73) 1.20 (.810-1.70) 3.80 (2.50-5.00) 8.00 (5.00-19.0) 19.0 (7.20-30.0) 952

01-02 * < LOD 3.13 (2.44-3.53) 6.99 (5.79-7.80) 11.5 (8.98-12.4) 1187 

03-04 * < LOD 4.85 (3.26-6.51) 11.1 (9.56-13.8) 17.2 (14.2-20.8) 928

Females 99-00 .954 (.599-1.52) 1.20 (.620-1.70) 2.90 (1.90-4.80) 7.50 (4.60-11.0) 11.0 (7.40-16.0) 997

01-02 * .290 (<LOD-.780) 2.58 (2.17-3.02) 5.93 (4.55-8.19) 10.4 (7.27-15.1) 1333 

03-04 * < LOD 4.39 (3.23-5.97) 9.39 (8.07-10.8) 13.5 (11.3-15.9) 1003 

Race/ethnicity 

Mexican Americans 99-00 1.22 (.740-2.01) 1.20 (.840-1.80) 4.10 (2.20-7.00) 11.0 (6.40-19.0) 18.0 (12.0-27.0) 672

01-02 * .600 (<LOD-1.63) 3.10 (2.27-3.72) 6.26 (5.00-7.82) 11.2 (7.82-12.3) 678

03-04 * 1.08 (<LOD-2.81) 5.58 (3.57-7.61) 10.8 (8.35-16.1) 17.7 (12.0-28.4) 473

Non-Hispanic blacks 99-00 1.56 (1.13-2.14) 1.60 (1.40-1.80) 4.30 (2.90-5.80) 10.0 (5.60-18.0) 18.0 (8.00-27.0) 509

01-02 * .890 (<LOD-2.42) 4.61 (3.30-6.52) 10.2 (7.40-14.0) 15.4 (9.93-24.2) 696

03-04 * .830 (<LOD-3.28) 6.83 (5.26-8.80) 12.2 (9.86-15.6) 16.2 (14.1-23.2) 578

Non-Hispanic whites 99-00 .981 (.579-1.66) 1.10 (.490-2.10) 3.30 (2.20-4.90) 7.70 (4.70-14.0) 14.0 (7.60-25.0) 595

01-02 * < LOD 2.44 (2.08-2.91) 5.56 (4.55-6.89) 10.2 (7.52-11.9) 948

03-04 * < LOD 4.16 (2.98-5.81) 9.74 (8.40-11.6) 14.8 (12.5-17.2) 752

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.2, 0.2, and 0.1, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 121

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

Urinary Diethylphosphate (DEP) (creatinine corrected) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .924 (.608-1.41) .920 (.570-1.40) 2.73 (1.68-4.60) 7.94 (4.40-12.2) 12.2 (8.00-19.6) 1949 

01-02 * < LOD 2.39 (2.06-2.69) 5.23 (4.64-5.98) 8.53 (6.94-10.2) 2519 

03-04 * < LOD 4.42 (3.45-5.74) 9.02 (7.45-11.2) 13.2 (10.5-16.1) 1928 

Age group 

6-11 years 99-00 1.43 (.870-2.34) 1.47 (1.02-2.41) 3.94 (2.20-8.57) 10.5 (4.55-20.8) 16.6 (10.5-32.7) 471

01-02 * .890 (<LOD-1.76) 4.02 (2.87-5.25) 8.85 (6.88-15.6) 18.4 (9.40-28.8) 576

03-04 * < LOD 6.10 (3.79-9.03) 11.9 (9.54-15.2) 16.1 (11.9-28.3) 308

12-19 years 99-00 .818 (.533-1.26) .790 (.560-1.25) 2.35 (1.37-3.75) 5.44 (2.82-14.4) 12.4 (4.66-34.2) 664

01-02 * < LOD 2.05 (1.54-2.67) 4.40 (3.40-5.28) 7.28 (5.28-9.75) 821

03-04 * .440 (<LOD-2.05) 4.47 (3.90-5.43) 10.1 (7.10-13.5) 14.7 (9.82-26.5) 699

20-59 years 99-00 .883 (.574-1.36) .860 (.500-1.35) 2.66 (1.54-4.95) 7.37 (4.32-12.1) 12.1 (8.00-17.5) 814

01-02 * < LOD 2.28 (2.01-2.56) 4.75 (3.92-5.83) 7.37 (5.93-9.72) 1122 

03-04 * < LOD 4.29 (2.98-5.71) 8.34 (6.09-11.3) 11.9 (9.02-14.7) 921

Gender 

Males 99-00 .855 (.566-1.29) .820 (.510-1.34) 2.61 (1.76-4.03) 7.69 (4.41-12.1) 12.2 (6.94-23.8) 952

01-02 * < LOD 2.04 (1.71-2.52) 4.31 (3.62-5.00) 6.88 (5.60-9.42) 1187 

03-04 * < LOD 4.03 (2.81-5.30) 8.34 (6.69-10.2) 12.1 (9.31-14.8) 927

Females 99-00 .996 (.620-1.60) .960 (.540-1.62) 2.81 (1.45-5.85) 8.00 (4.00-13.0) 12.1 (6.67-19.6) 997

01-02 * .750 (<LOD-1.27) 2.66 (2.24-3.23) 6.28 (4.75-7.37) 9.57 (6.61-13.6) 1332 

03-04 * < LOD 4.87 (3.82-6.50) 9.83 (7.54-11.9) 13.8 (10.5-20.3) 1001 

Race/ethnicity 

Mexican Americans 99-00 1.09 (.633-1.89) 1.05 (.650-1.98) 3.78 (2.11-6.46) 9.84 (5.66-15.7) 15.7 (8.61-29.0) 672

01-02 * .890 (<LOD-1.38) 2.38 (1.79-3.13) 5.00 (4.04-6.53) 7.66 (5.88-10.9) 678

03-04 * .960 (<LOD-2.67) 4.43 (3.03-6.69) 9.80 (7.56-13.3) 16.6 (9.94-22.5) 472

Non-Hispanic blacks 99-00 1.07 (.773-1.47) 1.18 (.830-1.54) 2.61 (1.89-3.47) 5.98 (3.94-9.56) 11.9 (5.98-22.2) 509

01-02 * .780 (<LOD-1.56) 2.80 (2.40-3.40) 7.19 (4.90-8.84) 9.75 (7.82-14.9) 695

03-04 * .710 (<LOD-1.98) 4.14 (3.46-5.09) 7.77 (6.57-10.5) 11.7 (10.5-13.4) 577

Non-Hispanic whites 99-00 .932 (.549-1.58) .900 (.430-1.68) 2.87 (1.51-5.88) 8.57 (4.40-14.4) 13.0 (8.21-23.8) 595

01-02 * < LOD 2.30 (1.92-2.74) 4.95 (3.93-5.93) 7.80 (6.15-10.7) 948

03-04 * < LOD 4.47 (3.37-5.80) 9.03 (7.53-11.3) 12.1 (10.1-15.7) 751

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 122 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

Urinary Dimethylphosphate (DMP) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * .740 (<LOD-1.40) 2.90 (2.10-4.00) 7.90 (6.20-8.90) 14.0 (10.0-19.0) 1949 

01-02 * < LOD 3.25 (2.77-3.67) 8.22 (6.95-9.27) 13.4 (10.9-15.6) 2519 

03-04 * < LOD 3.99 (3.29-4.96) 9.17 (7.33-11.9) 14.8 (12.4-17.8) 1965 

Age group 

6-11 years 99-00 1.58 (1.15-2.18) 1.10 (.580-2.20) 4.40 (2.80-6.80) 10.0 (7.80-21.0) 22.0 (15.0-33.0) 471

01-02 * .970 (<LOD-2.00) 5.04 (3.31-7.66) 12.2 (9.10-15.1) 18.3 (12.6-41.7) 576

03-04 * < LOD 4.53 (3.34-5.96) 11.0 (5.62-17.9) 16.2 (7.46-28.3) 310

12-19 years 99-00 * .670 (<LOD-1.80) 3.80 (2.50-4.90) 9.90 (6.20-18.0) 22.0 (13.0-29.0) 664

01-02 * .670 (<LOD-1.31) 4.27 (3.41-5.35) 9.27 (7.80-12.3) 14.7 (11.8-21.3) 822

03-04 * 1.20 (<LOD-2.27) 4.61 (3.47-6.72) 10.9 (7.90-15.0) 20.9 (12.5-26.8) 717

20-59 years 99-00 * .680 (<LOD-1.30) 2.70 (1.80-3.70) 6.60 (5.70-8.10) 9.70 (8.80-14.0) 814

01-02 * < LOD 2.95 (2.35-3.41) 6.95 (5.80-8.82) 11.5 (9.66-13.7) 1121 

03-04 * < LOD 3.75 (2.84-4.88) 8.52 (6.86-10.7) 14.1 (10.8-17.5) 938

Gender 

Males 99-00 * .670 (<LOD-1.30) 2.90 (2.20-4.00) 7.90 (6.00-9.30) 18.0 (10.0-24.0) 952

01-02 * < LOD 3.40 (2.49-4.30) 8.22 (6.67-10.3) 12.6 (10.9-14.7) 1187 

03-04 * < LOD 3.89 (2.97-4.89) 8.14 (6.34-10.4) 15.1 (10.8-20.4) 946

Females 99-00 * .790 (<LOD-1.60) 2.90 (2.00-4.20) 7.80 (5.70-9.00) 11.0 (9.00-18.0) 997

01-02 * < LOD 3.06 (2.59-3.67) 8.34 (6.70-9.64) 13.7 (10.9-17.2) 1332 

03-04 * < LOD 4.18 (3.24-5.73) 10.3 (7.39-13.6) 14.8 (12.6-19.6) 1019 

Race/ethnicity 

Mexican Americans 99-00 * 1.10 (<LOD-1.80) 3.80 (2.70-5.30) 9.60 (6.00-16.0) 16.0 (8.90-31.0) 672

01-02 * .670 (<LOD-1.51) 3.24 (2.46-4.27) 9.28 (7.10-10.7) 14.4 (10.7-21.0) 678

03-04 * < LOD 4.37 (3.15-6.88) 10.3 (6.92-17.8) 23.3 (9.61-32.5) 498

Non-Hispanic blacks 99-00 1.42 (1.16-1.74) 1.00 (.650-1.50) 3.60 (2.50-5.50) 8.90 (6.90-15.0) 21.0 (14.0-24.0) 509

01-02 * .910 (<LOD-2.29) 5.45 (3.81-6.78) 11.5 (8.77-14.9) 19.4 (14.1-23.3) 695

03-04 * < LOD 5.12 (4.11-6.37) 10.5 (8.31-12.0) 14.3 (11.7-19.6) 579

Non-Hispanic whites 99-00 * < LOD 2.90 (1.80-4.20) 7.90 (5.90-9.00) 11.0 (9.00-18.0) 595

01-02 * < LOD 3.01 (2.34-3.50) 7.39 (5.98-9.22) 12.3 (9.63-14.6) 948

03-04 * < LOD 3.75 (3.00-4.92) 8.35 (6.22-12.9) 14.6 (10.8-20.4) 757

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.58, 0.5, and 0.5, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 123

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

Urinary Dimethylphosphate (DMP) (creatinine corrected) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * .810 (<LOD-1.15) 2.93 (2.11-3.92) 8.50 (6.96-10.4) 16.1 (13.3-17.6) 1949 

01-02 * < LOD 3.00 (2.59-3.33) 7.83 (6.47-9.04) 12.7 (10.3-15.0) 2518 

03-04 * < LOD 3.86 (3.02-4.95) 9.54 (7.93-10.6) 14.6 (12.5-17.6) 1962 

Age group 

6-11 years 99-00 1.71 (1.29-2.27) 1.38 (.890-2.38) 4.48 (2.88-7.89) 16.7 (8.21-21.2) 22.1 (19.2-30.1) 471

01-02 * 1.93 (<LOD-2.97) 5.99 (4.32-8.28) 12.9 (9.34-18.5) 20.6 (13.3-34.9) 576

03-04 * < LOD 6.87 (3.79-9.00) 13.9 (9.68-19.4) 19.6 (13.9-25.9) 310

12-19 years 99-00 * .590 (<LOD-.950) 2.28 (1.70-2.80) 7.78 (4.16-14.4) 16.0 (8.70-35.3) 664

01-02 * .910 (<LOD-1.27) 3.29 (2.75-3.78) 6.29 (5.51-7.30) 9.83 (7.94-14.2) 821

03-04 * 1.00 (<LOD-1.68) 4.16 (3.37-5.07) 8.81 (7.78-10.2) 12.7 (10.3-17.7) 715

20-59 years 99-00 * .760 (<LOD-1.12) 2.88 (1.89-3.99) 8.11 (5.89-10.3) 14.6 (10.4-16.8) 814

01-02 * < LOD 2.55 (2.05-3.03) 6.92 (5.85-8.00) 11.5 (9.38-13.6) 1121 

03-04 * < LOD 3.77 (2.72-4.55) 8.78 (6.68-10.5) 13.5 (11.2-15.6) 937

Gender 

Males 99-00 * .620 (<LOD-.940) 2.38 (1.86-3.18) 7.58 (4.64-11.6) 15.2 (9.74-19.5) 952

01-02 * < LOD 2.61 (2.07-3.07) 6.25 (4.82-8.42) 10.5 (8.28-12.7) 1187 

03-04 * < LOD 2.95 (2.23-3.91) 7.93 (6.33-10.4) 12.5 (10.4-15.4) 945

Females 99-00 * 1.00 (<LOD-1.71) 3.63 (2.30-5.19) 9.12 (7.82-11.7) 16.4 (11.7-19.7) 997

01-02 * < LOD 3.43 (2.74-4.27) 9.00 (7.51-10.1) 15.0 (11.9-17.8) 1331 

03-04 * < LOD 5.00 (3.79-6.30) 10.1 (8.27-13.4) 16.0 (13.0-19.6) 1017 

Race/ethnicity 

Mexican Americans 99-00 * 1.06 (<LOD-1.55) 3.89 (2.54-5.45) 9.41 (7.69-11.5) 16.7 (11.7-23.6) 672

01-02 * .920 (<LOD-1.27) 3.03 (2.52-3.72) 8.03 (6.09-11.3) 14.6 (11.4-16.2) 678

03-04 * < LOD 4.14 (2.44-6.30) 12.3 (7.39-17.6) 19.5 (15.3-21.8) 497

Non-Hispanic blacks 99-00 .973 (.780-1.21) .690 (.530-1.06) 2.67 (1.89-3.77) 7.07 (5.09-11.4) 14.0 (10.6-19.1) 509

01-02 * .850 (<LOD-1.34) 3.36 (2.68-4.29) 7.63 (6.25-9.45) 13.2 (9.50-17.2) 694

03-04 * < LOD 3.38 (2.75-3.95) 6.94 (5.53-8.42) 10.8 (8.42-19.2) 578

Non-Hispanic whites 99-00 * < LOD 3.15 (1.97-4.32) 8.73 (5.89-13.3) 15.8 (10.0-21.2) 595

01-02 * < LOD 2.77 (2.20-3.37) 8.00 (5.91-9.86) 12.9 (9.85-17.7) 948

03-04 * < LOD 3.89 (3.01-5.54) 9.67 (7.96-11.2) 14.6 (11.4-18.2) 756

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 124 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

Urinary Diethylthiophosphate (DETP) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * .500 (<LOD-.690) .760 (.620-1.10) 1.40 (1.10-1.80) 2.20 (1.70-2.80) 1949 

01-02 .457 (.353-.592) .570 (.390-.880) 1.50 (1.25-1.79) 2.48 (2.22-3.04) 3.94 (3.17-4.95) 2519 

03-04 * < LOD .830 (.690-.950) 1.77 (1.42-2.31) 2.80 (2.31-3.78) 1905 

Age group 

6-11 years 99-00 * .600 (<LOD-.810) .910 (.720-1.30) 1.70 (1.20-3.20) 3.20 (1.70-7.30) 471

01-02 .453 (.350-.585) .550 (.350-.850) 1.58 (1.33-2.04) 2.75 (2.22-3.38) 4.08 (2.95-5.16) 575

03-04 * < LOD .820 (.580-.970) 1.45 (1.05-2.16) 2.18 (1.45-4.13) 296

12-19 years 99-00 * .210 (<LOD-.710) .780 (.600-1.20) 1.50 (1.20-2.30) 2.30 (1.60-4.30) 664

01-02 .505 (.388-.657) .690 (.440-.960) 1.61 (1.32-1.94) 2.57 (2.23-3.39) 4.08 (2.73-5.86) 822

03-04 * .260 (<LOD-.400) .930 (.750-1.13) 2.14 (1.75-2.89) 3.27 (2.69-4.83) 690

20-59 years 99-00 * .490 (<LOD-.670) .740 (.600-.930) 1.30 (.990-1.80) 2.00 (1.50-2.60) 814

01-02 .449 (.340-.592) .540 (.380-.880) 1.45 (1.19-1.79) 2.46 (2.11-3.17) 3.83 (2.96-5.34) 1122 

03-04 * < LOD .800 (.650-.960) 1.76 (1.37-2.32) 2.65 (2.31-3.89) 919

Gender 

Males 99-00 * .510 (<LOD-.700) .790 (.680-1.10) 1.50 (1.20-2.20) 2.70 (1.90-4.10) 952

01-02 .459 (.359-.587) .570 (.390-.860) 1.50 (1.30-1.78) 2.54 (2.16-3.34) 3.83 (2.76-6.15) 1187 

03-04 * < LOD .880 (.720-1.01) 2.20 (1.54-2.50) 2.95 (2.36-4.29) 907

Females 99-00 * < LOD .720 (.570-1.00) 1.30 (.910-1.60) 1.70 (1.30-3.20) 997

01-02 .455 (.336-.618) .550 (.380-.940) 1.48 (1.14-1.89) 2.45 (2.11-3.35) 3.94 (2.68-5.49) 1332 

03-04 * < LOD .780 (.590-.970) 1.47 (1.22-2.00) 2.57 (1.87-3.78) 998

Race/ethnicity 

Mexican Americans 99-00 * .570 (<LOD-.780) .840 (.740-.980) 1.50 (1.20-1.90) 2.20 (2.00-2.90) 672

01-02 .549 (.398-.759) .710 (.460-.960) 1.40 (1.01-1.98) 2.63 (1.98-3.47) 3.98 (2.74-5.21) 678

03-04 * .240 (<LOD-.380) .960 (.680-1.54) 2.22 (1.46-3.83) 3.97 (2.22-8.80) 478

Non-Hispanic blacks 99-00 .343 (.201-.584) .570 (<LOD-.750) .820 (.690-1.20) 1.80 (1.30-3.20) 3.60 (2.00-4.80) 509

01-02 .749 (.592-.949) 1.18 (.740-1.49) 1.86 (1.77-2.03) 3.55 (3.01-3.91) 5.27 (3.89-6.74) 695

03-04 .467 (.382-.570) .450 (<LOD-.730) 1.09 (.930-1.26) 2.32 (1.59-2.88) 3.26 (2.41-5.46) 553

Non-Hispanic whites 99-00 * .160 (<LOD-.700) .740 (.580-1.10) 1.30 (.960-1.90) 1.90 (1.50-2.80) 595

01-02 .425 (.303-.597) .510 (.280-.930) 1.46 (1.10-1.83) 2.41 (2.05-3.17) 3.73 (2.59-6.15) 948

03-04 * < LOD .710 (.560-.910) 1.73 (1.29-2.31) 2.64 (1.96-3.89) 745

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.09, 0.1, and 0.2, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 125

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

Urinary Diethylthiophosphate (DETP) (creatinine corrected) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * .250 (<LOD-.480) .710 (.460-1.07) 1.72 (1.17-2.32) 2.64 (2.08-3.06) 1949 

01-02 .453 (.348-.590) .520 (.330-.760) 1.33 (1.04-1.66) 2.84 (2.22-3.76) 4.61 (3.42-6.65) 2518 

03-04 * < LOD .700 (.580-.830) 1.47 (1.16-2.04) 2.62 (2.00-3.72) 1903 

Age group 

6-11 years 99-00 * .470 (<LOD-.870) 1.08 (.800-1.32) 1.75 (1.44-2.36) 2.45 (2.04-5.32) 471

01-02 .591 (.471-.742) .640 (.400-1.05) 1.63 (1.31-1.94) 3.22 (2.72-4.16) 5.70 (3.84-6.80) 575

03-04 * < LOD .870 (.590-1.09) 1.57 (1.08-2.67) 2.67 (1.57-4.05) 296

12-19 years 99-00 * .180 (<LOD-.400) .510 (.320-.820) 1.07 (.720-1.61) 1.97 (1.07-3.92) 664

01-02 .393 (.300-.515) .530 (.310-.740) 1.23 (.980-1.53) 2.19 (1.61-3.07) 3.14 (2.25-3.97) 821

03-04 * .300 (<LOD-.350) .640 (.560-.730) 1.49 (1.16-1.60) 1.97 (1.57-2.43) 689

20-59 years 99-00 * .250 (<LOD-.460) .680 (.440-1.08) 1.79 (1.08-2.39) 2.75 (2.02-3.22) 814

01-02 .447 (.335-.597) .490 (.320-.740) 1.32 (.990-1.71) 2.87 (2.08-3.95) 4.69 (3.20-7.81) 1122 

03-04 * < LOD .700 (.550-.880) 1.47 (1.11-2.23) 2.82 (2.02-3.80) 918

Gender 

Males 99-00 * .270 (<LOD-.470) .670 (.520-.840) 1.34 (1.08-2.17) 2.67 (1.67-3.23) 952

01-02 .372 (.285-.485) .460 (.270-.690) 1.11 (.940-1.33) 2.05 (1.55-3.11) 3.38 (2.47-4.71) 1187 

03-04 * < LOD .590 (.500-.760) 1.42 (.950-2.07) 2.62 (1.61-3.97) 906

Females 99-00 * < LOD .790 (.380-1.50) 1.89 (1.07-2.52) 2.52 (1.89-3.75) 997

01-02 .552 (.412-.739) .580 (.370-.910) 1.60 (1.18-2.42) 3.70 (2.77-4.99) 6.57 (3.92-8.82) 1331 

03-04 * < LOD .750 (.660-.900) 1.50 (1.22-2.23) 2.60 (2.08-3.98) 997

Race/ethnicity 

Mexican Americans 99-00 * .330 (<LOD-.790) .830 (.550-1.20) 1.69 (1.20-2.43) 2.71 (1.75-3.78) 672

01-02 .509 (.377-.688) .560 (.380-.840) 1.28 (1.03-1.67) 2.55 (1.77-3.72) 3.72 (2.58-6.30) 678

03-04 * .310 (<LOD-.390) .750 (.480-1.22) 1.92 (1.22-3.43) 3.66 (2.02-6.17) 478

Non-Hispanic blacks 99-00 .234 (.136-.403) .310 (<LOD-.580) .720 (.510-.850) 1.39 (1.03-2.10) 2.91 (1.49-4.24) 509

01-02 .535 (.444-.645) .710 (.550-.920) 1.43 (1.32-1.60) 2.73 (2.30-2.98) 4.00 (3.05-4.99) 694

03-04 .305 (.253-.368) .280 (<LOD-.380) .640 (.540-.820) 1.41 (.930-1.79) 2.13 (1.38-3.90) 552

Non-Hispanic whites 99-00 * .230 (<LOD-.550) .710 (.390-1.22) 1.88 (1.05-2.58) 2.64 (2.08-3.07) 595

01-02 .448 (.318-.630) .510 (.270-.800) 1.38 (1.00-1.88) 3.08 (2.29-4.23) 5.77 (3.42-8.44) 948

03-04 * < LOD .700 (.560-.840) 1.45 (1.06-2.08) 2.58 (1.73-3.97) 744

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 126 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

Urinary Dimethylthiophosphate (DMTP) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 1.82 (1.36-2.44) 2.70 (1.40-4.10) 11.0 (8.40-16.0) 38.0 (25.0-41.0) 48.0 (38.0-62.0) 1948 

01-02 * .470 (<LOD-1.41) 4.02 (2.92-5.70) 16.2 (12.4-22.9) 32.6 (26.6-45.3) 2518 

03-04 2.10 (1.83-2.40) 1.90 (1.61-2.26) 5.65 (4.63-6.80) 17.3 (14.5-20.1) 31.1 (26.5-40.0) 1965 

Age group 

6-11 years 99-00 2.72 (1.93-3.85) 4.20 (2.50-7.20) 20.0 (13.0-29.0) 40.0 (38.0-52.0) 62.0 (40.0-92.0) 471

01-02 * 1.46 (.600-2.69) 8.33 (5.75-14.0) 28.4 (19.7-41.4) 45.7 (28.5-74.5) 575

03-04 2.79 (2.25-3.45) 2.67 (1.81-3.88) 6.95 (5.64-8.58) 19.4 (10.5-27.4) 30.9 (19.4-76.5) 310

12-19 years 99-00 2.53 (1.64-3.92) 3.70 (1.70-6.80) 16.0 (11.0-31.0) 38.0 (33.0-58.0) 69.0 (38.0-260) 664

01-02 * 1.04 (<LOD-2.12) 4.83 (3.35-6.48) 20.8 (12.2-27.9) 34.9 (23.6-54.7) 822

03-04 2.21 (1.81-2.70) 1.83 (1.46-2.16) 5.91 (4.04-8.78) 18.7 (12.2-33.9) 47.1 (22.2-80.8) 717

20-59 years 99-00 1.59 (1.17-2.16) 2.30 (.830-3.80) 9.10 (7.10-13.0) 38.0 (19.0-39.0) 39.0 (38.0-58.0) 813

01-02 * < LOD 3.32 (2.29-4.96) 13.6 (9.50-20.0) 30.0 (20.5-45.3) 1121 

03-04 1.98 (1.71-2.30) 1.78 (1.48-2.18) 5.11 (4.31-6.53) 16.7 (12.1-20.8) 28.5 (24.1-40.0) 938

Gender 

Males 99-00 2.10 (1.48-2.98) 3.50 (2.20-4.80) 14.0 (8.00-24.0) 38.0 (21.0-49.0) 42.0 (38.0-53.0) 952

01-02 * .610 (<LOD-1.42) 4.21 (3.07-5.97) 18.3 (12.2-27.2) 31.1 (25.0-43.3) 1187 

03-04 2.13 (1.80-2.53) 1.94 (1.49-2.44) 6.09 (4.44-7.23) 16.1 (10.9-21.1) 26.8 (22.0-41.6) 946

Females 99-00 1.59 (1.23-2.06) 2.00 (.690-3.60) 9.70 (7.30-14.0) 38.0 (26.0-39.0) 52.0 (38.0-110) 996

01-02 * < LOD 3.76 (2.50-5.71) 15.9 (10.6-22.0) 34.3 (23.2-47.3) 1331 

03-04 2.06 (1.74-2.44) 1.86 (1.58-2.18) 5.21 (4.27-6.77) 19.8 (12.8-24.0) 33.8 (26.1-47.8) 1019 

Race/ethnicity 

Mexican Americans 99-00 1.79 (1.05-3.05) 2.00 (.530-4.40) 11.0 (6.70-17.0) 39.0 (32.0-62.0) 140 (46.0-230) 671

01-02 * < LOD 3.76 (2.66-5.18) 15.1 (11.1-19.1) 35.2 (19.1-46.0) 678

03-04 2.41 (1.86-3.11) 2.54 (1.41-4.04) 6.52 (4.90-8.13) 18.6 (11.7-22.3) 28.9 (19.2-39.8) 498

Non-Hispanic blacks 99-00 2.13 (1.57-2.88) 3.60 (2.10-4.70) 12.0 (8.80-18.0) 38.0 (20.0-41.0) 41.0 (37.0-110) 509

01-02 1.61 (1.19-2.19) 1.26 (.660-2.05) 5.54 (3.29-9.41) 20.6 (15.6-27.7) 42.9 (27.2-62.8) 695

03-04 2.10 (1.83-2.41) 1.85 (1.50-2.29) 5.12 (3.87-7.90) 20.4 (15.2-26.1) 32.0 (24.9-51.9) 579

Non-Hispanic whites 99-00 1.77 (1.23-2.53) 2.70 (.830-4.40) 11.0 (7.50-17.0) 38.0 (17.0-53.0) 48.0 (38.0-69.0) 595

01-02 * < LOD 3.99 (2.46-6.14) 17.3 (10.1-25.0) 33.1 (25.0-50.2) 947

03-04 2.10 (1.79-2.45) 1.90 (1.57-2.30) 5.71 (4.43-7.10) 17.3 (12.8-21.1) 31.3 (24.0-47.8) 757

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.18, 0.4, and 0.5, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 127

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

Urinary Dimethylthiophosphate (DMTP) (creatinine corrected) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 1.64 (1.22-2.20) 2.12 (1.22-3.35) 9.57 (6.59-15.8) 32.0 (23.9-41.1) 51.0 (39.0-70.1) 1948 

01-02 * .860 (<LOD-1.33) 3.79 (2.50-5.19) 13.3 (10.9-18.8) 27.2 (21.7-37.7) 2517 

03-04 1.97 (1.71-2.27) 1.75 (1.54-2.06) 5.21 (4.46-5.95) 15.7 (11.7-19.7) 30.4 (25.4-34.2) 1962 

Age group 

6-11 years 99-00 2.95 (2.25-3.86) 5.32 (3.75-6.33) 19.1 (12.2-28.0) 47.0 (32.1-60.3) 66.1 (50.9-95.0) 471

01-02 * 2.16 (1.32-3.12) 10.6 (7.84-13.6) 28.7 (18.8-45.0) 48.1 (33.4-71.1) 575

03-04 3.40 (2.70-4.28) 3.41 (2.40-4.17) 7.91 (6.43-12.2) 25.2 (16.8-34.2) 36.1 (25.4-67.7) 310

12-19 years 99-00 1.71 (1.07-2.75) 2.14 (.890-4.83) 13.5 (6.46-22.6) 36.0 (25.6-51.4) 61.5 (41.7-109) 664

01-02 * .930 (<LOD-1.56) 3.56 (2.38-5.57) 12.2 (8.96-16.0) 22.5 (13.2-34.7) 821

03-04 1.66 (1.37-2.03) 1.52 (1.18-1.82) 4.38 (3.29-5.66) 13.3 (9.94-20.5) 26.5 (15.5-36.0) 715

20-59 years 99-00 1.47 (1.07-2.02) 1.90 (.870-3.11) 8.09 (5.19-14.6) 27.0 (19.8-37.6) 47.5 (34.2-70.1) 813

01-02 * < LOD 3.16 (1.99-4.62) 11.9 (7.79-17.2) 25.2 (15.9-37.0) 1121 

03-04 1.88 (1.61-2.19) 1.67 (1.45-1.94) 4.88 (4.20-5.68) 13.9 (10.3-19.7) 30.4 (19.7-38.2) 937

Gender 

Males 99-00 1.61 (1.11-2.34) 2.39 (1.27-3.51) 9.27 (6.00-16.9) 28.9 (19.0-40.4) 41.1 (34.9-52.9) 952

01-02 * .750 (<LOD-1.08) 3.35 (2.26-4.60) 12.5 (8.54-15.9) 24.0 (14.6-38.9) 1187 

03-04 1.70 (1.43-2.02) 1.67 (1.38-1.96) 4.47 (3.63-5.36) 12.3 (8.47-17.7) 24.5 (17.6-32.5) 945

Females 99-00 1.66 (1.26-2.18) 2.01 (.870-3.33) 10.0 (6.67-16.2) 34.9 (26.2-47.1) 70.1 (39.0-118) 996

01-02 * < LOD 4.22 (2.40-7.00) 15.6 (11.3-22.6) 29.6 (24.8-43.8) 1330 

03-04 2.28 (1.91-2.72) 1.88 (1.59-2.44) 6.00 (4.80-8.30) 19.4 (12.8-26.2) 32.6 (27.3-42.0) 1017 

Race/ethnicity 

Mexican Americans 99-00 1.60 (.899-2.86) 1.83 (.680-4.23) 10.4 (5.95-16.9) 37.0 (23.1-63.1) 112 (40.5-190) 671

01-02 * < LOD 3.55 (2.52-4.93) 13.2 (9.61-22.7) 30.2 (22.7-47.7) 678

03-04 2.16 (1.58-2.94) 2.24 (1.67-3.00) 5.88 (4.14-8.71) 15.7 (10.7-20.1) 23.7 (18.9-36.9) 497

Non-Hispanic blacks 99-00 1.45 (1.03-2.06) 1.75 (1.17-3.06) 8.48 (4.36-13.4) 25.5 (15.4-39.3) 54.4 (25.5-97.6) 509

01-02 1.15 (.888-1.48) 1.02 (.670-1.35) 3.62 (2.33-5.18) 13.4 (9.69-18.8) 23.0 (17.5-43.8) 694

03-04 1.37 (1.23-1.53) 1.19 (1.06-1.31) 3.50 (2.69-5.07) 11.8 (7.95-16.2) 23.9 (13.3-27.1) 578

Non-Hispanic whites 99-00 1.68 (1.16-2.43) 2.22 (.870-3.51) 9.40 (5.58-17.0) 33.3 (20.6-49.4) 52.9 (39.0-71.1) 595

01-02 * < LOD 3.82 (2.19-6.38) 14.3 (10.1-22.1) 27.4 (21.7-43.8) 947

03-04 2.08 (1.76-2.46) 1.80 (1.59-2.27) 5.36 (4.46-6.23) 17.4 (11.4-21.6) 31.7 (24.2-38.2) 756

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 128 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

Urinary Diethyldithiophosphate (DEDTP) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * .090 (<LOD-.140) .210 (.140-.290) .470 (.380-.640) .870 (.640-1.10) 1949 

01-02 * < LOD < LOD .610 (.410-.770) .850 (.700-1.30) 2516 

03-04 * < LOD < LOD < LOD .320 (.170-.540) 1965 

Age group 

6-11 years 99-00 * .090 (<LOD-.160) .190 (.130-.280) .430 (.300-.650) .850 (.470-1.00) 471

01-02 * < LOD < LOD .630 (.380-.870) .940 (.690-1.42) 576

03-04 * < LOD < LOD < LOD .540 (<LOD-.650) 310

12-19 years 99-00 * .080 (<LOD-.180) .260 (.120-.350) .640 (.420-.840) .930 (.720-1.30) 664

01-02 * < LOD < LOD .560 (.330-.730) .820 (.610-.990) 822

03-04 * < LOD < LOD .150 (<LOD-.350) .450 (.370-.570) 717

20-59 years 99-00 * .090 (<LOD-.130) .210 (.130-.290) .450 (.360-.640) .900 (.610-1.10) 814

01-02 * < LOD < LOD .620 (.430-.760) .830 (.700-1.32) 1118 

03-04 * < LOD < LOD < LOD .220 (<LOD-.580) 938

Gender 

Males 99-00 * .090 (<LOD-.150) .220 (.140-.310) .490 (.380-.680) .870 (.680-1.10) 952

01-02 * < LOD < LOD .600 (.370-.740) .770 (.680-1.03) 1187 

03-04 * < LOD < LOD < LOD .390 (.130-.540) 946

Females 99-00 * .090 (<LOD-.130) .190 (.110-.310) .460 (.320-.840) .870 (.440-1.40) 997

01-02 * < LOD < LOD .660 (.460-.850) .990 (.700-1.42) 1329 

03-04 * < LOD < LOD < LOD .240 (<LOD-.700) 1019 

Race/ethnicity 

Mexican Americans 99-00 .130 (.099-.171) .100 (.050-.200) .310 (.230-.390) .650 (.530-.860) 1.10 (.860-1.60) 672

01-02 * < LOD < LOD .720 (.410-1.13) 1.12 (.700-1.58) 678

03-04 * < LOD < LOD .120 (<LOD-.550) .680 (.300-1.15) 498

Non-Hispanic blacks 99-00 .117 (.084-.162) .090 (<LOD-.230) .270 (.140-.410) .560 (.400-.830) .870 (.650-1.20) 509

01-02 * < LOD < LOD .630 (.410-.830) .820 (.730-.990) 694

03-04 * < LOD < LOD < LOD .310 (.160-.540) 579

Non-Hispanic whites 99-00 * .080 (<LOD-.160) .190 (.120-.290) .450 (.310-.720) .870 (.510-1.30) 595

01-02 * < LOD < LOD .610 (.360-.780) .830 (.650-1.36) 947

03-04 * < LOD < LOD < LOD .290 (<LOD-.540) 757

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.05, 0.1, and 0.1, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 129

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

Urinary Diethyldithiophosphate (DEDTP) (creatinine corrected) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * .070 (<LOD-.110) .200 (.140-.290) .550 (.390-.700) .860 (.670-1.14) 1949 

01-02 * < LOD < LOD .580 (.390-.750) 1.01 (.710-1.43) 2515 

03-04 * < LOD < LOD < LOD .410 (.330-.510) 1962 

Age group 

6-11 years 99-00 * .100 (<LOD-.140) .190 (.150-.270) .570 (.410-.760) 1.03 (.570-1.58) 471

01-02 * < LOD < LOD .780 (.610-1.12) 1.36 (1.02-1.86) 576

03-04 * < LOD < LOD < LOD .470 (<LOD-.970) 310

12-19 years 99-00 * .050 (<LOD-.080) .170 (.100-.220) .440 (.230-.730) .730 (.380-1.09) 664

01-02 * < LOD < LOD .360 (.250-.540) .670 (.380-.990) 821

03-04 * < LOD < LOD .230 (<LOD-.260) .330 (.240-.600) 715

20-59 years 99-00 * .080 (<LOD-.110) .210 (.140-.310) .550 (.360-.730) .860 (.650-1.20) 814

01-02 * < LOD < LOD .580 (.380-.740) 1.03 (.700-1.60) 1118 

03-04 * < LOD < LOD < LOD .400 (<LOD-.540) 937

Gender 

Males 99-00 * .070 (<LOD-.110) .190 (.140-.230) .410 (.340-.500) .720 (.520-.940) 952

01-02 * < LOD < LOD .380 (.300-.650) .740 (.580-1.03) 1187 

03-04 * < LOD < LOD < LOD .330 (.260-.410) 945

Females 99-00 * .090 (<LOD-.120) .220 (.140-.360) .670 (.410-.870) .890 (.660-1.62) 997

01-02 * < LOD < LOD .700 (.490-1.00) 1.24 (.800-1.86) 1328 

03-04 * < LOD < LOD < LOD .500 (<LOD-.640) 1017 

Race/ethnicity 

Mexican Americans 99-00 .116 (.084-.161) .090 (.060-.170) .300 (.190-.410) .810 (.570-.990) 1.19 (.860-2.66) 672

01-02 * < LOD < LOD .850 (.440-1.24) 1.29 (.880-1.78) 678

03-04 * < LOD < LOD .320 (<LOD-.450) .540 (.330-.940) 497

Non-Hispanic blacks 99-00 .080 (.057-.111) .070 (<LOD-.110) .170 (.110-.280) .450 (.300-.580) .700 (.500-1.02) 509

01-02 * < LOD < LOD .460 (.330-.580) .720 (.510-.960) 693

03-04 * < LOD < LOD < LOD .270 (.180-.400) 578

Non-Hispanic whites 99-00 * .070 (<LOD-.120) .200 (.140-.310) .560 (.380-.730) .880 (.600-1.38) 595

01-02 * < LOD < LOD .540 (.360-.780) 1.03 (.640-1.67) 947

03-04 * < LOD < LOD < LOD .370 (<LOD-.520) 756

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 130 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

Urinary Dimethyldithiophosphate (DMDTP) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * < LOD 2.30 (1.30-3.90) 13.0 (5.00-17.0) 19.0 (17.0-38.0) 1949 

01-02 * < LOD .890 (.210-1.30) 2.49 (1.88-3.40) 5.10 (3.55-8.35) 2518 

03-04 * < LOD .640 (.480-.800) 1.99 (1.38-3.30) 5.05 (3.30-7.16) 1930 

Age group 

6-11 years 99-00 .691 (.425-1.12) .740 (.080-1.80) 4.30 (2.40-8.60) 17.0 (6.90-37.0) 32.0 (17.0-44.0) 471

01-02 * < LOD 1.30 (.750-2.11) 3.53 (2.20-4.50) 7.33 (4.32-9.74) 575

03-04 * < LOD .900 (.620-1.14) 2.94 (1.14-5.48) 5.48 (2.94-8.53) 306

12-19 years 99-00 * < LOD 2.30 (1.40-4.50) 13.0 (5.40-20.0) 20.0 (17.0-38.0) 664

01-02 * < LOD .830 (.400-1.14) 2.52 (1.85-3.07) 4.63 (3.59-5.83) 821

03-04 * < LOD .580 (.350-.770) 1.46 (1.12-1.99) 2.67 (1.82-4.49) 699

20-59 years 99-00 * < LOD 2.10 (.840-3.60) 11.0 (4.00-17.0) 17.0 (7.70-50.0) 814

01-02 * < LOD .840 (<LOD-1.31) 2.32 (1.70-3.40) 4.90 (2.90-9.52) 1122 

03-04 * < LOD .610 (.350-.800) 2.00 (1.36-3.63) 5.07 (3.62-8.62) 925

Gender 

Males 99-00 * .110 (<LOD-.610) 2.30 (1.20-4.90) 16.0 (5.70-17.0) 19.0 (17.0-38.0) 952

01-02 * < LOD .840 (.190-1.28) 2.40 (1.83-3.28) 5.13 (3.53-7.86) 1187 

03-04 * < LOD .600 (.260-.910) 1.76 (1.07-3.35) 4.45 (2.24-7.97) 935

Females 99-00 * < LOD 2.20 (1.10-3.90) 11.0 (4.20-17.0) 20.0 (13.0-40.0) 997

01-02 * < LOD .960 (.170-1.39) 2.52 (1.94-3.68) 5.10 (3.31-10.6) 1331 

03-04 * < LOD .690 (.510-.850) 2.40 (1.43-4.15) 5.07 (3.35-10.3) 995

Race/ethnicity 

Mexican Americans 99-00 * .250 (<LOD-.870) 1.90 (1.10-3.00) 5.80 (4.10-9.70) 12.0 (5.90-28.0) 672

01-02 * < LOD 1.03 (.750-1.37) 2.67 (2.07-3.42) 4.47 (3.70-7.01) 678

03-04 * < LOD .730 (.360-1.21) 2.07 (1.36-3.15) 5.26 (2.30-6.99) 498

Non-Hispanic blacks 99-00 * .330 (<LOD-1.20) 3.20 (1.40-7.00) 14.0 (5.70-30.0) 19.0 (17.0-39.0) 509

01-02 * < LOD .770 (<LOD-1.67) 2.11 (1.55-4.18) 4.39 (2.51-8.66) 695

03-04 * < LOD .590 (.370-.720) 1.61 (1.05-3.11) 4.51 (2.23-6.97) 552

Non-Hispanic whites 99-00 * < LOD 2.00 (.800-4.00) 13.0 (3.90-20.0) 20.0 (16.0-40.0) 595

01-02 * < LOD .960 (<LOD-1.42) 2.49 (1.83-3.65) 5.74 (3.28-9.87) 947

03-04 * < LOD .640 (.380-.880) 1.96 (1.21-3.87) 5.05 (2.29-10.6) 752

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.08, 0.1, and 0.1, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 131

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolites

Urinary Dimethyldithiophosphate (DMDTP) (creatinine corrected) 

Metabolite of Several Organophosphorus Insecticides 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * < LOD 1.88 (.970-3.86) 10.1 (5.31-18.3) 21.7 (12.8-33.7) 1949 

01-02 * < LOD .670 (.330-1.08) 2.60 (1.85-3.69) 5.83 (4.23-7.75) 2517 

03-04 * < LOD .500 (.340-.650) 2.14 (1.21-3.18) 5.27 (2.69-7.61) 1927 

Age group 

6-11 years 99-00 .748 (.474-1.18) .790 (.190-1.60) 4.07 (2.31-7.18) 16.2 (8.22-27.0) 30.8 (20.2-38.9) 471

01-02 * < LOD 1.36 (.800-2.31) 4.10 (2.67-6.24) 6.98 (4.40-12.8) 575

03-04 * < LOD .960 (.580-1.57) 3.38 (2.28-6.15) 7.12 (4.48-7.55) 306

12-19 years 99-00 * < LOD 1.52 (.620-3.47) 9.48 (4.04-16.8) 21.5 (9.48-42.3) 664

01-02 * < LOD .540 (.310-.770) 2.02 (1.49-2.40) 3.13 (2.51-4.67) 820

03-04 * < LOD .360 (.240-.580) 1.02 (.630-1.57) 2.45 (1.33-3.39) 697

20-59 years 99-00 * < LOD 1.71 (.850-3.56) 8.50 (4.00-19.1) 20.5 (8.57-40.7) 814

01-02 * < LOD .600 (<LOD-1.05) 2.56 (1.64-4.03) 6.33 (3.96-8.17) 1122 

03-04 * < LOD .450 (.340-.580) 2.17 (1.10-3.64) 5.71 (2.47-10.1) 924

Gender 

Males 99-00 * .150 (<LOD-.370) 1.79 (.840-3.97) 11.0 (4.62-17.4) 18.1 (7.51-44.7) 952

01-02 * < LOD .580 (.270-.820) 2.01 (1.40-2.67) 4.67 (2.90-6.80) 1187 

03-04 * < LOD .370 (.260-.590) 1.57 (.730-3.32) 3.74 (2.14-6.53) 934

Females 99-00 * < LOD 2.06 (.940-4.00) 9.30 (4.96-25.5) 27.0 (9.66-47.5) 997

01-02 * < LOD .820 (.370-1.43) 2.92 (2.29-4.56) 7.73 (4.44-11.9) 1330 

03-04 * < LOD .560 (.390-.790) 2.62 (1.33-4.41) 5.88 (2.82-11.6) 993

Race/ethnicity 

Mexican Americans 99-00 * .270 (<LOD-.660) 1.35 (.860-2.53) 6.55 (3.83-11.8) 16.7 (6.25-38.8) 672

01-02 * < LOD .830 (.540-1.11) 2.59 (1.88-3.22) 4.86 (3.32-6.37) 678

03-04 * < LOD .650 (.320-1.10) 2.04 (1.09-3.84) 4.50 (2.11-5.88) 497

Non-Hispanic blacks 99-00 * .250 (<LOD-.700) 2.40 (.690-5.44) 9.41 (4.81-17.8) 17.9 (11.5-40.7) 509

01-02 * < LOD .430 (<LOD-.930) 1.80 (.830-3.50) 3.65 (2.33-5.91) 694

03-04 * < LOD .340 (.260-.430) .890 (.740-1.50) 2.33 (1.12-4.55) 551

Non-Hispanic whites 99-00 * < LOD 1.77 (.780-4.02) 11.4 (4.07-21.5) 21.5 (11.4-34.8) 595

01-02 * < LOD .710 (<LOD-1.31) 2.85 (1.91-4.96) 7.29 (4.25-9.47) 947

03-04 * < LOD .470 (.340-.700) 2.25 (1.02-4.03) 5.89 (2.47-10.1) 751

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 132 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Dialkyl Phosphate Metabolites 

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 134 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

Organophosphorus Insecticides: Specific 

Metabolites

General Information

The specific metabolites of the organophosphorus 

insecticides discussed in this section are those that are often 

measured in biomonitoring studies. These metabolites 

differ from the dialkyl phosphate metabolites because 

each specific metabolite derives from one or only a few 

parent insecticides. The table below shows the parent 

organophosphorus insecticides and their metabolites 

measured in this Report. For example, malathion is 

metabolized to malathion dicarboxylic acid; parathion and 

methyl parathion are metabolized to para-nitrophenol. In 

addition to reflecting exposure to the parent insecticide, the 

level may reflect exposure to the environmental degradation 

products of these pesticides. For general information about 

the organophosphorus class of insecticides, see the section 

titled “Organophosphorus Insecticides: Dialkyl Phosphate 

Metabolites.”

Organophosphorus insecticide 

(CAS number) 

Primary urinary metabolite 

(CAS number) 

Chlorpyrifos (2921-88-2) 

Chlorpyrifos-methyl (5598-13-0) 3,5,6-Trichloro-2-pyridinol (6515-38-4) 

Coumaphos (56-72-4) 3-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one/ol 

Diazinon (333-41-5) 2-Isopropyl-4-methyl-6-hydroxypyrimidine (2814-20-2) 

Malathion (121-75-5) Malathion dicarboxylic acid (1190-28-9) 

Ethyl parathion (56-38-2) 

Methyl parathion (298-00-0) para-Nitrophenol (100-02-7)

Pirimiphos-methyl (29232-93-7) 2-(Diethylamino)-6-methylpyrimidin-4-ol/one 
Fourth National Report on Human Exposure to Environmental Chemicals 135

 Organophosphorus Insecticides: Specific Metabolites 

Chlorpyrifos

CAS No. 2921-88-2

Chlorpyrifos-methyl

CAS No. 5598-13-0

General Information

The chemical 3,5,6-trichloro-2-pyridinol (TCPy) is a 

metabolite of chlorpyrifos and chlorpyrifos-methyl. 

Chlorpyrifos is a broad spectrum organophosphorus 

insecticide that has been widely used to control insects on 

food crops such as corn. It also has been applied directly 

on animals to kill mites, applied to structures to kill 

termites, and sprayed to kill mosquitoes. Approximately 

21-24 million pounds per year were used domestically 

from 1987-1998. After 2001, chlorpyrifos was no longer 

registered for indoor residential uses in the United States; 

pre- and post-construction structural applications for 

termite control were to be phased out by 2005 (U.S.EPA, 

2002). Chlorpyrifos-methyl is an organophosphorus 

insecticide also used in agriculture and not registered for 

residential use. Approximately 80,000 pounds are used 

per year. Chlorpyrifos is degraded in agricultural soils 

with a half-life of several months, and on plants for days 

to several weeks. It has low leachability, staying bound to 

soil particles, and is infrequently detected in ground water 

(IPCS, 1999; USGS, 2007), but can be detected in streams 

receiving runoff from application sites. Chlorpyrifos is very 

toxic to fish and aquatic invertebrates and shows modest 

degrees of bioconcentration.

The general population may be exposed to chlorpyrifos 

via oral, dermal, and inhalation routes. Estimated intakes 

from diet and water have not exceeded recommended 

intake limits, although some tolerances for specific food 

crops have been reduced in the past to avoid exceeding 

recommended intake limits for total dietary intake in 

special groups (U.S.EPA, 2002). Exposure can also result 

from contact with contaminated surfaces, air, and dust. 

For instance, in 142 urban homes and preschools in North 

Carolina, chlorpyrifos and TCPy were detected in all indoor 

air and dust samples (Morgan et al., 2005). Chlorpyrifos 

is not well absorbed through the skin but dermal exposure 

can be significant when other routes of exposure are low. 

Inhalational and dermal routes of exposure are important 

in pesticide formulators and applicators. Chlorpyrifos is 

Urinary 3,5,6-Trichloro-2-pyridinol 

Metabolite of Chlorpyrifos and Chlorpyrifos-methyl 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 1.77 (1.46-2.14) 1.70 (1.40-2.20) 3.50 (2.50-5.20) 7.30 (4.80-10.0) 10.0 (7.70-15.0) 1994 

01-02 1.76 (1.52-2.03) 2.22 (1.90-2.61) 4.95 (4.55-5.29) 8.80 (7.74-9.77) 12.4 (10.4-15.3) 2509 

Age group 

6-11 years 99-00 2.88 (1.99-4.16) 2.80 (1.60-4.90) 7.09 (3.40-10.0) 12.0 (7.70-17.0) 16.0 (10.0-28.0) 481

01-02 2.67 (2.13-3.35) 3.09 (2.50-4.22) 6.36 (4.97-7.97) 10.9 (7.98-15.3) 15.3 (11.5-24.0) 573

12-19 years 99-00 2.37 (1.89-2.97) 2.10 (1.60-3.00) 4.50 (2.90-7.10) 8.10 (5.50-14.0) 12.5 (8.00-24.0) 681

01-02 2.71 (2.19-3.35) 3.57 (2.66-4.34) 6.60 (5.61-7.59) 11.3 (8.66-15.1) 18.0 (13.7-23.7) 823

20-59 years 99-00 1.53 (1.29-1.83) 1.50 (1.30-1.80) 2.90 (2.20-4.30) 5.90 (3.90-8.90) 8.90 (6.70-11.0) 832

01-02 1.51 (1.32-1.72) 1.91 (1.44-2.26) 4.44 (3.90-4.80) 7.78 (7.00-8.91) 10.9 (9.52-12.4) 1113 

Gender 

Males 99-00 1.92 (1.60-2.32) 1.90 (1.50-2.40) 3.60 (2.70-5.60) 7.40 (5.04-10.0) 10.0 (7.70-16.0) 972

01-02 2.13 (1.81-2.51) 2.67 (2.20-3.25) 5.37 (4.87-6.25) 9.63 (8.20-11.5) 14.9 (10.9-18.9) 1183 

Females 99-00 1.63 (1.31-2.02) 1.50 (1.20-2.00) 3.30 (2.30-5.30) 7.20 (4.30-12.0) 11.0 (7.20-16.0) 1022 

01-02 1.45 (1.24-1.70) 1.74 (1.39-2.21) 4.38 (3.72-4.95) 7.71 (6.30-9.20) 10.4 (8.47-13.2) 1326 

Race/ethnicity 

Mexican Americans 99-00 1.61 (1.31-2.00) 1.67 (1.30-2.20) 3.20 (2.60-3.80) 5.10 (3.80-8.40) 7.40 (5.10-17.0) 697

01-02 2.02 (1.79-2.28) 2.63 (2.24-3.01) 4.60 (4.05-5.39) 9.02 (7.04-10.8) 12.2 (10.8-15.7) 660

Non-Hispanic blacks 99-00 2.17 (1.59-2.97) 1.90 (1.43-2.80) 4.30 (2.50-8.30) 9.40 (6.40-13.7) 13.0 (9.40-26.0) 521

01-02 2.19 (1.68-2.84) 2.89 (2.28-3.47) 5.47 (4.77-6.96) 9.27 (7.47-11.6) 12.3 (10.1-16.8) 701

Non-Hispanic whites 99-00 1.76 (1.51-2.05) 1.70 (1.50-2.10) 3.50 (2.50-4.86) 7.10 (4.30-11.0) 10.0 (7.20-14.0) 602

01-02 1.71 (1.43-2.03) 2.15 (1.62-2.64) 4.94 (4.44-5.37) 8.68 (7.47-9.97) 12.4 (9.77-15.9) 947

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.4 and 0.4. 
 136 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

rapidly absorbed following ingestion. Once absorbed, 

phosphorothioates such as chlorpyrifos are metabolically 

activated to the “oxon” form which has greater toxicity 

than the parent insecticide. Metabolic hydrolysis leads 

to the formation of TCPy, dialkyl phosphate metabolites 

(see section titled “Organophosphorus Insecticides: 

Dialkyl Phosphate Metabolites”), and other metabolites. 

Chlorpyrifos is eliminated from the body primarily in the 

urine with a half-life of approximately 27 hours (Nolan et 

al., 1984). In addition to being a metabolite of chlorpyrifos 

and chlorpyrifos-methyl in the body, TCPy can also occur 

in the environment from the breakdown of the parent 

compounds. TCPy is more persistent in the environment 

than chlorpyrifos itself (U.S.EPA, 2002). Thus, the 

detection of TCPy in a person’s urine may reflect exposure 

to the environmental degradates.

Human health effects from chlorpyrifos or chlorpyrifosmethyl at low environmental doses or at biomonitored 

levels from low environmental exposures are unknown. 

Chlorpyrifos and chlorpyrifos-methyl both demonstrate 

moderate acute toxicity in animal studies. These 

organophosphorus insecticides share a mechanism of 

toxicity: inhibition of the activity of acetylcholinesterase 

enzymes in the nervous system, resulting in excess 

acetylcholine at nerve terminals, and producing acute 

symptoms such as nausea, vomiting, cholinergic effects, 

weakness, paralysis, and seizures. The metabolite TCPy does 

not inhibit acetylcholinesterase enzymes. Overt cholinergic 

toxicity from chlorpyrifos has been described following 

suicidal ingestion and unintentional high level occupational 

exposure. Based on animal data and human cholinesterase 

monitoring during occupational exposure, ubiquitous lowlevel environmental exposures in humans would not be 

expected to result in inhibition of cholinesterase activity. 

Recent in vitro and in vivo animal studies suggest that 

effects on neuronal morphogenesis, neurotransmission, and 

behavior may occur at systemically nontoxic doses or at 

doses of chlorpyrifos that do not result in cholinergic signs 

(Aldridge et al., 2005; Betancourt et al., 2006; Howard et 

al., 2005; Ricceri et al., 2006; Roy et al., 2005; Slotkin et al., 

2006a, 2006b). In pesticide applicators, chronic exposure 

to chlorpyrifos may be associated with slight alterations in 

some components of neurophysiologic testing (Steenland 

et al., 2000). Two observational studies of pregnant 

women and their offspring exposed to chlorpyrifos at 

environmental levels have found inconsistent relationships 

with birth outcomes of weight and length (Eskenazi et al., 

Urinary 3,5,6-Trichloro-2-pyridinol (creatinine corrected) 

Metabolite of Chlorpyrifos and Chlorpyrifos-methyl 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 1.58 (1.35-1.85) 1.47 (1.24-1.74) 2.85 (2.12-3.59) 5.43 (4.22-6.68) 8.42 (6.25-11.6) 1994 

01-02 1.73 (1.49-2.01) 1.88 (1.64-2.24) 3.76 (2.91-4.62) 6.15 (4.99-8.31) 9.22 (6.94-12.3) 2508 

Age group 

6-11 years 99-00 3.11 (2.31-4.19) 3.20 (2.05-4.80) 6.39 (4.14-8.19) 10.1 (7.26-14.0) 14.1 (10.1-21.0) 481

01-02 3.48 (2.80-4.32) 3.76 (3.17-4.36) 6.22 (4.88-8.57) 12.2 (7.24-24.4) 16.9 (12.1-38.0) 573

12-19 years 99-00 1.60 (1.34-1.91) 1.45 (1.21-1.81) 2.58 (1.97-3.92) 4.82 (3.44-6.16) 6.16 (4.43-10.6) 681

01-02 2.09 (1.72-2.55) 2.24 (1.92-2.66) 3.97 (3.30-4.72) 6.33 (5.62-7.89) 10.3 (7.65-15.2) 822

20-59 years 99-00 1.41 (1.23-1.62) 1.33 (1.12-1.58) 2.37 (1.87-3.01) 4.29 (3.53-5.56) 6.42 (5.11-9.02) 832

01-02 1.49 (1.30-1.71) 1.64 (1.39-1.88) 3.11 (2.60-3.91) 5.50 (4.33-7.23) 7.44 (5.80-11.0) 1113 

Gender 

Males 99-00 1.48 (1.27-1.72) 1.44 (1.19-1.68) 2.54 (2.05-3.38) 4.95 (3.84-6.54) 7.63 (5.65-11.0) 972

01-02 1.71 (1.47-2.00) 1.88 (1.57-2.22) 3.46 (2.82-4.28) 5.93 (4.90-9.24) 10.5 (6.94-14.3) 1183 

Females 99-00 1.69 (1.42-2.01) 1.51 (1.25-1.85) 2.97 (2.24-4.01) 5.63 (4.27-7.39) 8.44 (5.79-13.3) 1022 

01-02 1.75 (1.49-2.07) 1.93 (1.59-2.33) 3.91 (3.06-4.85) 6.47 (5.00-8.11) 8.98 (6.83-11.8) 1325 

Race/ethnicity 

Mexican Americans 99-00 1.46 (1.20-1.77) 1.44 (1.05-1.93) 2.39 (2.09-2.96) 3.86 (3.24-5.08) 5.85 (3.88-9.57) 697

01-02 1.86 (1.63-2.12) 2.06 (1.83-2.35) 3.81 (3.17-4.56) 6.52 (5.64-7.58) 9.00 (7.66-11.8) 660

Non-Hispanic blacks 99-00 1.47 (1.09-1.99) 1.33 (.940-1.91) 2.86 (1.58-5.05) 5.91 (4.05-8.93) 9.02 (5.91-13.7) 521

01-02 1.56 (1.19-2.03) 1.92 (1.57-2.40) 3.53 (2.85-4.28) 5.58 (4.80-6.07) 7.06 (5.88-8.82) 700

Non-Hispanic whites 99-00 1.66 (1.45-1.91) 1.55 (1.31-1.83) 2.93 (2.09-3.97) 5.56 (4.21-6.75) 8.44 (6.25-12.3) 602

01-02 1.78 (1.49-2.14) 1.95 (1.56-2.35) 3.82 (2.70-4.97) 6.55 (4.88-10.5) 9.98 (7.00-13.7) 947
Fourth National Report on Human Exposure to Environmental Chemicals 137

 Organophosphorus Insecticides: Specific Metabolites 

2004; Perera et al., 2003; Whyatt et al., 2004).

Some reproductive and teratogenic effects in animal testing 

were only observed at high doses of chlorpyrifos that caused 

overt maternal toxicity. Chlorpyrifos is not considered to be 

mutagenic or carcinogenic (NTP, 1992; U.S.EPA, 2002).

Additional information about external exposure (i.e., 

environmental levels) and health effects is available from 

ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html and 

from U.S. EPA at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary TCPy levels reflect recent exposure. Levels of 

TCPy in the U.S. subsamples of NHANES 1999-2000 

and 2001-2002 (CDC, 2005) appear roughly similar to 

values reported for a nonrandom subsample of NHANES 

III (1988-1994) participants (Hill et al., 1995) and were 

similar to levels reported in studies of healthy adults in 

Germany (Koch et al., 2001) and Italy (Aprea et al., 1999). 

In a probability-based sample of 102 Minnesota children 

aged 3-13 years, the weighted population mean of TCPy 

measurements was approximately three times higher 

(Adgate, 2001) than the corresponding values reported for 

the group aged 6-11 years from the NHANES 1999-2000 

subsample (CDC, 2005). MacIntosh et al. (1999) reported 

mean urinary TCPy levels in a sample of Maryland adults 

that were about three times higher than adults in the U.S. 

population (CDC, 2005). Of 482 pregnant women living 

in an agricultural community, 76% had detectable levels 

of TCPy and levels were similar to those reported for 

NHANES 1999-2000 (Eskenazi et al., 2004). Other small 

studies of environmentally-exposed persons have shown a 

high frequency of detecting low levels of TCPy.

Following crack-and-crevice application of chlorpyrifos in 

their homes, urinary TCPy levels in children were reported 

not to have increased (Hore et al., 2005). Chlorpyrifos levels 

in house dust and hand rinses did not correlate with levels of 

TCPy in urine (Lioy et al., 2000). Replacing conventional 

diets with organic diets in 23 children led to about a fourfold 

decrease in urinary levels of chlorpyrifos; median urinary 

levels on the conventional diet were several fold higher 

than those in the NHANES 1999-2000 subsample (Lu et al., 

2006). Measurements of urinary TCPy in single spot urine 

collections show variability over time in environmentally 

exposed individuals and are poorly correlated between 

collections, suggesting changing low-level exposure and 

variance in collection timing with respect to exposure 

(Meeker et al., 2005). Estimation of dose or intake based on 

the urinary excretion of TCPy indicates that environmental 

doses are generally below recommended limits (Hore et al., 

2005; Koch et al., 2001).

In Iowa farm families using several different pesticides, 

but not chlorpyrifos, the geometric mean urinary TCPy 

levels were similar in parents and children, but levels were 

roughly four to six times higher than the geometric means 

in the U.S. representative subsample of NHANES 1999-

2000 (CDC, 2005; Curwin et al., 2007). In Minnesota and 

South Carolina farmers who used chlorpyrifos, urinary 

TCPy levels averaged about sixfold higher than those in 

the NHANES 1999-2000 subsample (Mandel et al., 2005; 

CDC, 2005). Urinary levels of TCPy have been found to 

be hundredsfold higher for chlorpyrifos manufacturing 

workers (Burns et al., 2006) and episodically many times 

higher for pesticide applicators than median levels from 

NHANES 1999-2000 (CDC, 2005).

Finding a measurable amount of TCPy in urine does not 

mean that the level will result in an adverse health effect. 

Biomonitoring studies of TCPy provide physicians and 

public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of chlorpyrifos or chlorpyrifos-methyl than are found 

in the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Adgate JL, Barr DB, Clayton CA, Eberly LE, Freeman NC, 

Lioy PJ, et al. Measurement of children’s exposure to pesticides: 

analysis of urinary metabolite levels in a probability-based 

sample. Environ Health Perspect 2001;109(6):583-590.

Aldridge JE, Meyer A, Seidler FJ, Slotkin TA. Alterations in 

central nervous system serotonergic and dopaminergic synaptic 

activity in adulthood after prenatal or neonatal chlorpyrifos 

exposure. Environ Health Perspect 2005;113(8):1027-1031.

Aprea C, Betta A, Catenacci G, Lotti A, Magnaghi S, Barisano 

A, et al.Reference values of urinary 3,5,6-trichloro-2-pyridinol 

in the Italian population—validation of analytical method 

and preliminary results (multicentric study). J AOAC Int 

1999;82(2):305-312.

Betancourt AM, Burgess SC, Carr RL. Effect of developmental 

exposure to chlorpyrifos on the expression of neurotrophin 

growth factors and cell-specific markers in neonatal rat brain. 

Toxicol Sci 2006;92(2):500-506.

Burns CJ, Garabrant D, Albers JW, Berent S, Giordani B, Haidar 

S, et al. Chlorpyrifos exposure and biological monitoring among 

manufacturing workers. Occup Environ Med 2006;63(3):218-

220.
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Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Curwin BD, Hein MJ, Sanderson WT, Striley C, Heederik D, 

Kromhout H, et al. Urinary pesticide concentrations among 

children, mothers and fathers living in farm and non-farm 

households in Iowa. Ann Occup Hyg 2007;51(1):53-65.

Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr 

DB, et al. Association of in utero organophosphate pesticide 

exposure and fetal growth and length of gestation in an agricultural 

population. Environ Health Perspect 2004;112(10):1116-1124.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, 

et al. Pesticide residues in urine of adults living in the United 

States: reference range concentrations. Environ Res 1995;71:99-

108.

Hore P, Robson M, Freeman N, Zhang J, Wartenberg D, Ozkaynak 

H, et al. Chlorpyrifos accumulation patterns for child-accessible 

surfaces and objects and urinary metabolite excretion by children 

for 2 weeks after crack-and-crevice application. Environ Health 

Perspect 2005;113(2):211-219.

Howard AS, Bucelli R, Jett DA, Bruun D, Yang D, Lein PJ. 

Chlorpyrifos exerts opposing effects on axonal and dendritic 

growth in primary neuronal cultures. Toxicol Appl Pharmacol 

2005;207(2):112-124.

International Programme on Chemical Safety-INCHEM (IPCS). 

Environmental Health Criteria 198. Chlorpyrifos. 1999. Available 

at URL: http://www.inchem.org/documents/jmpr/jmpmono/

v99pr03.htm. 4/7/09

Koch HM, Hardt J, Angerer J. Biological monitoring of exposure 

of the general population to the organophosphorus pesticides 

chlorpyrifos and chlorpyrifos-methyl by determination of their 

specific metabolite 3,5,6-trichloro-2-pyridinol. Int J Hyg Environ 

Health 2001;204(2-3):175-180.

Lioy PJ, Edwards RD, Freeman N, Gurunathan S, Pellizzari 

E, Adgate JL, et al. House dust levels of selected insecticides 

and a herbicide measured by the EL and LWW samplers and 

comparisons to hand rinses and urine metabolites. J Expo Anal 

Environ Epidemiol 2000;10(4):327-340.

Lu C, Toepel K, Irish R, Fenske RA, Barr DB, Bravo R. 

Organic diets significantly lower children’s dietary exposure 

to organophosphorus pesticides. Environ Health Perspect 

2006;114(2):260-263.

MacIntosh DL, Needham LL, Hammerstrom KA, Ryan PB. A 

longitudinal investigation of selected pesticide metabolites in 

urine. J Expo Anal Environ Epidemiol 1999;9(5):494-501.

Mandel JS, Alexander BH, Baker BA, Acquavella JF, Chapman 

P, Honeycutt R. Biomonitoring for farm families in the farm 

family exposure study. Scand J Work Environ Health 2005;31 

Suppl 1:98-104.

Meeker JD, Barr DB, Ryan L, Herrick RF, Bennett DH, Bravo 

R, et al. Temporal variability of urinary levels of nonpersistent 

insecticides in adult men. J Expo Anal Environ Epidemiol 

2005;15(3):271-281.

Morgan MK, Sheldon LS, Croghan CW, Jones PA, Robertson GL, 

Chuang JC, et al. Exposures of preschool children to chlorpyrifos 

and its degradation product 3,5,6-trichloro 2-pyridinol in 

their everyday environments. J Expo Anal Environ Epidemiol 

2005;15(4):297-309.

Nolan RJ, Rick DL, Freshour NL, Saunders JH. Chlorpyrifos: 

pharmacokinetics in human volunteers. Toxicol Appl Pharmacol 

1984;73:8-15.

National Toxicology Program (NTP). Executive summary 

of safety and toxicity information. chlorpyrifos. 2921-88-

2. February 5, 1992. Available at URL: http://ntp.niehs.nih.

gov/ntpweb/index.cfm?objectid=6F5E95EB-F1F6-975E7C20F4211536F46F. 4/7/09

Perera FP, Rauh V, Tsai WY, Kinney P, Camann D, Barr D, et 

al. Effects of transplacental exposure to environmental pollution 

on birth outcomes in a multiethnic population. Environ Health 

Perspect 2003;111(2):201-205.

Ricceri L, Venerosi A, Capone F, Cometa MF, Lorenzini P, Fortuna 

S, et al. Developmental neurotoxicity of organophosphorous 

pesticides: fetal and neonatal exposure to chlorpyrifos alters 

sex specific behaviors at adulthood in mice. Toxicol Sci 

2006;93(1):105-113.

Roy TS, Sharma V, Seidler FJ, Slotkin TA. Quantitative 

morphological assessment reveals neuronal and glial deficits in 

hippocampus after a brief subtoxic exposure to chlorpyrifos in 

neonatal rats. Brain Res Dev Brain Res 2005;155(1):71-80.

Slotkin TA, Levin ED, Seidler FJ. Comparative developmental 

neurotoxicity of organophosphate insecticides: effects on brain 

development are separable from systemic toxicity. Environ 

Health Perspect 2006a;114(5):746-751.

Slotkin TA, Tate CA, Ryde IT, Levin ED, Seidler FJ. 

Organophosphate insecticides target the serotonergic system in 

developing rat brain regions: disparate effects of diazinon and 

parathion at doses spanning the threshold for cholinesterase 

inhibition. Environ Health Perspect 2006b;114(10):1542-1546.

Steenland K, Dick RB, Howell RJ, Chrislip DW, Hines 

CJ, Reid TM, et al. Neurologic function among termiticide 

applicators exposed to chlorpyrifos. Environ Health Perspect 

2000;108(4):293-300.

U.S. Environmental Protection Agency (U.S. EPA). Interim 

registration eligibility decision for chlorpyrifos. EPA 738-R-
Fourth National Report on Human Exposure to Environmental Chemicals 139

 Organophosphorus Insecticides: Specific Metabolites 

01-007. February 2002. Available at URL: http://www.epa.gov/

oppsrrd1/REDs/chlorpyrifos_ired.pdf. 1/14/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s 

Waters. Pesticides in the Nation’s Streams and Ground Water, 

1992-2001. March 2006, revised February 15, 2007 [online]. 

Available at URL: http://pubs.usgs.gov/circ/2005/1291/. 6/1/09

Whyatt RM, Barr DB, Camann DE, Kinney PL, Barr JR, 

Andrews HF, et al. Contemporary-use pesticides in personal air 

samples during pregnancy and blood samples at delivery among 

urban minority mothers and newborns. Environ Health Perspect 

2003;111(5):749-56.
 140 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

Coumaphos

CAS No. 56-72-4

General Information

The chemical 3-chloro-7-hydroxy-4-methyl-2H-chromen2-one/ol is a metabolite of coumaphos. First registered 

in 1958, coumaphos is an organophosphorus insecticide 

that is used to control ticks, lice, mites, and arthropod 

pests on beef cattle, dairy cows, swine, and certain other 

farm animals. Also, it has limited use in controlling mites 

in honeybee hives. It is not registered for uses on food 

crops, ornamentals, or for residential use. Coumaphos may 

enter the environment from spillage of animal dipping 

and spraying solutions (U.S.EPA, 2000). Coumaphos is 

generally immobile in soils and can persist for up to a year 

in some types of soils. It degrades to chlorferon, 6-hydroxyl3-methylbenzofuran, and alkyl phosphates. Coumaphos 

is highly toxic to birds and aquatic invertebrates and 

moderately toxic to fish.

General population exposure to coumaphos is unlikely, 

though exposure through dietary meat and milk intake is 

possible. Estimated intakes from diet and water have not 

exceeded recommended intake limits (U.S.EPA, 2000). 

Farm and animal workers may have higher exposures as a 

result of absorption through dermal and inhalational routes. 

Once absorbed, phosphorothioates such as coumaphos are 

metabolically activated to the “oxon” form which has greater 

toxicity than the parent insecticide. Metabolic hydrolysis 

leads to the formation of 3-chloro-7-hydroxy-4-methyl2H-chromen-2-one/ol, dialkyl phosphate metabolites (see 

section titled “Organophosphorus Insecticides: Dialkyl 

Phosphate Metabolites”), and other metabolites. Animal 

studies indicate elimination in the urine over a period of a 

week.

Human health effects from coumaphos at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Coumaphos is considered to be 

an organophosphorus insecticide of moderate-to-high acute 

toxicity in animal studies. At high doses, coumaphos and 

other organophosphorus insecticides share a mechanism of 

toxicity: inhibition of the activity of acetylcholinesterase 

enzymes in the nervous system, resulting in excess 

acetylcholine at nerve terminals, and producing acute 

symptoms such as nausea, vomiting, cholinergic effects, 

weakness, paralysis, and seizures. Toxic effects below doses 

that cause inhibition of acetylcholinesterase are unknown, 

e.g., reproductive effects such as decrease litter size are 

unlikely at doses that do not inhibit acetylcholinesterase 

(Astroff et al., 1998). Coumaphos is not considered 

mutagenic and rated by the U.S.EPA as not likely to be 

carcinogenic in humans (U.S.EPA, 2000). Additional 

information about pesticides is available from U.S. EPA at: 

http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of 3-chloro-7-hydroxy-4-methyl-2Hchromen-2-one/ol reflect recent exposure. In the NHANES 

2001-2002 subsample, most of the measurements of 

3-chloro-7-hydroxy-4-methyl-2H-chromen-2-one/ol in 

urine were below the limit of detection, though the 95th

percentile was 0.200 μg/L for the non-Hispanic black 

subsample (CDC, 2005). In a nonrandom study of 140 

adults and children in the United States, Olsson et al. (2003) 

found that urinary levels of 3-chloro-7-hydroxy-4-methyl2H-chromen-2-one/ol were below the limit of detection.

Finding a measurable amount of 3-chloro-7-hydroxy-4-

methyl-2H-chromen-2-one/ol in urine does not mean that the 

level will result in an adverse health effect. Biomonitoring 

studies of 3-chloro-7-hydroxy-4-methyl-2H-chromen-2-

one/ol provide physicians and public health officials with 

reference values so that they can determine whether people 

have been exposed to higher levels of coumaphos than are 

found in the general population. Biomonitoring data can 

also help scientists plan and conduct research on exposure 

and health effects.
Fourth National Report on Human Exposure to Environmental Chemicals 141

 Organophosphorus Insecticides: Specific Metabolites 

Urinary 3-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one/ol 

Metabolite of Coumaphos 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2481 

Age group 

6-11 years 01-02 * < LOD < LOD < LOD .200 (<LOD-.210) 567

12-19 years 01-02 * < LOD < LOD < LOD < LOD 815

20-59 years 01-02 * < LOD < LOD < LOD < LOD 1099 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1169 

Females 01-02 * < LOD < LOD < LOD < LOD 1312 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 659

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD .200 (<LOD-.270) 701

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 920

Limit of detection (LOD, see Data Analysis section) for Survey year 01-02 is 0.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary 3-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one/ol (creatinine corrected) 

Metabolite of Coumaphos 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2480 

Age group 

6-11 years 01-02 * < LOD < LOD < LOD .670 (<LOD-1.27) 567

12-19 years 01-02 * < LOD < LOD < LOD < LOD 814

20-59 years 01-02 * < LOD < LOD < LOD < LOD 1099 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1169 

Females 01-02 * < LOD < LOD < LOD < LOD 1311 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 659

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD .380 (<LOD-.560) 700

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 920

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 142 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

References

Astroff AB, Freshwater KJ, Eigenberg DA. Comparative 

organophosphate-induced effects observed in adult and neonatal 

Sprague-Dawley rats during the conduct of multigeneration 

toxicity studies. Reprod Toxicol 1998;12(6):619-645.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Olsson AO, Nguyen JV, Sadowski MA, Barr DB. A 

liquid chromatography/electrospray ionization tandem 

mass spectrometry method for quantification of specific 

organophosphorus pesticide biomarkers in human urine. Anal 

Bioanal Chem 2003;376(6):808-815.

U.S. Environmental Protection Agency (U.S. EPA). Reregistration 

eligibility decision (RED) addendum and FPQA tolerance 

reassessment progress report: Coumaphos. September 2000. EPA 

738-R-00-010. Available at URL: http://www.epa.gov/oppsrrd1/

REDs/0018tred.pdf. 1/14/09
Fourth National Report on Human Exposure to Environmental Chemicals 143

 Organophosphorus Insecticides: Specific Metabolites 

Diazinon

CAS No. 333-41-5

General Information

The chemical 2-isopropyl-4-methyl-6-hydroxypyrimidine 

is a metabolite of diazinon, an organophosphorus insecticide 

that is used to control insects on nuts, fruits, vegetable, and 

forage crops. It is also used for cattle ear tag applications 

to control flies and ticks and, in the past, in some pest 

strips. Most granular formulations, aerial, seed and foliar 

applications are planned to be phased out (U.S.EPA, 2004). 

Prior to 2000, diazinon was widely used in residential 

and garden application, but these uses have been phased 

out; since 2004, diazinon cannot be sold for residential 

use. Before these restrictions, about 13 million pounds of 

diazinon were used annually on agricultural sites in the 

United States. Diazinon is biologically and chemically 

degraded in soils with a half-life of about a few weeks. 

It has been infrequently detected in general groundwater 

sampling but has been detected in streams receiving runoff 

from application sites (IPCS, 1998; USGS, 2007). It is 

toxic to birds, and particularly when it was ingested in 

granular form, diazinon produced wild bird kills before use 

restrictions were in place. Fish and aquatic invertebrates 

show modest degrees of bioconcentration and are very 

sensitive to toxic effects.

Human exposure to diazinon from dietary sources is 

expected to be low due to its limited applications to food 

crops and due to its rapid degradation. Estimated intakes 

from diet and water do not exceed recommended intake 

limits (U.S.EPA, 2004). Inhalational and dermal routes 

of exposure can be significant for pesticide applicators. 

Diazinon is not well-absorbed through the skin, but is 

rapidly absorbed orally (IPCS, 1998). Once absorbed, 

phosphorothioates such as diazinon are metabolically 

activated to the “oxon” form which has greater toxicity. 

Metabolic hydrolysis leads to the formation of 2-isopropyl4-methyl-6-hydroxypyrimidine, dialkyl phosphate 

metabolites (see section titled “Organophosphorus 

Insecticides: Dialkyl Phosphate Metabolites”), and other 

metabolites. Experimental diazinon exposure in people has 

demonstrated its rapid elimination into urine, as inferred 

Urinary 2-Isopropyl-4-methyl-6-hydroxypyrimidine 

Metabolite of Diazinon 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1842 

01-02 * < LOD < LOD < LOD < LOD 2535 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 454

01-02 * < LOD < LOD < LOD 1.45 (<LOD-3.11) 580

12-19 years 99-00 * < LOD < LOD < LOD < LOD 632

01-02 * < LOD < LOD < LOD < LOD 829

20-59 years 99-00 * < LOD < LOD < LOD < LOD 756

01-02 * < LOD < LOD < LOD < LOD 1126 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 894

01-02 * < LOD < LOD < LOD < LOD 1191 

Females 99-00 * < LOD < LOD < LOD < LOD 948

01-02 * < LOD < LOD < LOD < LOD 1344 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 644

01-02 * < LOD < LOD < LOD < LOD 678

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 484

01-02 * < LOD < LOD < LOD 1.49 (<LOD-2.05) 700

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 554

01-02 * < LOD < LOD < LOD < LOD 956

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 7.2 and 0.7. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 144 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

from dialkyl phosphate metabolite excretion (Garfitt et al., 

2002). In animals, diazinon does not accumulate in tissues 

(IPCS, 1998). In addition to being a human metabolite 

of diazinon, 2-isopropyl-4-methyl-6-hydroxypyrimidine 

can also occur in the environment from the breakdown of 

the parent compound. Thus, the detection of 2-isopropyl4-methyl-6-hydroxypyrimidine in a person’s urine may 

reflect exposure to the environmental degradate.

Human health effects from diazinon at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Diazinon has moderate acute 

toxicity in animal studies. At high doses, diazinon and 

other organophosphorus insecticides share a mechanism of 

toxicity: inhibition of the activity of acetylcholinesterase 

enzymes in the nervous system, resulting in excess 

acetylcholine at nerve terminals, and producing acute 

symptoms such as nausea, vomiting, cholinergic effects, 

weakness, paralysis, and seizures. Intoxications in humans 

from intentional overdose, agricultural, and indoor 

applications have been documented. There has been only 

limited study of diazinon at systemically non-toxic doses 

that do not result in cholinergic signs (Anthony et al., 1986

Rajendra et al., 1986; Seifert and Pewnim, 1992). Diazinon 

is not considered to be a mutagen, animal carcinogen, 

teratogen, or reproductive toxicant (IPCS, 1998). The 

U.S.EPA considers diazinon unlikely to be carcinogenic in 

humans. Additional information about external exposure 

(i.e., environmental levels) and health effects is available 

from ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html 

and from U.S. EPA at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of 2-isopropyl-4-methyl-6-

hydroxypyrimidine reflect recent exposure. In two 

nonrandom samples of United States adults and children, 

2-isopropyl-4-methyl-6-hydroxypyrimidine was detectable 

in 57% and 43% of the 130 and 140 participants, 

respectively (Baker et al., 2000; Olsson et al., 2003). In 

the U.S. subsamples of NHANES 1999-2000 and 2001-

2002, most of the measurements of 2-isopropyl-4-methyl6-hydroxypyrimidine in urine were below the limit of 

detection, although the 95th percentiles for children 6-11 

years old and for non-Hispanic blacks were 1.45 and 1.49 

μg/L, respectively, in the 2001-2002 subsample (CDC, 

Urinary 2-Isopropyl-4-methyl-6-hydroxypyrimidine (creatinine corrected) 

Metabolite of Diazinon 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1842 

01-02 * < LOD < LOD < LOD < LOD 2534 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 454

01-02 * < LOD < LOD < LOD 2.72 (<LOD-4.45) 580

12-19 years 99-00 * < LOD < LOD < LOD < LOD 632

01-02 * < LOD < LOD < LOD < LOD 828

20-59 years 99-00 * < LOD < LOD < LOD < LOD 756

01-02 * < LOD < LOD < LOD < LOD 1126 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 894

01-02 * < LOD < LOD < LOD < LOD 1191 

Females 99-00 * < LOD < LOD < LOD < LOD 948

01-02 * < LOD < LOD < LOD < LOD 1343 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 644

01-02 * < LOD < LOD < LOD < LOD 678

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 484

01-02 * < LOD < LOD < LOD 1.76 (<LOD-3.48) 699

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 554

01-02 * < LOD < LOD < LOD < LOD 956

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 145

 Organophosphorus Insecticides: Specific Metabolites 

2005). In 23 children, urinary 2-isopropyl-4-methyl-6-

hydroxypyrimidine was detected in less than 14% of multiple 

samples collected during varied diets (Lu et al., 2006). In 

a small number of men visiting fertility clinics in Missouri 

and Minnesota, Swan et al. (2003) found that 2-isopropyl4-methyl-6-hydroxypyrimidine was detectable in 96% and 

58% of the subjects. In 54 Canadian greenhouse workers, 

urinary 2-isopropyl-4-methyl-6-hydroxypyrimidine levels 

were below the limit of detection (Bouchard et al., 2006).

Finding a measurable amount of 2-isopropyl-4-methyl-6-

hydroxypyrimidine in urine does not mean that the level 

will result in an adverse health effect. Biomonitoring studies 

of 2-isopropyl-4-methyl-6-hydroxypyrimidine provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels of diazinon than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Anthony J, Banister E, Oloffs PC. Effect of sublethal levels of 

diazinon: histopathology of liver. Bull Environ Contam Toxicol 

1986;37(4):501-507.

Baker SE, Barr DB, Driskell WJ, Beeson MD, Needham LL. 

Quantification of selected pesticide metabolites in human urine 

using isotope dilution high-performance liquid chromatography/

tandem mass spectrometry. J Expo Anal Environ Epidemiol 

2000;10(6 Pt 2):789-798.

Bouchard M, Carrier G, Brunet RC, Dumas P, Noisel N. Biological 

monitoring of exposure to organophosphorus insecticides in 

a group of horticultural greenhouse workers. Ann Occup Hyg 

2006;50(5):505-515.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Garfitt SJ, Jones K, Mason HJ, Cocker J. Exposure to the 

organophosphate diazinon: data from a human volunteer study 

with oral and dermal doses. Toxicol Lett 2002;134(1-3):105-113.

International Programme on Chemical Safety-INCHEM (IPCS). 

Environmental Health Criteria 198. Diazinon. 1998. Available at 

URL: http://www.inchem.org/documents/ehc/ehc/ehc198.htm. 

4/7/09

Lu C, Toepel K, Irish R, Fenske RA, Barr DB, Bravo R. 

Organic diets significantly lower children’s dietary exposure 

to organophosphorus pesticides. Environ Health Perspect 

2006;114(2):260-263.

Olsson AO, Nguyen JV, Sadowski MA, Barr DB. A 

liquid chromatography/electrospray ionization tandem 

mass spectrometry method for quantification of specific 

organophosphorus pesticide biomarkers in human urine. Anal 

Bioanal Chem 2003;376(6):808-815.

Rajendra W, Oloffs PC, Banister EW. Effects of chronic intake of 

diazinon on blood and brain monoamines and amino acids. Drug 

Chem Toxicol 1986;9(2):117-131.

Seifert J, Pewnim T. Alteration of mice L-tryptophan metabolism 

by the organophosphorous acid triester diazinon. Biochem 

Pharmacol 1992;44(11):2243-2250.

Swan SH, Kruse RL, Liu F, Barr DB, Drobnis EZ, Redmon JB, 

et al. Study for Future Families Research Group. Semen quality 

in relation to biomarkers of pesticide exposure. Environ Health 

Perspect 2003;111(12):1478-1484.

U.S. Environmental Protection Agency (U.S. EPA). Interim 

reregistration eligibility decision (IRED. Diazinon. May 2004. 

EPA 738-R-04-006. Available at URL: http://www.epa.gov/

oppsrrd1/REDs/diazinon_ired.pdf. 1/14/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s 

Waters. Pesticides in the Nation’s Streams and Ground Water, 

1992-2001. March 2006, revised February 15, 2007 [online]. 

Available at URL: http://pubs.usgs.gov/circ/2005/1291/. 6/1/09
 146 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

Malathion 

CAS No. 121-75-5

General Information

Malathion dicarboxylic acid is a metabolite of malathion, 

which is an organophosphorus insecticide that is used on a 

wide variety of agricultural crops, as well as lawns, gardens, 

ornamental trees, shrubs, and plants. It is registered for use 

in public health mosquito control, in fruit fly control, and 

in government programs such as the USDA’s Boll Weevil 

Eradication Program. Most of the estimated 15 million 

pounds used annually are applied to cotton (U.S.EPA, 2006). 

When malathion is used on food or feed crops, usually only 

a small fraction of the crop is treated. It has a short halflife in soils and water and is not considered persistent in 

the environment. Malathion is infrequently detected in 

groundwater sampling (USGS, 2007). It is moderately to 

highly toxic to fish, depending on the species. It is highly 

toxic to aquatic invertebrates and rare fish kills have been 

reported from wide area applications onto surface waters 

and runoff into waters. Malathion is also used medically in 

lotion form (0.5%) to kill body lice.

Limited general population exposure occurs through the 

diet. Estimated intakes for the general population have not 

exceeded recommended intake limits. Pesticide applicators 

and agricultural workers can have higher exposures via 

dermal, inhalational, or oral routes (U.S.EPA, 2006). 

Malathion is slowly absorbed through the skin, but is 

more rapidly and efficiently absorbed via ingestion. 

Once they are absorbed, phosphorothioates such as 

malathion are metabolically activated to the “oxon” forms 

which have greater toxicity than the parent insecticide. 

Metabolism of malathion leads to the formation of 

malathion monocarboxylic acid, malathion dicarboxylic 

acid, dialkyl phosphate metabolites (see section titled 

“Organophosphorus Insecticides: Dialkyl Phosphate 

Metabolites”), and other metabolites. Malathion is rapidly 

eliminated from the body within 12-24 hours (Bouchard et 

al., 2003). About 31-35% of oral doses of malathion are 

excreted in the urine as malathion monocarboxylic acid 

(Krieger and Dinoff, 2000). In addition to being a metabolite 

of malathion, malathion dicarboxylic acid can also occur 

in the environment from the breakdown of the parent 

compound. Thus, the detection of malathion dicarboxylic 

acid in a person’s urine may also reflect exposure to the 

environmental degradate.

Human health effects from malathion at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. At high doses, malathion and other 

organophosphorus insecticides share a common mechanism 

of toxicity: inhibition of the activity of acetylcholinesterase 

enzymes in the nervous system, resulting in excess 

acetylcholine at nerve terminals, and producing acute 

symptoms such as nausea, vomiting, cholinergic effects, 

weakness, paralysis, and seizures. Compared with other 

organophosphorus insecticides, malathion has low acute 

toxicity. Severe toxicity or deaths have been reported from 

Urinary Malathion dicarboxylic acid 

Metabolite of Malathion 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1920 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD 2.80 (<LOD-5.50) 453

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660

20-59 years 99-00 * < LOD < LOD < LOD < LOD 807

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 937

Females 99-00 * < LOD < LOD < LOD < LOD 983

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 680

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 498

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 580

Limit of detection (LOD, see Data Analysis section) for Survey year 99-00 is 2.64. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 147

 Organophosphorus Insecticides: Specific Metabolites 

direct ingestion of agricultural strength solutions. Toxicity 

from unprotected bystander exposure during applications 

is rare (U.S.EPA, 2006). Human studies of single oral 

doses between 0.5 and 5.0 mg/kg/day have shown no 

acetylcholinesterase inhibition or other short term effects 

(IPCS, 2003). Malathion does not appear to produce human 

reproductive or teratogenic effects at environmental levels 

of exposure (Grether et al., 1987; Thomas et al., 1990), and 

it is not considered an animal teratogen or a reproductive 

toxicant. Malathion itself has not been considered 

genotoxic (U.S.EPA, 2006), but isomalathion, a malaoxon 

metabolite and a technical grade impurity tested positive 

in some chromosomal tests (Blasiak et al., 1999; Flessel 

et al., 1993; Giri et al., 2002; Pluth et al., 1996. IARC 

considers malathion not classifiable as a human carcinogen. 

Additional information about external exposure (i.e., 

environmental levels) and health effects is available from 

ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html and 

from U.S. EPA at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Levels of urinary malathion dicarboxylic acid reflect recent 

exposure. The 95th percentile urinary levels of malathion 

dicarboxylic acid in both urban and nonurban Minnesota 

children aged 3-13 years (adjusted for sociodemographic 

variables) in 1997 were several-fold higher than the analytical detection limits reported for children aged 6-11 years 

in the U.S. representative subsample from NHANES 1999-

2000 (Adgate, 2001; CDC, 2005). Malathion dicarboxylic 

acid was infrequently detected in multiple samples from 80 

Maryland residents in 1995-96 (MacIntosh et al., 1999). Of 

382 pregnant women living in an agricultural community, 

30% had detectable levels of malathion dicarboxylic acid 

at a detection limit about tenfold lower than the detection 

limit in the NHANES 1999-2000 analyses (Eskenazi et al., 

2004). A study of 13 children from an agricultural region of 

Washington State reported median levels that were below 

the detection limit in the NHANES 1999-2000 subsample 

(Kissel et al., 2005). Replacing conventional diets with 

organic diets in 23 children led to a tenfold decrease in 

urinary levels of malathion dicarboxylic acid; median 

urinary levels on the conventional diet were similar to 

the detection limit in the NHANES 1999-2000 subsample 

(CDC, 2005; Lu et al., 2006). A study of agricultural 

workers reported preshift urinary levels of malathion 

dicarboxylic acid that were twofold to eightfold higher than 

detection limits in the NHANES 1999-2000 subsample 

(Krieger and Dinoff, 2000); some of the postshift urine 

levels in duster-applicators were thousandsfold higher than 

the detection limits in the NHANES 1999-2000 subsample, 

but cholinesterase activity was not affected.

Finding a measurable amount of malathion dicarboxylic 

acid in urine does not mean that the level will result in an 

adverse health effect. Biomonitoring studies of malathion 

dicarboxylic acid provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels of 

malathion than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

Urinary Malathion dicarboxylic acid (creatinine corrected) 

Metabolite of Malathion 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1920 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD 3.74 (<LOD-5.50) 453

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660

20-59 years 99-00 * < LOD < LOD < LOD < LOD 807

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 937

Females 99-00 * < LOD < LOD < LOD < LOD 983

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 680

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 498

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 580

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 148 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

References

Adgate JL, Barr DB, Clayton CA, Eberly LE, Freeman NC, 

Lioy PJ, et al. Measurement of children’s exposure to pesticides: 

analysis of urinary metabolite levels in a probability-based 

sample. Environ Health Perspect 2001;109(6):583-590.

Blasiak J, Jaloszynski P, Trzeciak A, Szyfter K. In vitro studies on 

the genotoxicity of the organophosphorus insecticide malathion 

and its two analogues. Mutat Res 1999;445(2):275-283.

Bouchard M, Gosselin NH, Brunet RC, Samuel O, Dumoulin MJ, 

Carrier G. A toxicokinetic model of malathion and its metabolites 

as a tool to assess human exposure and risk through measurements 

of urinary biomarkers. Toxicol Sci 2003 May;73(1):182-94. 

Erratum in: Toxicol Sci 2003 Aug;74(2):following table of 

contents.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr 

DB, et al. Association of in utero organophosphate pesticide 

exposure and fetal growth and length of gestation in an agricultural 

population. Environ Health Perspect 2004;112(10):1116-1124.

Flessel P, Quintana PJ, Hooper K. Genetic toxicity of malathion: 

a review. Environ Mol Mutagen 1993;22(1):7-17.

Giri S, Prasad SB, Giri A, Sharma GD. Genotoxic effects 

of malathion: an organophosphorus insecticide using three 

mammalian bioassays in vivo. Mutat Res 2002;514(1-2):223-

231.

Grether JK, Harris JA, Neutra R, Kizer KW: Exposure to aerial 

malathion application and the occurrence of congenital anomalies 

and low birthweight. Am J Public Health 1987;77:1009-1010.

International Programme on Chemical Safety-INCHEM (IPCS). 

Pesticides residues in food: 2003 FAO/WHO Meeting on 

Pesticide Residues. Malathion (addendum). Available at URL: 

http://www.inchem.org/documents/jmpr/jmpmono/v2003pr06.

htm. 4/7/09

Kissel JC, Curl CL, Kedan G, Lu C, Griffith W, Barr DB, et al. 

Comparison of organophosphorus pesticide metabolite levels in 

single and multiple daily urine samples collected from preschool 

children in Washington State. J Expo Anal Environ Epidemiol 

2005;15(2):164-171.

Krieger RI, Dinoff TM. Malathion deposition, metabolite 

clearance, and cholinesterase status of date dusters and harvesters 

in California. Arch Environ Contam Toxicol 2000;38(4):546-553.

Lu C, Toepel K, Irish R, Fenske RA, Barr DB, Bravo R. 

Organic diets significantly lower children’s dietary exposure 

to organophosphorus pesticides. Environ Health Perspect 

2006;114(2):260-263.

MacIntosh DL, Needham LL, Hammerstrom KA, Ryan PB. A 

longitudinal investigation of selected pesticide metabolites in 

urine. J Expo Anal Environ Epidemiol 1999;9(5):494-501.

Pluth JM, Nicklas JA, O’Neill JP, Albertini RJ. Increased 

frequency of specific genomic deletions resulting from in vitro 

malathion exposure. Cancer Res 1996;56(10):2393-2399.

Thomas D, Goldhaber M, Petitti D, Swan SH, Rappaport E, 

Hertz-Picciotto I. Reproductive outcome in women exposed to 

malathion. Am J Epidemiol 1990;132(4):794-795.

U.S. Environmental Protection Agency (U.S. EPA). Reregistration 

eligibility decision (RED) Malathion. July 2006. EPA 738-R06-030. Available at URL: http://www.epa.gov/oppsrrd1/REDs/

malathion_red.pdf. 6/1/09

U.S. Geological Survey (USGS). The Quality of Our Nation’s 

Waters. Pesticides in the Nation’s Streams and Ground Water, 

1992-2001. March 2006, revised February 15, 2007 [online]. 

Available at URL: http://pubs.usgs.gov/circ/2005/1291/. 6/1/09
Fourth National Report on Human Exposure to Environmental Chemicals 149

 Organophosphorus Insecticides: Specific Metabolites 

Methyl Parathion

CAS No.298-00-0

Ethyl Parathion

CAS No. 56-38-2

General Information

Para-nitrophenol is a metabolite of the insecticides methyl 

parathion, ethyl parathion, O-ethyl-O-(4-nitrophenyl) 

phenylphosphonothioate, and of the chemical nitrobenzene. 

Methyl parathion use is highly restricted, with limited 

applications in agriculture. Many previous registered 

agricultural uses of methyl parathion have been cancelled 

(U.S.EPA, 2003). It had been applied to cotton, and to a 

lesser extent, on cereal grains. In the 1990s, peak domestic 

use was as high as 5-6 million pounds per year. Methyl 

parathion is not registered for residential use in the United 

States. Ethyl parathion, first registered in 1948, was once 

a restricted-use insecticide with limited applications on 

certain agricultural crops, but by 2003, all registered 

uses were voluntarily cancelled (U.S.EPA, 2000). Methyl 

parathion has low water solubility, binds tightly to soils 

resulting in low leachability, and has a short half-life in soils 

and on plants. Ethyl and methyl parathion are infrequently 

detected in groundwater sampling (USGS, 2007). Both are 

toxic to birds, fish, and aquatic invertebrates.

Given its limited use, the potential for human exposure to 

either ethyl or methyl parathion through the diet or drinking 

water is low. Estimated intakes from diet and drinking 

water have been below recommended limits. Increased 

risk of exposure via dermal, pulmonary, and oral routes 

can occur in pesticide and agricultural workers (Muttray et 

al., 2006). In animal studies, methyl parathion was rapidly 

absorbed after ingestion, more slowly absorbed through the 

skin, and eliminated rapidly from the body after absorption 

(Kramer et al., 2002; Morgan et al., 1977). Once absorbed, 

phosphorothioates such as methyl and ethyl parathion are 

metabolically activated to the “oxon” forms which have 

greater toxicity than the parent insecticides. Metabolism of 

ethyl or methyl parathion leads to the formation of paranitrophenol, dialkyl phosphate metabolites (see section 

titled “Organophosphorus Insecticides: Dialkyl Phosphate 

Urinary para-Nitrophenol

Metabolite of Ethyl Parathion, Methyl Parathion, and Nitrobenzene 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 2.50 (1.40-4.50) 5.00 (2.90-11.0) 1989 

01-02 * < LOD 1.33 (1.21-1.48) 2.70 (2.40-3.02) 3.71 (3.41-4.00) 2477 

Age group 

6-11 years 99-00 * < LOD .940 (<LOD-2.40) 2.67 (1.70-3.80) 4.30 (2.70-6.40) 479 

01-02 * .790 (<LOD-.910) 1.49 (1.36-1.61) 2.89 (2.22-3.58) 4.10 (3.01-4.74) 565 

12-19 years 99-00 * < LOD < LOD 3.40 (1.60-5.70) 5.70 (2.60-19.0) 680 

01-02 * .730 (<LOD-.910) 1.45 (1.32-1.61) 2.66 (2.15-3.11) 3.34 (3.11-4.01) 813 

20-59 years 99-00 * < LOD < LOD 2.30 (1.20-5.70) 4.50 (2.30-16.0) 830 

01-02 * < LOD 1.28 (1.09-1.47) 2.69 (2.32-3.10) 3.72 (3.37-4.24) 1099 

Gender 

Males 99-00 * < LOD < LOD 2.50 (1.40-4.50) 4.50 (2.50-14.0) 971 

01-02 * .770 (.300-.910) 1.50 (1.32-1.67) 3.00 (2.70-3.27) 4.10 (3.37-4.92) 1164 

Females 99-00 * < LOD < LOD 2.50 (1.30-5.70) 5.70 (2.90-9.50) 1018 

01-02 * < LOD 1.19 (.990-1.37) 2.26 (1.92-2.69) 3.46 (3.18-3.71) 1313 

Race/ethnicity 

Mexican Americans 99-00 * < LOD 1.70 (<LOD-3.50) 5.80 (2.60-24.0) 22.0 (3.60-36.0) 695 

01-02 * .700 (<LOD-.850) 1.32 (1.10-1.57) 2.62 (1.91-3.44) 3.85 (2.70-6.05) 660 

Non-Hispanic blacks 99-00 * < LOD 1.20 (<LOD-2.60) 2.90 (1.70-6.00) 4.80 (2.50-9.20) 518 

01-02 * .860 (<LOD-1.12) 1.80 (1.37-2.16) 3.21 (2.57-4.40) 5.60 (4.02-6.79) 679 

Non-Hispanic whites 99-00 * < LOD < LOD 2.10 (<LOD-6.33) 4.20 (2.10-11.0) 603 

01-02 * < LOD 1.28 (1.13-1.45) 2.71 (2.30-3.10) 3.70 (3.28-4.01) 941 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.8 and 0.1. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 150 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

Metabolites”), and other metabolites. In addition to being a 

metabolite of methyl and ethyl parathion, para-nitrophenol 

can also occur in the environment from the breakdown of 

the parent these organophosphorus pesticides and from 

nitrobenzene. Thus, the detection of para-nitrophenol 

in a person’s urine may also reflect exposure to the 

environmental degradate.

Human health effects from parathion or ethyl parathion at 

low environmental doses or at biomonitored levels from 

low environmental exposures are unknown. Parathion and 

methyl parathion have high acute toxicity in animal testing. 

In large doses, methyl parathion, ethyl parathion, and other 

organophosphorus insecticides share a common mechanism 

of toxicity: inhibition of the activity of acetylcholinesterase 

enzymes in the nervous system, resulting in excess 

acetylcholine at nerve terminals, and producing acute 

symptoms such as nausea, vomiting, cholinergic effects, 

weakness, paralysis, and seizures. The metabolite, paranitrophenol, does not inhibit acetylcholinesterase enzymes. 

At high animal doses of methyl parathion, retinal atrophy 

and sciatic nerve degeneration have also been observed 

(IPCS, 1995; WHO, 2004). Recent in vitro and in vivo animal 

studies suggest that parathion may have additional neuronal 

and glial cell effects at lower doses (Guizzetti et al., 2005; 

Karanth and Pope et al., 2003; Slotkin et al., 2006; Zurich et 

al., 2004). Overt cholinergic toxicity and death from methyl 

and ethyl parathion have been described following suicidal 

ingestion, accidental exposure, and unintentional acute or 

chronic high-level occupational exposure (Hill et al., 1990; 

Jaga and Dharmani, 2006; Lores et al., 1978; Orsorio et 

al., 1991). Methyl parathion is not considered genotoxic, 

teratogenic, or generally to have reproductive toxicity at 

doses below those causing acetylcholinesterase inhibition in 

most animal studies (IPCS, 1995). IARC does not consider 

ethyl parathion and methyl parathion classifiable as human 

carcinogens. U.S.EPA considers methyl parathion unlikely 

to be carcinogenic to humans, but lists ethyl parathion as a 

possible human carcinogen. Additional information about 

external exposure (i.e., environmental levels) and health 

effects is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html and from U.S. EPA at: http://www.epa.

gov/pesticides/.

Urinary para-Nitrophenol (creatinine corrected) 

Metabolite of Ethyl Parathion, Methyl Parathion, and Nitrobenzene 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 2.08 (1.33-3.91) 4.25 (2.15-10.2) 1989 

01-02 * < LOD .970 (.830-1.10) 1.91 (1.72-2.03) 2.89 (2.44-3.23) 2476 

Age group 

6-11 years 99-00 * < LOD .940 (<LOD-1.95) 2.80 (1.94-4.00) 4.20 (3.33-6.70) 479 

01-02 * .720 (<LOD-.870) 1.60 (1.30-1.82) 2.78 (2.31-3.11) 3.67 (3.11-4.61) 565 

12-19 years 99-00 * < LOD < LOD 1.80 (1.08-3.04) 4.00 (1.57-7.29) 680 

01-02 * .370 (<LOD-.500) .840 (.790-.950) 1.59 (1.37-1.78) 2.10 (1.78-2.43) 812 

20-59 years 99-00 * < LOD < LOD 2.00 (1.17-4.25) 4.29 (2.13-12.3) 830 

01-02 * < LOD .880 (.690-1.07) 1.79 (1.56-2.05) 2.89 (2.35-3.33) 1099 

Gender 

Males 99-00 * < LOD < LOD 1.90 (1.01-3.39) 3.39 (1.77-7.55) 971 

01-02 * .430 (.310-.530) .980 (.850-1.08) 1.87 (1.57-2.09) 2.97 (2.14-3.57) 1164 

Females 99-00 * < LOD < LOD 2.26 (1.48-4.88) 6.92 (2.76-14.1) 1018 

01-02 * < LOD .930 (.730-1.23) 1.96 (1.78-2.15) 2.82 (2.44-3.06) 1312 

Race/ethnicity 

Mexican Americans 99-00 * < LOD 1.55 (<LOD-3.17) 4.86 (2.21-21.9) 17.4 (3.94-47.7) 695 

01-02 * .400 (<LOD-.540) .930 (.720-1.20) 1.88 (1.41-2.60) 3.04 (2.38-3.84) 660 

Non-Hispanic blacks 99-00 * < LOD .680 (<LOD-1.79) 2.07 (1.33-3.71) 3.71 (1.98-7.20) 518 

01-02 * .440 (<LOD-.640) 1.01 (.800-1.31) 1.73 (1.60-2.21) 3.01 (2.16-4.30) 678 

Non-Hispanic whites 99-00 * < LOD < LOD 1.97 (<LOD-4.29) 3.83 (1.97-10.2) 603 

01-02 * < LOD .970 (.790-1.13) 1.96 (1.67-2.26) 2.93 (2.35-3.45) 941 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 151

 Organophosphorus Insecticides: Specific Metabolites 

Biomonitoring Information

Urinary levels of para-nitrophenol reflect recent exposure. 

Levels of para-nitrophenol in the NHANES 1999-2000 and 

2001-2002 subsamples were similar or slightly lower than 

those in a nonrandom subsample of NHANES III (1988-

1994) participants (CDC, 2005; Hill et al., 1995), and 

levels were similar or slightly lower that those in a small 

convenience sample of the U.S. population (Olsson et al., 

2003) and in 482 pregnant females from an agricultural 

region of California (Eskenazi et al., 2004). A study of 13 

children from an agricultural region of Washington State 

reported median levels that were more than threefold 

higher than median levels in the NHANES 1999-2000 

subsample (Kissel et al., 2005). Children and adults living 

in residences where methyl parathion was applied indoors 

had urinary levels of para-nitrophenol which were several 

hundred times higher than those in the NHANES 1999-

2000 subsample, and many residents were symptomatic 

(Barr et al., 2002; CDC, 2005; McCann et al., 2002; Rubin 

et al., 2002).

Pesticide workers may have much higher levels following 

pesticide applications. ACGIH recommends a BEI of 0.5 

mg (500 μg)/g creatinine for workers at the end of shift. 

In a study of workers who handle parathion, end-of-shift 

urinary para-nitrophenol levels ranged from 190 to 410 μg/

gram of creatinine (Leng and Lewalter, 1999), a range of 

values several hundred times higher than levels found in 

the U.S. general population (CDC, 2005).

Finding a measurable amount of para-nitrophenol in urine 

does not mean that the level will result in an adverse 

health effect. Biomonitoring studies of para-nitrophenol 

can provide physicians and public health officials with 

reference values so that they can determine whether people 

have been exposed to higher levels of parathion than are 

found in the general population. Biomonitoring data can 

also help scientists plan and conduct research on exposure 

and health effects.

References

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JR, et al. Measurement of p-nitrophenol in the urine of residents 

whose homes were contaminated with methyl parathion. Environ 

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Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr 

DB, et al. Association of in utero organophosphate pesticide 

exposure and fetal growth and length of gestation in an agricultural 

population. Environ Health Perspect 2004;112(10):1116-1124.

Guizzetti M, Pathak S, Giordano G, Costa LG. Effect of 

organophosphorus insecticides and their metabolites on astroglial 

cell proliferation. Toxicology 2005;215(3):182-190.

Hill RH Jr, Alley CC, Ashley DL, Cline RE, Head SL, Needham 

LL, et al. Laboratory investigation of a poisoning epidemic in 

Sierra Leone. J Anal Toxicol 1990;14(4):213-216.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, 

et al. Pesticide residues in urine of adults living in the United 

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International Programme on Chemical Safety-INCHEM (IPCS). 

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www.inchem.org/documents/jmpr/jmpmono/v95pr14.htm. 

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Jaga K, Dharmani C. Methyl parathion: an organophosphate 

insecticide not quite forgotten. Rev Environ Health 2006;21(1):57-

67.

Karanth S, Pope C. Age-related effects of chlorpyrifos and 

parathion on acetylcholine synthesis in rat striatum. Neurotoxicol 

Teratol 2003;25(5):599-606.

Kissel JC, Curl CL, Kedan G, Lu C, Griffith W, Barr DB, et al. 

Comparison of organophosphorus pesticide metabolite levels in 

single and multiple daily urine samples collected from preschool 

children in Washington State. J Expo Anal Environ Epidemiol 

2005;15(2):164-171.

Kramer RE, Wellman SE, Rockhold RW, Baker RC. 

Pharmacokinetics of methyl parathion: a comparison following 

single intravenous, oral or dermal administration. J Biomed Sci 

2002;9:311-320.

Leng G, Lewalter J. Role of individual susceptibility in risk 

assessment of pesticides. Occup Environ Med 1999;56(7):449-

553.

Lores EM, Bradway DE, Moseman RF. Organophosphorus 

pesticide poisonings in humans: determination of residues 

and metabolites in tissues and urine. Arch Environ Health 

1978;33(5):270-276.

McCann KG, Moomey CM, Runkle KD, Hryhorczuk DO, Clark 

JM, Barr DB. Chicago area methyl parathion response. Environ 

Health Perspect 2002;110 Suppl 6:1075-1078.

Morgan DP, Hetzler HL, Slach EF, Lin LI. Urinary excretion 

of paranitrophenol and alkyl phosphates following ingestion 

of methyl or ethyl parathion by human subjects. Arch Environ 

Contam Toxicol 1977;6(2-3):159-173.
 152 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

Muttray A, Backer G, Jung D, Hill G, Letzel S. External and 

internal exposure of wine growers spraying methyl parathion. 

Toxicol Lett 2006;162(2-3):219-224.

Olsson AO, Nguyen JV, Sadowski MA, Barr DB. A 

liquid chromatography/electrospray ionization tandem 

mass spectrometry method for quantification of specific 

organophosphorus pesticide biomarkers in human urine. Anal 

Bioanal Chem 2003;376(6):808-815.

Osorio AM, Ames RG, Rosenberg J, Mengle DC. Investigation 

of a fatality among parathion applicators in California. Am J Ind 

Med 1991;20(4):533-546.

Rubin C, Esteban E, Kieszak S, Hill RH Jr, Dunlop B, Yacovac 

R, et al. Assessment of human exposure and human health effects 

after indoor application of methyl parathion in Lorain County, 

Ohio, 1995-1996. Environ Health Perspect 2002;110 Suppl 

6:1047-1051.

Slotkin TA, Tate CA, Ryde IT, Levin ED, Seidler FJ. 

Organophosphate insecticides target the serotonergic system in 

developing rat brain regions: disparate effects of diazinon and 

parathion at doses spanning the threshold for cholinesterase 

inhibition. Environ Health Perspect 2006;114(10):1542-1546.

U.S. Environmental Protection Agency (U.S. EPA). R.E.D. Facts. 

Ethyl parathion. September 2000. EPA-738-FOO-009. Available 

at URL: http://www.epa.gov/oppsrrd1/REDs/factsheets/0155fct.

pdf. 1/14/09

U.S. Environmental Protection Agency (U.S. EPA). Interim 

reregistration eligibility decision (IRED) for Methyl Parathion. 

Case No. 0153. May 2003. Available at URL: http://www.epa.

gov/oppsrrd1/REDs/methylparathion_ired.pdf. 1/12/07

U.S. Geological Survey (USGS). The Quality of Our Nation’s 

Waters. Pesticides in the Nation’s Streams and Ground Water, 

1992-2001. March 2006, revised February 15, 2007 [online]. 

Available at URL: http://pubs.usgs.gov/circ/2005/1291/. 6/1/09

World Health Organization (WHO). Methyl parathion in drinking 

water. WHO/SDE/WSH/03.04/106. 2004. Available at URL: 

http://www.who.int/water_sanitation_health/dwq/chemicals/

methylparathion.pdf. 5/19/09

Zurich MG, Honegger P, Schilter B, Costa LG, Monnet-Tschudi 

F. Involvement of glial cells in the neurotoxicity of parathion and 

chlorpyrifos. Toxicol Appl Pharmacol 2004;201(2):97-104.
Fourth National Report on Human Exposure to Environmental Chemicals 153

 Organophosphorus Insecticides: Specific Metabolites 

Pirimiphos-methyl

CAS No. 29232-93-7

General Information

The chemical 2-(diethylamino)-6-methylpyrimidin-4-ol/

one is a metabolite of the organophosphorus insecticide 

pirimiphos-methyl, which has limited applications for 

control of beetles, weevils, and moths on stored grain 

products such as corn, sorghum, and seed. It has a 

lesser use as a cattle ear tag application to control flies. 

Pirimiphos-methyl is not registered for residential use in 

the United States. It easily hydrolyzes in the environment 

to 2-(diethylamino)-6-methylpyrimidine and other 

breakdown products, and it is not considered persistent. 

Though considered moderately-to-highly toxic in birds, 

fish, and aquatic invertebrates, occurrence of such toxicity 

is mitigated by its rapid degradation and its use in closed 

storage systems.

In the general population, infrequent dietary exposure to 

pirimiphos-methyl residues may occur from ingestion 

of food products containing stored corn or other treated 

grain (FDA, 2003). Estimated intakes from diet and 

water have not exceeded recommended intake limits 

(U.S.EPA, 2006). In animal studies, pirimiphos-methyl 

is rapidly absorbed and metabolized to 12 metabolites, 

which are mainly excreted in the urine (IPCS, 1992). Once 

absorbed, phosphorothioates such as pirimiphos-methyl 

are metabolically activated to the “oxon” form which has 

greater toxicity than the parent insecticide. Metabolic 

hydrolysis leads to the formation of 2-(diethylamino)-6-

methylpyrimidin-4-ol/one, dialkyl phosphate metabolites 

(see section titled “Organophosphorus Insecticides: Dialkyl 

Phosphate Metabolites”), and other metabolites. In addition 

to being a human metabolite of pirimiphos-methyl in the 

body, 2-(diethylamino)-6-methylpyrimidin-4-ol/one can 

also occur in the environment. Thus, the detection of 

2-(diethylamino)-6-methylpyrimidin-4-ol/one may also 

reflect exposure to the environmental degradate.

Human health effects from pirimiphos-methyl at low 

environmental doses or at biomonitored levels from 

low environmental exposures are unknown. Pirimiphosmethyl has low acute toxicity in animal studies. At high 

doses, pirimiphos-methyl and other organophosphorus 

insecticides share a mechanism of toxicity: inhibition of 

the activity of acetylcholinesterase enzymes in the nervous 

system, resulting in excess acetylcholine at nerve terminals, 

and producing acute symptoms such as nausea, vomiting, 

cholinergic effects, weakness, paralysis, and seizures. The 

metabolite 2-(diethylamino)-6-methylpyrimidin-4-ol/one 

does not inhibit acetylcholinesterase enzymes. Toxic effects 

below doses that cause inhibition of acetylcholinesterase are 

unknown. Pirimiphos-methyl is not considered mutagenic, 

teratogenic, or known to cause delayed neurotoxicity, 

or reproductive toxicity (IPCS, 1992; U.S.EPA, 2006). 

Additional information about pesticides is available from 

U.S. EPA at: http://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of 2-(diethylamino)-6-methylpyrimidin-4-

ol/one reflect recent exposure. In the U.S. subsample of 

NHANES 2001-2002, most of the urinary measurements 

of 2-(diethylamino)-6-methylpyrimidin-4-ol/one were 

below the limit of detection, although the 95th percentile 

was characterized at 0.47 μg/L for the total population 

(CDC, 2005). In a nonrandom sample of 140 urine 

specimens obtained from adults and children in the United 

States, Olsson et al. (2003) detected 2-(diethylamino)-

6-methylpyrimidin-4-ol/one in 7.1% of the sampled 

population.

Finding a measurable amount of 2-(diethylamino)-6-

methylpyrimidin-4-ol/one in urine does not mean that the 

level will result in an adverse health effect. Biomonitoring 

studies of 2-(diethylamino)-6-methylpyrimidin-4-ol/

one provide physicians and public health officials with 

reference values so that they can determine whether people 

have been exposed to higher levels of pirimiphos-methyl 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.
 154 Fourth National Report on Human Exposure to Environmental Chemicals 

Organophosphorus Insecticides: Specific Metabolites 

Urinary 2-(Diethylamino)-6-methylpyrimidin-4-ol/one 

Metabolite of Pirimiphos-methyl 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD .470 (.210-.770) 2481 

Age group 

6-11 years 01-02 * < LOD < LOD .250 (<LOD-.820) .840 (.210-1.64) 567

12-19 years 01-02 * < LOD < LOD < LOD .610 (<LOD-1.94) 810

20-59 years 01-02 * < LOD < LOD < LOD .430 (<LOD-.670) 1104 

Gender 

Males 01-02 * < LOD < LOD < LOD .850 (.300-1.55) 1165 

Females 01-02 * < LOD < LOD < LOD .210 (<LOD-.460) 1316 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD .410 (<LOD-1.15) 669

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 687

Non-Hispanic whites 01-02 * < LOD < LOD < LOD .500 (.200-.840) 929

Limit of detection (LOD, see Data Analysis section) for Survey year 01-02 is 0.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary 2-(Diethylamino)-6-methylpyrimidin-4-ol/one (creatinine corrected) 

Metabolite of Pirimiphos-methyl 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD .780 (.700-.930) 2481 

Age group 

6-11 years 01-02 * < LOD < LOD .680 (<LOD-.950) 1.17 (.740-1.27) 567

12-19 years 01-02 * < LOD < LOD < LOD .670 (<LOD-1.31) 810

20-59 years 01-02 * < LOD < LOD < LOD .760 (<LOD-.880) 1104 

Gender 

Males 01-02 * < LOD < LOD < LOD .740 (.580-1.07) 1165 

Females 01-02 * < LOD < LOD < LOD .780 (<LOD-1.08) 1316 

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD .780 (<LOD-1.21) 669

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 687

Non-Hispanic whites 01-02 * < LOD < LOD < LOD .780 (.700-1.00) 929

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 155

 Organophosphorus Insecticides: Specific Metabolites 

References

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Food and Drug Administration (FDA). Total Diet Study: 

Summary of Residues Found Ordered by Pesticide, Market 

Baskets 91-3-01-4. June 2003. Available at URL: http://www.

cfsan.fda.gov/~acrobat/tds1byps.pdf. 4/7/09

International Programme on Chemical Safety-INCHEM (IPCS). 

Pesticides residues in food: 1992 evaluations Part II Toxicology. 

850. Pirimiphos-methyl. Available at URL: http://www.inchem.

org/documents/jmpr/jmpmono/v92pr16.htm. 4/7/09

Olsson AO, Nguyen JV, Sadowski MA, Barr DB. A 

liquid chromatography/electrospray ionization tandem 

mass spectrometry method for quantification of specific 

organophosphorus pesticide biomarkers in human urine. Anal 

Bioanal Chem 2003;376(6):808-815.

U.S. Environmental Protection Agency (U.S. EPA). Finalization 

of interim registration eligibility decision for pirimiphos-methyl. 

Case No. 2535. July 2006. Available at URL: http://www.epa.

gov/oppsrrd1/REDs/pirimiphos-methyl_ired.pdf. 1/14/09
 156 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Pyrethroid Pesticides

General Information

Pyrethroid pesticides are synthetic analogues of pyrethrins, 

which are natural chemicals found in chrysanthemum 

flowers. Pyrethroid pesticides are used to control a wide 

range of insects in public and commercial buildings, animal 

facilities, warehouses, agricultural fields, and greenhouses. 

They are also applied on livestock to control insects. In 

agriculture, cypermethrin, cyfluthrin, and deltamethrin 

have been used frequently on cotton. Pyrethroid 

insecticides are the most common active ingredient in 

commercially available insect sprays and are also used 

as structural termiticides. Certain pyrethroid insecticides 

(such as permethrin, resmethrin, and sumithrin) are also 

registered for use in mosquito-control programs in the 

United States. Outside the U.S., deltamethrin has been used 

for indoor protection against mosquitoes that carry malaria, 

in some situations replacing the use of DDT. About two 

million pounds of permethrin and one million pounds of 

cypermethrin have been applied annually (U.S. EPA, 2006a, 

2006b). Permethrin is also used in skin lotions and shampoos 

as medical treatments for lice and scabies. Pyrethroid 

pesticides are generally formulated as complex mixtures 

of different chemical isomers, solvent oils, and synergists, 

such as piperonyl butoxide. Pyrethroid pesticides have low 

volatility, bind to soils, and are rarely detected in ground 

waters (USGS, 2007). Generally, they are not persistent in 

the environment due to their rapid degradation within days 

to several months. This class of pesticides has low toxicity 

in birds and mammals, but pyrethroids are highly toxic to 

fish and some aquatic invertebrates, so usage is restricted 

near water (U.S.EPA, 2002). There are about 30 different 

pyrethroid pesticides in use. The table shows the urinary 

pyrethroid metabolites measured in this Report.

The general population may be exposed to pyrethroid 

insecticides primarily from the ingestion of food or from 

residential use. Estimated intakes from diet and drinking 

water are below recommended limits. Dermal exposure 

with the potential for inadvertent ingestion may occur 

when lotions or shampoos are applied to treat lice or 

scabies. Pesticide applicators can be exposed to pyrethroid 

pesticides via dermal and inhalation routes from powders 

and liquid formulations. Pyrethroids are not well absorbed 

through the skin (ATSDR, 2003; Woollen et al., 1992). 

After absorption from inhalation or ingestion, pyrethroids 

are rapidly metabolized, by either ester hydrolysis 

or hydroxylation, followed by conjugation, and then 

eliminated over several days in urine and bile (Kuhn et al., 

1999; Leng et al., 1997; Soderlund et al., 2002; Woollen et 

al., 1992). Unmetabolized pyrethroids have been measured 

in breast milk, but may be poorly transferred across the 

placenta (ATSDR, 2003; WHO, 2005).

Human health effects from pyrethroid pesticides at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Compared with 

other classes of insecticides such as organochlorines, 

organophosphorus, or carbamate pesticides, pyrethroid 

pesticides have less acute toxicity in animals and people. 

They are ranked as having moderate acute oral toxicity. 

Adverse effects from large doses are related to the 

action of pyrethroids on the nervous system, where these 

chemicals prolong sodium channel opening when a nerve 

cell is depolarized (Shafer et al., 2005; Soderlund et al., 

2002). Possible other additional actions on neuroreceptors 

Pyrethroid Insecticides Metabolites in this Report

Pyrethroid (CAS number) Urinary metabolite (CAS number)

Cyfluthrin (68359-37-5) 4-Fluoro-3-phenoxybenzoic acid (77279-89-1) 

Cypermethrin (52315-07-8) 

Cyfluthrin (68359-37-5) and 

Permethrin (52645-53-1) 

cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

(55701-05-8 ) 

trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic 

acid (55701-03-6)

Deltamethrin (52918-63-5) cis-3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid 

Cyhalothrin (68359-37-5) 

Cypermethrin (52315-07-8) 

Deltamethrin (52918-63-5) 

Fenpropathrin (39515-41-8) 

Permethrin (52645-53-1) 

Tralomethrin (66841-25-6) 

3-Phenoxybenzoic acid (3739-38-6) 
Fourth National Report on Human Exposure to Environmental Chemicals 157

 Pyrethroid Pesticides 

and other ion channels may also explain some pyrethroid 

effects. Human cases of systemic poisoning are rare and 

usually result from accidental exposure or intentional 

ingestion of pyrethroid insecticides. Signs and symptoms 

of acute pyrethroid poisoning after massive ingestions 

include agitation, hypersensitivity, tremor, salivation, 

choreoathetosis, and seizures (ATSDR, 2003; Ray et al., 

2000; Soderlund et al., 2002). Concomitant exposure to 

organophosphorus insecticides may increase pyrethroid 

toxicity by slowing metabolic clearance of the pyrethroid. 

In California, cyfluthrin was the most frequent pyrethroid 

associated with symptomatic effects (irritant respiratory 

and dermal effects, paresthesias) reported in agricultural 

workers from 1996 to 2002 (Spencer and O’Malley, 2006). 

Transient dermal paresthesias have been reported among 

pesticide applicators after direct contact with certain 

types of pyrethroid pesticides. No relationship of indoor 

air or housedust concentrations of permethrin and irritant 

symptoms was found in a study of urban residents in 80 

private homes (Berger-Preiss et al., 2002).

In developing rodents, neurochemical changes in 

cholinergic, dopaminergic, and catecholaminergic 

pathways and behavioral changes have been demonstrated 

at subacute and subchronic doses for some pyrethroid 

pesticides (Aziz et al., 2001; Elwan et al., 2006; Eriksson 

and Fredriksson, 1991; Lazarini et al., 2001; Shafer, et al., 

2005). The pyrethroids in general use are not considered 

teratogenic or to have significant reproductive toxicity 

(ATSDR, 2003; WHO, 2005), though a few pyrethroid 

pesticides and some metabolites have shown weak or 

inconsistent estrogenic effects on standardized assays 

(ATSDR, 2003; Garey and Wolff, 1998; Go et al., 1999; 

Hu et al., 2003; Kim et al., 2004; Kunimatsu et al., 2002; 

McCarthy et al., 2006; Moniz et al., 2005). Generally, the 

pyrethroids are not considered genotoxic in in vitro testing 

or carcinogenic in animal testing (WHO, 2005). IARC 

considers deltamethrin and permethrin as not classifiable 

as to their human carcinogenicity. Additional information 

about pesticides is available from U.S. EPA at: http://www.

epa.gov/pesticides/ and from ATSDR at: http://www.atsdr.

cdc.gov/toxpro2.html.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for pyrethrins and pyrethroids. September 

2003. Available from URL: http://www.atsdr.cdc.gov/toxprofiles/

tp155.html.1/15/09

Aziz MH, Agrawal AK, Adhami VM, Shukla Y, Seth PK. 

Neurodevelopmental consequences of gestational exposure 

(GD14-GD20) to low dose deltamethrin in rats. Neurosci Lett 

2001;300(3):161-165.

Berger-Preiss E, Levsen K, Leng G, Idel H, Sugiri D, Ranft U. 

Indoor pyrethroid exposure in homes with woollen textile floor 

coverings. Int J Hyg Environ Health 2002;205(6):459-472.

Elwan MA, Richardson JR, Guillot TS, Caudle WM, Miller GW. 

Pyrethroid pesticide-induced alterations in dopamine transporter 

function. Toxicol Appl Pharmacol 2006;211(3):188-197.

Eriksson P, Fredriksson A. Neurotoxic effects of two different 

pyrethroids, bioallethrin and deltamethrin, on immature and adult 

mice: changes in behavioral and muscarinic receptor variables. 

Toxicol Appl Pharmacol 1991;108(1):78-85.

Garey J, Wolff MS. Estrogenic and antiprogestagenic activities 

of pyrethroid insecticides. Biochem Biophys Res Commun 

1998;251(3):855-859.

Go V, Garey J, Wolff MS, Pogo BG. Estrogenic potential of certain 

pyrethroid compounds in the MCF-7 human breast carcinoma 

cell line. Environ Health Perspect 1999;107(3):173-177.

Hu JY, Wang SL, Zhao RC, Yang J, Chen JH, Song L, et al. 

[Effects of fenvalerate on reproductive and endocrine systems of 

male rats] Zhonghua Nan Ke Xue 2002;8(1):18-21.

Kim IY, Shin JH, Kim HS, Lee SJ, Kang IH, Kim TS, et al. 

Assessing estrogenic activity of pyrethroid insecticides using in 

vitro combination assays. J Reprod Dev 2004;50(2):245-255.

Kuhn K, Wieseler B, Leng G, Idel H. Toxicokinetics of pyrethroids 

in humans: consequences for biological monitoring. Bull Environ 

Contam Toxicol 1999;62:101-108.

Kunimatsu T, Yamada T, Ose K, Sunami O, Kamita Y, Okuno 

Y, et al. Lack of (anti-) androgenic or estrogenic effects of three 

pyrethroids (esfenvalerate, fenvalerate, and permethrin) in the 

Hershberger and uterotrophic assays. Regul Toxicol Pharmacol 

2002;35(2 Pt 1):227-237.

Lazarini CA, Florio JC, Lemonica IP, Bernardi MM. Effects of 

prenatal exposure to deltamethrin on forced swimming behavior, 

motor activity, and striatal dopamine levels in male and female 

rats. Neurotoxicol Teratol 2001;23(6):665-673.

Leng G, Leng A, Kuhn KH, Lewalter J, Pauluhn J. Human doseexcretion studies with the pyrethroid insecticide cyfluthrin: 

urinary metabolite profile following inhalation. Xenobiotica 

1997;27(12):1273-1283.

McCarthy AR, Thomson BM, Shaw IC, Abell AD. Estrogenicity 

of pyrethroid insecticide metabolites. J Environ Monit 

2006;8(1):197-202.

Moniz AC, Cruz-Casallas PE, Salzgeber SA, Varoli FM, Spinosa 

HS, Bernardi MM. Behavioral and endocrine changes induced 

by perinatal fenvalerate exposure in female rats. Neurotoxicol 

Teratol 2005;27(4):609-614.
 158 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Ray DE, Forshaw PJ. Pyrethroid insecticides: poisoning 

syndromes, synergies, and therapy. J Toxicol Clin Toxicol 

2000;38:95-101.

Shafer TJ, Meyer DA, Crofton KM. Developmental neurotoxicity 

of pyrethroid insecticides: critical review and future research 

needs. Environ Health Perspect 2005;113(2):123-136.

Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo 

VJ, Sargent D, et al. Mechanisms of pyrethroid neurotoxicity: 

implications for cumulative risk assessment. Toxicology 

2002;171:3-59.

Spencer J, O’Malley M. Pyrethroid illnesses in California, 1996-

2002. Rev Environ Contam Toxicol 2006;186:57-72.

U.S. Environmental Protection Agency (U.S. EPA). Permethrin, 

resmethrin, sumithrin synthetic pyrethroids for mosquito control. 

April 2002. Available at URL: http://www.epa.gov/pesticides/

health/mosquitoes/pyrethroids4mosquitoes.htm. 5/26/09

U.S. Environmental Protection Agency (U.S. EPA). Permethrin 

Facts (Reregistration Eligibility Decision Fact Sheet). June 

2006a. Available at URL: http://www.epa.gov/oppsrrd1/REDs/

factsheets/permethrin_fs.htm. 5/26/09

U.S. Environmental Protection Agency (U.S. EPA). Reregistration 

Eligibility Decision for Cypermethrin. June 2006b. Available at 

URL: http://www.epa.gov/oppsrrd1/REDs/cypermethrin_red.

pdf. 5/26/09

U.S. Geological Survey (USGS). Pesticides in the Nation’s 

Streams and Ground Water, 1992–2001. March 2006, Revised 

February 25, 2007. Available at URL: http://pubs.usgs.gov/

circ/2005/1291/. 5/26/09

Woollen BH, Marsh JR, Laird WJ, Lesser JE. The metabolism 

of cypermethrin in man: differences in urinary metabolite 

profiles following oral and dermal administration. Xenobiotica 

1992;22(8):983-991.

World Health Organization (WHO). Pesticide and Evaluation 

Scheme. Safety of pyrethroids for public health use. 2005. 

Available at URL: http://whqlibdoc.who.int/hq/2005/WHO_

CDS_WHOPES_GCDPP_2005.10.pdf. 5/26/09
Fourth National Report on Human Exposure to Environmental Chemicals 159

 Pyrethroid Pesticides 

Cyfluthrin

CAS No.68359-37-5

General Information

The chemical 4-fluoro-3-phenoxybenzoic acid is a 

specific metabolite of the pyrethroid insecticide cyfluthrin. 

Cyfluthrin accounted for one-third of pyrethroid-related 

worker illnesses reported in California from 1996-2002; 

most of which were dermal and respiratory irritations 

(Spencer and O’Malley, 2006). Cyfluthrin is rapidly 

metabolized and eliminated from the body. Following an 

indoor application exposure, the mean elimination half-life 

of cyfluthrin from the plasma was 16 hours (Williams et 

al., 2003).

Degradation of cyfluthrin to 4-fluoro-3-phenoxybenzoic 

acid occurs in the environment. Thus, the presence of 

4-fluoro-3-phenoxybenzoic acid in urine not only reflects 

the metabolic transformation of cyfluthrin, but it can also 

reflect direct exposure to 4-fluoro-3-phenoxybenzoic acid 

formed in the environment.

Biomonitoring Information

Urinary levels of 4-fluoro-3-phenoxybenzoic acid reflect 

recent exposure to cyfluthrin or its environmental degradate. 

Urinary levels of 4-fluoro-3-phenoxybenzoic acid were 

generally below the limit of detection (0.2 μg/L) in the 

U.S. representative subsample in NHANES 2001-2002 

(CDC, 2005). In an analysis of 217 urine specimens from a 

nonrandom sample of United States residents, Baker et al. 

(2004) reported a geometric mean concentration of 4-fluoro3-phenoxybenzoic acid of 0.95 μg/L. Studies in Germany 

of 396 children and adolescents (Becker et al., 2006) and 

1177 urban adults and children (Heudorf et al., 2001) 

showed that urinary levels of 4-fluoro-3-phenoxybenzoic 

acid at the 95th percentile ranged from either slightly higher 

or lower than the detection limit in the U.S. representative 

2001-2002 NHANES subsample (CDC, 2005). Urinary 

levels for adults and children in these studies were similar 

(Heudorf et al., 2001, 2006) and estimated daily intakes 

based on urinary levels in children were considered to be 

below acceptable daily intakes (Heudorf et al., 2004).

In 57 volunteers entering areas previously spot-sprayed 

with various pyrethroid pesticides (including cyfluthrin), 

median urinary levels of 4-fluoro-3-phenoxybenzoic 

acid were slightly less than the limit of detection in the 

NHANES 2001-2002 subsample (CDC, 2005; Leng et al., 

2003). Seven individuals participating in floor exercises on 

cyfluthrin treated carpet demonstrated a rise in the urinary 

excretion of 4-fluoro-3-phenoxybenzoic acid in the 72 

hours following the activity (Williams et al., 2003).

Finding a measurable amount of 4-fluoro-3-phenoxybenzoic 

acid in urine does not mean that the level will result in an 

adverse health effect. Biomonitoring studies of 4-fluoro3-phenoxybenzoic acid in urine provide physicians and 

public health officials with reference values so that they 

can determine whether other people have been exposed to 

higher levels of cyfluthrin than levels found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.
 160 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Urinary 4-Fluoro-3-phenoxybenzoic acid 

Metabolite of Cyfluthrin 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1949 

01-02 * < LOD < LOD < LOD < LOD 2539 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 473

01-02 * < LOD < LOD < LOD < LOD 580

12-19 years 99-00 * < LOD < LOD < LOD < LOD 662

01-02 * < LOD < LOD < LOD < LOD 831

20-59 years 99-00 * < LOD < LOD < LOD < LOD 814

01-02 * < LOD < LOD < LOD < LOD 1128 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 950

01-02 * < LOD < LOD < LOD < LOD 1193 

Females 99-00 * < LOD < LOD < LOD < LOD 999

01-02 * < LOD < LOD < LOD < LOD 1346 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 666

01-02 * < LOD < LOD < LOD < LOD 680

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 517

01-02 * < LOD < LOD < LOD < LOD 701

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 594

01-02 * < LOD < LOD < LOD < LOD 957

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.2 and 0.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 161

 Pyrethroid Pesticides 

Urinary 4-Fluoro-3-phenoxybenzoic acid (creatinine corrected) 

Metabolite of Cyfluthrin 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1949 

01-02 * < LOD < LOD < LOD < LOD 2538 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 473

01-02 * < LOD < LOD < LOD < LOD 580

12-19 years 99-00 * < LOD < LOD < LOD < LOD 662

01-02 * < LOD < LOD < LOD < LOD 830

20-59 years 99-00 * < LOD < LOD < LOD < LOD 814

01-02 * < LOD < LOD < LOD < LOD 1128 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 950

01-02 * < LOD < LOD < LOD < LOD 1193 

Females 99-00 * < LOD < LOD < LOD < LOD 999

01-02 * < LOD < LOD < LOD < LOD 1345 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 666

01-02 * < LOD < LOD < LOD < LOD 680

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 517

01-02 * < LOD < LOD < LOD < LOD 700

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 594

01-02 * < LOD < LOD < LOD < LOD 957

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 162 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

References

Baker SE, Olsson AO, Barr DB. Isotope dilution highperformance liquid chromatography-tandem mass spectrometry 

method for quantifying urinary metabolites of synthetic pyrethroid 

insecticides. Arch Environ Contam Toxicol 2004;46(3):281-288.

Becker K, Seiwert M, Angerer J, Kolossa-Gehring M, Hoppe HW, 

Ball M, et al. GerES IV pilot study: assessment of the exposure of 

German children to organophosphorus and pyrethroid pesticides. 

Int J Hyg Environ Health 2006;209(3):221-233.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Heudorf U, Angerer J, Drexler H. Current internal exposure to 

pesticides in children and adolescents in Germany: urinary levels 

of metabolites of pyrethroid and organophosphorus insecticides. 

Int Arch Occup Environ Health 2004;77(1):67-72.

Heudorf U, Angerer J. Metabolites of pyrethroid insecticides 

in urine specimens: current exposure in an urban population in 

Germany. Environ Health Perspect 2001;109(3):213-217.

Heudorf U, Butte W, Schulz C, Angerer J. Reference values for 

metabolites of pyrethroid and organophosphorous insecticides in 

urine for human biomonitoring in environmental medicine. Int J 

Hyg Environ Health 2006;209(3):293-299.

Leng G, Ranft U, Sugiri D, Hadnagy W, Berger-Preiss E, Idel H. 

Pyrethroids used indoors—biological monitoring of exposure to 

pyrethroids following an indoor pest control operation. Int J Hyg 

Environ Health 2003;206(2):85-92.

Spencer J, O’Malley M. Pyrethroid illnesses in California, 1996-

2002. Rev Environ Contam Toxicol 2006;186:57-72.

Williams RL, Bernard CE, Krieger RI. Human exposure to 

indoor residential cyfluthrin residues during a structured activity 

program. J Expo Anal Environ Epidemiol 2003;13(2):112-119.
Fourth National Report on Human Exposure to Environmental Chemicals 163

 Pyrethroid Pesticides 

Cyfluthrin

CAS No.68359-37-5

Cypermethrin

CAS No. 52315-07-8

Permethrin

CAS No.52645-53-1

General Information

Several pyrethroid pesticides are formulated as a mixture 

of cis- and trans-isomers. In the body, cis-3-(2,2-

dichlorovinyl)-2,2-dimethylcyclopropane carboxylic 

acid is a metabolite formed from cis-permethrin, ciscypermethrin and cis-cyfluthrin. The chemical trans-3-

(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic 

acid is a metabolite formed from trans-permethrin, transcypermethrin and trans-cyfluthrin. The cis-isomer of 

permethrin has more potent insecticidal activity than transpermethrin. Generally, more of the trans-metabolite than 

the cis-metabolite is found in the urine.

The presence of cis-3-(2,2-dichlorovinyl)-2,2-

dimethylcyclopropane carboxylic acid in urine not only 

reflects the metabolic transformation of any of the three 

pesticides, cis-permethrin, cis-cypermethrin, and ciscyfluthrin, but it can also reflect exposure to cis-3-(2,2-

dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

that is formed in the environment from the degradation 

of these pesticides (George, 1985; Kuhn et al., 1999). 

Similarly, the presence of trans-3-(2,2-dichlorovinyl)-

2,2-dimethylcyclopropane carboxylic acid in urine not 

only reflects the metabolic transformation of any of the 

three pesticides, trans-permethrin, trans-cypermethrin, and 

trans-cyfluthrin, but can also reflect exposure to trans-3-

(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic 

acid formed in the environment from the degradation of 

these pesticides (George, 1985; Kuhn et al., 1999).

Biomonitoring Information

Urinary levels of cis- or trans-3-(2,2-dichlorovinyl)-

Urinary cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

Metabolite of cis-Permethrin, Cyfluthrin, and cis-Cypermethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD .270 (.220-.340) .600 (.490-.710) 1.12 (.770-1.68) 1951 

01-02 * < LOD .160 (.120-.210) .500 (.380-.680) .890 (.740-1.10) 2539 

Age group 

6-11 years 99-00 * < LOD .330 (.210-.550) .740 (.580-1.53) 1.77 (.680-3.15) 468 

01-02 * < LOD .110 (<LOD-.200) .370 (.280-.610) .730 (.490-.870) 580 

12-19 years 99-00 * < LOD .300 (.200-.410) .670 (.460-1.11) 1.44 (.670-2.21) 667 

01-02 * < LOD .160 (<LOD-.210) .440 (.300-.630) .730 (.630-.920) 831 

20-59 years 99-00 * < LOD .260 (.200-.330) .570 (.430-.690) 1.07 (.670-1.80) 816 

01-02 * < LOD .170 (.120-.230) .510 (.400-.740) .960 (.790-1.28) 1128 

Gender 

Males 99-00 * < LOD .250 (.200-.310) .530 (.420-.600) .790 (.600-1.50) 947 

01-02 * < LOD .150 (.110-.200) .470 (.380-.630) .880 (.650-1.35) 1193 

Females 99-00 * < LOD .280 (.220-.380) .680 (.490-1.08) 1.47 (.950-2.54) 1004 

01-02 * < LOD .180 (.120-.240) .510 (.370-.770) .890 (.790-1.08) 1346 

Race/ethnicity 

Mexican Americans 99-00 * < LOD .200 (.110-.240) .460 (.300-.610) .730 (.470-1.32) 671 

01-02 * < LOD .140 (.110-.180) .300 (.250-.410) .510 (.380-.580) 680 

Non-Hispanic blacks 99-00 .202 (.155-.262) .160 (.120-.200) .380 (.270-.520) .820 (.490-1.68) 1.68 (.910-5.43) 518 

01-02 * < LOD .270 (.220-.350) .640 (.570-.700) .850 (.710-1.24) 701 

Non-Hispanic whites 99-00 * < LOD .270 (.220-.340) .630 (.460-.780) 1.13 (.740-2.35) 591 

01-02 * < LOD .140 (<LOD-.220) .500 (.340-.790) .900 (.670-1.28) 957 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.1 and 0.1. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 164 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

2,2-dimethylcyclopropane carboxylic acid reflect recent 

exposure to either their parent pyrethroid pesticides or 

their environmental degradates. Studies in Germany of 396 

children and adolescents (Becker et al., 2006) and 1177 

urban adults and children (Heudorf et al., 2001) showed 

urinary levels of cis- and trans-3-(2,2-dichlorovinyl)-2,2-

dimethylcyclopropane carboxylic acids at the 95th percentile 

that were similar or slightly less than the 95th percentiles in 

the U.S. representative NHANES 2001-2002 subsample 

(CDC, 2005). Urinary levels of the two chemicals in adults 

were similar to those in children in these studies (Heudorf 

et al., 2001, 2006). Estimated daily pyrethroid intakes based 

on urinary levels in the German children were below the 

acceptable daily tolerances (Heudorf et al., 2004). These 

studies indicated that intake is mainly from the diet and that 

dermal absorption contributes little to intake (Heudorf et 

al., 2004, 2006; Schettgen et al., 2002). Other studies have 

provided evidence that urinary levels of cis- and trans-3-

(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic 

acids in children were related to residential pesticide use 

and house dust levels (Becker et al., 2006; Lu et al., 2006).

In a study of urban residents in Germany (Berger-Preiss et 

al., 2002), urinary levels of cis-3-(2,2-dichlorovinyl)-2,2-

dimethylcyclopropane carboxylic acid at the 95th percentile 

were about half the 95th percentile in the NHANES 2001-

2002 subsample (CDC, 2005). In the same residents, urinary 

trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane 

carboxylic acid levels at the 95th percentile were about 

one-third of the 95th percentile in the NHANES 2001-

2002 subsample (CDC, 2005). In a study of volunteers, the 

median and 95th percentile of urinary levels of cis-3-(2,2-

dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

did not increase at 24-72 hours after exposure to nearby 

pest control operations (Leng et al., 2003); the levels at 

24-72 hours were slightly less than the 95th percentile in 

the NHANES 2001-2002 subsample (CDC, 2005). In 

these volunteers, median urinary levels of trans-3-(2,2-

dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

did not increase, though the 95th percentile levels increased 

several fold after exposure to nearby pest control operations 

(Leng et al., 2003); the levels at 24-72 hours were slightly 

less than the 95th percentile in the NHANES 2001-2002 

subsample (CDC, 2005)

In a small group of indoor pest-control operators, postUrinary cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (creatinine corrected) 

Metabolite of cis-Permethrin, Cyfluthrin, and cis-Cypermethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD .260 (.230-.290) .540 (.440-.700) 1.12 (.690-1.59) 1951 

01-02 * < LOD .220 (.200-.250) .440 (.370-.520) .780 (.640-1.03) 2538 

Age group 

6-11 years 99-00 * < LOD .400 (.250-.550) .900 (.550-1.67) 1.67 (.700-2.31) 468 

01-02 * < LOD .250 (<LOD-.320) .600 (.430-.700) .750 (.640-.890) 580 

12-19 years 99-00 * < LOD .200 (.150-.270) .430 (.320-.590) .810 (.430-1.49) 667 

01-02 * < LOD .160 (<LOD-.200) .300 (.250-.380) .530 (.370-.780) 830 

20-59 years 99-00 * < LOD .260 (.230-.290) .530 (.380-.830) 1.11 (.680-1.59) 816 

01-02 * < LOD .230 (.210-.250) .440 (.390-.560) .890 (.640-1.08) 1128 

Gender 

Males 99-00 * < LOD .220 (.180-.250) .420 (.340-.570) .800 (.510-1.11) 947 

01-02 * < LOD .170 (.150-.190) .350 (.300-.410) .680 (.450-1.03) 1193 

Females 99-00 * < LOD .290 (.270-.340) .640 (.470-1.33) 1.59 (1.12-2.21) 1004 

01-02 * < LOD .270 (.230-.300) .500 (.440-.580) .920 (.750-1.11) 1345 

Race/ethnicity 

Mexican Americans 99-00 * < LOD .190 (.130-.260) .380 (.280-.540) .710 (.400-1.24) 671 

01-02 * < LOD .170 (.150-.190) .300 (.260-.350) .540 (.370-.640) 680 

Non-Hispanic blacks 99-00 .138 (.104-.182) .120 (.080-.170) .260 (.200-.340) .590 (.360-1.11) 1.29 (.710-3.37) 518 

01-02 * < LOD .180 (.140-.220) .390 (.290-.550) .840 (.550-1.11) 700 

Non-Hispanic whites 99-00 * < LOD .280 (.250-.300) .550 (.450-.880) 1.33 (.680-1.80) 591 

01-02 * < LOD .240 (<LOD-.270) .450 (.390-.560) .840 (.580-1.14) 957 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 165

 Pyrethroid Pesticides 

application median urinary levels of summed cis- and 

trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane 

carboxylic acid (Hardt and Angerer, 2003) were similar to 

the 95th percentiles for adults in the NHANES 2001-2002 

subsample (CDC, 2005). The maximum post-application 

urinary levels, however, were up to 27 times higher than 

the 95th percentile for adults in the NHANES 2001-2002 

subsample (CDC, 2005).

Finding a measurable amount of cis- or trans-3-(2,2-

dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

in urine does not mean that the level causes an adverse 

health effect. Biomonitoring studies on urinary levels of cisor trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane 

carboxylic acid provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels 

of pyrethroid pesticides than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Urinary trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

Metabolite of Cyfluthrin, trans-Cypermethrin, and trans-Permethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD .560 (.480-.700) 1.40 (1.17-1.77) 3.42 (2.39-5.56) 1976 

01-02 * < LOD .420 (<LOD-.570) 1.20 (.910-1.77) 2.54 (1.68-3.70) 2525 

Age group 

6-11 years 99-00 * < LOD .970 (.700-1.66) 2.91 (1.76-4.19) 4.19 (2.97-11.7) 478 

01-02 * < LOD .470 (<LOD-.760) 1.39 (1.03-1.68) 2.50 (1.55-3.54) 576 

12-19 years 99-00 * < LOD .710 (.520-.860) 2.07 (1.25-3.42) 4.28 (2.12-6.23) 675 

01-02 * < LOD .490 (<LOD-.670) 1.20 (.800-1.60) 2.01 (1.49-3.77) 826 

20-59 years 99-00 * < LOD .500 (.400-.620) 1.17 (.910-1.68) 2.94 (1.49-5.56) 823 

01-02 * < LOD < LOD 1.17 (.850-1.85) 2.56 (1.64-4.66) 1123 

Gender 

Males 99-00 * < LOD .560 (.500-.670) 1.28 (1.11-1.63) 2.25 (1.55-5.10) 961 

01-02 * < LOD .410 (<LOD-.500) 1.09 (.810-1.63) 2.37 (1.55-4.48) 1184 

Females 99-00 * < LOD .550 (.410-.820) 1.77 (1.07-3.08) 4.19 (3.08-6.81) 1015 

01-02 * < LOD .440 (<LOD-.660) 1.26 (.920-1.95) 2.56 (1.76-3.58) 1341 

Race/ethnicity 

Mexican Americans 99-00 * < LOD .470 (.410-.530) 1.23 (.830-1.60) 1.87 (1.49-3.35) 691 

01-02 * < LOD .410 (<LOD-.520) .940 (.680-1.16) 1.59 (1.11-2.01) 680 

Non-Hispanic blacks 99-00 * < LOD .780 (.490-1.13) 1.84 (1.08-4.69) 4.69 (1.41-14.5) 518 

01-02 * < LOD .580 (.460-.750) 1.27 (1.03-1.68) 2.22 (1.68-2.95) 690 

Non-Hispanic whites 99-00 * < LOD .560 (.460-.730) 1.41 (1.14-2.14) 3.89 (2.14-6.43) 595 

01-02 * < LOD .400 (<LOD-.610) 1.20 (.840-1.90) 2.62 (1.60-4.66) 954 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.4 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 166 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Urinary trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (creatinine corrected) 

Metabolite of Cyfluthrin, trans-Cypermethrin, and trans-Permethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD .700 (.610-.780) 1.56 (1.33-1.87) 2.65 (2.15-3.89) 1976 

01-02 * < LOD .720 (<LOD-.780) 1.45 (1.22-1.88) 2.55 (2.15-3.10) 2524 

Age group 

6-11 years 99-00 * < LOD 1.31 (.720-1.74) 2.37 (1.56-5.07) 5.60 (1.91-11.3) 478 

01-02 * < LOD .900 (<LOD-1.13) 2.16 (1.40-2.61) 2.86 (2.34-3.44) 576 

12-19 years 99-00 * < LOD .530 (.440-.730) 1.42 (.820-2.19) 2.19 (1.34-4.31) 675 

01-02 * < LOD .530 (<LOD-.660) .970 (.800-1.29) 1.57 (1.07-2.60) 825 

20-59 years 99-00 * < LOD .700 (.570-.770) 1.33 (1.12-1.87) 2.39 (1.87-3.36) 823 

01-02 * < LOD < LOD 1.47 (1.22-2.00) 2.55 (2.07-3.11) 1123 

Gender 

Males 99-00 * < LOD .560 (.480-.670) 1.26 (1.07-1.42) 2.15 (1.47-2.74) 961 

01-02 * < LOD .520 (<LOD-.580) 1.08 (.880-1.35) 2.20 (1.45-2.57) 1184 

Females 99-00 * < LOD .880 (.720-1.11) 1.91 (1.48-2.39) 3.67 (2.30-6.28) 1015 

01-02 * < LOD .880 (<LOD-1.00) 1.75 (1.47-2.15) 2.81 (2.30-3.19) 1340 

Race/ethnicity 

Mexican Americans 99-00 * < LOD .580 (.500-.750) 1.35 (1.02-1.65) 2.00 (1.56-2.80) 691 

01-02 * < LOD .570 (<LOD-.640) 1.08 (.930-1.22) 1.87 (1.27-2.15) 680 

Non-Hispanic blacks 99-00 * < LOD .570 (.470-.740) 1.70 (.850-3.13) 3.36 (1.87-8.91) 518 

01-02 * < LOD .470 (.410-.540) 1.12 (.800-1.41) 1.98 (1.20-2.68) 689 

Non-Hispanic whites 99-00 * < LOD .760 (.700-.850) 1.64 (1.33-2.00) 3.31 (2.00-5.60) 595 

01-02 * < LOD .780 (<LOD-.850) 1.48 (1.27-2.07) 2.55 (2.15-3.11) 954 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 167

 Pyrethroid Pesticides 

References

Becker K, Seiwert M, Angerer J, Kolossa-Gehring M, Hoppe HW, 

Ball M, et al. GerES IV pilot study: assessment of the exposure of 

German children to organophosphorus and pyrethroid pesticides. 

Int J Hyg Environ Health 2006;209(3):221-233.

Berger-Preiss E, Levsen K, Leng G, Idel H, Sugiri D, Ranft U. 

Indoor pyrethroid exposure in homes with woollen textile floor 

coverings. Int J Hyg Environ Health 2002;205(6):459-472.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

George DA. Permethrin and its two metabolite residues in seven 

agricultural crops. J AOAC 1985;68(6):1160-1163.

Hardt J, Angerer J. Biological monitoring of workers after the 

application of insecticidal pyrethroids. Int Arch Occup Environ 

Health 2003;76(7):492-498.

Heudorf U, Angerer J, Drexler H. Current internal exposure to 

pesticides in children and adolescents in Germany: urinary levels 

of metabolites of pyrethroid and organophosphorus insecticides. 

Int Arch Occup Environ Health 2004;77(1):67-72.

Heudorf U, Angerer J. Metabolites of pyrethroid insecticides 

in urine specimens: current exposure in an urban population in 

Germany. Environ Health Perspect 2001;109(3):213-217.

Heudorf U, Butte W, Schulz C, Angerer J. Reference values for 

metabolites of pyrethroid and organophosphorous insecticides in 

urine for human biomonitoring in environmental medicine. Int J 

Hyg Environ Health 2006;209(3):293-299.

Kuhn K, Wieseler B, Leng G, Idel H. Toxicokinetics of pyrethroids 

in humans: consequences for biological monitoring. Bull Environ 

Contam Toxicol 1999;62:101-108.

Leng G, Ranft U, Sugiri D, Hadnagy W, Berger-Preiss E, Idel H. 

Pyrethroids used indoors—biological monitoring of exposure to 

pyrethroids following an indoor pest control operation. Int J Hyg 

Environ Health 2003;206(2):85-92.

Lu C, Barr DB, Pearson M, Bartell S, Bravo R. A longitudinal 

approach to assessing urban and suburban children’s exposure to 

pyrethroid pesticides. Environ Health Perspect 2006;114(9):1419-

1423.

Schettgen T, Heudorf U, Drexler H, Angerer J. Pyrethroid 

exposure of the general population-is this due to diet? Toxicol 

Lett 2002;134(1-3):141-145.
 168 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Deltamethrin

CAS No. 52918-63-5

General Information

Cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane 

carboxylic acid is a metabolite of the pyrethroid insecticide 

deltamethrin. Outside the U.S., deltamethrin has been used 

against mosquitoes that carry malaria, in some situations 

replacing the use of DDT. Deltamethrin can degrade to cis-3-

(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic 

acid in the environment (IPCS, 1990). Thus, in detection 

of cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane 

carboxylic acid in the urine may reflect exposure 

to deltamethrin or to cis-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropane carboxylic acid formed in the 

environment.

Biomonitoring Information

Urinary levels of cis-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropane carboxylic acid reflect recent 

exposure to deltamethrin or its environmental degradate. 

In the NHANES 2001-2002 subsample, urinary levels 

of cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane 

carboxylic acid were below the limit of detection (CDC, 

2005). In an analysis of 217 urine specimens from a 

nonrandom sample of United States residents, Baker et al. 

(2004) reported a geometric mean concentration of cis-3-

(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic 

acid of 0.39 μg/L. Studies in Germany of 396 children and 

adolescents (Becker et al., 2006) and 1177 urban adults and 

children (Heudorf et al., 2001) showed that urinary levels 

of cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane 

carboxylic acid at the 95th percentile ranged slightly higher 

(0.3-0.5 μg/L) than the detection limit (0.1 μg/L) for the 

NHANES 2001-2002 subsample (CDC, 2005). Urinary 

levels for adults and children in these studies were similar 

(Heudorf et al., 2001, 2006) and estimated daily intakes 

based on urinary levels in children were considered to be 

below acceptable daily intakes (Heudorf et al., 2004).

Following residential spraying with deltamethrin for 

malaria protection in Mexico, mean peak urinary levels 

of cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane 

carboxylic acid in children increased at least 450-fold 

relative to the non-detectable background levels for several 

days and mean levels remained slightly above background 

levels 45 days after the spraying (Ortiz-Perez et al., 2005). 

The peak mean levels in these children were more than 

800-fold higher than the detection limit in the 2001-2002 

NHANES subsample.

Finding a measurable amount of cis-3-(2,2-dibromovinyl)-

2,2-dimethylcyclopropane carboxylic acid in urine does not 

mean that the level will result in an adverse health effect. 

Biomonitoring studies provide physicians and public health 

officials with reference values so that they can determine 

whether other people have been exposed to higher levels 

of deltamethrin than levels found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.
Fourth National Report on Human Exposure to Environmental Chemicals 169

 Pyrethroid Pesticides 

Urinary cis-3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid 

Metabolite of Deltamethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1698 

01-02 * < LOD < LOD < LOD < LOD 2539 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 415 

01-02 * < LOD < LOD < LOD < LOD 580 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 570 

01-02 * < LOD < LOD < LOD < LOD 831 

20-59 years 99-00 * < LOD < LOD < LOD < LOD 713 

01-02 * < LOD < LOD < LOD < LOD 1128 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 818 

01-02 * < LOD < LOD < LOD < LOD 1193 

Females 99-00 * < LOD < LOD < LOD < LOD 880 

01-02 * < LOD < LOD < LOD < LOD 1346 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 578 

01-02 * < LOD < LOD < LOD < LOD 680 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 445 

01-02 * < LOD < LOD < LOD < LOD 701 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 527 

01-02 * < LOD < LOD < LOD < LOD 957 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.1 and 0.1. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 170 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Urinary cis-3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (creatinine corrected) 

Metabolite of Deltamethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1698 

01-02 * < LOD < LOD < LOD < LOD 2538 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 415 

01-02 * < LOD < LOD < LOD < LOD 580 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 570 

01-02 * < LOD < LOD < LOD < LOD 830 

20-59 years 99-00 * < LOD < LOD < LOD < LOD 713 

01-02 * < LOD < LOD < LOD < LOD 1128 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 818 

01-02 * < LOD < LOD < LOD < LOD 1193 

Females 99-00 * < LOD < LOD < LOD < LOD 880 

01-02 * < LOD < LOD < LOD < LOD 1345 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 578 

01-02 * < LOD < LOD < LOD < LOD 680 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 445 

01-02 * < LOD < LOD < LOD < LOD 700 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 527 

01-02 * < LOD < LOD < LOD < LOD 957 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 171

 Pyrethroid Pesticides 

References

Becker K, Seiwert M, Angerer J, Kolossa-Gehring M, Hoppe HW, 

Ball M, et al. GerES IV pilot study: assessment of the exposure of 

German children to organophosphorus and pyrethroid pesticides. 

Int J Hyg Environ Health 2006;209(3):221-233.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Heudorf U, Angerer J, Drexler H. Current internal exposure to 

pesticides in children and adolescents in Germany: urinary levels 

of metabolites of pyrethroid and organophosphorus insecticides. 

Int Arch Occup Environ Health 2004;77(1):67-72.

Heudorf U, Angerer J. Metabolites of pyrethroid insecticides 

in urine specimens: current exposure in an urban population in 

Germany. Environ Health Perspect 2001;109(3):213-217.

Heudorf U, Butte W, Schulz C, Angerer J. Reference values for 

metabolites of pyrethroid and organophosphorous insecticides in 

urine for human biomonitoring in environmental medicine. Int J 

Hyg Environ Health 2006;209(3):293-299.

International Programme On Chemical Safety (IPCS). 

Environmental Health Criteria 97. Deltamethrin. [online] 1990. 

Available at URL: http://www.inchem.org/documents/ehc/ehc/

ehc97.htm. 5/26/09

Ortiz-Perez MD, Torres-Dosal A, Batres LE, Lopez-Guzman OD, 

Grimaldo M, Carranza C, et al. Environmental health assessment 

of deltamethrin in a malarious area of Mexico: environmental 

persistence, toxicokinetics, and genotoxicity in exposed children. 

Environ Health Perspect 2005;113(6):782-786.
 172 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Cyhalothrin

CAS No. 68359-37-5

Cypermethrin

CAS No.52315-07-8

Deltamethrin

CAS No. 52918-63-5

Fenpropathrin

CAS No. 39515-41-8

Permethrin

CAS No. 52645-53-1

Tralomethrin 

CAS No. 66841-25-6

General Information

The chemical 3-phenoxybenzoic acid is a metabolite and 

an environmental degradate of the six pyrethroid pesticides 

listed above. Thus, the presence of 3-phenoxybenzoic acid 

in urine not only reflects the metabolic transformation 

of any of the six pesticides listed above, but can reflect 

direct exposure to 3-phenoxybenzoic acid formed in the 

environment from the degradation of these pesticides.

Biomonitoring Information

Urinary levels of 3-phenoxybenzoic acid reflect recent 

exposure to the parent pyrethroid pesticides. In an analysis 

of 217 urine specimens from a nonrandom sample of 

United States residents, Baker et al. (2004) reported 

geometric mean levels of 3-phenoxybenzoic acid that were 

approximately sixfold higher than levels for adults in the 

NHANES 2001-2002 subsample (CDC, 2005). Median 

levels of urinary 3-phenoxybenzoic acid were 67-fold 

higher in 307 pregnant New York City women who used 

indoor pesticides compared with the median levels for 

adults in the NHANES 2001-2002 subsample (Berkowitz 

et al., 2003; CDC, 2005). In the New York City study, a 

temporal variation in levels was observed and considered 

to correspond to seasonal spraying of pesticides. A study 

of 396 German children (Becker et al., 2006) showed that 

urinary levels of 3-phenoxybenzoic acid at the 95th percentile 

were similar to levels at the 95th percentile for children in 

the U.S. representative NHANES 2001-2002 subsample 

(CDC, 2005). Urinary levels of 3-phenoxybenzoic acid in 

children were found to be related to residential pesticide 

use and house dust levels (Lu et al., 2006; Becker et al., 

2006). A small sample of occupationally unexposed Italian 

residents had median levels of urinary 3-phenoxybenzoic 

acid that were about fourfold higher than for adults in the 

NHANES 2001-2002 subsample (CDC, 2005; Saieva et al., 

2004). In one study of 145 urban residents in 80 private 

homes in Germany, urinary 3-phenoxybenzoic acid levels 

at the 95th percentile were about threefold lower than the 

levels at the 95th percentile in the 2001-2002 NHANES 

subsample (Berger-Preiss et al., 2002; CDC, 2005).

In 57 volunteers entering areas previously spot-sprayed 

with various pyrethroid pesticides, median urinary levels 

of 3-phenoxybenzoic acid were slightly less than median 

levels in the NHANES 2001-2002 subsample (Leng et 

al., 2003; CDC, 2005). Following residential spraying 

with deltamethrin for malaria protection in Mexico, mean 

peak urinary levels of 3-phenoxybenzoic acid in children 

increased at least sixtyfold over non-detectable background 

levels for several days and mean levels remained slightly 

above background levels 45 days after the spraying (OrtizPerez et al., 2005). The mean peak levels in these children 

were 83-fold higher than the geometric mean for children 

in the NHANES 2001-2002 subsample (CDC, 2005). In 

a small group of indoor pest-control operators, the postapplication median urinary levels of 3-phenoxybenzoic 

acid were 24-fold higher than those for adults in the 

NHANES 2001-2002 subsample (CDC, 2005; Hardt and 

Angerer, 2003).

Finding a measurable amount in urine does not mean that the 

level will result in an adverse health effect. Biomonitoring 

studies of 3-phenoxybenzoic acid provide physicians and 

public health officials with reference values so that they 

can determine whether other people have been exposed to 

higher levels of pyrethroids than levels found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.
Fourth National Report on Human Exposure to Environmental Chemicals 173

 Pyrethroid Pesticides 

Urinary 3-Phenoxybenzoic acid 

Metabolite of Cypermethrin, Deltamethrin, and Permethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 .292 (.247-.345) .250 (.190-.320) .730 (.590-.850) 1.75 (1.49-2.16) 4.33 (2.62-6.30) 1998 

01-02 .321 (.276-.374) .280 (.230-.340) .700 (.560-.830) 1.69 (1.41-2.33) 3.32 (2.52-5.25) 2539 

Age group 

6-11 years 99-00 .417 (.292-.595) .320 (.210-.490) 1.12 (.700-1.60) 4.18 (2.02-6.54) 8.63 (3.89-71.1) 483

01-02 .325 (.260-.406) .300 (.200-.420) .760 (.570-1.05) 1.81 (1.42-2.78) 3.38 (2.25-4.12) 580

12-19 years 99-00 .336 (.265-.427) .290 (.200-.440) .870 (.620-1.04) 1.93 (1.49-2.90) 4.33 (1.83-11.1) 682

01-02 .353 (.288-.434) .300 (.250-.390) .800 (.560-1.13) 1.86 (1.48-2.35) 3.45 (2.14-6.69) 831

20-59 years 99-00 .267 (.227-.314) .230 (.160-.300) .640 (.510-.820) 1.49 (1.25-1.78) 3.21 (2.04-5.41) 833

01-02 .314 (.271-.364) .270 (.220-.340) .670 (.530-.780) 1.65 (1.27-2.34) 3.25 (2.51-6.16) 1128 

Gender 

Males 99-00 .273 (.226-.330) .250 (.180-.330) .710 (.570-.820) 1.49 (1.29-1.73) 2.41 (1.92-3.79) 974

01-02 .328 (.277-.387) .300 (.230-.370) .680 (.560-.750) 1.55 (1.26-2.35) 3.23 (2.56-5.78) 1193 

Females 99-00 .311 (.253-.384) .250 (.190-.340) .740 (.510-.990) 2.30 (1.63-3.36) 6.03 (3.27-11.8) 1024 

01-02 .315 (.266-.373) .260 (.210-.320) .740 (.550-.940) 1.76 (1.48-2.39) 3.38 (2.34-6.16) 1346 

Race/ethnicity 

Mexican Americans 99-00 .260 (.230-.295) .230 (.190-.270) .600 (.430-.750) 1.35 (1.16-1.53) 2.18 (1.53-3.26) 697

01-02 .297 (.238-.369) .260 (.200-.360) .650 (.490-.810) 1.30 (.830-2.26) 2.71 (1.51-3.44) 680

Non-Hispanic blacks 99-00 .454 (.352-.586) .450 (.350-.610) 1.13 (.750-1.46) 2.32 (1.45-5.35) 5.35 (2.32-21.1) 524

01-02 .507 (.428-.601) .520 (.430-.630) .960 (.840-1.12) 2.01 (1.65-2.28) 3.25 (2.52-4.62) 701

Non-Hispanic whites 99-00 .288 (.233-.355) .240 (.160-.320) .710 (.530-.850) 1.78 (1.41-3.05) 5.34 (2.62-8.43) 603

01-02 .298 (.246-.362) .240 (.190-.320) .590 (.470-.800) 1.72 (1.27-2.46) 3.50 (2.25-7.64) 957

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.1 and 0.1. 
 174 Fourth National Report on Human Exposure to Environmental Chemicals 

Pyrethroid Pesticides 

Urinary 3-Phenoxybenzoic acid (creatinine corrected) 

Metabolite of Cypermethrin, Deltamethrin, and Permethrin 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 .261 (.224-.304) .250 (.200-.280) .550 (.460-.630) 1.40 (1.13-1.73) 3.19 (2.16-4.55) 1998 

01-02 .316 (.274-.365) .280 (.240-.330) .580 (.490-.720) 1.48 (1.13-1.91) 3.10 (2.21-4.88) 2538 

Age group 

6-11 years 99-00 .450 (.299-.677) .370 (.240-.590) 1.13 (.730-1.62) 3.96 (1.75-8.07) 9.91 (2.43-64.0) 483

01-02 .423 (.335-.534) .380 (.300-.500) .860 (.590-1.35) 2.21 (1.61-2.95) 3.32 (2.64-5.40) 580

12-19 years 99-00 .227 (.178-.290) .210 (.160-.270) .490 (.380-.730) 1.37 (1.03-1.62) 2.52 (1.41-4.44) 682

01-02 .274 (.229-.328) .240 (.190-.310) .540 (.420-.730) 1.11 (.860-1.63) 2.35 (1.36-6.19) 830

20-59 years 99-00 .246 (.216-.278) .240 (.200-.270) .510 (.400-.590) 1.11 (.860-1.49) 2.53 (1.73-4.09) 833

01-02 .311 (.271-.357) .280 (.240-.330) .550 (.440-.670) 1.44 (1.02-1.91) 3.22 (1.91-4.92) 1128 

Gender 

Males 99-00 .210 (.173-.253) .190 (.150-.250) .510 (.390-.580) 1.09 (.840-1.41) 1.72 (1.49-2.52) 974

01-02 .264 (.226-.309) .240 (.200-.280) .490 (.410-.570) 1.17 (.960-1.60) 2.81 (1.60-4.00) 1193 

Females 99-00 .323 (.270-.387) .270 (.240-.330) .610 (.480-.740) 1.94 (1.35-3.00) 5.04 (3.19-6.90) 1024 

01-02 .378 (.321-.446) .330 (.290-.400) .720 (.530-.930) 1.67 (1.25-2.37) 3.43 (2.25-5.19) 1345 

Race/ethnicity 

Mexican Americans 99-00 .234 (.202-.272) .220 (.190-.230) .480 (.370-.590) 1.04 (.700-1.39) 1.67 (1.06-3.00) 697

01-02 .275 (.230-.329) .240 (.210-.320) .510 (.400-.650) 1.03 (.750-1.67) 1.83 (1.15-2.74) 680

Non-Hispanic blacks 99-00 .309 (.238-.401) .270 (.220-.350) .640 (.460-.930) 1.49 (1.05-3.43) 3.86 (1.51-7.25) 524

01-02 .362 (.300-.437) .350 (.280-.410) .640 (.530-.760) 1.36 (1.17-1.83) 2.84 (1.63-3.80) 700

Non-Hispanic whites 99-00 .272 (.225-.329) .250 (.200-.290) .550 (.440-.670) 1.55 (1.09-2.27) 4.02 (2.07-5.49) 603

01-02 .312 (.261-.372) .280 (.230-.330) .560 (.440-.810) 1.54 (1.09-2.35) 3.43 (1.88-5.48) 957
Fourth National Report on Human Exposure to Environmental Chemicals 175

 Pyrethroid Pesticides 

References

Baker SE, Olsson AO, Barr DB. Isotope dilution highperformance liquid chromatography-tandem mass spectrometry 

method for quantifying urinary metabolites of synthetic pyrethroid 

insecticides. Arch Environ Contam Toxicol 2004;46(3):281-288.

Becker K, Seiwert M, Angerer J, Kolossa-Gehring M, Hoppe HW, 

Ball M, et al. GerES IV pilot study: assessment of the exposure of 

German children to organophosphorus and pyrethroid pesticides. 

Int J Hyg Environ Health 2006;209(3):221-233.

Berger-Preiss E, Levsen K, Leng G, Idel H, Sugiri D, Ranft U. 

Indoor pyrethroid exposure in homes with woollen textile floor 

coverings. Int J Hyg Environ Health 2002;205(6):459-472.

Berkowitz GS, Obel J, Deych E, Lapinski R, Godbold J, Liu Z, et al. 

Exposure to indoor pesticides during pregnancy in a multiethnic, 

urban cohort. Environ Health Perspect 2003;111(1):79-84.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Hardt J, Angerer J. Biological monitoring of workers after the 

application of insecticidal pyrethroids. Int Arch Occup Environ 

Health 2003;76(7):492-498.

Leng G, Ranft U, Sugiri D, Hadnagy W, Berger-Preiss E, Idel H. 

Pyrethroids used indoors—biological monitoring of exposure to 

pyrethroids following an indoor pest control operation. Int J Hyg 

Environ Health 2003;206(2):85-92.

Lu C, Barr DB, Pearson M, Bartell S, Bravo R. A longitudinal 

approach to assessing urban and suburban children’s exposure to 

pyrethroid pesticides. Environ Health Perspect 2006;114(9):1419-

1423.

Ortiz-Perez MD, Torres-Dosal A, Batres LE, Lopez-Guzman OD, 

Grimaldo M, Carranza C, et al. Environmental health assessment 

of deltamethrin in a malarious area of Mexico: environmental 

persistence, toxicokinetics, and genotoxicity in exposed children. 

Environ Health Perspect 2005;113(6):782-786.
 176 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Antimony

CAS No. 7440-36-0

General Information

Antimony is found in ores or other minerals, often combined 

with oxygen to form antimony trioxide or with sulfur to 

form stibnite. Antimony can exist in one of four valences 

in its various chemical and physical forms: -3, 0, +3, and 

+5. It is used in metal alloys, storage batteries, solder, sheet 

and pipe metal, ammunition, metal bearings, castings, 

and pewter. It is also used in paints, ceramics, fireworks, 

enamels, and glass, and as a fire-retardant in textiles and 

plastics. Stibine is a metal hydride form of antimony used 

in the semiconductor industry. Two antimony compounds 

(sodium stibogluconate and antimony potassium tartrate) 

have been used as antiparasitic medications.

Antimony enters the environment from natural sources and 

from its use in industry. People are exposed to antimony 

primarily through food and, to a lesser extent, from air and 

drinking water. Workplace exposures can occur at smelters, 

coal-fired plants, and refuse incinerators that process or 

release antimony. Dermal contact with soil, water, or 

other substances containing antimony is another means of 

exposure. The absorption, distribution, and excretion of 

antimony vary depending on its oxidation state. Urinary 

excretion appears to be greater for pentavalent antimony 

Urinary Antimony 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .132 (.120-.145) .130 (.120-.150) .220 (.200-.230) .330 (.300-.350) .430 (.390-.470) 2276

01-02 .134 (.126-.142) .130 (.130-.140) .190 (.180-.200) .270 (.250-.310) .350 (.320-.400) 2690

03-04 * .080 (<LOD-.090) .130 (.120-.150) .200 (.190-.220) .280 (.250-.320) 2558

Age group 

6-11 years 99-00 .176 (.154-.200) .190 (.160-.210) .260 (.230-.280) .350 (.300-.400) .440 (.320-.600) 316

01-02 .146 (.134-.160) .150 (.130-.160) .200 (.180-.210) .270 (.240-.330) .340 (.280-.440) 368

03-04 .099 (.087-.114) .100 (.070-.120) .160 (.120-.200) .240 (.190-.310) .310 (.230-.330) 290

12-19 years 99-00 .158 (.141-.178) .170 (.150-.180) .240 (.210-.270) .350 (.290-.420) .460 (.350-.510) 663

01-02 .169 (.156-.184) .160 (.150-.180) .240 (.220-.260) .350 (.320-.410) .460 (.400-.500) 762

03-04 .105 (.095-.115) .100 (.090-.120) .150 (.140-.160) .230 (.200-.270) .290 (.250-.370) 725

20 years and older 99-00 .123 (.112-.137) .120 (.110-.130) .200 (.180-.220) .310 (.290-.350) .430 (.390-.470) 1297

01-02 .128 (.119-.136) .130 (.120-.130) .180 (.170-.190) .250 (.220-.300) .330 (.280-.390) 1560

03-04 * .070 (<LOD-.080) .120 (.100-.140) .190 (.170-.210) .270 (.220-.320) 1543

Gender 

Males 99-00 .143 (.131-.157) .150 (.130-.160) .240 (.220-.260) .350 (.330-.390) .470 (.390-.570) 1132

01-02 .145 (.136-.154) .140 (.130-.150) .200 (.190-.210) .310 (.280-.330) .390 (.350-.440) 1335

03-04 .095 (.088-.103) .090 (.080-.100) .140 (.130-.160) .220 (.200-.250) .320 (.270-.350) 1281

Females 99-00 .122 (.109-.137) .120 (.110-.140) .200 (.180-.220) .300 (.280-.340) .400 (.350-.460) 1144

01-02 .125 (.117-.133) .120 (.120-.130) .180 (.160-.190) .240 (.220-.280) .320 (.260-.360) 1355

03-04 * < LOD .120 (.090-.140) .180 (.150-.220) .230 (.190-.330) 1277

Race/ethnicity 

Mexican Americans 99-00 .132 (.108-.161) .140 (.120-.170) .210 (.180-.240) .300 (.260-.390) .430 (.330-.560) 787

01-02 .142 (.130-.154) .130 (.130-.150) .200 (.170-.230) .260 (.240-.320) .360 (.300-.400) 683

03-04 .093 (.079-.110) .090 (<LOD-.120) .140 (.120-.160) .190 (.160-.260) .270 (.210-.330) 618

Non-Hispanic blacks 99-00 .175 (.148-.207) .180 (.150-.200) .260 (.230-.300) .400 (.310-.490) .490 (.410-.710) 554

01-02 .180 (.164-.197) .170 (.160-.190) .250 (.220-.280) .360 (.320-.410) .460 (.370-.530) 667

03-04 .108 (.098-.119) .110 (.100-.120) .160 (.150-.190) .230 (.200-.280) .310 (.250-.360) 723

Non-Hispanic whites 99-00 .128 (.115-.144) .130 (.110-.140) .210 (.190-.230) .330 (.280-.350) .400 (.360-.500) 768

01-02 .126 (.117-.135) .130 (.120-.130) .180 (.170-.190) .250 (.230-.300) .340 (.310-.390) 1132

03-04 * .070 (<LOD-.080) .130 (.110-.140) .190 (.170-.210) .280 (.230-.320) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.04, 0.04, and 0.07, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 177

 Metals

than for trivalent compounds (Elinder and Friberg, 1986). 

An elimination half-life of approximately 95 hours has 

been estimated after occupational exposures (Kentner et 

al., 1995).

Human health effects from antimony at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Inorganic antimony salts irritate 

the mucous membranes, skin, and eyes. Acute inhalation 

of antimony has been associated with irritation of the 

respiratory tract and impaired pulmonary function (Renes, 

1953). Pulmonary edema may occur in severe cases of 

inhalation exposure (Cordasco et al., 1973). Dysrhythmias 

and T-wave changes on electrocardiogram have also been 

noted after both therapeutic (Berman, 1988; Ming-Hsin 

et al., 1958) and occupational exposures (Briegner et al., 

1954). Histopathologic inflammatory and degenerative 

changes in the lung, myocardium, liver, and kidney have 

been demonstrated in high dose animal studies depending 

on the dose, species, and route of exposure (Elinder and 

Friberg, 1986). Acute antimony poisoning may cause 

a metallic taste, and gastrointestinal symptoms such as 

vomiting, diarrhea, abdominal pain, and ulcers (Werrin, 

1962). The toxicity of stibine after acute inhalational 

exposure is similar to that of arsine, resulting in hemolysis 

with abdominal and back pain (Dernehl et al., 1944).

Workplace standards and recommendations for air exposure 

Urinary Antimony (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .124 (.108-.143) .119 (.102-.143) .185 (.164-.214) .276 (.233-.333) .385 (.333-.430) 2276

01-02 .126 (.119-.134) .120 (.115-.126) .173 (.162-.188) .267 (.242-.300) .364 (.320-.414) 2689

03-04 * .080 (<LOD-.086) .135 (.119-.143) .208 (.192-.230) .277 (.250-.294) 2558

Age group 

6-11 years 99-00 .191 (.147-.248) .185 (.156-.220) .250 (.200-.417) .447 (.271-.741) .741 (.333-1.30) 316

01-02 .178 (.159-.200) .173 (.150-.193) .228 (.200-.272) .338 (.265-.480) .471 (.313-.727) 368

03-04 .116 (.103-.130) .118 (.098-.136) .167 (.146-.187) .256 (.194-.317) .333 (.250-.500) 290

12-19 years 99-00 .121 (.104-.140) .120 (.095-.146) .176 (.146-.207) .259 (.206-.310) .310 (.228-.421) 663

01-02 .121 (.112-.131) .115 (.106-.127) .160 (.138-.186) .224 (.199-.245) .266 (.244-.310) 762

03-04 .075 (.068-.082) .068 (.061-.077) .100 (.092-.113) .156 (.126-.173) .193 (.172-.255) 725

20 years and older 99-00 .118 (.104-.135) .111 (.097-.135) .175 (.149-.209) .263 (.227-.320) .352 (.320-.391) 1297

01-02 .122 (.115-.129) .115 (.108-.121) .167 (.153-.181) .265 (.241-.300) .364 (.318-.405) 1559

03-04 * .079 (<LOD-.087) .135 (.116-.145) .209 (.195-.233) .278 (.250-.294) 1543

Gender 

Males 99-00 .112 (.099-.127) .109 (.095-.127) .164 (.146-.181) .226 (.204-.268) .320 (.235-.391) 1132

01-02 .114 (.107-.123) .108 (.103-.115) .153 (.138-.171) .228 (.205-.250) .333 (.281-.438) 1334

03-04 .080 (.076-.084) .075 (.069-.081) .122 (.111-.132) .192 (.173-.209) .253 (.230-.278) 1281

Females 99-00 .137 (.117-.161) .131 (.108-.164) .213 (.176-.247) .320 (.263-.417) .429 (.357-.485) 1144

01-02 .139 (.131-.148) .132 (.124-.140) .196 (.178-.211) .295 (.267-.317) .371 (.333-.444) 1355

03-04 * < LOD .143 (.125-.161) .225 (.188-.261) .288 (.250-.333) 1277

Race/ethnicity 

Mexican Americans 99-00 .120 (.107-.135) .114 (.105-.129) .167 (.148-.203) .250 (.209-.315) .333 (.280-.357) 787

01-02 .138 (.128-.149) .130 (.117-.143) .182 (.159-.203) .269 (.229-.308) .338 (.308-.429) 682

03-04 .086 (.076-.098) .082 (<LOD-.092) .129 (.107-.151) .189 (.154-.238) .238 (.185-.321) 618

Non-Hispanic blacks 99-00 .114 (.099-.133) .112 (.098-.130) .163 (.144-.183) .236 (.195-.338) .343 (.255-.425) 554

01-02 .123 (.113-.134) .115 (.106-.127) .163 (.150-.181) .233 (.208-.267) .300 (.248-.373) 667

03-04 .078 (.071-.085) .074 (.069-.082) .109 (.096-.124) .170 (.148-.192) .222 (.179-.257) 723

Non-Hispanic whites 99-00 .129 (.109-.152) .125 (.102-.152) .195 (.167-.225) .298 (.239-.352) .400 (.333-.444) 768

01-02 .127 (.117-.138) .120 (.113-.130) .176 (.159-.198) .280 (.241-.317) .380 (.318-.471) 1132

03-04 * .081 (<LOD-.089) .139 (.124-.147) .217 (.200-.238) .286 (.253-.333) 1074

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 178 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

to antimony have been established by OSHA and ACGIH, 

respectively, and a drinking water standard has been 

established by the U.S. EPA. Antimony trioxide is rated by 

IARC as a possible human carcinogen. Information about 

external exposure (i.e., environmental levels) and health 

effects is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html.

Biomonitoring Information

Levels of urinary antimony reflect recent exposure. Earlier 

measurements in general populations (Minoia et al., 

1990; Paschal et al., 1998) or compiled reference ranges 

(Hamilton et al., 1994) have reported values slightly 

higher than those in this Report, which may be due to 

methodologic, population, or exposure differences. Levels 

of urinary antimony in infants appeared to be similar to 

those reported by CDC (2005) for young children (Cullen 

et al., 1998; Dezateux et al., 1997). Urinary antimony was 

not associated with locally elevated soil levels in a study 

of more than 200 German residents (Gebel et al., 1998). 

Several investigations of airborne antimony exposures in 

workers have found urinary levels that are many times 

higher than those seen in NHANES 1999-2000, 2001-

2002, and 2003-2004, even when exposure levels were 

below workplace air standards (Bailly et al., 1991; Iavicoli 

et al., 2002; Kentner et al., 1995; Liao Y-H et al., 2004; 

Ludersdorf et al., 1987).

Finding a measurable amount of antimony in urine does not 

mean that the level of antimony causes an adverse health 

effect. Biomonitoring studies on levels of urinary antimony 

can provide physicians and public health officials with 

reference values so that they can determine whether people 

have been exposed to higher levels of antimony than are 

found in the general population. Biomonitoring data can 

also help scientists plan and conduct research on exposure 

and health effects.

References

Berman JD. Chemotherapy for leishmaniasis: Biochemical 

mechanisms, clinical efficacy, and future strategies. Rev Infect 

Dis 1988;10(3):560-586.

Bailly R, Lauwerys R, Buchet JP, Mahieu P, Konings J. 

Experimental and human studies on antimony metabolism: their 

relevance for the biological monitoring of workers exposed to 

inorganic antimony. Br J Ind Med 1991;48:93-97.

Briegner H, Semisch CW, Stasney J, Piatnek DA. Industrial 

antimony poisoning. Industrial Medicine and Surgery 

(Dec.)1954;521-523.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Cordasco EM, Stone FD. Pulmonary edema of environmental 

origin. Chest 1973;64(2):182-185.

Cullen A, Kiberd B, Matthews T, Mayne P, Delves HT, O’Regan 

M. Antimony in blood and urine of infants. J Clin Pathol 

1998;51:238-240.

Dernehl CU, Stead FM, Nau CA. Arsine, stibine, and hydrogen 

sulfide. Industrial Medicine 1944;13:361-362.

Dezateux C, Delves HT, Stocks J, Wade A, Pilgrim L, Costeloe 

K. Urinary antimony in infancy. Arch Dis Child 1997;76:432-

436.

Elinder CG, Friberg L. Antimony. In: Friberg L, Nordberg GF, 

Vouk VB, eds. Handbook on the toxicology of metals. 2nd ed. 

New York: Elsevier; 1986. pp. 26-42.

Gebel TW, Roland H, Suchenwirth R, Bolten C, Dunkelberg, 

HH. Human biomonitoring of arsenic and antimony in case 

of an elevated geogenic exposure. Environ Health Perspect 

1998;106:33-39.

Hamilton EI, Sabbioni E, Van der Venne MT. Element reference 

values in tissues from inhabitants of the European community. 

VI. Review of elements in blood, plasma and urine and a 

critical evaluation of reference values for the United Kingdom 

population. Sci Total Environ 1994;158:165-190.

Iavicoli I, Caroli S, Alimonti A, Petrucci F, Carelli G. 

Biomonitoring of a worker population exposed to low antimony 

trioxide levels. J Trace Elem Med Biol 2002;16: 33-39.

Kentner M, Leinemann M, Schaller KH, Weltle D, Lenert 

G. External and internal antimony exposure in starter battery 

production. Int Arch Occup Environ Health 1995;67:119-123.

Liao Y-H, Yu H-S, Ho C-K, Wu M-T, Yang C-Y, Chen J-R, et 

al. Biological monitoring of exposures to aluminum, gallium, 

indium, arsenic, and antimony in optoelectronic industry workers. 

J Occup Environ Med 2004;46:931-936.

Luedersdorf R, Fuchs A, Mayer P, Skulsukai G, Schacke G. 

Biological assessment of exposure to antimony and lead in 

the glass-producing industry. Int Arch Occup Environ Health 

1987;59:469-474.

Ming-Hsin H, Shao-Chi C, Ju-Sun P, Kuo-Juie Y, Cheng-Wei L, 

Chia-Yu H, et al. Mechanism and treatment of cardiac arrhythmias 

in tartar emetic intoxication. Chin Med J 1958;76(2):103-115.

Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini 

M, et al. Trace element reference values in tissues from 

inhabitants of the European community I. A study of 46 elements 
Fourth National Report on Human Exposure to Environmental Chemicals 179

 Metals

in urine, blood, and serum of Italian subjects. Sci Total Environ 

1990;95:89-105.

Paschal DC, Ting BG, Morrow JC, Pirkle JL, Jackson RJ, 

Sampson EJ, et al. Trace metals in urine of United States residents: 

reference range concentrations. Environ Res 1998;76(1):53-59.

Renes LE. Antimony poisoning in industry. Industrial Hygiene 

and Occupational Medicine 1953;99-108.

Werrin M. Chemical food poisoning. Quarterly Bulletin of the 

Association of Food and Drug Officials 1962; 27:38-45.
 180 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Arsenic

CAS No. 7440-38-2

General Information

Arsenic is an element that is widely distributed in the earth’s 

surface in small amounts. In nature, it is found in over 200 

crystalline or mineral forms, such as arsenopyrite (FeAsS) 

and realgar (As4S4), or rarely as elemental metalloids 

(yellow, black, and gray forms). Arsenic can combine with 

such non-carbon chemicals as sulfur and oxygen to form 

arsenides, arsenites, and arsenates (oxidation states of -3, 

+3 and +5), referred to as inorganic arsenic compounds. 

Arsenic trioxide (As2O3, a trivalent compound known as 

white arsenic) is a common natural and commercial form 

that can be released into the air during volcanic action; the 

smelting of copper, lead, and other metals; and, to a lesser 

extent, from coal burning. The United States no longer 

produces arsenic from mining but imports about 22,000 

metric tons annually, mostly for use in wood preservation 

(ATSDR, 2005). Various forms of inorganic arsenic can 

occur in groundwater from natural sources or as a result 

of soil application or industrial waste. Arsenic can also 

combine with organic substances in nature to form such 

organic arsenic compounds as arsenobetaine, arsenocholine, 

trimethylarsine oxide, and arsenosugars. Arsine (AsH3

) is a 

reactive, gaseous hydride manufactured in small quantities 

for use in the semiconductor industry.

Arsenic and its compounds have had many uses in 

the past and present as medicines, pesticides, alloys, 

semiconductors, and as homicidal poisons. Before the 20th 

century, arsenic compounds, particularly arsenic trioxide, 

were used as treatments for syphilis, psoriasis, cancers, 

mental disorders, and as a cosmetic to lighten complexion. 

Various arsenic compounds were used in paint pigments and 

for tanning animal hides. In the last century, lead hydrogen 

arsenate, copper arsenates, sodium arsenite, cacodylic acid, 

and monosodium methyl arsenate were used as pesticides 

but contemporary uses are restricted. Roxarsone and other 

organic arsenicals are anticoccidial agents added to poultry 

feed. Since the 1940s, chromated copper arsenate (CCA) 

has been used to treat outdoor timbers and pressure-treated 

woods to prevent wood rot. Although it is still widely used 

in the United States, CCA-treated wood has been restricted 

since 2003 and no longer can be used in residential 

applications such as decks, retaining walls, and play sets. 

Arsenic trioxide is approved to treat acute promyelocytic 

leukemia. Gallium, aluminum, and indium arsenides 

are used in the semiconductor industry. Also, arsenic as 

elemental metalloids may be used in some ammunition, 

solders, as alloy in metal bearings, and in lead-acid storage 

battery grids.

General population exposure to inorganic arsenic can occur 

through consumption of drinking water and, to a lesser 

extent, meats, grain, and produce. Arsenic is measurable in 

most soils, ocean and fresh waters, and foods. Water sources 

contain mostly inorganic arsenate, though in some locations 

arsenite may be prevalent (WHO, 2001). Groundwater 

Urinary Total Arsenic 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 8.30 (7.19-9.57) 7.70 (6.90-8.90) 16.0 (14.1-18.7) 37.4 (31.6-43.5) 65.4 (48.7-83.3) 2557

Age group 

6-11 years 03-04 7.08 (5.66-8.84) 6.80 (5.90-7.70) 10.9 (8.90-14.2) 24.6 (13.8-61.8) 46.9 (17.5-178) 290

12-19 years 03-04 8.55 (7.34-9.97) 8.10 (6.80-9.40) 15.2 (12.2-17.8) 30.5 (23.1-40.4) 46.1 (32.9-62.5) 725

20 years and older 03-04 8.41 (7.25-9.77) 7.90 (7.00-9.10) 17.0 (15.0-19.7) 40.5 (34.9-46.2) 66.2 (51.2-93.1) 1542

Gender 

Males 03-04 9.50 (8.34-10.8) 8.90 (7.70-9.80) 17.6 (15.2-20.1) 41.6 (32.5-52.8) 65.8 (48.7-95.4) 1281

Females 03-04 7.30 (6.02-8.84) 6.90 (5.90-8.30) 15.0 (11.3-19.5) 33.4 (26.5-41.7) 60.5 (40.8-77.1) 1276

Race/ethnicity 

Mexican Americans 03-04 9.29 (8.12-10.6) 9.20 (8.10-10.3) 16.2 (13.5-19.9) 34.4 (24.0-60.5) 68.2 (41.3-111) 618

Non-Hispanic blacks 03-04 11.6 (9.50-14.1) 10.4 (7.90-11.8) 21.5 (14.9-34.4) 43.5 (36.2-61.8) 78.0 (43.6-141) 722

Non-Hispanic whites 03-04 7.12 (6.13-8.27) 7.00 (6.10-7.90) 13.7 (11.3-15.8) 29.0 (22.6-35.9) 53.1 (38.4-65.6) 1074

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.74. 
Fourth National Report on Human Exposure to Environmental Chemicals 181

 Metals

sources of drinking water often have measurable arsenic 

and several regions of the United States have naturally 

higher arsenic levels than the U.S. EPA’s maximum 

contaminant level (Hughes, 2006; U.S. EPA, 2001). 

Extremely high groundwater arsenic levels, as observed in 

Bangladesh where millions of people have been exposed, 

have caused clinical arsenic poisoning. Though modest 

bioconcentration occurs in some aquatic life, arsenic does 

not show biomagnification in the food chain (WHO, 2001). 

Children may have additional exposures from ingestion of 

contaminated soils (e.g., mine tailings), dust, and contact 

with CCA-preserved wood structures. Smelter workers can 

have significant inhalational exposures to airborne arsenic 

trioxide for which air standards have been established. 

Smoking tobacco is also a source of inorganic arsenic. 

The semiconductor dopants, gallium arsenide and indium 

arsenide, are used in enclosed ultraclean operations within 

the semiconductor industry, so exposure to the general 

population is extremely limited.

Inorganic arsenic is well absorbed from the gastrointestinal 

tract and absorbed to a lesser degree through inhalation, 

but is poorly absorbed dermally (WHO, 2001). After 

absorption, inorganic arsenic is widely distributed within 

the body. Arsenate is reduced in the body to arsenite 

(oxidation state +3), though some reduction may occur 

in the gut prior to absorption. Arsenite is then oxidatively 

methylated to the monomethylarsonic acid (MMA) and 

dimethylarsinic acid (DMA) with subsequent excretion 

primarily in the urine (NRC, 2001). Inorganic arsenic and 

its metabolites have elimination half-lives of approximately 

2–4 days (Lauwerys and Hoet, 2001; NRC, 2001). Some 

studies suggest that variation in the degree of methylation 

among persons is related to the susceptibility of arsenicinduced disease and may involve consideration of genetic 

polymorphisms, dose level, age, selenium, and folate status 

(Chen et al., 2007; Chowdhury et al., 2003; Gamble et al., 

2006; Steinmaus et al., 2007; Tseng, 2007; WHO, 2001). 

Direct exposure to DMA and MMA may result from use of 

the two pesticides, cacodylic acid and monosodium methyl 

arsenate.

Fish, shellfish, kelp, and some other seafood can contain 

organic forms of arsenic including arsenobetaine, 

arsenocholine, trimethylarsine oxide (TMAO), and 

arsenosugars. In aquatic organisms, arsenocholine is 

converted to arsenobetaine and also to small amounts 

of TMAO (Christakopoulos et al., 1988). TMAO is also 

formed in the environment from microbiological action and 

is a metabolite of arsenic in certain mammals. In aquatic 

sediments, organic arsenic can be converted back to 

methylated and inorganic arsenic. Ingestion of arsenosugars 

in kelp and algae can also lead to the excretion of DMA. 

These organic forms of arsenic from seafood are absorbed 

and quickly excreted in the urine (WHO, 2001).

Inorganic forms of arsenic demonstrate high acute toxicity, 

with trivalent inorganic arsenic (arsenite) being more toxic 

than pentavalent inorganic arsenic (arsenate) (NRC, 2001, 

WHO, 2001). The reduced form of MMA (oxidation state 

Urinary Total Arsenic (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 8.24 (7.07-9.59) 7.04 (5.93-8.51) 14.1 (11.6-17.2) 30.4 (26.0-38.7) 50.4 (40.3-64.5) 2557

Age group 

6-11 years 03-04 8.25 (6.58-10.3) 7.18 (5.93-9.45) 11.7 (9.10-16.3) 22.2 (12.0-69.5) 40.1 (14.7-188) 290

12-19 years 03-04 6.11 (5.23-7.13) 5.06 (4.47-6.04) 9.66 (7.44-11.2) 17.8 (12.0-26.0) 27.8 (20.7-35.9) 725

20 years and older 03-04 8.64 (7.38-10.1) 7.47 (6.20-9.01) 15.4 (12.7-18.8) 33.8 (27.3-41.2) 53.9 (45.4-64.5) 1542

Gender 

Males 03-04 8.00 (6.81-9.40) 6.75 (5.66-8.35) 13.7 (11.0-18.0) 28.7 (25.1-36.4) 45.6 (35.3-62.1) 1281

Females 03-04 8.47 (7.12-10.1) 7.33 (6.10-8.75) 14.4 (11.7-17.7) 32.3 (24.2-46.6) 58.4 (42.8-75.0) 1276

Race/ethnicity 

Mexican Americans 03-04 8.61 (7.33-10.1) 7.76 (6.30-9.44) 12.6 (10.2-15.9) 24.0 (17.7-34.8) 42.4 (24.8-62.4) 618

Non-Hispanic blacks 03-04 8.31 (6.99-9.88) 6.88 (5.66-8.41) 13.8 (11.5-17.0) 27.6 (17.9-56.0) 54.3 (27.5-120) 722

Non-Hispanic whites 03-04 7.50 (6.25-9.01) 6.32 (5.28-7.96) 12.5 (9.86-17.1) 26.8 (21.8-32.0) 40.0 (31.3-53.9) 1074
 182 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

+3) shows greater toxicity than arsenite itself (Aposhian et 

al., 2000; Bredfeldt et al., 2006; Cohen et al., 2006) and 

newly discovered thioarsenic metabolites may also be 

as toxic (Naranmandura et al., 2007; Raml et al., 2007). 

Arsenic has many actions demonstrated in cellular studies, 

including inhibition of numerous enzymes, substitution in 

phosphate metabolism, interference in signal transduction 

pathways, and altered gene expression. Such actions may 

lead to decreased energy production, increased oxidative 

stress, apoptosis, cytotoxicity, and endothelial injury 

(Kumagai and Sumi, 2007; NRC; 2001). Acutely, arsenite 

will inhibit cellular pyruvate dehydrogenase by binding 

to the sulfhydryl groups of dihydrolipoamide, and it also 

will inhibit succinate dehydrogenase, leading to a decrease 

in adenosine triphosphate energy production. Cellular 

glucose uptake, gluconeogenesis, fatty acid oxidation, and 

production of glutathione may be affected as well. Although 

arsenate is reduced in the body to arsenite, it may have its 

own separate toxic action by substituting for phosphate in 

glycolysis and other pathways, and by uncoupling oxidative 

phosphorylation (NRC, 2001; WHO, 2001).

Acute toxicity resulting from the ingestion of large 

amounts of trivalent arsenic (e.g., arsenic trioxide) 

includes hemorrhagic gastritis with nausea, vomiting, 

and diarrhea, which can lead to dehydration and shock. 

Cardiac arrhythmias, hepatotoxicity, renal failure, and 

peripheral neuropathy may also occur with large doses or 

after surviving an acute overdose. Chronic human intake 

of arsenic at less than acutely toxic doses, including 

drinking water sources with elevated arsenic levels 

(e.g., Bangladesh, Taiwan, Chile), can cause peripheral 

sensorimotor neuropathies, peripheral vascular disease, 

noncirrhotic portal hypertension, hematocytopenias, 

hyperkeratosis, and hyperpigmentation of the skin (NRC, 

2001; WHO, 2001). With chronic exposure, some of these 

effects may take years to develop. Chronic elevated arsenic 

intakes have been associated with diabetes, hypertension, 

and childhood neurodevelopmental effects in observational 

human studies, but additional or confirmatory research is 

needed (Kapaj et al., 2006; WHO, 2001). The organic forms 

of arsenic occurring in seafood have little known toxicity. 

Acute unintentional inhalation of arsine gas can produce 

hemolysis of red blood cells.

Chronic arsenic exposure in humans is considered to be a 

cause of skin, lung, and bladder cancer (IARC, 2004; NRC, 

2001). The risk of lung cancer appears more pronounced 

when large environmental exposures start in childhood 

(Smith et al., 2006) or when exposure occurs in smokers 

(Chen et al., 2004). Studies of arsenic at levels typical of 

U.S. drinking water have not been associated with increased 

cancer rates (Schoen et al., 2004). Laboratory studies using 

inorganic arsenic have shown chromosomal aberrations, 

cell transformations, and DNA repair inhibition (Cohen et 

al., 2006; U.S.EPA, 1998; WHO, 2001). OSHA and ACGIH 

have established workplace standards and guidelines 

for arsenic exposure and monitoring, respectively. The 

U.S.EPA has established drinking water, food residue, 

and environmental standards for arsenic and arsenic 

Urinary Arsenic (V) Acid 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD 1.10 (<LOD-1.50) 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD 1.10 (<LOD-1.30) 292

12-19 years 03-04 * < LOD < LOD < LOD 1.20 (<LOD-1.60) 728

20 years and older 03-04 * < LOD < LOD < LOD 1.10 (<LOD-1.50) 1548

Gender 

Males 03-04 * < LOD < LOD < LOD 1.20 (<LOD-1.50) 1284

Females 03-04 * < LOD < LOD < LOD 1.10 (<LOD-1.30) 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD 1.20 (<LOD-1.60) 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD 1.20 (<LOD-1.80) 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD 1.10 (<LOD-1.50) 1078

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.0. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 183

 Metals

compounds, and the FDA has established a bottled drinking 

water standard. IARC and NTP recognize inorganic 

arsenic and arsenic compounds as human carcinogens. 

DMA produced bladder cancer in some chronic rat studies 

(Cohen et al., 2006). In animal studies, arsenic has been 

fetotoxic and teratogenic, but generally only at maternally 

toxic doses (WHO, 2001). Additional information about 

external exposure (i.e., environmental levels) and health 

effects is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html.

Biomonitoring Information

Urinary arsenic levels reflect recent exposures and are 

moderately to highly correlated with arsenic intakes 

from drinking water and dietary sources (Ahsan et al., 

2000; Calderon et al., 1999; Pellizzari and Clayton, 2006; 

WHO, 2001). Daily variation in creatinine-corrected 

urinary arsenic is relatively small when intake is constant 

(Calderon et al., 1999). Urinary arsenic levels were a better 

predictor for risk of arsenical skin lesions than were arsenic 

levels in drinking water in Bangladesh (Ahsan et al., 2000). 

Consequently, urinary arsenic levels have been accepted as 

a good biomarker of dose (WHO, 2001). Several studies 

have shown that urinary arsenic levels are not correlated 

with low levels of arsenic measured in house dust or in 

washings taken from hands (Hysong et al., 2003; Pellizzari 

and Clayton, 2006; Shalat et al., 2006), though air levels of 

arsenic fume and dust are correlated with urinary arsenic 

levels at higher occupational inhalational exposures

(Jakubowski et al., 1998; Offergelt et al., 1992; Vahter et 

al., 1986). Though CCA-treated wood contains several 

thousand times more arsenic than untreated wood, hand 

washings from children playing on CCA-treated wood 

compared to children playing on non-CCA-treated wood 

playground equipment were slightly to fivefold higher 

(Kwon et al., 2004; Shalat et al., 2006), although urinary 

arsenic levels were not associated with CCA contact (Shalat 

et al., 2006).

Levels of total urinary arsenic in the U.S. population in 

the National Health and Nutrition Examination Survey 

(NHANES) 2003–2004 were similar to levels reported in the 

National Human Exposure Assessment Survey (NHEXAS) 

1995–1996 for about 80 children residing in the Great 

Lakes region (Caldwell et al., 2008; Pellizzari and Clayton 

2006). In the German Environmental Survey III of 1998, 

median urinary total arsenic levels in 4052 adults varied 

with seafood intake, had decreased since the prior 1990–

1992 survey, and were about two-fold lower than those for 

the U.S. population in NHANES 2003–2004 (Schulz et 

al., 2007; Caldwell et al., 2008). In a Nevada town where 

groundwater levels were naturally elevated, the median 

total urinary arsenic in about 200 people was approximately 

four times higher than that of the U.S. population (Rubin 

et al., 2007; Caldwell et al., 2008). Compared with this 

Report, higher mean or median total urinary arsenic levels 

have been reported among people living in specific western 

areas of North America (Calderon et al., 1999; Josyula et 

al., 2006; Meza et al., 2004; Valenzuela et al., 2005) and 

Urinary Arsenic (V) Acid (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD 3.04 (<LOD-3.50) 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD 2.80 (<LOD-4.00) 292

12-19 years 03-04 * < LOD < LOD < LOD 1.75 (<LOD-2.41) 728

20 years and older 03-04 * < LOD < LOD < LOD 3.18 (<LOD-3.70) 1548

Gender 

Males 03-04 * < LOD < LOD < LOD 2.61 (<LOD-3.18) 1284

Females 03-04 * < LOD < LOD < LOD 3.33 (<LOD-3.89) 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD 2.69 (<LOD-3.50) 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD 1.75 (<LOD-2.19) 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD 3.33 (<LOD-3.95) 1078

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 184 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

other areas of the world (Ahsan et al., 2000; Aposhian et 

al., 2000; Caceres et al., 2005; Sun et al., 2007) with higher 

levels of arsenic in the drinking water. Median and mean 

total urinary arsenic levels for residents in some districts 

in Bangladesh were reported to be about 50-fold higher 

than respective levels in the U.S. population (Ahsan et al., 

2000; Caldwell et al., 2008; Chowdhury et al., 2003). For 

residents of Inner Mongolia, China, geometric mean levels 

were about 70-fold higher than for the U.S. population 

(Sun et al., 2007). Some noncancer effects of arsenic (e.g., 

dermal keratosis, vasospasm, and peripheral neuropathy) 

have been associated with urinary levels as low as 50–100 

μg/L in chronically exposed populations (ACGIH, 2001; 

Blom et al., 1985; Tseng et al., 2005; Valenzuela et al., 

2005; WHO, 2001). These associations are stronger at 

higher urinary levels, and other factors such as nutrition, 

methylation capacity, and duration of exposure are also 

considered important.

Total arsenic measured in the urine includes all species 

of inorganic and organic arsenic. Individually measurable 

species resulting from inorganic arsenic exposure are 

arsenate, arsenite, and two methylated metabolic products, 

DMA and MMA. Measurable organic arsenic species in 

this Report are three biologically generated environmental 

forms, arsenobetaine, arsenocholine, and TMAO. Arsenate, 

arsenite, arsenocholine, and TMAO were detected in only 

7.6, 4.6, 1.8, and 0.3% of a representative sample of the 

U.S. population in the NHANES 2003–2004 subsample, 

respectively, with DMA, MMA, and arsenobetaine being 

the main contributors to the total urinary arsenic levels 

(Caldwell et al., 2008). When seafood intake is avoided, as 

evidenced by trace or nondetectable levels of arsenobetaine 

and arsenocholine in the urine, DMA and MMA compose 

most (about 75%) of the total arsenic species measured in 

urine. After recent seafood ingestion, arsenobetaine and 

arsenocholine will greatly increase the level of total urinary 

arsenic and comprise the highest percentage of the total 

urinary arsenic level. The higher percentiles of total urinary 

arsenic levels in the U.S. population showed a higher 

contribution of arsenobetaine (Caldwell et al., 2008). In most 

human studies, DMA has been the predominant metabolite 

composing the majority of measurable inorganic-related 

arsenic in the urine (i.e., when seafood organic arsenic 

is subtracted). Levels of DMA and MMA increase in 

approximate proportion to the intake of inorganic arsenic. 

In the late 1980s, a control population of 696 Tacoma 

residents had median urinary DMA levels similar to those for 

NHANES 2003–2004 (Kalman et al., 1990; Caldwell et al., 

2008). Also, in NHEXAS 1995–1996, Great Lakes region 

residents had median urinary DMA levels that were slightly 

less than median levels in NHANES 2003-2004 (Caldwell 

et al., 2008; Pellizzari and Clayton, 2006). In the residents 

of a Chilean town who consumed water with high levels of 

arsenic, median levels of urinary DMA were about 40-fold 

higher than the adult median reported in NHANES 2003–

2004, and urinary DMA represented about 67% of the total 

urinary arsenic (Hopenhayn-Rich et al., 1996; Caldwell et 

al., 2008). Detectable levels of MMA reported in NHANES 

2003–2004 were found only at the upper percentiles and, 

Urinary Arsenobetaine 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 1.55 (1.31-1.83) 1.00 (.800-1.40) 5.20 (4.00-6.50) 16.8 (12.7-22.3) 35.0 (27.6-44.6) 2568

Age group 

6-11 years 03-04 * < LOD 1.80 (.800-4.00) 8.80 (3.90-29.9) 29.9 (6.20-190) 292

12-19 years 03-04 * .600 (.400-.800) 3.20 (2.00-4.70) 13.9 (7.20-25.1) 31.8 (17.2-35.8) 728

20 years and older 03-04 1.74 (1.48-2.05) 1.30 (1.00-1.60) 6.10 (4.90-7.10) 18.5 (14.0-23.5) 35.5 (26.8-50.5) 1548

Gender 

Males 03-04 1.66 (1.43-1.93) 1.20 (.900-1.50) 5.80 (4.40-7.10) 18.6 (13.9-23.7) 35.0 (26.8-40.5) 1284

Females 03-04 1.45 (1.17-1.80) .900 (.700-1.40) 4.70 (3.40-6.20) 15.6 (11.1-25.3) 32.7 (21.1-51.3) 1284

Race/ethnicity 

Mexican Americans 03-04 1.19 (.871-1.62) .800 (.500-1.30) 3.20 (1.80-5.20) 10.2 (6.70-21.4) 31.4 (16.3-39.1) 621

Non-Hispanic blacks 03-04 2.29 (1.60-3.28) 2.00 (1.20-3.50) 7.70 (5.00-12.0) 23.7 (13.2-38.7) 45.6 (25.1-94.0) 725

Non-Hispanic whites 03-04 1.37 (1.11-1.68) .800 (.700-1.20) 4.30 (2.50-6.30) 13.3 (9.70-21.4) 29.3 (21.4-35.5) 1078

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 185

 Metals

as with DMA, these levels were much lower than those 

found in other studies where environmental exposures were 

highly elevated (Chowdhury et al., 2003; Sun et al., 2007).

In recent years, occupational monitoring and research 

studies have focused on the sum of inorganic-related 

species (arsenate + arsenite + DMA + MMA) as a measure 

of inorganic arsenic intake. Studies of small groups of metal 

and sulfuric acid smelter workers with varying industrial 

hygiene conditions have reported urinary inorganic arsenic 

levels (arsenate + arsenite + DMA + MMA) ranging as high 

as several hundreds of μg/L during or after work exposure 

(Jakubowski et al., 1998; Offergelt et al., 1992; Vahter et 

al., 1986; WHO, 2001). Timber treatment workers had 

median urinary DMA levels that were about 15-fold higher 

than the general adult median levels reported in NHANES 

2003–2004 (Morton et al., 2006; Caldwell et al., 2008).

The American Conference of Governmental Industrial 

Hygienists (ACGIH) provides an occupational biologic 

effect index (BEI) for urinary inorganic arsenic plus 

metabolites equal to 35 μg/L (ACGIH, 2001). The 95th 

percentile of the U.S. population for the sum of inorganic 

related species was 18.9 μg/L, which is below the ACGIH 

BEI (Caldwell et al., 2008). Information about the biological 

exposure indices is provided here for comparison, not to 

imply a safety level for general population exposure.

Finding a measurable amount of arsenic in urine does not 

mean that the level of arsenic causes an adverse health 

effect. Biomonitoring studies of urinary arsenic can provide 

physicians and public health officials with reference 

values so that they can determine whether people have 

been exposed to higher levels of arsenic than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Urinary Arsenobetaine (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 1.54 (1.30-1.82) 1.16 (.959-1.43) 5.00 (3.62-6.91) 16.2 (12.5-20.3) 29.4 (24.0-36.4) 2568

Age group 

6-11 years 03-04 * < LOD 2.00 (1.15-4.83) 12.2 (4.13-39.7) 29.6 (6.80-153) 292

12-19 years 03-04 * .531 (.400-.638) 2.14 (1.39-3.51) 9.29 (4.29-14.7) 17.3 (10.4-28.7) 728

20 years and older 03-04 1.79 (1.51-2.12) 1.47 (1.15-1.88) 5.91 (4.32-7.72) 17.2 (13.4-21.8) 30.1 (26.1-36.4) 1548

Gender 

Males 03-04 1.40 (1.18-1.67) 1.11 (.909-1.28) 4.78 (3.61-6.70) 14.4 (11.1-18.5) 26.5 (18.6-29.9) 1284

Females 03-04 1.68 (1.37-2.05) 1.25 (.938-1.67) 5.58 (3.50-7.43) 17.2 (12.3-24.5) 32.9 (25.6-46.3) 1284

Race/ethnicity 

Mexican Americans 03-04 1.10 (.786-1.55) .877 (.612-1.40) 2.93 (1.78-5.21) 8.88 (5.50-15.4) 19.0 (9.64-29.4) 621

Non-Hispanic blacks 03-04 1.65 (1.19-2.30) 1.53 (.901-2.45) 5.81 (4.25-7.82) 13.6 (9.76-27.9) 32.9 (13.4-82.1) 725

Non-Hispanic whites 03-04 1.44 (1.15-1.80) 1.05 (.833-1.36) 4.47 (2.73-6.83) 14.3 (10.9-18.6) 26.5 (18.6-32.0) 1078

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 186 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Urinary Arsenocholine 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD < LOD 292

12-19 years 03-04 * < LOD < LOD < LOD < LOD 728

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1548

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1284

Females 03-04 * < LOD < LOD < LOD < LOD 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 1078

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.6. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary Arsenocholine (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD < LOD 292

12-19 years 03-04 * < LOD < LOD < LOD < LOD 728

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1548

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1284

Females 03-04 * < LOD < LOD < LOD < LOD 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 1078

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 187

 Metals

Urinary Arsenous (III) Acid 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD < LOD 292

12-19 years 03-04 * < LOD < LOD < LOD 1.40 (<LOD-1.70) 728

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1548

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1284

Females 03-04 * < LOD < LOD < LOD < LOD 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD 2.00 (<LOD-3.00) 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD 1.20 (<LOD-1.80) 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 1078

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary Arsenous (III) Acid (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD < LOD 292

12-19 years 03-04 * < LOD < LOD < LOD 1.95 (<LOD-2.76) 728

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1548

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1284

Females 03-04 * < LOD < LOD < LOD < LOD 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD 3.08 (<LOD-4.44) 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD 2.00 (<LOD-2.29) 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 1078

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 188 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Urinary Dimethylarsinic Acid 

Metabolite of Arsenic 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 3.71 (3.33-4.14) 3.90 (3.00-4.00) 6.00 (5.00-7.00) 11.0 (9.20-12.0) 16.0 (13.0-17.8) 2568

Age group 

6-11 years 03-04 3.73 (3.12-4.45) 4.00 (3.00-4.00) 6.00 (5.00-7.00) 9.00 (7.00-12.0) 12.0 (8.00-22.0) 292

12-19 years 03-04 3.85 (3.34-4.42) 4.00 (3.00-4.00) 6.00 (5.00-7.10) 9.30 (7.70-12.0) 13.0 (10.0-16.0) 728

20 years and older 03-04 3.69 (3.31-4.11) 3.70 (3.00-4.00) 6.00 (5.00-7.00) 11.0 (10.0-12.0) 16.0 (13.0-19.0) 1548

Gender 

Males 03-04 4.12 (3.60-4.71) 4.00 (3.70-4.30) 6.00 (5.60-7.70) 11.0 (9.00-15.0) 17.0 (12.1-22.0) 1284

Females 03-04 3.37 (3.00-3.78) 3.00 (3.00-4.00) 5.50 (4.80-6.20) 10.0 (8.00-11.0) 14.0 (11.0-17.7) 1284

Race/ethnicity 

Mexican Americans 03-04 4.72 (4.27-5.22) 4.80 (4.00-5.00) 7.00 (6.00-9.00) 12.0 (10.0-16.0) 17.0 (12.0-25.0) 621

Non-Hispanic blacks 03-04 4.27 (3.71-4.92) 4.00 (3.50-5.00) 7.00 (6.00-8.00) 11.6 (9.00-15.0) 16.0 (14.0-18.7) 725

Non-Hispanic whites 03-04 3.27 (2.95-3.62) 3.00 (3.00-3.80) 5.00 (4.60-6.00) 9.00 (7.00-10.0) 12.0 (9.50-15.0) 1078

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.7. 

Urinary Dimethylarsinic Acid (creatinine corrected) 

Metabolite of Arsenic 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 3.69 (3.24-4.19) 3.37 (2.94-3.91) 5.71 (4.69-6.74) 9.09 (7.61-11.5) 13.0 (10.7-16.0) 2568

Age group 

6-11 years 03-04 4.34 (3.57-5.28) 4.03 (3.20-4.80) 6.32 (4.65-8.33) 10.3 (7.00-13.9) 13.9 (7.86-21.8) 292

12-19 years 03-04 2.74 (2.39-3.14) 2.55 (2.27-2.94) 3.77 (3.17-4.44) 5.88 (4.65-6.67) 7.18 (6.16-11.7) 728

20 years and older 03-04 3.79 (3.34-4.31) 3.48 (3.00-4.00) 5.95 (4.86-7.05) 9.45 (8.00-12.0) 13.5 (11.1-18.6) 1548

Gender 

Males 03-04 3.48 (2.95-4.10) 3.16 (2.70-3.82) 5.46 (4.17-6.90) 8.59 (6.92-12.0) 12.3 (8.84-18.9) 1284

Females 03-04 3.89 (3.49-4.34) 3.57 (3.13-4.06) 5.78 (4.95-6.67) 9.32 (8.00-11.5) 13.7 (10.6-18.6) 1284

Race/ethnicity 

Mexican Americans 03-04 4.38 (3.80-5.05) 4.11 (3.29-4.90) 6.25 (4.84-8.15) 10.3 (8.00-11.8) 12.9 (11.1-15.2) 621

Non-Hispanic blacks 03-04 3.08 (2.69-3.52) 2.86 (2.60-3.24) 4.34 (3.82-5.05) 7.81 (5.82-9.45) 10.4 (7.61-16.9) 725

Non-Hispanic whites 03-04 3.44 (2.97-3.98) 3.17 (2.80-3.73) 5.16 (4.03-6.49) 8.00 (6.32-10.9) 11.1 (8.00-15.4) 1078
Fourth National Report on Human Exposure to Environmental Chemicals 189

 Metals

Urinary Monomethylarsonic Acid 

Metabolite of Arsenic 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD 1.20 (1.00-1.30) 1.90 (1.60-2.10) 2.40 (2.00-2.80) 2567

Age group 

6-11 years 03-04 * < LOD 1.00 (<LOD-1.40) 1.80 (1.30-2.60) 2.30 (1.70-2.90) 292

12-19 years 03-04 * < LOD 1.50 (1.10-1.80) 2.20 (1.70-3.00) 2.90 (2.20-3.60) 728

20 years and older 03-04 * < LOD 1.20 (1.00-1.30) 1.80 (1.50-2.10) 2.30 (2.00-2.60) 1547

Gender 

Males 03-04 * < LOD 1.30 (1.10-1.60) 2.00 (1.80-2.40) 2.60 (2.10-3.00) 1283

Females 03-04 * < LOD 1.00 (<LOD-1.20) 1.60 (1.30-1.90) 2.10 (1.70-2.60) 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD 1.50 (1.20-1.90) 2.20 (1.70-2.80) 2.80 (2.00-4.40) 621

Non-Hispanic blacks 03-04 * < LOD 1.10 (<LOD-1.30) 1.80 (1.40-2.00) 2.20 (1.70-2.70) 725

Non-Hispanic whites 03-04 * < LOD 1.10 (.900-1.30) 1.80 (1.40-2.00) 2.10 (1.80-2.50) 1077

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.9. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary Monomethylarsonic Acid (creatinine corrected) 

Metabolite of Arsenic 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD 1.33 (1.18-1.54) 2.22 (1.82-2.57) 2.86 (2.40-3.53) 2567

Age group 

6-11 years 03-04 * < LOD 1.63 (<LOD-1.81) 2.31 (1.88-2.50) 2.52 (2.31-3.07) 292

12-19 years 03-04 * < LOD 1.10 (.853-1.23) 1.53 (1.30-1.85) 2.07 (1.71-2.22) 728

20 years and older 03-04 * < LOD 1.36 (1.18-1.58) 2.28 (1.82-2.79) 3.00 (2.43-3.53) 1547

Gender 

Males 03-04 * < LOD 1.20 (1.05-1.36) 1.88 (1.53-2.34) 2.50 (2.07-3.45) 1283

Females 03-04 * < LOD 1.50 (<LOD-1.77) 2.40 (1.96-2.86) 3.00 (2.61-3.53) 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD 1.46 (1.11-1.93) 2.30 (1.84-3.00) 3.16 (2.40-3.85) 621

Non-Hispanic blacks 03-04 * < LOD .816 (<LOD-.985) 1.37 (1.14-1.61) 1.88 (1.46-2.17) 725

Non-Hispanic whites 03-04 * < LOD 1.33 (1.15-1.62) 2.28 (1.73-2.86) 2.86 (2.35-3.75) 1077

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 190 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Urinary Trimethylarsine oxide 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD < LOD 292

12-19 years 03-04 * < LOD < LOD < LOD < LOD 728

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1548

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1284

Females 03-04 * < LOD < LOD < LOD < LOD 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 1078

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.0. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Urinary Trimethylarsine oxide (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 2568

Age group 

6-11 years 03-04 * < LOD < LOD < LOD < LOD 292

12-19 years 03-04 * < LOD < LOD < LOD < LOD 728

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1548

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1284

Females 03-04 * < LOD < LOD < LOD < LOD 1284

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 621

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 725

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 1078

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 191

 Metals

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for arsenic. September 2005 [online]. 

Available at: http://www.atsdr.cdc.gov/toxpro2.html. 8/7/08

Ahsan H, Perrin M, Rahman A, Parvez F, Stute M, Zheng Y, 

et al. Associations between drinking water and urinary arsenic 

levels and skin lesions in Bangladesh. J Occup Environ Med 

2000;42(12):1195-1201.

American Conference of Government Industrial Hygienists 

(ACGIH). Documentation of biological exposure indices. 7th 

edition. Cincinnati (OH): ACGIH Worldwide; 2001.

Aposhian HV, Gurzau ES, Le XC, Gurzau A, Healy SM, Lu X, et 

al. Occurrence of monomethylarsonous acid in urine of humans 

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Fourth National Report on Human Exposure to Environmental Chemicals 193

 Metals

Barium

CAS No. 7440-39-3

General Information

Elemental barium is a silver-white metal which comprises 

approximately 0.05% of the earth’s crust. In nature, it 

combines with other chemicals such as sulfur or carbon 

and oxygen. Some barium salts are freely soluble in water, 

whereas others are practically insoluble (e.g., barium 

sulfate and barium carbonate). Barium compounds are used 

by the oil and gas industries to make drilling muds. Barium 

compounds are also used commercially in paint, bricks, 

tiles, glass, rubber, depilatories, fireworks, and ceramics. 

Medically, barium sulfate is used as a contrast medium 

for taking radiographs of the gastrointestinal tract. Barium 

salts have also been available as rodenticides.

The general population can be exposed to low amounts of 

barium in air, water, and food. Certain foods, such as brazil 

nuts, are high in barium (Genter, 2001). Small amounts 

of barium can be released into the air during mining and 

other industrial processes. Workers employed by industries 

that make or use barium compounds can be exposed to 

barium dust. In single dose animal studies, soluble forms 

of barium, such as barium chloride, were relatively well 

absorbed following inhalation (60-80% of a dose) or 

ingestion (11-32 % of a dose). Ingested soluble barium 

Urinary Barium 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 1.50 (1.35-1.66) 1.60 (1.50-1.90) 3.10 (2.70-3.40) 5.40 (4.60-6.10) 6.90 (6.20-8.40) 2180

01-02 1.52 (1.41-1.65) 1.63 (1.50-1.76) 3.12 (2.77-3.51) 5.24 (4.73-5.84) 7.48 (6.54-8.12) 2690

03-04 1.49 (1.36-1.64) 1.51 (1.35-1.72) 2.91 (2.64-3.28) 5.36 (4.86-5.71) 7.54 (6.93-8.63) 2558

Age group 

6-11 years 99-00 2.15 (1.70-2.72) 2.20 (1.90-2.50) 4.00 (2.60-6.10) 6.40 (5.20-8.30) 8.30 (5.00-76.2) 297

01-02 1.80 (1.44-2.26) 2.09 (1.74-2.49) 3.63 (2.86-4.39) 5.37 (4.26-7.38) 6.88 (5.37-8.49) 368

03-04 2.21 (1.81-2.71) 2.50 (1.81-2.75) 4.76 (3.80-5.65) 8.63 (5.59-11.8) 11.8 (6.87-14.8) 290

12-19 years 99-00 1.97 (1.78-2.19) 2.00 (1.70-2.30) 3.50 (3.10-4.00) 5.90 (4.80-7.00) 9.70 (5.90-13.1) 621

01-02 2.03 (1.76-2.34) 2.27 (1.96-2.53) 4.11 (3.48-4.72) 6.73 (5.55-7.87) 9.02 (7.25-11.4) 762

03-04 2.16 (1.93-2.41) 2.35 (2.06-2.63) 4.11 (3.48-4.71) 7.18 (6.00-8.29) 9.63 (8.15-11.4) 725

20 years and older 99-00 1.36 (1.24-1.51) 1.50 (1.30-1.70) 2.80 (2.60-3.20) 5.10 (4.30-5.50) 6.40 (5.70-8.40) 1262

01-02 1.43 (1.32-1.54) 1.50 (1.39-1.65) 2.85 (2.55-3.27) 4.86 (4.53-5.47) 7.14 (6.08-8.12) 1560

03-04 1.34 (1.20-1.50) 1.39 (1.19-1.56) 2.54 (2.21-2.91) 4.61 (3.99-5.30) 6.61 (5.57-7.43) 1543

Gender 

Males 99-00 1.70 (1.54-1.88) 1.90 (1.80-2.00) 3.20 (3.00-3.60) 5.50 (4.20-6.70) 7.50 (5.90-9.70) 1083

01-02 1.64 (1.47-1.82) 1.80 (1.65-1.98) 3.15 (2.76-3.73) 5.52 (4.82-6.35) 7.87 (6.49-9.32) 1335

03-04 1.62 (1.47-1.78) 1.69 (1.49-1.85) 3.09 (2.81-3.54) 5.65 (5.14-6.16) 8.56 (6.71-9.67) 1281

Females 99-00 1.33 (1.15-1.53) 1.50 (1.20-1.60) 2.80 (2.30-3.30) 5.20 (4.20-5.90) 6.80 (5.60-10.4) 1097

01-02 1.43 (1.30-1.56) 1.44 (1.29-1.63) 3.11 (2.74-3.43) 4.93 (4.44-5.88) 7.15 (6.32-7.86) 1355

03-04 1.38 (1.24-1.54) 1.39 (1.18-1.57) 2.71 (2.41-3.15) 4.95 (4.29-5.51) 6.87 (5.65-8.10) 1277

Race/ethnicity 

Mexican Americans 99-00 1.35 (1.25-1.46) 1.40 (1.20-1.50) 2.60 (2.30-2.90) 4.50 (4.10-5.30) 6.30 (5.50-6.80) 692

01-02 1.21 (1.06-1.37) 1.25 (1.11-1.46) 2.56 (2.04-2.91) 4.35 (3.65-5.49) 6.43 (5.21-8.22) 683

03-04 1.40 (1.15-1.70) 1.45 (1.22-1.73) 2.62 (1.78-3.38) 4.07 (2.95-6.37) 6.01 (4.01-7.88) 618

Non-Hispanic blacks 99-00 1.34 (1.12-1.62) 1.40 (1.20-1.60) 2.50 (2.30-2.90) 5.10 (3.70-6.60) 7.40 (5.40-13.9) 540

01-02 1.30 (1.14-1.48) 1.42 (1.22-1.62) 2.61 (2.31-2.82) 4.30 (3.70-5.18) 5.99 (4.87-7.26) 667

03-04 1.27 (1.17-1.39) 1.38 (1.26-1.48) 2.34 (2.05-2.59) 3.77 (3.35-4.36) 5.86 (4.76-7.45) 723

Non-Hispanic whites 99-00 1.56 (1.36-1.80) 1.80 (1.60-2.00) 3.30 (2.80-3.70) 5.50 (4.50-6.30) 7.50 (6.20-8.80) 765

01-02 1.61 (1.46-1.77) 1.68 (1.54-1.85) 3.31 (2.87-3.74) 5.66 (4.94-6.30) 7.73 (6.61-8.49) 1132

03-04 1.56 (1.37-1.78) 1.61 (1.28-1.92) 3.12 (2.75-3.70) 5.57 (5.04-6.43) 8.08 (6.87-9.53) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.12, 0.12, and 0.31, respectively. 
 194 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

was eliminated primarily in feces and to a lesser extent, in 

urine. Following intravenous injection in animals, about 75 

% of a dose of soluble barium was eliminated within 3 days 

(Reeves, 1986). Insoluble barium salts, such as those used 

in medical radiographic procedures, are not absorbed when 

administered.

Human health effects from barium at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. The health effects of exposure to 

barium compounds depend on the dose, chemical form, 

water solubility, and route of exposure. Toxicity from 

soluble barium salts is rare, but can occur after intentional 

or accidental ingestion of barium carbonate in rodenticides 

(Genter, 2001). Barium blocks cellular efflux of potassium 

resulting in profound hypokalemia. Symptoms following 

acute high dose include perioral paresthesias, vomiting, 

diarrhea, weakness, paralysis, hypertension, and cardiac 

dysrhythmias. Chronic accumulation of inhaled barium 

dust in the lung tissue may cause baritosis, a benign 

condition that may occur among barite ore miners. Chronic 

exposures to natural low levels of barium in drinking water 

have not produced general health effects or evidence of 

cardiovascular risk (Brenniman and Levy, 1984; Wones et 

al., 1990). Chronic high doses in animals resulted in kidney 

damage (McCauley et al., 1985; NTP, 1994; Perry et al., 

1989). Barium is not rated for human carcinogenicity.

Urinary Barium (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 1.40 (1.26-1.56) 1.41 (1.28-1.54) 2.54 (2.20-2.91) 4.68 (3.85-5.47) 6.33 (5.47-8.09) 2180

01-02 1.44 (1.31-1.58) 1.49 (1.35-1.63) 2.76 (2.51-3.03) 4.58 (4.15-4.96) 6.24 (5.28-7.27) 2689

03-04 1.48 (1.37-1.60) 1.41 (1.31-1.58) 2.68 (2.44-2.89) 4.92 (4.39-5.45) 7.10 (6.29-7.77) 2558

Age group 

6-11 years 99-00 2.37 (1.68-3.32) 2.38 (1.84-2.92) 4.47 (2.55-6.46) 10.2 (3.75-22.0) 11.4 (5.46-22.0) 297

01-02 2.20 (1.91-2.52) 2.41 (2.19-2.83) 3.91 (3.29-4.51) 5.01 (4.58-6.00) 6.71 (5.20-8.47) 368

03-04 2.58 (2.22-2.99) 3.00 (2.35-3.29) 4.45 (3.57-5.54) 6.69 (5.59-7.70) 10.3 (6.53-21.0) 290

12-19 years 99-00 1.51 (1.34-1.70) 1.40 (1.26-1.59) 2.48 (1.97-3.06) 4.36 (3.23-5.39) 7.62 (4.24-11.4) 621

01-02 1.45 (1.33-1.59) 1.56 (1.31-1.77) 2.89 (2.68-3.12) 4.52 (3.84-5.20) 5.55 (4.81-6.10) 762

03-04 1.54 (1.36-1.75) 1.59 (1.39-1.87) 2.60 (2.24-3.48) 4.97 (4.34-5.58) 6.47 (5.38-7.77) 725

20 years and older 99-00 1.30 (1.19-1.42) 1.33 (1.20-1.46) 2.32 (2.08-2.62) 4.29 (3.63-4.96) 5.65 (5.28-6.33) 1262

01-02 1.37 (1.24-1.50) 1.40 (1.24-1.52) 2.53 (2.23-2.84) 4.38 (4.02-5.00) 6.55 (5.00-7.64) 1559

03-04 1.38 (1.26-1.50) 1.32 (1.22-1.41) 2.39 (2.13-2.70) 4.39 (3.77-5.16) 7.00 (5.45-8.50) 1543

Gender 

Males 99-00 1.32 (1.22-1.42) 1.36 (1.23-1.47) 2.39 (2.11-2.57) 4.24 (3.48-5.00) 5.61 (4.39-10.2) 1083

01-02 1.30 (1.16-1.45) 1.34 (1.19-1.50) 2.46 (2.14-2.83) 4.51 (3.73-4.96) 5.42 (4.81-7.51) 1334

03-04 1.36 (1.26-1.47) 1.31 (1.19-1.43) 2.60 (2.37-2.75) 4.36 (3.97-4.72) 6.01 (5.45-6.96) 1281

Females 99-00 1.49 (1.27-1.74) 1.48 (1.29-1.68) 2.65 (2.13-3.46) 4.91 (3.96-6.38) 7.36 (5.25-11.3) 1097

01-02 1.59 (1.45-1.75) 1.64 (1.48-1.79) 2.98 (2.75-3.30) 4.76 (4.38-5.31) 6.97 (5.86-7.52) 1355

03-04 1.60 (1.45-1.77) 1.55 (1.35-1.73) 2.78 (2.34-3.25) 5.50 (4.43-6.86) 7.88 (6.28-11.5) 1277

Race/ethnicity 

Mexican Americans 99-00 1.21 (1.10-1.33) 1.18 (1.05-1.38) 2.39 (2.10-2.59) 4.00 (3.33-4.80) 5.31 (4.80-6.51) 692

01-02 1.18 (1.03-1.34) 1.16 (1.00-1.38) 2.33 (1.90-2.61) 3.68 (3.29-4.10) 4.96 (4.24-6.80) 682

03-04 1.29 (1.08-1.55) 1.28 (1.03-1.53) 2.25 (1.73-2.97) 3.99 (2.79-5.03) 4.99 (4.24-6.56) 618

Non-Hispanic blacks 99-00 .881 (.703-1.11) .905 (.710-1.06) 1.64 (1.36-2.00) 3.27 (2.26-4.76) 4.84 (3.57-10.8) 540

01-02 .891 (.777-1.02) .921 (.754-1.11) 1.64 (1.44-2.03) 2.86 (2.48-3.37) 4.02 (3.52-4.68) 667

03-04 .915 (.832-1.01) .963 (.880-1.04) 1.51 (1.39-1.75) 2.62 (2.29-3.04) 3.76 (3.22-4.72) 723

Non-Hispanic whites 99-00 1.56 (1.38-1.77) 1.55 (1.36-1.74) 2.72 (2.27-3.24) 5.00 (3.81-6.02) 6.60 (5.52-10.2) 765

01-02 1.62 (1.49-1.76) 1.66 (1.49-1.82) 3.04 (2.76-3.32) 4.96 (4.55-5.41) 6.74 (5.57-7.64) 1132

03-04 1.64 (1.49-1.82) 1.60 (1.40-1.76) 2.88 (2.56-3.26) 5.38 (4.67-6.28) 7.57 (6.69-9.27) 1074
Fourth National Report on Human Exposure to Environmental Chemicals 195

 Metals

Workplace standards for external air exposure to various 

barium salts have been established by OSHA, and a 

drinking water standard has been established by U.S. EPA. 

Information about external exposure (i.e., environmental 

levels) and health effects is available from ATSDR at: 

http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Levels of urinary barium reflect recent exposure. Studies 

reporting urinary levels of barium in general populations 

have found values generally similar to those reported in 

NHANES 1999-2000, 2001-2002, and 2003-2004 (CDC, 

2005; Minoia et al., 1990; Paschal et al., 1998). Barium 

levels determined in clinically submitted specimens were 

broadly comparable (Komaromy-Hiller et al., 2000) to 

levels in NHANES 1999-2000 and 2001-2002. Welders of 

barium-containing electrodes had median urinary levels of 

barium that were 60 times higher than the median levels 

in this Report; the welders had no obvious adverse clinical 

effects (Zschiesche et al., 1992). Urinary concentrations in 

acute poisonings are often hundreds to thousands of times 

higher than in this Report.

Finding a measurable amount of barium in urine does not 

mean that the level of barium causes an adverse health 

effect. Biomonitoring studies of levels of barium provide 

physicians and public health officials with reference 

values so that they can determine whether people have 

been exposed to higher levels of barium than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Brenniman GR, Levy, PS. Epidemiological study of barium in 

Illinois drinking water supplies. In: Calabrese EJ, ed. Advances 

in modern toxicology. Princeton (NJ): Princeton Scientific 

Publications; 1984. p. 231-249.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Genter MB. Magnesium, calcium, strontium, barium, and radium 

In: Bingham A, Cohressen B, Powell C, eds. Patty’s toxicology. 

5th ed. New York: John Wiley & Sons, Inc.; 2001. p. 221-252

Komaromy-Hiller G, Ash KO, Costa R, Howerton K. Comparison 

of representative ranges based on U.S. patient population and 

literature reference intervals for urinary trace elements. Clin 

Chim Acta 2000;296(1-2):71-90.

McCauley PT, Douglas BH, Laurie RD, et al., Investigations 

into the effect of drinking water barium on rats. In: Inorganics 

in drinking water and cardiovascular disease. Calabrese EJ, ed. 

Princeton NJ: Princeton Scientific Publications, 1985; pp.197-

210.

Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini 

M, et al. Trace element reference values in tissues from 

inhabitants of the European community I. A study of 46 elements 

in urine, blood, and serum of Italian subjects. Sci Total Environ 

1990;95:89-105.

National Toxicology Program (NTP). NTP, technical report on 

the toxicology and carcinogenesis studies of barium chloride 

dehydrate (CAS no. 10326-27-9) in F344/N rats and B6C3F1 

mice (drinking water studies). 1994; [online]. Available at 

URL: http://ntp.niehs.nih.gov:8080/cs.html?charset=iso-8859-

1&url=http%3A//ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr432.pd

f&qt=barium+chloride+dehydrate+1994&col=020rpt&n=3&la=

en. 4/8/09

Paschal DC, Ting BG, Morrow JC, Pirkle JL, Jackson RJ, 

Sampson EJ, et al. Trace metals in urine of United States residents: 

reference range concentrations. Environ Res 1998;76(1):53-59.

Perry HM, Jr, Kopp SJ, Perry EF, et al., Hypertension and 

associated cardiovascular abnormalities induced by chronic 

barium feeding. J Toxicol Environ Health. 1989;28(3):373-388.

Reeves AL. Barium. In Friberg L, Nordberg GF, Vouk VB, eds. 

Handbook on the Toxicology of Metals, Vol 2: Specific Metals., 

2nd Ed. New York: Elsevier; 1986. p. 84-94.

Wones RG, Stadler BL, Frohman, LA. Lack of effect of drinking 

water barium on cardiovascular risk factor. Environ Health 

Perspect 1990;85:355-359.

Zschiesche W, Schaller KH, Weltle D. Exposure to soluble 

barium compounds: an interventional study in arc welders. Int 

Arch Occup Environ Health 1992;64(1):13-23.
 196 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Beryllium

CAS No. 7440-41-7

General Information

Pure beryllium is a hard gray metal, the lightest of all metals, 

and can be found in mineral rocks, coal, soil, and volcanic 

dust. Beryllium compounds are commercially mined, and 

refined beryllium is used in mirrors and special metal alloys 

for the automobile, computer, nuclear, electrical, aircraft, 

and machine-parts industries. Beryllium is also used in 

the production of sports equipment such as golf clubs and 

bike frames. In medicine, beryllium is used in instruments, 

x-ray machines, and dental bridges. Burning coal and oil 

can produce small amounts of beryllium dust that can be 

released into the air.

Exposure to beryllium occurs mostly in the workplace, near 

some hazardous waste sites, and from breathing tobacco 

smoke. Two types of minerals, bertrandite and beryl, are 

mined for commercial recovery of beryllium. Low-level 

beryllium exposure in the general population can occur 

through breathing air, eating food, or drinking water 

containing the metal. In studies of laboratory animals, 

inhaled insoluble beryllium sulfate was retained in the 

lungs and nearby lymph nodes; less than one percent of 

the inhaled dose was slowly absorbed into the blood and 

eventually incorporated into the skeleton. A half-life of 450 

Urinary Beryllium 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * < LOD < LOD < LOD < LOD 2465

01-02 * < LOD < LOD < LOD < LOD 2690

03-04 * < LOD < LOD < LOD < LOD 2558

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 340

01-02 * < LOD < LOD < LOD < LOD 368

03-04 * < LOD < LOD < LOD < LOD 290

12-19 years 99-00 * < LOD < LOD < LOD < LOD 719

01-02 * < LOD < LOD < LOD .140 (<LOD-.170) 762

03-04 * < LOD < LOD < LOD < LOD 725

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1406

01-02 * < LOD < LOD < LOD < LOD 1560

03-04 * < LOD < LOD < LOD < LOD 1543

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 1227

01-02 * < LOD < LOD < LOD .130 (<LOD-.150) 1335

03-04 * < LOD < LOD < LOD < LOD 1281

Females 99-00 * < LOD < LOD < LOD < LOD 1238

01-02 * < LOD < LOD < LOD < LOD 1355

03-04 * < LOD < LOD < LOD < LOD 1277

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 884

01-02 * < LOD < LOD < LOD .130 (<LOD-.160) 683

03-04 * < LOD < LOD < LOD < LOD 618

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 568

01-02 * < LOD < LOD < LOD < LOD 667

03-04 * < LOD < LOD < LOD < LOD 723

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 822

01-02 * < LOD < LOD < LOD < LOD 1132

03-04 * < LOD < LOD < LOD < LOD 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.13, 0.13, and 0.13, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 197

 Metals

days has been calculated for beryllium elimination from the 

human skeleton (IPCS, 1990).

Human health effects from beryllium at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. The effects of occupational 

exposure to beryllium depend on the concentration 

of beryllium in the inhaled air and the duration of air 

exposure. Air levels greater than 100 μg/m3 can result in 

erythema and edema of the lung mucosa, which produces 

pneumonitis. Chronic beryllium disease, or berylliosis, is 

a granulomatous interstitial lung disease that is caused by 

chronic beryllium inhalation and the resultant immunologic 

response. Genetic factors modify individual sensitivity 

to beryllium and susceptibility to developing chronic 

beryllium disease (McCanlies et al., 2003; Maier, 2002). 

Skin exposure can result in delayed hypersensitivity 

reactions, including contact dermatitis and subcutaneous 

nodules.

Workplace air standards and guidelines for external 

exposure have been established by OSHA and ACGIH, 

respectively; and drinking water and environmental 

standards have been established by U. S. EPA. IARC has 

classified beryllium as a human carcinogen, based upon 

excess lung and central nervous system cancers in studies 

of workers. NTP considers beryllium to be a known human 

carcinogen. More information about external exposure 

Urinary Beryllium (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * < LOD < LOD < LOD < LOD 2465

01-02 * < LOD < LOD < LOD < LOD 2689

03-04 * < LOD < LOD < LOD < LOD 2558

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 340

01-02 * < LOD < LOD < LOD < LOD 368

03-04 * < LOD < LOD < LOD < LOD 290

12-19 years 99-00 * < LOD < LOD < LOD < LOD 719

01-02 * < LOD < LOD < LOD .231 (<LOD-.273) 762

03-04 * < LOD < LOD < LOD < LOD 725

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1406

01-02 * < LOD < LOD < LOD < LOD 1559

03-04 * < LOD < LOD < LOD < LOD 1543

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 1227

01-02 * < LOD < LOD < LOD .281 (<LOD-.333) 1334

03-04 * < LOD < LOD < LOD < LOD 1281

Females 99-00 * < LOD < LOD < LOD < LOD 1238

01-02 * < LOD < LOD < LOD < LOD 1355

03-04 * < LOD < LOD < LOD < LOD 1277

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 884

01-02 * < LOD < LOD < LOD .346 (<LOD-.391) 682

03-04 * < LOD < LOD < LOD < LOD 618

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 568

01-02 * < LOD < LOD < LOD < LOD 667

03-04 * < LOD < LOD < LOD < LOD 723

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 822

01-02 * < LOD < LOD < LOD < LOD 1132

03-04 * < LOD < LOD < LOD < LOD 1074

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 198 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

(i.e., environmental levels) and health effects is available 

from ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Urinary beryllium levels represent recent and accumulated 

exposure. Levels of beryllium in urine for the U.S. population 

were generally undetectable in NHANES 1999-2000, 2001-

2002, and 2003-2004. In other studies, urinary levels for 

general populations have been either undetectable or had 

different detection limits than in this Report (KomaromyHiller et al., 2000; Minoia et al., 1990; Paschal et al., 1998). 

Hamilton et al. (1994) noted that analytical methods used in 

several general population studies appeared to have limits 

of detection that were insufficiently low (i.e., less than 0.1 

μg/L). Apostoli and Schaller (2001) stated that detection 

limits in earlier studies were inadequate to estimate nonoccupational exposures. They reported urinary beryllium 

levels ranging from 0.12 to 0.15 μg/L in workers exposed 

at the recommended threshold limit value (Apostoli and 

Schaller, 2001). Given these results, which approximate 

this Report’s limit of detection, 0.13 μg/L, and the 95th

percentile for males in NHANES 2001-2002, and the fact 

that most NHANES participant levels were undetectable, it 

is likely that urinary beryllium levels in the U.S. population 

are lower than levels in workers.

Finding a measurable amount of beryllium in urine does 

not mean that the level of beryllium causes an adverse 

health effect. Biomonitoring studies on levels of beryllium 

provide physicians and public health officials with reference 

values so that they can determine whether people have been 

exposed to higher levels of beryllium than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Apostoli P, Schaller KH. Urinary beryllium--a suitable tool for 

assessing occupational and environmental beryllium exposure. 

Int Arch Occup Environ Health 2001;74:162-166.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA) 2005.

Hamilton EI, Sabbioni E, Van der Venne MT. Element reference 

values in tissues from inhabitants of the European community. 

VI. Review of elements in blood, plasma and urine and a 

critical evaluation of reference values for the United Kingdom 

population. Sci Total Environ 1994;158:165-190.

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria. 106. Beryllium [online]. 1990. 

Available at URL: http://www.inchem.org/documents/ehc/ehc/

ehc106.htm. 3/27/08

Komaromy-Hiller G, Ash KO, Costa R, Howerton K. Comparison 

of representative ranges based on U.S. patient population and 

literature reference intervals for urinary trace elements. Clin 

Chim Acta 2000;296(1-2):71-90.

Maier L. Genetic and exposure risks for chronic beryllium 

disease. Clin Chest Med 2002;23:827-839.

McCanlies EC, Kriess K, Andrew M, Weston A. HLA-DPB1 

and chronic beryllium disease: a HuGE review. Am J Epidemiol 

2003;157:388-398.

Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini 

M, et al. Trace element reference values in tissues from 

inhabitants of the European community I. A study of 46 elements 

in urine, blood, and serum of Italian subjects. Sci Total Environ 

1990;95:89-105.

Paschal DC, Ting BG, Morrow JC, Pirkle JL, Jackson RJ, 

Sampson EJ, et al. Trace metals in urine of United States residents: 

reference range concentrations. Environ Res 1998;76(1):53-59.
Fourth National Report on Human Exposure to Environmental Chemicals 199

 Metals

Cadmium

CAS No. 7440-43-9

General Information

Cadmium is a soft, malleable, bluish-white metal that 

is obtained chiefly as a by-product of processing zinccontaining ores (principally sphalerite, as zinc sulfide) and 

to a lesser extent, during refining of lead and copper from 

sulfide ore. The predominant commercial use of cadmium 

is in battery manufacturing. Other uses include pigment 

production, coatings and plating, plastic stabilizers, and 

nonferrous alloys. Since 2001, U.S. cadmium use has 

declined in response to environmental concerns (http://

minerals.usgs.gov/minerals/pubs/commodity/cadmium).

Important sources of airborne cadmium in the environment 

are burning fossil fuels such as coal or oil, and incineration 

of municipal waste materials. Cadmium also may be emitted 

into the air from zinc, lead, or copper smelters (U.S. EPA, 

Blood Cadmium 

Geometric mean and selected percentiles of blood concentrations (in μg/L) for the U.S. population from the National Health and 

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .412 (.378-.449) .400 (.300-.400) .600 (.500-.700) 1.00 (1.00-1.10) 1.40 (1.30-1.40) 7970

01-02 * .300 (.300-.400) .500 (.500-.600) 1.00 (.900-1.10) 1.40 (1.20-1.70) 8945

03-04 .304 (.289-.320) .300 (.300-.300) .500 (.500-.600) 1.10 (1.00-1.20) 1.60 (1.50-1.60) 8372

Age group 

1-5 years 99-00 * < LOD .300 (<LOD-.400) .400 (.300-.400) .400 (.300-.700) 723

01-02 * < LOD < LOD < LOD .300 (.300-.300) 898

03-04 * < LOD < LOD .200 (.200-.300) .200 (.200-.400) 910

6-11 years 99-00 * < LOD .300 (<LOD-.400) .400 (.300-.500) .500 (.400-.500) 905

01-02 * < LOD < LOD .300 (.300-.300) .400 (.400-.400) 1044

03-04 * < LOD .200 (<LOD-.200) .300 (.200-.300) .300 (.300-.300) 856

12-19 years 99-00 .333 (.304-.366) .300 (.300-.400) .400 (.400-.500) .800 (.600-1.00) 1.10 (.900-1.20) 2135

01-02 * < LOD .300 (.300-.400) .500 (.400-.700) .900 (.700-1.20) 2231

03-04 * .200 (<LOD-.200) .300 (.300-.300) .600 (.500-.700) .900 (.800-1.10) 2081

20 years and older 99-00 .468 (.426-.513) .400 (.400-.500) .700 (.600-.800) 1.10 (1.00-1.20) 1.50 (1.40-1.60) 4207

01-02 .425 (.400-.452) .400 (.400-.400) .600 (.600-.700) 1.10 (1.00-1.30) 1.60 (1.40-1.90) 4772

03-04 .378 (.359-.398) .400 (.300-.400) .600 (.600-.700) 1.20 (1.20-1.30) 1.80 (1.60-1.90) 4525

Gender 

Males 99-00 .403 (.368-.441) .400 (.300-.400) .600 (.500-.700) 1.00 (.900-1.10) 1.40 (1.30-1.50) 3913

01-02 * .300 (<LOD-.300) .500 (.500-.600) 1.00 (.900-1.10) 1.50 (1.20-1.80) 4339

03-04 .283 (.266-.300) .300 (.200-.300) .500 (.500-.500) 1.10 (1.00-1.20) 1.60 (1.50-1.60) 4131

Females 99-00 .421 (.386-.460) .400 (.400-.400) .600 (.500-.700) 1.00 (1.00-1.10) 1.30 (1.20-1.40) 4057

01-02 .382 (.362-.403) .400 (.300-.400) .600 (.500-.600) 1.00 (.900-1.10) 1.40 (1.20-1.70) 4606

03-04 .326 (.309-.344) .300 (.300-.300) .600 (.500-.600) 1.10 (1.00-1.20) 1.60 (1.50-1.70) 4241

Race/ethnicity 

Mexican Americans 99-00 .395 (.367-.424) .400 (.400-.400) .500 (.500-.600) .800 (.700-1.00) 1.20 (.900-1.30) 2742

01-02 * < LOD .400 (.400-.500) .600 (.500-.800) 1.00 (.700-1.30) 2268

03-04 .235 (.216-.255) .200 (.200-.300) .400 (.300-.400) .600 (.500-.800) 1.00 (.800-1.50) 2085

Non-Hispanic blacks 99-00 .393 (.361-.427) .400 (.300-.400) .600 (.500-.600) 1.00 (.900-1.20) 1.40 (1.20-1.60) 1842

01-02 * .300 (<LOD-.300) .500 (.500-.600) 1.00 (.900-1.10) 1.40 (1.20-1.70) 2219

03-04 .304 (.275-.337) .300 (.300-.300) .500 (.400-.600) 1.00 (.900-1.20) 1.50 (1.30-1.70) 2292

Non-Hispanic whites 99-00 .420 (.376-.470) .400 (.300-.500) .600 (.500-.700) 1.10 (1.00-1.20) 1.40 (1.30-1.50) 2716

01-02 * .300 (.300-.400) .600 (.500-.600) 1.00 (.900-1.20) 1.50 (1.30-1.80) 3806

03-04 .313 (.296-.331) .300 (.300-.300) .600 (.500-.600) 1.10 (1.00-1.20) 1.60 (1.50-1.70) 3478

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.3, 0.3, and 0.14, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 200 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

2000). Cadmium in soil is absorbed by plants, including 

many food crops such as cereal grains, wheat, rice, potatoes, 

and various seeds. To a lesser extent, drinking water is a 

source for cadmium intake.

Cadmium is absorbed via inhalation and ingestion. 

Inhalation of cigarette smoke is a predominant source of 

exposure in smokers, whose body burdens of cadmium can 

be approximately twice that of nonsmokers. For nonsmokers 

who are not exposed to cadmium in the workplace, 

ingestion through food is the largest source of exposure. 

The gastrointestinal absorption of dietary cadmium is about 

5% in adult men and 10% or higher in women (Diamond 

et al., 2003; Horiguchi et al., 2004a; Kikuchi et al., 2003), 

however, individual values vary and are affected by factors 

such as dietary intake of essential nutrients (iron, calcium, 

zinc, copper) and protein. Cadmium absorption may be 

increased with iron deficiency (Berglund et al., 1994), 

a factor that may contribute to the higher absorption of 

cadmium by women (Diamond et al., 2003). With chronic 

exposure, cadmium accumulates in the liver and kidneys 

where it is bound to metallothionein, an inducible metal 

binding protein. About one-third to one half of the total 

body burden accumulates in the kidney tissues (Nordberg 

and Nordberg, 2001). The estimated half-life of cadmium 

in the kidney is from one to four decades (ATSDR, 1999; 

Diamond et al., 2003).

The kidney is a critical target and shows the earliest sign of 

cadmium toxicity. Renal tubular and glomerular damage, 

Urinary Cadmium 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey.** 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 .193 (.169-.220) .232 (.214-.249) .475 (.436-.519) .858 (.763-.980) 1.20 (1.06-1.34) 2257 

01-02 .210 (.189-.235) .230 (.207-.255) .458 (.423-.482) .839 (.753-.919) 1.20 (1.07-1.28) 2690 

03-04 .211 (.196-.226) .210 (.200-.230) .450 (.400-.500) .800 (.730-.880) 1.15 (.980-1.26) 2543 

Age group 

6-11 years 99-00 * .078 (.061-.101) .141 (.115-.173) .219 (.178-.233) .279 (.211-.507) 310 

01-02 .061 (<LOD-.081) .077 (.067-.092) .140 (.112-.160) .219 (.184-.262) .282 (.260-.326) 368 

03-04 .077 (.065-.090) .080 (.060-.090) .120 (.100-.160) .180 (.160-.310) .310 (.170-.610) 287 

12-19 years 99-00 .092 (.067-.126) .128 (.107-.148) .203 (.183-.232) .329 (.272-.372) .426 (.366-.596) 648 

01-02 .109 (.087-.136) .135 (.114-.157) .210 (.189-.247) .327 (.289-.366) .452 (.366-.480) 762 

03-04 .121 (.109-.134) .130 (.110-.150) .200 (.170-.210) .300 (.260-.360) .390 (.330-.490) 724 

20 years and older 99-00 .281 (.253-.313) .306 (.261-.339) .551 (.510-.623) .980 (.836-1.13) 1.32 (1.13-1.57) 1299 

01-02 .273 (.249-.299) .280 (.261-.308) .545 (.493-.607) .972 (.855-1.06) 1.28 (1.20-1.43) 1560 

03-04 .260 (.238-.284) .270 (.240-.300) .530 (.470-.580) .890 (.800-.990) 1.25 (1.09-1.46) 1532 

Gender 

Males 99-00 .199 (.165-.241) .227 (.193-.263) .462 (.381-.539) .892 (.748-1.15) 1.41 (.980-1.83) 1121 

01-02 .201 (.177-.229) .223 (.191-.257) .445 (.393-.481) .875 (.741-1.03) 1.22 (1.12-1.38) 1335 

03-04 .206 (.190-.222) .210 (.190-.230) .440 (.390-.490) .790 (.700-.870) 1.01 (.890-1.25) 1277 

Females 99-00 .187 (.153-.229) .239 (.220-.255) .492 (.456-.540) .818 (.705-.980) 1.10 (1.01-1.19) 1136 

01-02 .219 (.192-.251) .234 (.202-.265) .466 (.433-.519) .817 (.733-.886) 1.17 (.918-1.36) 1355 

03-04 .216 (.195-.238) .210 (.200-.240) .450 (.400-.530) .820 (.700-.960) 1.20 (1.02-1.37) 1266 

Race/ethnicity 

Mexican Americans 99-00 .191 (.157-.233) .202 (.167-.221) .447 (.351-.551) .813 (.686-.977) 1.12 (.886-1.38) 780 

01-02 .160 (.135-.189) .181 (.171-.198) .322 (.285-.362) .559 (.430-.733) .766 (.633-1.15) 683 

03-04 .175 (.151-.203) .170 (.150-.210) .350 (.290-.430) .680 (.520-.820) 1.04 (.820-1.20) 614 

Non-Hispanic blacks 99-00 .283 (.208-.387) .316 (.243-.412) .633 (.498-.806) 1.22 (.892-1.38) 1.48 (1.30-1.72) 546 

01-02 .277 (.229-.336) .302 (.257-.354) .589 (.476-.713) 1.04 (.843-1.38) 1.51 (1.28-1.74) 667 

03-04 .265 (.237-.295) .270 (.220-.320) .550 (.440-.640) .960 (.810-1.17) 1.52 (1.06-1.82) 717 

Non-Hispanic whites 99-00 .175 (.148-.206) .220 (.194-.246) .455 (.388-.510) .848 (.714-1.01) 1.17 (.963-1.47) 760 

01-02 .204 (.179-.231) .221 (.191-.255) .445 (.394-.479) .817 (.717-.875) 1.17 (.989-1.24) 1132 

03-04 .209 (.192-.226) .200 (.190-.220) .440 (.390-.500) .790 (.700-.860) 1.13 (.940-1.26) 1070 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.06, 0.06, and 0.06, respectively. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

**All results are corrected for molybdenum oxide interference in the ICP-MS method. 
Fourth National Report on Human Exposure to Environmental Chemicals 201

 Metals

manifested by irreversible proteinuria and progressive 

reduction in glomerular filtration rate, can result from high 

dose chronic exposure, most often a result of occupational 

exposure (Roels et al., 1999). Most studies of relatively 

low level environmental exposure to cadmium have 

demonstrated associations between higher urine or blood 

cadmium levels and an increased prevalence of various 

biomarkers of renal tubular effects (Alfven et al., 2002; 

Jarup et al., 2000; Noonan et al., 2002; Olsson et al., 2002; 

Staessen et al., 1996, 1999). However, two studies in Japan 

did not find an association between cadmium in urine 

and renal biomarkers (Ezaki et al., 2003; Horiguchi et al., 

2004b). Whether the markers of renal tubular effects found 

in populations with low environmental exposure are likely 

to progress or predict an increased risk for developing 

clinically evident renal dysfunction is unknown (Hotz et 

al., 1999).

During the 1950’s and 1960’s, a condition known as “itaiitai” (“ouch-ouch”) affected postmenopausal women 

living in a cadmium-polluted region of Japan. This 

condition of painful osteomalacia or osteoporosis was 

associated with advanced renal tubular damage that led to 

increased urinary excretion of calcium and phosphorus and 

decreased hydroxylation of vitamin D metabolites. Kidney 

dysfunction that led to osteoporosis was associated with 

very high urine cadmium levels in residents of an area of 

China where extensive environmental cadmium pollution 

occurred (Jin et al., 2004). At lower environmental 

exposures, older adults and postmenopausal women with 

Urinary Cadmium (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey.** 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 .181 (.157-.209) .219 (.199-.238) .423 (.391-.446) .712 (.645-.757) .941 (.826-1.07) 2257 

01-02 .199 (.181-.218) .212 (.194-.232) .404 (.377-.440) .690 (.630-.754) .919 (.813-.998) 2689 

03-04 .210 (.201-.219) .208 (.189-.226) .412 (.381-.438) .678 (.650-.716) .940 (.833-1.04) 2543 

Age group 

6-11 years 99-00 * .085 (.063-.107) .148 (.123-.182) .210 (.171-.316) .316 (.184-.607) 310 

01-02 .075 (<LOD-.094) .100 (.083-.112) .166 (.136-.192) .233 (.206-.281) .318 (.221-.440) 368 

03-04 .090 (.078-.104) .091 (.075-.104) .126 (.111-.156) .200 (.147-.350) .308 (.178-.415) 287 

12-19 years 99-00 .071 (.051-.098) .093 (.084-.106) .147 (.130-.163) .215 (.204-.240) .283 (.222-.404) 648 

01-02 .078 (.067-.091) .091 (.085-.101) .137 (.123-.143) .191 (.175-.234) .280 (.234-.321) 762 

03-04 .086 (.077-.096) .084 (.074-.097) .122 (.113-.135) .176 (.154-.198) .234 (.187-.274) 724 

20 years and older 99-00 .267 (.247-.289) .288 (.261-.304) .484 (.433-.545) .769 (.727-.818) 1.07 (.927-1.17) 1299 

01-02 .261 (.236-.289) .273 (.247-.303) .481 (.426-.518) .779 (.691-.850) .979 (.874-1.12) 1559 

03-04 .268 (.255-.281) .270 (.247-.292) .490 (.444-.538) .767 (.688-.830) 1.02 (.909-1.14) 1532 

Gender 

Males 99-00 .154 (.131-.182) .176 (.158-.191) .329 (.293-.382) .617 (.537-.700) .789 (.696-.929) 1121 

01-02 .159 (.143-.177) .168 (.157-.182) .335 (.304-.364) .536 (.491-.653) .757 (.690-.856) 1334 

03-04 .173 (.161-.187) .162 (.143-.185) .325 (.300-.352) .591 (.560-.631) .740 (.678-.795) 1277 

Females 99-00 .211 (.170-.261) .267 (.239-.308) .473 (.423-.551) .783 (.690-.917) 1.09 (.813-1.38) 1136 

01-02 .245 (.216-.278) .263 (.228-.297) .479 (.414-.541) .792 (.687-.884) .985 (.876-1.16) 1355 

03-04 .252 (.238-.266) .253 (.227-.288) .487 (.438-.533) .802 (.716-.906) 1.06 (.940-1.21) 1266 

Race/ethnicity 

Mexican Americans 99-00 .175 (.137-.223) .181 (.144-.225) .331 (.266-.418) .622 (.441-.828) .856 (.674-1.13) 780 

01-02 .156 (.136-.178) .170 (.150-.184) .282 (.263-.340) .501 (.388-.614) .693 (.507-.839) 682 

03-04 .163 (.147-.181) .159 (.140-.183) .296 (.256-.311) .531 (.418-.667) .718 (.562-.950) 614 

Non-Hispanic blacks 99-00 .183 (.140-.240) .202 (.168-.241) .414 (.343-.472) .663 (.516-.827) .873 (.722-.962) 546 

01-02 .190 (.156-.232) .196 (.174-.225) .387 (.336-.449) .686 (.559-.850) .917 (.725-1.08) 667 

03-04 .190 (.173-.210) .185 (.168-.207) .338 (.288-.431) .700 (.500-.818) .865 (.708-1.10) 717 

Non-Hispanic whites 99-00 .175 (.146-.209) .219 (.191-.250) .432 (.387-.470) .729 (.666-.783) 1.00 (.826-1.16) 760 

01-02 .205 (.184-.229) .224 (.208-.242) .421 (.382-.470) .719 (.668-.784) .931 (.806-1.05) 1132 

03-04 .220 (.207-.235) .221 (.197-.253) .434 (.398-.476) .687 (.647-.767) 1.00 (.830-1.08) 1070 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

**All results are corrected for molybdenum oxide interference in the ICP-MS method. 
 202 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

greater urine cadmium levels may have an increased risk 

for bone fracture and diminished bone mineral density 

(Alfven et al., 2002; Staessen et al., 1999).

Acute and heavy exposure to airborne dusts and fumes, 

as may occur from welding cadmium-alloyed metals, has 

resulted in severe, potentially fatal pneumonitis (Fernandez 

et al., 1996). Chronic inhalation exposure to cadmium 

particulates was associated with changes in pulmonary 

function and chest radiographs that were consistent with 

emphysema (Davidson et al., 1988). Workplace exposure 

to airborne cadmium particulates was associated with 

decreases in olfactory function (Mascagni et al., 2003). 

Animal studies have demonstrated reproductive and 

teratogenic effects. Small epidemiologic studies have 

noted an inverse relationship between cadmium in cord 

blood, maternal blood or maternal urine and birth weight 

(Nishijo et al., 2002; Salpietro et al., 2002) and length at 

birth (Nishijo et al., 2004; Zhang et al., 2004).

Cadmium can produce lung, pituitary gland and kidney 

tumors in animals and has been associated with lung cancer 

in humans in occupational epidemiologic studies. Both 

IARC and NTP consider cadmium a human carcinogen. 

Waalkes (2003) provides an overview and summarizes 

potential mechanisms for carcinogenicity. Workplace 

standards and guidelines for air exposure to cadmium 

have been established by OSHA and ACGIH, respectively, 

and drinking water and environmental standards have 

been established by U.S. EPA. Information about external 

exposure (i.e., environmental levels) and health effects 

is available from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html.

Biomonitoring Information

Blood cadmium reflects both recent and cumulative 

exposures. In the typical environmental exposure, urinary 

cadmium reflects both cumulative exposure and the 

concentration of cadmium in the kidney.

Surveys of populations not known to have increased 

cadmium exposure have reported similar urine and blood 

levels (Becker et al., 2002; Becker et al., 2003; CDC, 

2005; Friedman et al., 2006; Komaromy-Hiller et al., 2000; 

Wennberg et al., 2006; Wilhelm et al., 2006). Women had 

higher blood and urine cadmium levels compared to men 

of similar ages, with peak values observed in the fifth to 

sixth decades (CDC, 2005; Horiguchi et al., 2004b; Olsson 

et al., 2002; Wennberg et al., 2006). For NHANES 1999-

2000, blood cadmium was also slightly higher in Mexican 

Americans and participants 20 years and older (CDC, 

2005). Blood and urine cadmium levels are typically higher 

in cigarette smokers, intermediate in former smokers 

and lower in never-smokers (Becker et al., 2003; Becker 

et al., 2002; Mannino et al., 2004; Olsson et al., 2002). 

Blood cadmium levels are about twice as high in smokers 

compared to nonsmokers (Becker et al., 2003; Becker et al., 

2002; Olsson et al., 2002). Several studies of populations 

residing in areas with higher cadmium soil concentrations 

or with frank cadmium pollution have reported mean blood 

and urine cadmium levels considerably higher (as much 

as 10 times higher) than control groups or representative 

U.S. data (CDC, 2005; Ezaki et al., 2003; Jarup et al., 

2000; Jin et al., 2004; Staessen et al., 1999; Staessen et al., 

1996; Suwazono et al., 2000). Creatinine-corrected urine 

cadmium values in U.S. study subjects living near a former 

zinc smelter were similar to those from an unexposed 

community and to those in this Report (Noonan et al., 

2002).

People who are occupationally exposed may have blood 

and urine cadmium levels that are higher than those of the 

general population. The 95th percentiles for cadmium levels 

in this Report were less than the OSHA standards for both 

blood cadmium (5 mg/L) and urine cadmium (3 mg/gram 

of creatinine). Occupational standards are provided here 

for comparison only, not to imply a safety level for general 

population exposure.

Subtle increases in markers of renal tubular effects have 

been associated with urine cadmium levels as low as 

approximately 1 mg/gram of creatinine (Akesson et al., 

2005; Ezaki et al., 2003; Jarup et al., 2000; Moriguchi et 

al., 2004; Noonan et al., 2002). However, two studies of 

women in Japan with lower exposures found no correlation 

between renal tubular effect markers and blood or urine 

cadmium levels (geometric means were 1.26 and 3.46 

mg/gram of creatinine) (Ezaki et al., 2003; Horiguchi et 

al., 2004b). In postmenopausal women, decreased bone 

density was correlated with mean urinary cadmium levels 

of approximately 1 mg/gram of creatinine (Staessen et al., 

1999). In adults aged 60 years and older, the risk of low 

bone mineral density increased by nearly three-fold when 

the blood cadmium exceeded 1.1 mg/L (Alfven et al., 2002). 

In this Report the urinary and blood cadmium levels at the 

95th and 90th percentiles, respectively, approached these 

values associated with subclinical changes in renal function 

and bone mineral density. Further research is needed to 

address the public health consequences of such exposure in 

the United States.

Finding a measurable amount of cadmium in blood or 

urine does not mean that the levels of cadmium cause an 

adverse health effect. Biomonitoring studies on levels of 

cadmium provide physicians and public health officials 
Fourth National Report on Human Exposure to Environmental Chemicals 203

 Metals

with reference values so they can determine whether people 

have been exposed to higher levels of cadmium than are 

found in the general population. Biomonitoring data can 

also help scientists plan and conduct research on exposure 

and health effects.

References

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C, et al. Tubular and glomerular kidney effects in Swedish 

women with low environmental cadmium exposure. Environ 

Health Perspect 2005;13(11):1627-1631.

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for cadmium update. 1999 [online]. 

Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp5.html. 

4/8/09

Alfven T, Jarup L, Elinder CG. Cadmium and lead in blood in 

relation to low bone mineral density and tubular proteinuria. 

Environ Health Perspect 2002;110:699-702.

Becker K, Kaus S, Krause C, Lepom P, Schulz C, Seiwert M, et al. 

German Environmental Survey 1998 (GerES III): environmental 

pollutants in blood of the German population. Int J Hyg Environ 

Health 2002;205:297-308.

Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German 

environmental survey 1998 (GerES III): environmental pollutants 

in the urine of the German population. Int J Hyg Environ Health 

2003; 206:15-24.

Berglund M, Akesson A, Nermell B, Vahter M. Intestinal 

absorption of dietary cadmium in women depends on body iron 

stores and fiber intake. Environ Health Perspect 1994; 102:1058-

1066.

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(GA). 2005.

Davison AG, Fayers PM, Taylor AJ, Venables KM, Darbyshire J, 

Pickering CA, et al. Cadmium fume inhalation and emphysema. 

Lancet 1988;1(8587):663-667.

Diamond GL, Thayer WC, Choudhury H. Pharmacokinetic/

pharmacodynamics (PK/PD) modeling of risks of kidney toxicity 

from exposure to cadmium: estimates of dietary risks in the U.S. 

population. J Toxicol Environ Health 2003;66(Pt A):2141-2164.

Ezaki T, Tsukahara T, Moriguchi J, Furuki K, Fukui Y, Ukai H, 

et al. No clear-cut evidence for cadmium-induced renal tubular 

dysfunction among over 10,000 women in the Japanese general 

population: a nationwide large-scale survey. Int Arch Occup 

Environ Health 2003;76:186-196.

Fernandez MA, Sanz P, Palomar M, Serra J, Gadea E. Fatal 

chemical pneumonitis due to cadmium fumes. Occup Med 

1996;46:372-374.

Friedman LS, Lukyanova EM, Kundiev YT, ShkiryakNizhnyk AZ, Chislovska NV, Mucha A, et al. Anthropometric, 

environmental, and dietary predictors of elevated blood cadmium 

levels in Ukranian children: Ukraine ELSPAC group. Environ 

Res 2006;102:83-89.

Horiguchi H, Oguma E, Sasaki S, Miyamoto K, Ikeda Y, 

Machida M, et al. Comprehensive study of the effects of age, iron 

deficiency, diabetes mellitus, and cadmium burden on dietary 

cadmium absorption in cadmium-exposed female Japanese 

farmers. Toxicol Appl Pharmacol 2004a; 196:114-123. 

Horiguchi H, Oguma E, Sasaki S, Miyamoto K, Ikeda Y, Machida 

M, et al. Dietary exposure to cadmium at close to the current 

provisional tolerable weekly intake does not affect renal function 

among female Japanese farmers. Environ Res 2004b;95:20–31.

Hotz P, Buchet JP, Bernard A, Lison D, Lauwerys R. Renal effects 

of low-level environmental cadmium exposure: 5-year follow-up 

of a subcohort from the Cadmibel study. Lancet 1999;354:1508–

1513.

Jarup L, Hellstrom L, Alfven T, Carlsson MD, Grubb A, Persson 

B, et al. Low level exposure to cadmium and early kidney damage: 

the OSCAR study [published erratum appears in Occup Environ 

Med 2002;59:497]. Occup Environ Med 2000;57:668-672.

Jin T, Nordberg G, Ye T, Bo M, Wang H, Zhu G, et al. Osteoporosis 

and renal dysfunction in a general population exposed to cadmium 

in China. Environ Res 2004;96:353-359. 

Kikuchi Y, Nomiyama T, Kumagai N, Dekio F, Uemura T, 

Takebayashi T, et al. Uptake of cadmium in meals from the 

digestive tract of young non-smoking Japanese female volunteers. 

J Occup Health 2003;45:43-52. 

Komaromy-Hiller G, Ash KO, Costa R, Howerton K. Comparison 

of representative ranges based on U.S. patient population and 

literature reference intervals for urinary trace elements. Clin 

Chim Acta 2000;296(1-2):71-90.

Mannino DM, Holguin F, Greves HM, Savage-Brown A, Stock 

AL, Jones RL. Urinary cadmium levels predict lower lung 

function in current and former smokers: data from the Third 

National Health and Nutrition Examination Survey. Thorax 

2004;59:194-8.

Mascagni P, Consonni D, Bregante G, Chiappino G, Toffoletto 

F. Olfactory function in workers exposed to moderate airborne 

cadmium levels. Neurotoxicology 2003;24:717-724.

Moriguchi J, Ezaki T, Tsukahara T, Furuki K, Fukui Y, 

Okamoto S, et al. a1-Microglobulin as a promising marker of 

cadmium-induced tubular dysfunction, possibly better than b2-

microglobulin. Toxicol Lett 2004;148(1-2):11-20.
 204 Fourth National Report on Human Exposure to Environmental Chemicals 

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Nishijo M, Nakagawa H, Honda R, Tanebe K, et al. Effects of 

maternal exposure to cadmium on pregnancy outcome and breast 

milk. Occup Environ Med 2002;59:394-397.

Nishijo M, Tawara K, Honda R, Nakagawa H, Tanebe K, Saito S. 

Relationship between newborn size and mother’s blood cadmium 

levels, Toyama, Japan. Arch Environ Health. 2004;59(1):22-25.

Noonan CW, Sarasua SM, Campagna D, Kathman SJ, 

Lybarger JA, Mueller PW. Effects of exposure to low levels of 

environmental cadmium on renal biomarkers. Environ Health 

Perspect 2002;110:151-155.

Nordberg GF, Nordberg M. Biological monitoring of cadmium. 

In: Clarkson TW, Friberg L, Nordberg GF, Sager PR, eds. 

Biological monitoring of toxic metals. New York: Plenum Press; 

2001. pp. 151-168.

Olsson IM, Bensryd I, Lundh T, Ottosson H, Skerfving S, 

Oskarsson A. Cadmium in blood and urine – impact of sex, age, 

dietary intake, iron status, and former smoking – association of 

renal effects. Environ Health Perspect 2002;110:1185-1190.

Roels HA, Hoet P, Lison D. Usefulness of biomarkers of 

exposure to inorganic mercury, lead, or cadmium in controlling 

occupational and environmental risks of nephrotoxicity. Ren Fail 

1999;21(3-4):251-262.

Salpietro CD, Gangemi S, Minciullo PL, Bruiglia S, Merlino MV, 

Stelitano A, et al. Cadmium concentration in maternal and cord 

blood and infant birth weight: a study on healthy non-smoking 

women. J Perinat Med 2002;30(5):395-399.

Staessen JA, Buchet JP, Ginucchio G, Lauwerys R, Lijnen P, 

Roels H, et al. Public health implications of environmental 

exposure to cadmium and lead: an overview of epidemiological 

studies in Belgium. J Cardiovasc Risk 1996;3:26-41.

Staessen J, Roels HA, Emelianov D, Kuznetsova T, Thijs L, 

Vangronsveld J, et al. Environmental exposure to cadmium, 

forearm bone density, and risk of fractures: prospective population 

study. Lancet 1999;353:1140-1144.

Suwazono Y, Kobayashi E, Okubo Y, Nogawa K, Kido T, 

Nakagawa H. Renal effects of cadmium exposure in cadmium 

nonpolluted areas in Japan. Environ Res 2000;84 (Section A):44-

55. 

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2000. Cadmium compounds. Hazard Summary, created 1992, 

Revised 2000 [online]. Available at URL: www.epa.gov/ttn/atw/

hlthef/cadmium.html. 4/8/09

Waalkes MP. Cadmium carcinogenesis. Mutat Res 2003;533(1-

2):107-120.

Wennberg M, Lundh T, Bergdahl IA, Gallmans G, Jansson J-H, 

Stegmayr B, et al. Time trends in burdens of cadmium, lead, 

and mercury in the population of northern Sweden. Environ Res 

2006;100:330-338.

Wilhelm M, Schultz C, Schwenk M. Revised and new reference 

values for arsenic, cadmium, lead, and mercury in blood or urine 

of children: Basis for validation of human biomonitoring data in 

environmental medicine. Int J Hyg Environ Health 2006;209:301-

305.

Zhang YL, Zhao YC, Wang JX, Zhu HD, Liu QF, Fan YG, et 

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Fourth National Report on Human Exposure to Environmental Chemicals 205

 Metals

Cesium

CAS No. 7440-46-2

General Information

Cesium is a silver-white metal that is found naturally in 

rock, soil, and clay. Inorganic cesium compounds are used 

in photomultiplier and vacuum tubes, scintillation counters, 

infrared lamps, semiconductors, photographic emulsions, 

and high-power gas-ion devices, and as polymerization 

catalysts. Radioactive 137Cs has been used medically to treat 

cancer.

Most human exposure to cesium occurs through the diet. 

For absorbed cesium salts, the body half-life is estimated to 

be 70-109 days based on 137Cs exposures. Little is known 

about the health effects of this metal, although cesium was 

generally of low toxicity when given to animals. However, 

cesium hydroxide is corrosive and irritating at high 

concentrations. Case investigations of ingestions of large 

doses of cesium chloride have reported decreased appetite, 

nausea, diarrhea, and cardiac arrhythmia (ATSDR, 2004). 

Human health effects from cesium at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Workplace guidelines for cesium 

hydroxide are available from ACGIH and NIOSH. Whether 

cesium compounds are carcinogenic is unknown.

Urinary Cesium 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 4.35 (4.00-4.74) 4.90 (4.40-5.40) 7.10 (6.60-7.70) 9.60 (8.80-10.3) 11.5 (10.2-13.0) 2464

01-02 4.81 (4.40-5.26) 5.49 (5.12-5.90) 7.91 (7.47-8.39) 10.4 (9.56-11.4) 12.6 (11.1-13.8) 2690

03-04 4.67 (4.39-4.97) 5.14 (4.84-5.49) 7.68 (7.20-8.21) 10.6 (9.55-11.4) 12.7 (11.5-13.9) 2558

Age group 

6-11 years 99-00 4.87 (4.08-5.81) 5.70 (4.60-6.70) 7.30 (6.70-8.00) 9.00 (7.90-10.1) 9.70 (9.00-10.8) 340

01-02 4.87 (4.08-5.82) 5.64 (4.69-6.56) 7.96 (6.77-8.84) 9.88 (8.64-10.6) 11.1 (10.2-12.4) 368

03-04 5.21 (4.74-5.71) 5.50 (4.76-6.37) 8.08 (7.10-8.83) 11.5 (8.86-12.9) 12.9 (10.8-13.6) 290

12-19 years 99-00 4.55 (4.09-5.05) 5.20 (4.40-5.60) 6.90 (6.10-7.80) 8.80 (8.10-9.50) 10.7 (8.90-12.5) 718

01-02 5.22 (4.57-5.95) 5.62 (5.16-6.12) 7.55 (7.13-8.04) 9.77 (9.12-11.1) 12.0 (10.0-15.0) 762

03-04 5.04 (4.59-5.54) 5.70 (5.16-6.07) 7.53 (6.91-8.37) 9.71 (8.80-10.4) 11.6 (9.92-13.2) 725

20 years and older 99-00 4.26 (3.94-4.62) 4.80 (4.40-5.30) 7.10 (6.50-7.60) 9.80 (8.90-10.7) 11.7 (10.2-13.4) 1406

01-02 4.74 (4.32-5.20) 5.43 (5.05-5.87) 7.97 (7.43-8.52) 10.6 (9.73-11.5) 12.9 (11.2-14.2) 1560

03-04 4.56 (4.23-4.90) 5.03 (4.60-5.42) 7.66 (7.01-8.34) 10.7 (9.40-11.5) 12.9 (11.5-14.9) 1543

Gender 

Males 99-00 4.84 (4.35-5.38) 5.50 (4.60-6.00) 7.50 (7.00-8.20) 9.70 (8.80-11.3) 11.7 (10.3-13.0) 1226

01-02 5.34 (4.89-5.84) 6.13 (5.61-6.64) 8.27 (7.84-9.08) 10.8 (10.1-12.1) 12.8 (11.3-15.0) 1335

03-04 5.03 (4.73-5.36) 5.59 (5.17-6.00) 7.98 (7.31-8.63) 11.0 (9.53-11.8) 12.9 (11.5-16.1) 1281

Females 99-00 3.95 (3.63-4.29) 4.50 (4.20-4.90) 6.70 (6.20-7.30) 9.10 (8.30-10.0) 11.2 (9.90-12.9) 1238

01-02 4.36 (3.95-4.81) 4.87 (4.45-5.25) 7.33 (6.71-8.01) 9.77 (9.07-11.0) 12.4 (10.4-13.8) 1355

03-04 4.35 (4.03-4.70) 4.79 (4.25-5.26) 7.30 (6.87-7.81) 10.2 (9.40-11.0) 12.1 (11.2-13.6) 1277

Race/ethnicity 

Mexican Americans 99-00 4.32 (3.82-4.89) 4.80 (4.30-5.20) 6.70 (6.40-7.20) 9.10 (8.00-9.90) 11.1 (9.60-12.7) 884

01-02 4.63 (4.10-5.24) 5.29 (4.59-5.89) 7.08 (6.42-7.99) 9.13 (7.86-11.3) 11.3 (8.81-14.9) 683

03-04 4.94 (4.64-5.27) 5.62 (5.01-6.09) 7.86 (7.15-8.46) 10.3 (8.99-11.3) 11.9 (10.7-14.7) 618

Non-Hispanic blacks 99-00 4.94 (4.33-5.64) 5.40 (4.80-6.40) 7.50 (6.90-8.40) 9.80 (8.80-10.8) 11.6 (9.80-13.1) 568

01-02 4.93 (4.70-5.17) 5.33 (5.05-5.64) 7.36 (6.97-7.59) 9.44 (8.71-9.68) 10.7 (10.1-12.3) 667

03-04 4.71 (4.47-4.97) 5.12 (4.71-5.49) 7.17 (6.72-7.60) 9.13 (8.52-9.99) 10.7 (9.99-11.4) 723

Non-Hispanic whites 99-00 4.25 (3.83-4.72) 4.80 (4.20-5.50) 7.20 (6.60-7.90) 9.70 (8.90-10.7) 11.8 (10.3-13.3) 821

01-02 4.77 (4.27-5.32) 5.49 (4.99-6.05) 7.98 (7.45-8.61) 10.4 (9.54-11.4) 12.6 (11.0-13.8) 1132

03-04 4.56 (4.22-4.94) 5.02 (4.59-5.42) 7.60 (7.00-8.23) 10.7 (9.26-11.8) 12.9 (11.5-14.7) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.14, 0.14, and 0.2, respectively. 
 206 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Biomonitoring Information

Urinary cesium levels reflect recent exposure. Two small 

studies of European populations reported urinary cesium 

levels similar to U.S. population results shown in this 

Report (Alimonti et al., 2005; Minoia et al., 1990). Using 

clinically submitted specimens, Komaromy-Hiller et al. 

(2000) found urinary cesium levels that were slightly lower 

than those reported for the U.S. population. Urinary cesium 

levels were similar in a group of forest fire fighters and 

residents living near the fire area (Wolfe et al., 2004), and 

were also roughly similar to those in this Report.

Finding a measurable amount of cesium in the urine 

does not mean that the levels of cesium cause an adverse 

health effect. Biomonitoring studies on levels of cesium 

can provide physicians and public health officials with 

reference values so that they can determine whether people 

have been exposed to higher levels of cesium than are 

found in the general population. Biomonitoring data can 

also help scientists plan and conduct research on exposure 

and health effects.

Urinary Cesium (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 4.10 (3.96-4.25) 4.13 (3.97-4.27) 5.41 (5.21-5.70) 7.14 (6.83-7.50) 8.64 (8.00-9.30) 2464

01-02 4.54 (4.30-4.79) 4.44 (4.20-4.64) 6.06 (5.66-6.47) 8.18 (7.62-8.95) 10.2 (8.84-11.7) 2689

03-04 4.64 (4.42-4.87) 4.42 (4.21-4.74) 6.11 (5.76-6.48) 8.51 (7.99-9.15) 10.6 (9.75-11.0) 2558

Age group 

6-11 years 99-00 5.34 (5.03-5.67) 5.42 (5.03-6.04) 6.63 (6.18-7.13) 8.23 (7.13-9.41) 9.90 (7.88-10.1) 340

01-02 5.95 (5.48-6.46) 5.91 (5.43-6.53) 7.77 (7.00-8.28) 9.27 (8.35-11.9) 11.9 (9.38-12.3) 368

03-04 6.07 (5.63-6.53) 6.02 (5.45-6.49) 8.30 (7.16-8.99) 10.8 (9.15-11.8) 11.9 (10.3-15.8) 290

12-19 years 99-00 3.43 (3.29-3.58) 3.54 (3.29-3.68) 4.35 (4.17-4.56) 5.31 (4.97-5.79) 6.67 (5.33-8.09) 718

01-02 3.73 (3.41-4.08) 3.55 (3.36-3.74) 4.74 (4.40-5.14) 6.10 (5.35-7.63) 8.08 (6.44-9.82) 762

03-04 3.60 (3.37-3.85) 3.51 (3.33-3.72) 4.53 (4.24-4.87) 6.08 (5.14-6.94) 7.27 (6.13-9.07) 725

20 years and older 99-00 4.08 (3.88-4.29) 4.06 (3.85-4.29) 5.39 (5.04-5.85) 7.17 (6.84-7.58) 8.61 (7.91-9.30) 1406

01-02 4.54 (4.30-4.78) 4.43 (4.20-4.59) 5.94 (5.64-6.40) 8.15 (7.46-8.97) 10.2 (8.74-11.7) 1559

03-04 4.68 (4.46-4.91) 4.47 (4.27-4.80) 6.11 (5.83-6.43) 8.47 (7.76-9.17) 10.5 (9.68-11.2) 1543

Gender 

Males 99-00 3.78 (3.65-3.91) 3.78 (3.61-3.96) 4.96 (4.72-5.20) 6.50 (6.18-6.70) 7.71 (7.01-8.64) 1226

01-02 4.22 (3.96-4.51) 4.10 (3.87-4.41) 5.60 (5.27-6.03) 7.67 (6.90-8.48) 9.46 (8.22-11.5) 1334

03-04 4.24 (3.99-4.50) 4.12 (3.89-4.37) 5.66 (5.19-6.06) 7.66 (6.90-8.40) 9.00 (8.36-10.3) 1281

Females 99-00 4.43 (4.20-4.68) 4.45 (4.14-4.77) 5.92 (5.36-6.47) 7.70 (7.16-8.07) 9.41 (8.00-10.4) 1238

01-02 4.86 (4.58-5.16) 4.72 (4.50-5.06) 6.54 (5.93-7.00) 8.50 (7.84-9.79) 10.3 (8.95-12.2) 1355

03-04 5.05 (4.77-5.35) 4.77 (4.44-5.14) 6.58 (6.14-7.22) 9.43 (8.56-10.5) 11.3 (10.7-12.3) 1277

Race/ethnicity 

Mexican Americans 99-00 3.99 (3.73-4.25) 3.95 (3.65-4.17) 5.09 (4.79-5.39) 6.65 (6.08-7.10) 7.98 (7.20-8.95) 884

01-02 4.51 (4.00-5.08) 4.51 (3.82-4.95) 5.91 (5.31-6.64) 7.77 (6.60-10.0) 10.0 (7.60-20.5) 682

03-04 4.58 (4.16-5.05) 4.51 (4.10-4.92) 5.74 (5.42-6.09) 7.53 (6.59-8.91) 9.44 (8.24-10.6) 618

Non-Hispanic blacks 99-00 3.21 (2.90-3.56) 3.26 (3.05-3.44) 4.30 (4.00-4.55) 5.50 (5.00-5.98) 6.33 (5.91-7.04) 568

01-02 3.38 (3.19-3.57) 3.35 (3.05-3.60) 4.41 (4.15-4.78) 5.87 (5.63-6.29) 6.75 (6.41-7.03) 667

03-04 3.38 (3.21-3.56) 3.30 (3.08-3.50) 4.31 (4.02-4.62) 5.79 (5.12-6.47) 6.98 (6.38-7.18) 723

Non-Hispanic whites 99-00 4.26 (4.07-4.47) 4.28 (4.05-4.50) 5.66 (5.26-6.05) 7.27 (6.84-7.83) 8.75 (7.93-9.38) 821

01-02 4.81 (4.55-5.08) 4.63 (4.42-4.96) 6.33 (5.91-6.68) 8.46 (7.84-9.39) 10.3 (9.04-11.8) 1132

03-04 4.81 (4.52-5.12) 4.56 (4.31-4.98) 6.28 (5.95-6.71) 8.63 (7.99-9.28) 10.6 (9.43-11.0) 1074
Fourth National Report on Human Exposure to Environmental Chemicals 207

 Metals

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for cesium.2004 [online]. Available at URL: 

http://www.atsdr.cdc.gov/toxprofiles/tp157.html. 4/8/09

Alimonti A, Forte G, Spezia S, Gatti A, Mincione G, Ronchi P, et 

al. Uncertainty of inductively coupled plasma mass spectrometry 

based measurements: An application to the analysis of urinary 

barium, cesium, antimony and tungsten. Rapid Commun Mass 

Spectrom 2005;19:3131-3138.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA) 2005.

Komaromy-Hiller G, Ash KO, Costa R, Howerton K. Comparison 

of representative ranges based on U.S. patient population and 

literature reference intervals for urinary trace elements. Clin 

Chim Acta 2000;296(1-2):71-90.

Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini 

M, et al. Trace element reference values in tissues from 

inhabitants of the European community I. A study of 46 elements 

in urine, blood, and serum of Italian subjects. Sci Total Environ 

1990;95:89-105.

Wolfe MI, Mott JA, Voorhees RE, Sewell CM, Paschal D, Wood 

CM, et al. Assessment of urinary metals following exposure to a 

large vegetative fire, New Mexico, 2000. J Expo Anal Environ 

Epidemiol 2004;14:120-128.
 208 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Cobalt

CAS No. 7440-48-4

General Information

Cobalt is a magnetic element that occurs in nature either 

as a steel-gray, shiny, hard metal or in combination 

with other elements. The cobalt used in U.S. industry 

is imported or obtained by recycling scrap metal that 

contains cobalt. Among its many uses are manufacturing 

superalloys used in gas turbines in aircraft engines, hard 

metal (alloys of cobalt and tungsten carbide), blue-colored 

pigments, and fertilizers. Cobalt is used as a drying agent 

in paints, varnishes, and inks. It is also a component of 

porcelain enamel applied to steel bathroom fixtures, large 

appliances, and kitchenware. Cobalt compounds are used 

as catalysts in producing oil and gas, and in synthesizing 

polyester and other materials. Cobalt compounds are also 

used in manufacturing battery electrodes, steel-belted 

radial tires, automobile airbags, diamond-polishing wheels, 

and magnetic recording media. Medical uses include joint 

and dental prostheses and radioactive cobalt in cancer 

chemotherapy.

Cobalt occurs naturally in airborne dust, seawater, and soil. 

It is emitted into the environment from burning coal and oil 

and car and truck exhaust. Usual human exposure is from 

food sources. Cobalt may be released into the systemic 

circulation of patients who receive joint prostheses that are 

Urinary Cobalt 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .375 (.336-.419) .410 (.370-.450) .630 (.570-.680) .950 (.890-1.03) 1.32 (1.16-1.48) 2465

01-02 .379 (.355-.404) .410 (.380-.430) .610 (.570-.660) .940 (.870-1.00) 1.28 (1.15-1.44) 2690

03-04 .316 (.291-.343) .330 (.300-.350) .520 (.490-.550) .820 (.750-.890) 1.16 (1.08-1.26) 2558

Age group 

6-11 years 99-00 .499 (.427-.583) .530 (.450-.640) .750 (.610-.900) 1.03 (.880-1.12) 1.22 (1.03-1.50) 340

01-02 .452 (.377-.543) .520 (.430-.610) .710 (.670-.810) 1.07 (.940-1.21) 1.32 (1.17-1.53) 368

03-04 .454 (.393-.523) .460 (.410-.520) .750 (.590-.900) 1.24 (.910-1.47) 1.68 (1.26-1.81) 290

12-19 years 99-00 .519 (.463-.581) .520 (.490-.570) .820 (.670-.890) 1.17 (1.01-1.47) 1.52 (1.26-2.56) 719

01-02 .515 (.469-.564) .520 (.480-.570) .750 (.690-.840) 1.24 (1.07-1.32) 1.59 (1.37-1.99) 762

03-04 .461 (.428-.496) .480 (.450-.520) .740 (.650-.800) 1.03 (.940-1.23) 1.60 (1.14-1.92) 725

20 years and older 99-00 .343 (.305-.386) .370 (.330-.420) .570 (.520-.640) .880 (.810-.980) 1.28 (1.07-1.39) 1406

01-02 .352 (.333-.373) .380 (.350-.410) .560 (.520-.590) .860 (.800-.930) 1.15 (1.04-1.42) 1560

03-04 .285 (.259-.313) .300 (.270-.330) .460 (.410-.510) .690 (.660-.730) 1.06 (.890-1.14) 1543

Gender 

Males 99-00 .371 (.331-.416) .410 (.370-.450) .580 (.540-.640) .820 (.740-.900) 1.01 (.900-1.12) 1227

01-02 .367 (.338-.399) .390 (.360-.420) .550 (.520-.600) .790 (.740-.850) 1.05 (.960-1.14) 1335

03-04 .294 (.270-.319) .320 (.290-.340) .480 (.440-.500) .670 (.620-.710) .870 (.790-.920) 1281

Females 99-00 .379 (.333-.431) .410 (.340-.460) .680 (.590-.790) 1.17 (.930-1.36) 1.50 (1.28-2.05) 1238

01-02 .390 (.364-.417) .430 (.400-.450) .670 (.620-.700) 1.06 (.980-1.16) 1.46 (1.22-1.81) 1355

03-04 .339 (.308-.372) .340 (.310-.370) .580 (.540-.610) 1.04 (.900-1.13) 1.47 (1.33-1.73) 1277

Race/ethnicity 

Mexican Americans 99-00 .418 (.348-.502) .470 (.370-.530) .670 (.630-.770) 1.05 (.950-1.19) 1.47 (1.25-1.67) 884

01-02 .398 (.373-.424) .430 (.410-.450) .650 (.600-.710) .950 (.850-1.03) 1.20 (1.06-1.48) 683

03-04 .374 (.350-.398) .350 (.340-.390) .580 (.530-.620) 1.09 (.920-1.16) 1.33 (1.16-1.73) 618

Non-Hispanic blacks 99-00 .434 (.405-.465) .430 (.390-.470) .680 (.620-.760) 1.17 (1.04-1.26) 1.45 (1.23-2.04) 568

01-02 .435 (.388-.487) .420 (.380-.460) .650 (.540-.810) 1.16 (.850-1.64) 1.75 (1.32-2.22) 667

03-04 .380 (.348-.414) .380 (.360-.410) .600 (.540-.680) 1.01 (.890-1.09) 1.28 (1.01-2.03) 723

Non-Hispanic whites 99-00 .369 (.316-.431) .410 (.350-.460) .630 (.550-.700) .930 (.830-1.08) 1.29 (1.02-1.65) 822

01-02 .359 (.327-.394) .390 (.360-.430) .590 (.520-.660) .870 (.800-.950) 1.16 (1.04-1.32) 1132

03-04 .301 (.270-.334) .310 (.280-.340) .500 (.460-.540) .760 (.690-.850) 1.09 (.950-1.26) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.07, 0.07, and 0.08, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 209

 Metals

fabricated from cobalt alloys (Lhotka et al., 2003). Cobalt 

constitutes 4% by weight of vitamin B-12 (cobalamin), 

an essential human nutrient. A nutritional requirement for 

cobalt other than that contained within dietary cobalamin 

has not been established. Exposure in the workplace may 

come from electroplating, refining or processing alloys, 

using hard metal cutting tools, or using diamond-polishing 

wheels that contain cobalt metal. Workplace standards and 

guidelines for external air exposure to cobalt and several 

of its compounds have been established by OSHA and 

ACGIH, respectively.

Cobalt is absorbed by oral and pulmonary routes. Human 

studies with 60Co administered as soluble cobalt chloride 

have reported oral absorption ranging from approximately 1 

to 25 % (Smith et al., 1972). Once absorbed and distributed 

in the body, cobalt is excreted predominantly in the urine, 

and to a lesser extent, in the feces. Elimination reflects a 

multi-compartmental model dominated by compartments 

with half-lives on the order of several hours to a week, but 

with a minor fraction (10-15 %) exhibiting a half-life of 

several years (Mosconi et al., 1994; Smith et al., 1972). A 

portion of cobalt retained for long periods is concentrated 

in the liver. Lung retention of relatively insoluble cobalt 

compounds such as cobalt oxide may be prolonged, with 

pulmonary clearance half-lives of from one to two years 

(Hedge et al., 1979). Recent inhalation exposure to soluble 

cobalt compounds can be monitored by measuring cobalt in 

urine or blood (Lison et al., 1994).

Urinary Cobalt (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .353 (.319-.391) .328 (.302-.365) .515 (.457-.581) .821 (.679-.963) 1.16 (.938-1.50) 2465

01-02 .358 (.333-.384) .335 (.313-.360) .523 (.487-.562) .844 (.750-.955) 1.16 (1.00-1.28) 2689

03-04 .314 (.303-.325) .290 (.278-.306) .455 (.434-.481) .737 (.703-.781) 1.02 (.911-1.10) 2558

Age group 

6-11 years 99-00 .547 (.467-.640) .554 (.449-.647) .774 (.626-.938) 1.00 (.833-1.49) 1.25 (.895-1.50) 340

01-02 .552 (.508-.599) .548 (.503-.609) .756 (.660-.829) 1.00 (.900-1.27) 1.30 (1.03-1.73) 368

03-04 .529 (.471-.593) .500 (.463-.543) .689 (.634-.750) 1.04 (.760-1.29) 1.29 (1.04-1.36) 290

12-19 years 99-00 .391 (.353-.433) .378 (.329-.407) .537 (.469-.595) .824 (.638-1.17) 1.44 (.821-3.54) 719

01-02 .368 (.343-.396) .352 (.327-.372) .534 (.471-.611) .851 (.673-.949) 1.06 (.932-1.24) 762

03-04 .329 (.304-.355) .316 (.277-.348) .495 (.442-.561) .738 (.630-.847) .952 (.792-1.09) 725

20 years and older 99-00 .328 (.297-.362) .306 (.280-.328) .471 (.428-.522) .727 (.632-.905) 1.12 (.861-1.36) 1406

01-02 .337 (.313-.363) .313 (.294-.337) .475 (.435-.513) .792 (.704-.955) 1.15 (.963-1.33) 1559

03-04 .293 (.282-.304) .271 (.257-.286) .400 (.380-.429) .691 (.616-.744) .976 (.829-1.10) 1543

Gender 

Males 99-00 .290 (.259-.324) .279 (.248-.301) .402 (.365-.449) .608 (.534-.728) .838 (.667-1.10) 1227

01-02 .290 (.272-.310) .278 (.256-.297) .392 (.361-.425) .644 (.574-.707) .848 (.786-.929) 1334

03-04 .247 (.237-.259) .234 (.215-.250) .333 (.313-.352) .513 (.476-.585) .700 (.630-.753) 1281

Females 99-00 .426 (.378-.479) .407 (.362-.457) .606 (.550-.694) .960 (.781-1.29) 1.50 (1.11-1.83) 1238

01-02 .435 (.404-.468) .408 (.382-.438) .635 (.560-.708) 1.00 (.879-1.19) 1.29 (1.12-1.60) 1355

03-04 .393 (.378-.409) .361 (.342-.381) .554 (.513-.615) .937 (.850-1.00) 1.29 (1.10-1.33) 1277

Race/ethnicity 

Mexican Americans 99-00 .386 (.339-.439) .376 (.333-.419) .598 (.500-.669) .898 (.826-1.00) 1.23 (1.11-1.35) 884

01-02 .388 (.361-.417) .361 (.333-.394) .591 (.500-.662) .872 (.777-.990) 1.10 (.990-1.27) 682

03-04 .346 (.326-.368) .327 (.296-.349) .542 (.487-.594) .850 (.753-.963) 1.14 (.963-1.35) 618

Non-Hispanic blacks 99-00 .282 (.275-.289) .257 (.243-.279) .417 (.378-.462) .723 (.600-.785) .975 (.757-1.60) 568

01-02 .298 (.275-.323) .268 (.251-.296) .444 (.393-.505) .728 (.582-.917) 1.03 (.740-1.55) 667

03-04 .273 (.248-.300) .259 (.239-.281) .388 (.344-.461) .700 (.563-.842) .964 (.733-1.15) 723

Non-Hispanic whites 99-00 .369 (.324-.421) .352 (.313-.387) .533 (.452-.611) .861 (.667-1.16) 1.25 (.895-1.57) 822

01-02 .362 (.331-.396) .343 (.313-.368) .523 (.479-.562) .830 (.736-.983) 1.16 (.983-1.33) 1132

03-04 .317 (.301-.334) .291 (.274-.309) .457 (.425-.488) .738 (.683-.804) 1.00 (.857-1.13) 1074
 210 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Toxic effects of cobalt have been encountered in workplace 

settings. Cobalt compounds are a recognized cause of 

allergic contact dermatitis (Dickel et al., 2001; Lisi, 2003; 

Thomassen et al., 2001). Occupational exposure to cobaltcontaining dusts has caused occupational asthma (Pisati 

and Zedda, 1994; Shirakawa et al., 1989). “Hard metal” 

disease, an interstitial lung disorder with findings that range 

from alveolitis to pulmonary fibrosis, has been associated 

with exposure to dusts that contain cobalt, usually in 

combination with tungsten carbide (Cugell et al., 1990). 

The extent to which cobalt exposure alone causes interstitial 

lung disease is unknown (Linna et al., 2003; Swennen et al., 

1993).

Cobalt was once added as a foaming agent to beer, and this 

caused outbreaks of cardiomyopathy among heavy drinkers 

in the mid-1960’s (Alexander et al., 1972). Case reports have 

also suggested a link between occupational cobalt exposure 

and cardiomyopathy (Jarvis et al., 1992). Cobalt compounds 

appear to stimulate erythropoietin production and were 

formerly used in the treatment of anemia (Goldberg et al., 

1988). Pharmaceutical preparations of cobalt used in the 

past as hematinics were associated with the development 

of overt hypothyroidism (Kriss et al., 1955). A subclinical 

decrease in thyroid production was observed in a study of 

cobalt production workers (Swennen et al., 1993).

Cobalt compounds elicited numerous genotoxic effects in 

both in vitro and in vivo assays (De Boeck et al., 2003) 

and produced lung cancer in rats and mice after chronic 

inhalation (Bucher et al., 1999). An industry-wide study 

of hard metal workers in France observed an increased 

mortality from lung cancer (Moulin et al., 1998). IARC 

has classified cobalt metal with tungsten carbide and other 

soluble cobalt salts as possibly carcinogenic to humans. 

Information about external exposure (i.e., environmental 

levels) and health effects is available from ATSDR at: 

http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Urinary levels of cobalt decline rapidly within 24 hours 

after exposure ceases (Alexandersson et al., 1988). Urinary 

measurements mainly reflect recent exposure, although 

substantial occupational exposures have produced elevated 

urinary levels for many weeks. Smaller population surveys 

of European adults reported urinary cobalt levels that were 

roughly similar U.S. population results in this Report

(Kristiansen et al., 1997; White and Sabbioni, 1998). Small 

studies of patients with hip replacements using metal alloy 

prostheses reported increased urinary cobalt concentrations, 

with mean levels that were about 15-20 times higher than 

in the general U.S. population (CDC, 2005; Daniel et al., 

2006; Dunstan et al., 2005; Iavicoli et al., 2006; MacDonald 

et al., 2003).

Persons with occupational exposure to cobalt often have 

urinary cobalt levels that are many times higher than 

those of the general population. The ACGIH biological 

exposure index (BEI) for inorganic forms of cobalt (except 

insoluble cobalt oxides) is 15 mg/L. Information about the 

BEI is provided here for comparison, not to imply that 

the BEI is a safe level for general population exposure. 

For workers exposed to cobalt in the air, a distinction is 

made between soluble and insoluble (oxides and metallic) 

cobalt (Christensen and Poulsen, 1994; Lison et al., 1994). 

Exposure to soluble cobalt salts will produce proportionately 

higher urinary levels because they are absorbed better. 

Correlations between air exposure levels and urinary 

cobalt levels in hard metal fabricators are well documented 

(Ichikawa et al., 1985; Krause et al., 2001; Lauwerys and 

Hoet, 2001; Linnainmaa and Kiilunen, 1997).

Finding a measurable amount of cobalt in the urine does 

not mean that the levels of cobalt cause an adverse health 

effect. Biomonitoring studies on levels of cobalt provide 

physicians and public health officials with reference 

values so that they can determine whether people have 

been exposed to higher levels of cobalt than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

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Alexandersson R. Blood and urinary concentrations as estimators 

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Cugell DW, Morgan WKC, Perkins DG, Rubin A. The respiratory 
Fourth National Report on Human Exposure to Environmental Chemicals 211

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effects of cobalt. Arch Intern Med 1990;150:177-183.

Daniel J, Ziaee H, Salama A, Pradhan C, McMinn DJ. The effect 

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erythropoietin gene: evidence that the oxygen sensor is a heme 

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V, Salvatori S, et al. The release of metals from metal-onmetal surface arthroplasty of the hip. J Trace Elem Med Biol 

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1992;34:620-626.

Kraus T, Schramel P, Schaller KH, Zobelein P, Weber A, Angerer 

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Kriss JP, Carnes WH, Gross RT. Hypothyroidism and thyroid 

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Kristiansen J, Christensen JM, Iversen BS, Sabbioni E. Toxic 

trace element reference levels in blood and urine: influence of 

gender and lifestyle factors. Sci Total Environ 1997;204:147-160.

Lauwerys RB, Hoet P. Industrial Chemical Exposure: Guidelines 

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Lhotka C, Szekeres T, Steffan I, Zhuber K, Zweymuller K. 

Four-year study of cobalt and chromium blood levels in 

patients managed with two different metal-on-metal total hip 

replacements. J Orthop Res 2003;21(2):189-195.

Linna A, Oksa P, Palmroos P, Roto P, Laippala P, Uitti J. 

Respiratory health of cobalt production workers. Am J Ind Med 

2003;44:124-132.

Linnainmaa M, Kiilunen M. Urinary cobalt as a measure of 

exposure in the wet sharpening of hard metal and satellite blades. 

Int Arch Occup Environ Health 1997;69(3):193-200.

Lisi P. Co-sensitivity between cobalt and other transition metals. 

Contact Dermatitis 2003;48:172-173.

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CH, Cleland D, et al. Metal-on-metal versus polyethylene in hip 

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excretion in urine: results of a study on workers producing 

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Moulin JJ, Wild P, Romazini S, Lasfargues G, Peltier A, Bozec 

C, et al. Lung cancer risk in hard-metal workers. Am J Epidemiol 

1998;148:241-248.

Pisati G, Zedda S. Outcome of occupational asthma due to cobalt 

hypersensitivity. Sci Total Environ 1994;150(1-3):167-171.

Shirakawa T, Kusaka Y, Fujimura N, Goto S, Kato M, Heki S, 

et al. Occupational asthma from cobalt sensitivity in workers 

exposed to hard metal dust. Chest 1989;95:29-37.

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cobalt in man by whole-body counting. Health Phys 1972;22:359-

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cobalt salts, and cobalt metals. Br J Ind Med 1993;50(9):835-842.

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 212 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Lead

CAS No. 7439-92-1

General Information

Elemental lead is a soft, malleable, dense, blue-gray metal 

that occurs naturally in soils and rocks. Lead is most often 

mined from ores or recycled from scrap metal or batteries. 

Elemental lead can be combined with other elements 

to form inorganic and organic compounds, such as lead 

phosphate and tetraethyl lead. Lead has a variety of uses 

in manufacturing: storage batteries, solders, metal alloys 

(e.g. brass, bronze), plastics, leaded glass, ceramic glazes, 

ammunition, antique-molded or cast ornaments, and for 

radiation shielding. In the past, lead was added to gasoline 

and residential paints and used in soldering the seams of 

food cans. Lead was used in plumbing for centuries and 

may still be present.

Before the 1980’s, the main source of lead exposure for the 

general U.S. population was aerosolized lead emitted from 

combustion engines that used leaded gasoline. Aerosolized 

lead is either inhaled or ingested after it is deposited on 

surfaces and food crops. Since lead has been eliminated 

from gasoline, adult lead exposures tend to be limited to 

Blood Lead 

Geometric mean and selected percentiles of blood concentrations (in μg/dL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 1.66 (1.60-1.72) 1.60 (1.60-1.70) 2.50 (2.40-2.60) 3.80 (3.60-4.00) 5.00 (4.70-5.50) 7970

01-02 1.45 (1.39-1.51) 1.40 (1.40-1.50) 2.20 (2.10-2.30) 3.40 (3.20-3.60) 4.50 (4.20-4.70) 8945

03-04 1.43 (1.36-1.50) 1.40 (1.30-1.50) 2.10 (2.10-2.20) 3.20 (3.10-3.30) 4.20 (3.90-4.40) 8373

Age group 

1-5 years 99-00 2.23 (1.96-2.53) 2.20 (1.90-2.50) 3.40 (2.80-3.90) 4.90 (4.00-6.60) 7.00 (6.10-8.30) 723

01-02 1.70 (1.55-1.87) 1.60 (1.50-1.80) 2.50 (2.20-2.90) 4.20 (3.50-5.20) 5.80 (4.70-6.90) 898

03-04 1.77 (1.60-1.95) 1.70 (1.50-1.90) 2.50 (2.30-2.80) 3.90 (3.30-4.60) 5.10 (4.10-6.60) 911

6-11 years 99-00 1.51 (1.36-1.66) 1.40 (1.30-1.60) 2.10 (1.80-2.50) 3.30 (2.80-3.80) 4.50 (3.40-6.20) 905

01-02 1.25 (1.14-1.36) 1.20 (1.00-1.30) 1.70 (1.60-2.00) 2.80 (2.50-3.10) 3.70 (3.00-4.70) 1044

03-04 1.25 (1.12-1.39) 1.20 (1.10-1.40) 1.80 (1.50-2.10) 2.60 (2.10-3.10) 3.30 (2.50-4.60) 856

12-19 years 99-00 1.10 (1.04-1.17) 1.10 (1.00-1.20) 1.50 (1.40-1.70) 2.30 (2.10-2.40) 2.90 (2.70-3.00) 2135

01-02 .942 (.899-.986) .900 (.900-1.00) 1.30 (1.20-1.40) 2.00 (1.90-2.10) 2.70 (2.40-2.90) 2231

03-04 .946 (.878-1.02) .900 (.800-1.00) 1.30 (1.20-1.40) 1.90 (1.70-2.10) 2.60 (2.20-3.00) 2081

20 years and older 99-00 1.75 (1.68-1.81) 1.70 (1.60-1.80) 2.60 (2.50-2.70) 3.90 (3.70-4.10) 5.20 (4.80-5.60) 4207

01-02 1.56 (1.49-1.62) 1.60 (1.50-1.60) 2.30 (2.30-2.40) 3.60 (3.40-3.70) 4.60 (4.30-5.00) 4772

03-04 1.52 (1.45-1.60) 1.50 (1.40-1.60) 2.30 (2.20-2.40) 3.30 (3.20-3.50) 4.30 (4.00-4.60) 4525

Gender 

Males 99-00 2.01 (1.93-2.09) 1.90 (1.90-2.00) 2.90 (2.80-3.00) 4.50 (4.10-4.80) 6.00 (5.50-6.50) 3913

01-02 1.78 (1.71-1.86) 1.80 (1.70-1.80) 2.70 (2.50-2.80) 3.90 (3.80-4.10) 5.40 (5.00-5.50) 4339

03-04 1.69 (1.62-1.75) 1.60 (1.50-1.70) 2.50 (2.40-2.60) 3.70 (3.40-3.90) 4.80 (4.50-5.20) 4132

Females 99-00 1.37 (1.32-1.43) 1.30 (1.30-1.40) 2.00 (1.90-2.10) 3.10 (2.90-3.30) 4.00 (3.80-4.20) 4057

01-02 1.19 (1.14-1.25) 1.20 (1.10-1.20) 1.80 (1.70-1.90) 2.60 (2.50-2.80) 3.60 (3.10-4.00) 4606

03-04 1.22 (1.14-1.31) 1.20 (1.10-1.30) 1.80 (1.70-2.00) 2.70 (2.50-3.00) 3.50 (3.10-3.80) 4241

Race/ethnicity 

Mexican Americans 99-00 1.83 (1.75-1.91) 1.80 (1.70-1.90) 2.80 (2.60-2.90) 4.20 (3.90-4.60) 5.80 (5.10-6.60) 2742

01-02 1.46 (1.34-1.60) 1.50 (1.30-1.60) 2.30 (2.10-2.60) 3.60 (3.40-4.20) 5.40 (4.40-6.70) 2268

03-04 1.55 (1.43-1.69) 1.50 (1.40-1.60) 2.30 (2.10-2.50) 3.50 (2.90-4.20) 4.90 (3.90-6.40) 2085

Non-Hispanic blacks 99-00 1.87 (1.75-2.00) 1.80 (1.70-2.00) 2.80 (2.60-3.00) 4.30 (4.00-4.60) 5.70 (5.20-6.10) 1842

01-02 1.65 (1.52-1.80) 1.60 (1.40-1.70) 2.60 (2.30-2.90) 4.20 (3.80-4.70) 5.80 (5.30-6.50) 2219

03-04 1.69 (1.52-1.89) 1.60 (1.40-1.80) 2.60 (2.20-3.00) 4.10 (3.50-4.70) 5.30 (4.60-6.60) 2293

Non-Hispanic whites 99-00 1.62 (1.55-1.69) 1.60 (1.50-1.70) 2.40 (2.30-2.50) 3.60 (3.40-3.90) 5.00 (4.40-5.70) 2716

01-02 1.43 (1.37-1.48) 1.40 (1.30-1.50) 2.20 (2.10-2.20) 3.20 (3.10-3.40) 4.20 (3.90-4.50) 3806

03-04 1.37 (1.32-1.43) 1.30 (1.30-1.40) 2.10 (2.00-2.10) 3.00 (2.80-3.20) 3.90 (3.60-4.30) 3478

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.3, 0.3, and 0.28, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 213

 Metals

occupational (e.g., battery and radiator manufacturing) 

and recreational sources. However, the primary source of 

exposure in children is from deteriorated lead-based paint 

and the resulting dust and soil contamination (Manton et 

al., 2000). Children may also be exposed to lead brought 

into the home on the work clothes of adults whose work 

involves lead. Less common sources of incidental or unique 

lead exposure are numerous: lead-glazed ceramic pottery; 

stained glass framing; pewter utensils and drinking vessels; 

older plumbing systems with leaded pipes or lead soldered 

connections; lead-based painted surfaces undergoing 

renovation or demolition; imported children’s trinkets and 

toys; lead-containing folk remedies and cosmetics; bullet 

fragments retained in human tissue; lead-contaminated 

dust in indoor firing ranges; and contact with soil, dust, 

or water contaminated by mining or smelting operations. 

Small amounts of environmental lead also may result from 

burning fossil fuels (ATSDR, 2007; CDC, 1991).

Lead is absorbed into the body after fine lead particulates 

or fumes are inhaled, or after soluble lead compounds are 

ingested. Absorption of ingested lead can be as much as 

five times greater in children than adults and even greater 

when intakes of dietary minerals are deficient. In the 

blood, absorbed lead is bound to erythrocytes and then is 

distributed initially to multiple soft tissues and eventually 

into bone. Approximately half of the absorbed lead may be 

incorporated into bone, which is the site of approximately 

Urinary Lead 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .766 (.708-.828) .800 (.800-.900) 1.40 (1.30-1.50) 2.20 (2.00-2.30) 2.90 (2.60-3.30) 2465

01-02 .677 (.637-.718) .700 (.700-.800) 1.20 (1.20-1.30) 2.00 (1.90-2.20) 2.70 (2.50-2.80) 2690

03-04 .636 (.595-.680) .640 (.580-.690) 1.04 (.960-1.12) 1.73 (1.52-1.86) 2.29 (2.03-2.62) 2558

Age group 

6-11 years 99-00 1.07 (.955-1.20) 1.10 (.900-1.30) 1.50 (1.40-1.70) 2.40 (1.80-3.10) 3.40 (2.40-5.00) 340

01-02 .753 (.661-.857) .800 (.600-.900) 1.20 (1.10-1.40) 2.10 (1.60-2.40) 2.60 (2.10-3.70) 368

03-04 .795 (.671-.941) .790 (.640-.900) 1.35 (.970-1.86) 2.27 (1.62-4.09) 3.33 (2.23-4.41) 290

12-19 years 99-00 .659 (.579-.749) .700 (.600-.800) 1.10 (.900-1.30) 1.80 (1.40-2.20) 2.20 (1.90-2.80) 719

01-02 .564 (.526-.605) .600 (.500-.600) 1.00 (.800-1.10) 1.60 (1.40-1.70) 2.00 (1.80-2.40) 762

03-04 .604 (.553-.660) .630 (.570-.680) .920 (.810-1.02) 1.32 (1.14-1.80) 1.86 (1.44-2.29) 725

20 years and older 99-00 .752 (.691-.818) .800 (.700-.900) 1.40 (1.30-1.50) 2.20 (2.00-2.40) 2.90 (2.60-3.30) 1406

01-02 .688 (.641-.738) .700 (.700-.800) 1.20 (1.20-1.30) 2.00 (1.90-2.30) 2.80 (2.50-2.90) 1560

03-04 .625 (.579-.674) .620 (.560-.700) 1.04 (.960-1.11) 1.70 (1.52-1.80) 2.21 (2.04-2.49) 1543

Gender 

Males 99-00 .923 (.822-1.04) .900 (.900-1.00) 1.60 (1.40-1.80) 2.50 (2.20-2.90) 3.40 (2.90-3.80) 1227

01-02 .808 (.757-.862) .800 (.800-.900) 1.40 (1.30-1.50) 2.50 (2.20-2.70) 3.20 (2.90-3.50) 1335

03-04 .731 (.680-.785) .730 (.680-.800) 1.17 (1.07-1.27) 2.03 (1.78-2.22) 2.66 (2.33-2.91) 1281

Females 99-00 .642 (.589-.701) .700 (.600-.800) 1.20 (1.10-1.30) 1.90 (1.60-2.20) 2.40 (2.10-3.00) 1238

01-02 .573 (.535-.613) .600 (.600-.600) 1.10 (1.00-1.10) 1.60 (1.50-1.80) 2.20 (1.90-2.40) 1355

03-04 .558 (.506-.616) .540 (.480-.620) .920 (.820-1.04) 1.49 (1.24-1.75) 1.82 (1.59-2.30) 1277

Race/ethnicity 

Mexican Americans 99-00 1.02 (.915-1.13) 1.10 (.900-1.20) 1.80 (1.60-1.90) 2.90 (2.50-3.40) 4.30 (3.10-5.40) 884

01-02 .833 (.745-.931) .900 (.700-1.00) 1.50 (1.20-1.70) 2.50 (2.00-2.90) 3.30 (2.70-3.80) 683

03-04 .815 (.710-.935) .840 (.700-.990) 1.31 (1.18-1.59) 2.19 (1.86-2.50) 2.66 (2.13-3.97) 618

Non-Hispanic blacks 99-00 1.11 (1.00-1.23) 1.10 (1.00-1.20) 1.90 (1.50-2.10) 3.00 (2.40-3.50) 4.20 (3.30-5.70) 568

01-02 .940 (.833-1.06) .900 (.800-1.00) 1.60 (1.30-1.80) 2.70 (2.10-3.40) 3.70 (2.90-4.80) 667

03-04 .848 (.729-.986) .850 (.710-1.00) 1.40 (1.10-1.72) 2.14 (1.78-2.64) 2.82 (2.31-3.89) 723

Non-Hispanic whites 99-00 .695 (.625-.773) .700 (.700-.900) 1.30 (1.10-1.40) 2.00 (1.80-2.40) 2.70 (2.30-3.10) 822

01-02 .610 (.572-.651) .700 (.600-.700) 1.10 (1.10-1.20) 1.90 (1.70-2.00) 2.40 (2.30-2.60) 1132

03-04 .591 (.556-.628) .590 (.540-.650) .960 (.910-.990) 1.52 (1.40-1.75) 2.14 (1.78-2.51) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.1, 0.1, and 0.33, respectively. 
 214 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

90% of the body lead burden in most adults. The skeleton 

acts as a storage depot, and approximately 40 to 70% of 

lead in blood comes from the skeleton in environmentally 

exposed adults (Smith et al., 1996). Lead can cross the 

placenta and enter the developing fetal brain. Lead is cleared 

from the blood and soft tissues with a half-life of 1 to 2 

months and more slowly from the skeleton, with a half-life 

of years to decades. Approximately 70% of lead excretion 

occurs via the urine, with lesser amounts eliminated via the 

feces; scant amounts are lost through sweat, hair, and nails 

(Leggett, 1993; O’Flaherty, 1993).

The toxic effects of lead result from its interference with the 

physiologic actions of calcium, zinc, and iron, through the 

inhibition of certain enzymes, and through binding to ion 

channels and regulatory proteins. Additional mechanisms 

include generating reactive oxygen species and altering 

gene expression (ATSDR, 2007). Large amounts of lead in 

the body can cause anemia, kidney injury, abdominal pain, 

seizures, encephalopathy, and paralysis. Equilibrated blood 

lead levels (BLLs) after chronic intake are associated with 

certain toxic effects. BLLs and associated toxic effects differ 

in children and adults. For instance, BLLs near 10 μg/dL 

can affect blood pressure in adults and neurodevelopment 

in children (Bellinger, 2004; CDC, 1991; Nash et al., 2003; 

Schwartz, 1995; Staessen et al., 1995). In 1991, based on 

prospective population studies, the Centers for Disease 

Control and Prevention (CDC) established a BLL of 10 

Urinary Lead (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .721 (.700-.742) .701 (.677-.725) 1.11 (1.05-1.15) 1.70 (1.62-1.85) 2.38 (2.22-2.79) 2465

01-02 .639 (.603-.677) .635 (.588-.676) 1.03 (.963-1.08) 1.52 (1.43-1.61) 2.03 (1.89-2.22) 2689

03-04 .632 (.603-.662) .622 (.594-.655) .979 (.920-1.03) 1.49 (1.33-1.64) 1.97 (1.73-2.26) 2558

Age group 

6-11 years 99-00 1.17 (.975-1.41) 1.06 (.918-1.22) 1.55 (1.22-1.97) 2.71 (1.67-4.66) 4.66 (1.97-18.0) 340

01-02 .918 (.841-1.00) .870 (.800-.933) 1.27 (1.12-1.43) 2.33 (1.59-3.64) 3.64 (1.89-5.56) 368

03-04 .926 (.812-1.06) .914 (.781-1.03) 1.45 (1.17-1.72) 2.14 (1.62-3.47) 3.47 (2.19-5.31) 290

12-19 years 99-00 .496 (.460-.535) .469 (.408-.508) .709 (.655-.828) 1.11 (.981-1.28) 1.65 (1.15-2.79) 719

01-02 .404 (.380-.428) .375 (.342-.400) .603 (.541-.702) .990 (.882-1.18) 1.41 (1.07-1.63) 762

03-04 .432 (.404-.461) .404 (.383-.436) .623 (.551-.730) .938 (.828-1.06) 1.23 (1.09-1.35) 725

20 years and older 99-00 .720 (.683-.758) .712 (.667-.739) 1.10 (1.02-1.18) 1.69 (1.53-1.87) 2.31 (2.15-2.62) 1406

01-02 .658 (.617-.703) .652 (.608-.702) 1.05 (.992-1.11) 1.51 (1.40-1.61) 2.00 (1.85-2.19) 1559

03-04 .641 (.606-.679) .633 (.605-.670) .988 (.917-1.04) 1.47 (1.28-1.63) 1.94 (1.72-2.12) 1543

Gender 

Males 99-00 .720 (.679-.763) .693 (.645-.734) 1.10 (.992-1.22) 1.68 (1.50-2.09) 2.43 (2.15-3.03) 1227

01-02 .639 (.607-.673) .638 (.586-.686) 1.01 (.957-1.08) 1.55 (1.41-1.61) 2.06 (1.88-2.43) 1334

03-04 .615 (.588-.644) .593 (.561-.639) .914 (.862-.977) 1.44 (1.25-1.53) 2.00 (1.71-2.28) 1281

Females 99-00 .722 (.681-.765) .707 (.667-.746) 1.11 (1.05-1.18) 1.74 (1.50-2.02) 2.38 (2.03-2.88) 1238

01-02 .639 (.594-.688) .625 (.571-.682) 1.03 (.946-1.11) 1.50 (1.39-1.61) 1.98 (1.85-2.15) 1355

03-04 .648 (.601-.698) .649 (.604-.718) 1.03 (.938-1.10) 1.56 (1.34-1.73) 1.96 (1.72-2.20) 1277

Race/ethnicity 

Mexican Americans 99-00 .940 (.876-1.01) .887 (.796-1.03) 1.43 (1.37-1.58) 2.38 (2.08-2.77) 3.46 (2.78-4.18) 884

01-02 .810 (.731-.898) .774 (.702-.893) 1.29 (1.09-1.44) 2.05 (1.75-2.50) 2.78 (2.56-3.33) 682

03-04 .755 (.681-.838) .708 (.612-.851) 1.18 (1.09-1.31) 1.86 (1.50-2.26) 2.31 (1.98-2.92) 618

Non-Hispanic blacks 99-00 .722 (.659-.790) .671 (.583-.753) 1.11 (.988-1.20) 2.00 (1.56-2.51) 2.83 (2.20-3.88) 568

01-02 .644 (.559-.742) .608 (.510-.710) .962 (.853-1.20) 1.79 (1.36-2.33) 2.75 (2.04-3.98) 667

03-04 .609 (.529-.701) .569 (.492-.698) .900 (.793-1.03) 1.48 (1.11-1.97) 2.24 (1.65-2.88) 723

Non-Hispanic whites 99-00 .696 (.668-.725) .677 (.645-.718) 1.07 (.997-1.14) 1.66 (1.50-1.83) 2.31 (1.94-2.82) 822

01-02 .615 (.579-.654) .621 (.571-.667) 1.00 (.933-1.07) 1.46 (1.37-1.52) 1.88 (1.62-2.03) 1132

03-04 .623 (.592-.655) .618 (.587-.657) .971 (.914-1.03) 1.44 (1.25-1.61) 1.85 (1.64-2.10) 1074
Fourth National Report on Human Exposure to Environmental Chemicals 215

 Metals

μg/dL or higher as the level of concern in children. Recent 

studies have suggested that neurodevelopmental effects 

may occur at BLLs lower than 10 μg/dL (Canfield et al., 

2003; Lanphear et al., 2000). Many animal studies have 

established the multiple neurotoxic effects of lead (ATSDR, 

2007).

In occupationally exposed adults, subtle or nonspecific 

neurocognitive effects have been reported at BLLs as low 

as 20-30 μg/dL (Mantere et al., 1984; Schwartz et al., 

2001), with overt encephalopathy, seizures, and peripheral 

neuropathy generally occurring at much higher levels 

(e.g., higher than 100-200 μg/dL). BLLs higher than 

40 mg/dL can result in proximal tubular dysfunction and 

decreased glomerular filtration rate leading to interstitial 

and peritubular fibrosis when high body burdens persist. 

Low level environmental lead exposure may be associated 

with small decrements in renal function (Kim et al., 1996; 

Muntner et al., 2003; Payton et al., 1994). Results of studies 

of adults with either occupational or environmental lead 

exposure have shown consistent associations between 

increased BLLs and increased blood pressure (Nash et 

al., 2003; Schwartz, 1995; Staessen et al., 1995) and 

associations between increased bone lead concentrations 

and blood pressure (Hu et al., 1996; Korrick et al., 1999). 

High dose occupational lead exposure, usually with BLLs 

greater than 40 mg/dL, may alter sperm morphology, reduce 

sperm count, and decrease fertility (Alexander et al., 1996; 

Telisman et al., 2000). At low environmental exposures, 

lead in women may be associated with hypertension during 

pregnancy, premature delivery, and spontaneous abortion 

(Baghurst et al., 1987; Bellinger 2005; Borja-Aburto et al., 

1999).

Workplace standards and guidelines for lead exposure and 

monitoring have been established by OSHA and ACGIH, 

respectively. Both drinking water and ambient air standards 

for lead have been established by the U.S. EPA. IARC 

considers inorganic lead compounds probable human 

carcinogens, and organic lead compounds not classifiable 

with respect to human carcinogenicity. NTP considers lead 

and its compounds reasonably anticipated to be human 

carcinogens. Information about external exposure (i.e., 

environmental levels) and health effects is available from 

ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Blood lead measurement is the preferred method of 

evaluating lead exposure and its human health effects. BLLs 

reflect both recent intake and equilibration with stored lead 

in other tissues, particularly in the skeleton. Urine levels 

may reflect recently absorbed lead, though there is greater 

individual variation in urine lead than in blood and greater 

potential for contamination.

The Adult Blood Lead Epidemiology and Surveillance 

program has tracked BLLs reported by states for mostly 

for occupational but also for non-occupational exposure 

in U.S. adult residents. Overall, the national prevalence 

rate for adults with BLLs 25 mg/dL or higher was 7.5 per 

100,000 adults; the prevalence rate has declined annually 

since 1994 (CDC, 2006). A decrease in BLLs is evident 

also in adult NHANES results reported over past decades 

(CDC, 2005a). The U.S. adult population has similar or 

slightly lower BLLs than adults in other developed nations 

(CDC, 2005b). A general population survey of adults 

Germany in 1998 reported a geometric mean blood lead 

concentration of 3.07 μg/dL (Becker et al., 2002), almost 

double the geometric mean of 1.75 μg/dL in U.S. adults 

in the 1999-2000 NHANES sample. A general population 

survey of adults in Italy tested in 2000 found BLLs slightly 

more than double those reported for U.S. adults in the 1999-

2000 NHANES sample (Apostoli et al., 2002a).

In NHANES 1999-2002 in children 1-5 years old, both the 

geometric mean (1.9 μg/dL) and percentage of children with 

BLLs greater than 10 μg/dL (1.6%) were lower than those 

from NHANES 1991-1994, when the geometric mean BLL 

was 2.7 μg/dL and 4.4% of children had BLLs of 10μg/dL 

or higher (CDC, 2005b; Pirkle et al., 1998). More recently, 

Jones et al (2009) showed that the prevalence of BLLs of 

10 μg/dL or greater decreased from 8.6% in NHANES 

1988-1991 to 1.4% in NHANES 1999-2004, which is an 

84% decline. Temporal declines in children’s BLLs have 

been found in other developed countries (Wilhelm et al., 

2006). Surveillance data reported by U.S. state childhood 

lead programs also show a decline in the percentage of 

children younger than 6 years of age who had BLLs of 10 

mg/dL or higher. Data submitted through state public health 

programs from 2006 showed that 1.21% of approximately 

3.3 million children tested had BLLs of 10 mg/dL or higher 

(http://www.cdc.gov/nceh/lead/surv/database/State_

Confirmed_byYear_1997_to_2006.xls). However, BLLs 

greater than 10 μg/dL continue to be more prevalent among 

children with known risk factors, including minority race or 

ethnicity; urban residence; residing in housing built before 

the 1950’s; and low family income (CDC, 1991; CDC, 2002; 

Jones et al., 2009). For example, approximately 11,000 

higher-risk children and adolescents who were tested from 

2001 to 2002 at an urban medical center had higher BLLs 

than the NHANES sample; the geometric mean BLL was 

3.2 μg/dL in males and 3.0 μg/dL in females (Soldin et al., 

2003).
 216 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Biomonitoring studies on levels of lead provide physicians 

and public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of lead than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

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Health 2002;205:297-308.

Bellinger D. Lead. Pediatrics 2004;113(4):1016-1022.

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Borja-Aburto VH, Hertz-Picciotto I, Rojas LM, Farias P, Rios 

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gov/mmwr/preview/mmwrhtml/mm5420a5.htm. 4/14/09

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[online]. Available at URL: http://www.cdc.gov/nceh/lead/

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Chiodo LM, Jacobson SW, Jacobson JL. Neurodevelopmental 

effects of postnatal lead exposure at very low levels. Neurotoxicol 

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to Humans. Inorganic and Organic Lead Compounds. IARC 

Monogr Eval Carcinog Risks Hum 2006;87:1-471.

Jones RL, Homa DM, Meyer PA, Brody DJ, Caldwell KL, Pirkle 

JL, et al. Trends in blood lead levels and blood lead testing 

among US children aged 1 to 5 yeas, 1988-2004. Pediatrics 

2009;123:e376-e385. doi:10.1542/peds:2007-3608.

Kim R, Rotnitzky A, Sparrow D, Weiss ST, Wager C, Hu H. A 

longitudinal study of low-level lead exposure and impairment 

of renal function: the Normative Aging Study. JAMA 

1996;275:1177-1181.

Korrick SA, Hunter DJ, Rotnitzky A, Hu H, Speizer FE. Lead and 

hypertension in a sample of middle-aged women. Am J Public 

Health 1999;89:330-335.

Lanphear BP, Dietrich K, Auinger P, Cox C. Cognitive deficits 

with blood lead concentrations < 10 μg/dL in US children and 

adolescents. Public Health Rep 2000;115:521-529.

Leggett RW. Age-specific kinetic model of lead metal in humans. 

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results from NHANES III. Kidney Int 2003;63:1044-1050.

Nash D, Magder L, Lustberg M, Sherwin R, Rubin R, 

Kaufmann R, et al. Blood lead, blood pressure, and hypertension 

in perimenopausal and postmenopausal women. JAMA 

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O’Flaherty EJ. Physiologically based models for bone-seeking 

elements. IV. Kinetics of lead disposition in humans. Toxicol 

Appl Pharmacol 1993;118:16-29.

Payton M, Hu H, Sparrow D, Weiss ST. Low-level lead exposure 

and renal function in the Normative Aging Study. Am J Epidemiol 

1994;140:821-829.

Pirkle JL, Kaufmann RB, Brody DJ, Hickman T, Gunter EW, 

Paschal DC. Exposure of the U.S. population to lead: 1991-1994. 

Environ Health Perspect 1998;106:745-750.

Schwartz BS, Lee BK, Lee GS, Stewar WF, Lee SS, Hwang 

KY, et al. Association of blood lead, dimercaptosuccinic acidchelatable lead, and tibia lead with neurobehavioral test scores in 

South Korean lead workers. Am J Epidemiol 2001;153(5):453-

464.

Schwartz J. Lead, blood pressure and cardiovascular disease in 

men. Arch Environ Health 1995; 50:31-37.

Soldin OP, Hanak B, Soldin SJ. Blood lead concentrations in 

children: new ranges. Clin Chim Acta 2003;327:109-113.

Smith DR, Osterloh JD, Flegal AR. Use of endogenous, stable 

lead isotopes to determine release of lead from the skeleton. 

Environ Health Perspect 1996;104(1):60-66.

Staessen JA, Roels H, Lauwerys RR, Amery A. Low-level lead 

exposure and blood pressure. J Hum Hypertens 1995;9:303-327.

Telisman S, Cvitkovic P, Jurasovic J, Pizent A, Gavella M, Rocic 

B. Semen quality and reproductive endocrine function in relation 

to biomarkers of lead, cadmium, zinc, and copper in men. Environ 

Health Perspect 2000;108(1):45-53.

Wilhelm M, Schulz D, Schwenk M. Revised and new reference 

values for arsenic, cadmium, lead, and mercury in blood or urine 

of children: basis for validation of human biomonitoring data in 

environmental medicine. Int J Hyg Environ Health 2006;209:301-

305.
 218 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Mercury

CAS No. 7439-97-6

General Information

Mercury is a naturally occurring metal that has elemental 

(metallic), inorganic, and organic forms. Elemental mercury 

is a shiny, silver-white liquid (quicksilver) obtained 

predominantly from the refining of mercuric sulfide 

in cinnabar ore. Elemental mercury is used to produce 

chlorine gas and caustic soda for industrial applications. 

Other major uses include electrical equipment (e.g., 

thermostats and switches), electrical lamps, thermometers, 

sphygmomanometers and barometers, and dental amalgam. 

Inhalation of elemental mercury volatilized from dental 

amalgam is a major source of mercury exposure in the 

general population (Halbach, 1994; Kingman et al., 1998; 

Woods et al., 2007). Accidental spills of elemental mercury, 

which create an episodic potential for volatization and 

inhalation of mercury vapor, have often required public 

health intervention (Zeitz et al., 2002). Also, elemental 

mercury is used in rituals practiced in some Latin American 

and Caribbean communities.

Elemental mercury is released into the air from the 

combustion of fossil fuels (primarily coal), solid-waste 

incineration, and mining and smelting. Atmospheric 

elemental mercury can be deposited on land and water. In 

addition, water can be contaminated by the direct release 

of elemental and inorganic mercury from industrial 

discharges. Metabolism of mercury by microorganisms 

in aquatic sediments creates methyl mercury, an organic 

form of mercury, which can bioaccumulate in aquatic 

and terrestrial food chains. The ingestion of methyl 

mercury, predominantly from fish and other seafood, 

constitutes the main source of dietary mercury exposure 

in the general population. Apart from methyl mercury, 

synthetic organomercury compounds were once used in 

pharmaceutical applications, and mercury compounds are 

still used as preservatives (e.g., thimerosal, phenylmercuric 

acetate) or topical antiseptics (e.g., merbromin).

Inorganic mercury exists in two oxidative states (mercurous 

and mercuric) that combine with other elements, such as 

chlorine (e.g., mercuric chloride), sulfur, or oxygen, to form 

inorganic mercury compounds or salts. Inorganic mercury 

compounds such as mercuric oxide are used in producing 

batteries and pigments and in synthesizing many organic 

chemicals. Some cosmetic skin creams from countries other 

than the U.S. may contain inorganic mercury. Imported folk 

and alternative medicines occasionally are contaminated 

with inorganic mercury.

The kinetics of the different forms of mercury vary 

considerably. Poorly absorbed from the gastrointestinal 

tract, elemental mercury is absorbed mainly by inhaling 

volatilized vapor, and is distributed to most tissues, with 

the highest concentrations occurring in the kidneys 

(Barregard et al., 1999 ; Hursh et al., 1980; IARC, 1993). 

After elemental mercury is absorbed, it is oxidized in 

Total Blood Mercury—2003-2004 

Geometric mean and selected percentiles of blood concentrations (in μg/L) for the U.S. population from the National Health and 

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 .797 (.703-.903) .800 (.700-.900) 1.70 (1.50-1.90) 3.30 (2.90-3.90) 4.90 (4.30-5.50) 8373

Age group 

1-5 years 03-04 .326 (.285-.372) .300 (.300-.300) .500 (.500-.700) 1.00 (.800-1.60) 1.80 (1.30-2.50) 911

6-11 years 03-04 .419 (.363-.484) .400 (.400-.500) .700 (.700-.900) 1.30 (1.00-1.60) 1.90 (1.40-3.50) 856

12-19 years 03-04 .490 (.418-.574) .500 (.400-.600) 1.00 (.800-1.20) 1.80 (1.40-2.30) 2.60 (2.10-3.30) 2081

20 years and older 03-04 .979 (.860-1.12) 1.00 (.800-1.10) 2.00 (1.70-2.30) 3.80 (3.20-4.40) 5.40 (4.60-6.70) 4525

Gender 

Males 03-04 .814 (.714-.927) .800 (.700-.900) 1.80 (1.50-2.00) 3.70 (3.20-4.30) 5.40 (4.60-6.50) 4132

Females 03-04 .781 (.689-.886) .800 (.700-.900) 1.60 (1.40-1.80) 3.00 (2.50-3.50) 4.40 (3.60-5.30) 4241

Race/ethnicity 

Mexican Americans 03-04 .563 (.472-.672) .600 (.500-.700) 1.00 (.800-1.30) 1.90 (1.60-2.40) 3.00 (2.20-3.80) 2085

Non-Hispanic blacks 03-04 .877 (.753-1.02) .900 (.800-1.00) 1.60 (1.40-1.80) 3.00 (2.30-4.00) 4.40 (3.30-6.00) 2293

Non-Hispanic whites 03-04 .776 (.655-.919) .800 (.700-.900) 1.70 (1.40-2.00) 3.20 (2.60-3.90) 4.70 (4.00-5.60) 3478

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.2. 
Fourth National Report on Human Exposure to Environmental Chemicals 219

 Metals

the tissues to mercurous and mercuric inorganic forms. 

Blood concentrations decline initially with a rapid halflife of approximately 1-3 days followed by a slower 

half-life of approximately 1-3 weeks (Barregard et al., 

1992; Sandborgh-Englund et al., 1998). The slow-phase 

half-life may be several weeks longer in persons with 

chronic occupational exposure (Sallsten et al., 1993). After 

exposure to elemental mercury, excretion of mercury occurs 

predominantly through the kidney (Sandborgh-Englund et 

al., 1998), and peak urine levels can lag behind peak blood 

levels by days to a few weeks (Barregard et al., 1992); 

thereafter, for both acute and chronic exposures, urinary 

mercury levels decline with a half-life of approximately 1-3 

months (Roels et al., 1991; Jonsson et al., 1999).

Less than 15% of inorganic mercury is absorbed from the 

human gastrointestinal tract (Rahola et al., 1973). Lesser 

penetration of inorganic mercury occurs through the bloodbrain barrier than occurs with either elemental or methyl 

mercury (Hattula and Rahola, 1975; Vahter et al., 1994). 

The half-life of inorganic mercury in blood is similar to 

the slow-phase half-life of mercury after inhalation of 

elemental mercury. Excretion occurs by renal and fecal 

routes.

The fraction of methyl mercury absorbed from the 

gastrointestinal tract is about 95% (Aberg et al., 1969; 

Miettinen et al., 1971). Methyl mercury enters the brain and 

other tissues (Vahter et al., 1994) and then undergoes slow 

dealkylation to inorganic mercury. Human pharmacokinetic 

studies indicate that methyl mercury declines in blood 

and the whole body with a half-life of approximately 50 

days, with most elimination occurring through in the feces 

(Sherlock et al., 1984; Smith et al., 1994; Smith and Farris, 

1996). Methyl mercury is incorporated into growing hair, 

a measure of accumulated dose (Cernichiari et al., 1995; 

Suzuki et al., 1993), and a useful marker of exposure in 

epidemiologic studies (Grandjean et al., 1992 and 1999; 

McDowell et al., 2004; Myers et al., 2003).

Transplacental transport of methyl mercury and elemental 

mercury has been demonstrated in animals (Kajiwara et 

al., 1996; Vimy et al., 1990). Mercury levels in the cord 

blood are higher than in the mother’s blood (Stern and 

Smith, 2003), and the newborn’s levels decline gradually 

over several weeks (Bjornberg et al., 2005). Inorganic 

mercury and methyl mercury are distributed into human 

breast milk in relatively low concentrations; the transfer 

Total Blood Mercury−1999-2002

Survey Sample

years size

Age Group

1-5 years (females and males) 99-00 .343 (.297-.395) .300 (.200-.300) .500 (.500-.600) 1.40 (1.00-2.30) 2.30 (1.20-3.50) 705

01-02 .318 (.268-.377) .300 (.200-.300) .700 (.500-.800) 1.20 (.900-1.60) 1.90 (1.40-2.90) 872

Females 99-00 .377 (.299-.475) .200 (.200-.300) .800 (.500-1.10) 1.60 (1.00-2.80) 2.70 (1.30-5.50) 318

01-02 .329 (.265-.407) .300 (.200-.300) .700 (.500-.800) 1.30 (1.00-2.10) 2.60 (1.30-4.90) 432

Males 99-00 .317 (.269-.374) .200 (.200-.300) .500 (.500-.600) 1.10 (.800-1.60) 2.10 (1.10-3.50) 387

01-02 .307 (.256-.369) .300 (.200-.300) .600 (.400-.700) 1.30 (.900-1.70) 1.70 (1.40-2.00) 440

16-49 years (females only) 99-00 1.02 (.825-1.27) .900 (.800-1.20) 2.00 (1.50-3.00) 4.90 (3.70-6.30) 7.10 (5.30-11.3) 1709

01-02 .833 (.738-.940) .700 (.700-.800) 1.70 (1.40-1.90) 3.00 (2.70-3.50) 4.60 (3.70-5.90) 1928

Race/ethnicity

(females, 16-49 years)

Mexican Americans 99-00 .820 (.664-1.01) .900 (.700-1.00) 1.40 (1.20-2.00) 2.60 (2.00-3.60) 4.00 (2.70-5.50) 579

01-02 .667 (.541-.824) .700 (.500-.800) 1.10 (1.00-1.40) 2.10 (1.70-3.00) 3.50 (2.30-4.40) 527

Non-hispanic blacks 99-00 1.35 (1.06-1.73) 1.30 (1.10-1.70) 2.60 (1.80-3.40) 4.80 (3.30-6.60) 5.90 (4.20-11.7) 370

01-02 1.06 (.871-1.29) 1.10 (.800-1.20) 1.80 (1.50-2.20) 3.20 (2.20-3.90) 4.10 (3.30-6.00) 436

Non-hispanic whites 99-00 .944 (.726-1.23) .900 (.700-1.10) 1.90 (1.30-3.30) 5.00 (3.00-6.90) 6.90 (4.50-12.0) 588

01-02 .800 (.697-.919) .800 (.700-.800) 1.50 (1.30-2.00) 3.00 (2.20-3.70) 4.60 (3.30-6.80) 806

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.14 and 0.14.

mean (95% confidence interval)

95th

Geometric mean and selected percentiles of blood concentrations (in μg/L) for males and females aged 1 to 5 years and

females aged 16 to 49 years in the U.S. population, National Health and Nutrition Examination Survey, 1999-2002.

(95% conf. interval) 50th 75th 90th

Geometric Selected percentiles
 220 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

may be more efficient for inorganic mercury (Grandjean et 

al., 1995; Oskarsson et al., 1996). Mercury levels in breast 

milk also decline in the weeks after birth (Bjornberg et al., 

2005; Drexler and Schaller, 1998; Sakamoto et al., 2002; 

Sakamoto et al., 2004).

The health effects of mercury are diverse and can depend 

on the form of the mercury to which a person is exposed 

and the dose and the duration of exposure. Acute, high-dose 

exposure to elemental mercury vapor may cause severe 

pneumonitis. At levels below those that cause acute lung 

injury, overt signs and symptoms of chronic inhalation 

may include tremor, gingivitis, and neurocognitive 

and behavioral disturbances, particularly irritability, 

depression, short-term memory loss, fatigue, anorexia, 

and sleep disturbance (Bidstrup et al., 1951; Smith et al., 

1970; Smith et al., 1983). Low-level exposure from dental 

amalgams has not been associated with neurologic effects 

in children or adults (Bates et al., 2004; Bellinger et al., 

2006; DeRouen et al., 2006; Factor-Litvak et al., 2003). 

Occupational exposure to elemental mercury vapor has 

been associated with subclinical effects on biomarkers of 

renal dysfunction (Cardenas et al., 1993).

Inorganic mercury exposure usually occurs by ingestion. 

Large amounts may cause irritant or corrosive effects on 

the gastrointestinal tract (Sanchez-Sicilia et al., 1963). 

Once absorbed, the most prominent effect is on the kidneys 

where mercury accumulates and may lead to renal tubular 

necrosis. Acrodynia is a sporadic and predominantly 

pediatric syndrome historically associated with calomel 

(mercuric oxide) in teething powders and occasionally other 

inorganic forms of mercury. The constellation of findings 

may include anorexia, insomnia, irritability, hypertension, 

maculopapular rash, pain in the extremities, and pinkish 

discoloration of the hands and feet (Tunnessen et al., 1987). 

Overt poisoning from methyl mercury primarily affects 

the central nervous system, causing parasthesias, ataxia, 

dysarthria, hearing impairment, and progressive constriction 

of the visual fields, typically after a latent period of weeks 

to months. High-level prenatal exposure may result in a 

constellation of developmental deficits that includes mental 

retardation, cerebellar ataxia, dysarthria, limb deformities, 

altered physical growth, sensory impairments, and cerebral 

palsy (NRC, 2000). In recent epidemiologic studies, 

lower levels of prenatal exposure due to maternal seafood 

consumption have been associated with an increased risk 

for abnormal neurocognitive test results in children (NRC, 

2000; Rice, 2004). Although recent investigations have 

suggested a possible link between chronic ingestion of 

methyl mercury and an increased risk for cardiovascular 

disease, the existence of a causal relation is unresolved 

(Chan and Egeland, 2004; Rissanen et al., 2000; Salonen et 

al., 1995; Stern 2005; Vupputuri et al., 2005).

Workplace standards for inorganic mercury exposure have 

been established by OSHA and ACGIH, and a drinking water 

Inorganic Blood Mercury 

Geometric mean and selected percentiles of blood concentrations (in μg/L) for the U.S. population from the National Health and 

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD < LOD .600 (.500-.600) .700 (.700-.700) 8147 

Age group 

1-5 years 03-04 * < LOD < LOD < LOD .500 (<LOD-.600) 792

6-11 years 03-04 * < LOD < LOD < LOD .600 (.500-.600) 842

12-19 years 03-04 * < LOD < LOD .500 (<LOD-.500) .600 (.500-.600) 2060 

20 years and older 03-04 * < LOD < LOD .600 (.500-.600) .700 (.700-.800) 4453 

Gender 

Males 03-04 * < LOD < LOD .500 (.500-.600) .600 (.600-.700) 4015 

Females 03-04 * < LOD < LOD .600 (.500-.600) .700 (.700-.800) 4132 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD .500 (.500-.600) .700 (.600-.800) 2007 

Non-Hispanic blacks 03-04 * < LOD < LOD .600 (.500-.600) .700 (.600-.800) 2240 

Non-Hispanic whites 03-04 * < LOD < LOD .600 (.500-.600) .700 (.600-.700) 3406 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.42. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 221

 Metals

standard for inorganic mercury has been established by 

U.S. EPA. IARC considers methylmercury to be a possible 

human carcinogen and elemental and inorganic mercury 

to be unclassifiable with regard to human carcinogenicity. 

Information about external exposure (i.e., environmental 

levels) and health effects is available from the U.S. EPA at: 

http://www.epa.gov/mercury and from ATSDR at: http://

www.atsdr.cdc.gov/toxprofiles.

Biomonitoring Information

In the general population, the total blood mercury 

concentration is due mostly to the dietary intake of organic 

forms, particularly methyl mercury. Urinary mercury 

consists mostly of inorganic mercury (Cianciola et al., 1997; 

Kingman et al., 1998). These distinctions can help interpret 

mercury blood levels in people. Total blood mercury levels 

increase with greater fish consumption (Dewailly et al., 

2001; Grandjean et al., 1995; Mahaffey et al., 2004; Sanzo 

et al., 2001; Schober et al., 2003). Urine mercury levels 

increase as more occlusal surfaces of teeth are filled with 

mercury-containing amalgams (Becker et al., 2003).

In Germany the geometric mean for blood mercury was 0.58 

μg/L for 4645 adults, aged 18 to 69 years, who participated 

in a 1998 representative population survey (Becker et al., 

2002). From 1996 through 1998, Benes et al. (2000) studied 

1216 blood donors in the Czech Republic (896 men and 320 

women, average age 33 years; 758 children, average age 

9.9 years); the median concentration of blood mercury was 

0.78 μg/L for adults and 0.46 μg/L for children. A cohort 

of 1127 U.S. military veterans (mean age 52.8 years, range 

40 years to 78 years) had an average total blood mercury 

concentration of 2.55 μg/L. These men had no occupational 

exposure to mercury but previously had received dental 

amalgams at military facilities (Kingman et al., 1998).

Over the NHANES 1999-2006 survey periods, total blood 

mercury geometric mean levels in females aged 16-49 

years did not change, although non-Hispanic black females 

had higher levels than non-Hispanic white or Mexican 

American females. Among the three racial/ethnic groups, 

total blood mercury increased with age, and the age-related 

changes differed across the groups (Caldwell et al., 2009). 

During the same survey periods, total blood mercury levels 

declined slightly in non-Hispanic black and Mexican 

American children, and increased slightly in non-Hispanic 

white children (Caldwell, et al., 2009). In NHANES 1999-

2002, slightly higher total blood mercury levels were 

found in U.S. adult women in several ethnic subgroups 

(Hightower et al., 2006).

Clinically observable signs of ataxia and paresthesias may 

occur when blood mercury levels increase to approximately 

100 μg/L after methyl mercury poisoning. However, the 

developing fetus may be the most susceptible to the effects 

of ongoing methyl mercury exposure (NRC, 2000). A cord 

blood mercury level of 85 μg/L (lower 95% confidence 

bound = 58 μg/L) is associated with a 5% increase in the 

prevalence of an abnormal Boston Naming Test (NRC, 

Urinary Mercury—2003-2004 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 .447 (.406-.492) .420 (.360-.480) 1.00 (.870-1.14) 2.08 (1.78-2.42) 3.19 (2.76-3.55) 2538

Age group 

6-11 years 03-04 .254 (.213-.304) .200 (.160-.250) .440 (.330-.580) 1.16 (.610-1.61) 1.96 (1.13-2.97) 287

12-19 years 03-04 .358 (.313-.408) .330 (.290-.370) .700 (.530-.840) 1.60 (1.14-2.52) 2.93 (1.88-3.66) 722

20 years and older 03-04 .495 (.442-.555) .480 (.410-.570) 1.12 (.930-1.29) 2.20 (1.85-2.65) 3.33 (2.76-3.88) 1529

Gender 

Males 03-04 .433 (.405-.463) .400 (.350-.460) .940 (.840-1.05) 1.88 (1.63-2.18) 2.68 (2.34-3.05) 1266

Females 03-04 .460 (.396-.534) .430 (.330-.530) 1.07 (.870-1.28) 2.26 (1.77-2.90) 3.54 (2.76-4.31) 1272

Race/ethnicity 

Mexican Americans 03-04 .416 (.340-.509) .360 (.280-.430) .960 (.700-1.23) 2.19 (1.39-3.24) 3.16 (1.99-6.30) 619

Non-Hispanic blacks 03-04 .476 (.413-.549) .430 (.360-.530) .890 (.770-1.00) 1.96 (1.60-2.31) 3.09 (2.03-4.89) 713

Non-Hispanic whites 03-04 .441 (.382-.509) .420 (.330-.520) 1.01 (.840-1.23) 2.08 (1.67-2.46) 3.24 (2.67-3.60) 1066

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.14. 
 222 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

2000). Levels in U.S. women of childbearing age have 

generally been much lower than these levels (CDC, 2005). 

ACGIH recommends that the blood levels due to inorganic 

mercury exposure in workers not exceed 15 μg/L. Blood 

mercury levels of women and children in NHANES 1999-

2006 were also below levels established as occupational 

exposure guidelines (Caldwell, et al., 2009). Information 

about the biological exposure indices is provided here 

for comparison, not to imply a safety level for general 

population exposure.

Urinary mercury levels in recent German (Becker et al., 

2003), Czech (Benes et al., 2002), and Italian (Apostoli 

et al., 2002) adult population surveys were similar to 

those in a U.S. representative sample of women aged 16-

49 years reported in NHANES 1999-2006 (Caldwell, 

et al., 2009). In the study of U.S. military veterans with 

dental amalgams, mean urinary mercury was 3.1 μg/L. 

Urine mercury and the number of dental amalgams were 

correlated, and on average, the urine mercury increased 

by approximately 0.1 μg/L for each surface with a dental 

amalgam (Kingman et al., 1998). Recent studies in children 

with dental amalgams and urinary levels less than 5 μg/g 

of creatinine did not have changes in cognitive-behavioral 

testing when followed for 5-7 years (Bellinger et al., 2006; 

DeRouen et al., 2006). An expert-panel report recently 

prepared for the U.S. Department of Health and Human 

Services noted that several studies have observed a modest, 

reversible increase in urinary N-acetyl-glucosaminidase, a 

biomarker of perturbation in renal tubular function, among 

workers with urinary mercury concentrations of 25-35 

μg/L or greater (Barregard et al., 1988; Langworth et al., 

1992). The ACGIH (2007) currently recommends that 

urinary inorganic mercury in workers not exceed 35 μg/g 

of creatinine.

Finding a measurable amount of mercury in blood or urine 

does not mean that the level of mercury causes an adverse 

health effect. Biomonitoring studies provide physicians and 

public health officials with reference ranges so that they 

can determine whether people have been exposed to higher 

levels of mercury than are found in the general population. 

Biomonitoring data will also help scientists plan and 

conduct research on exposure and health effects.

Urinary Mercury (creatinine corrected)—2003-2004 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 .443 (.404-.486) .447 (.392-.498) .909 (.785-1.00) 1.65 (1.40-1.86) 2.35 (1.88-2.85) 2537

Age group 

6-11 years 03-04 .297 (.246-.358) .276 (.208-.347) .485 (.391-.630) 1.25 (.667-1.79) 1.79 (1.11-2.61) 286

12-19 years 03-04 .255 (.225-.289) .217 (.196-.275) .464 (.376-.535) 1.06 (.714-1.39) 1.67 (1.13-2.03) 722

20 years and older 03-04 .508 (.455-.566) .525 (.447-.616) 1.00 (.875-1.09) 1.76 (1.46-2.11) 2.54 (2.04-3.00) 1529

Gender 

Males 03-04 .365 (.333-.400) .362 (.309-.417) .696 (.620-.784) 1.31 (1.18-1.44) 1.87 (1.51-2.30) 1266

Females 03-04 .532 (.472-.599) .545 (.455-.652) 1.06 (.969-1.21) 1.88 (1.64-2.30) 2.77 (2.12-3.56) 1271

Race/ethnicity 

Mexican Americans 03-04 .384 (.307-.480) .365 (.280-.455) .768 (.619-.990) 1.62 (1.23-2.16) 2.32 (1.78-4.01) 618

Non-Hispanic blacks 03-04 .343 (.301-.391) .306 (.265-.368) .587 (.522-.687) 1.28 (.964-1.63) 2.13 (1.41-2.87) 713

Non-Hispanic whites 03-04 .463 (.400-.537) .476 (.385-.588) .970 (.800-1.07) 1.67 (1.32-2.11) 2.40 (1.88-2.90) 1066
Fourth National Report on Human Exposure to Environmental Chemicals 223

 Metals

Urinary Mercury−Females Aged 16-49 Years Old, 1999-2002

Survey Sample

years size

Age group (females)

16-49 years 99-00 .719 (.622-.831) .760 (.610-.910) 1.62 (1.43-1.94) 3.15 (2.55-3.92) 5.00 (3.59-5.79) 1748

01-02 .606 (.553-.665) .580 (.500-.670) 1.37 (1.23-1.55) 2.91 (2.53-3.17) 3.99 (3.50-4.63) 1960

Race/ethnicity

(females, 16-49 years)

Mexican Americans 99-00 .724 (.656-.799) .650 (.560-.810) 1.69 (1.45-2.07) 3.68 (3.10-4.45) 5.62 (4.91-7.38) 595

01-02 .592 (.502-.699) .560 (.420-.710) 1.35 (1.09-1.76) 2.84 (2.32-3.85) 4.13 (2.81-6.24) 531

Non-Hispanic blacks 99-00 1.06 (.832-1.35) 1.03 (.850-1.51) 2.30 (1.83-3.03) 4.81 (3.41-6.18) 6.98 (5.04-10.3) 381

01-02 .772 (.616-.966) .740 (.540-.930) 1.76 (1.30-2.37) 3.50 (2.57-4.97) 5.18 (3.61-6.92) 442

Non-Hispanic whites 99-00 .657 (.557-.774) .710 (.520-.870) 1.50 (1.31-1.77) 2.84 (2.39-3.32) 4.05 (3.16-5.52) 594

01-02 .565 (.501-.637) .540 (.450-.650) 1.31 (1.09-1.56) 2.70 (2.22-3.16) 3.62 (3.13-4.54) 826

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 01-02 are 0.14 and 0.14.

(95% conf. interval)

mean (95% confidence interval)

50th 75th 90th 95th

Geometric mean and selected percentiles of urine concentrations (in μg/L) for females aged 16 to 49 years in the U.S.

population, National Health and Nutrition Examination Survey, 1999-2002.

Geometric Selected percentiles

Urinary Mercury (creatinine corrected)−Females Aged 16-49 Years Old, 1999-2002

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for females aged 16 to 49 years

in the U.S. population, National Health and Nutrition Examination Survey, 1999-2002.

Survey Sample

years size

Age group (females)

16-49 years 99-00 .710 (.624-.806) .723 (.636-.833) 1.41 (1.24-1.65) 2.48 (2.10-2.97) 3.27 (2.85-3.92) 1748

01-02 .620 (.579-.664) .650 (.582-.709) 1.27 (1.15-1.42) 2.30 (2.07-2.45) 3.00 (2.68-3.39) 1960

Race/ethnicity

(females, 16-49 years)

Mexican Americans 99-00 .685 (.580-.809) .639 (.508-.790) 1.45 (1.27-1.61) 2.89 (2.21-3.42) 4.51 (3.07-5.68) 595

01-02 .600 (.526-.686) .596 (.426-.709) 1.32 (1.04-1.47) 2.41 (2.14-2.77) 3.21 (2.65-4.46) 531

Non-Hispanic blacks 99-00 .658 (.520-.831) .615 (.475-.892) 1.22 (.909-1.79) 2.56 (1.69-3.99) 3.99 (2.76-5.14) 381

01-02 .522 (.410-.665) .516 (.387-.664) 1.03 (.742-1.47) 1.97 (1.42-3.25) 3.21 (1.87-4.44) 442

Non-Hispanic whites 99-00 .706 (.605-.824) .721 (.631-.846) 1.41 (1.23-1.72) 2.46 (1.99-2.97) 3.05 (2.46-4.00) 594

01-02 .632 (.578-.691) .655 (.569-.744) 1.28 (1.14-1.45) 2.30 (2.03-2.56) 2.95 (2.45-3.53) 826

(95% conf. interval) 50th 75th 90th 95th

mean

Geometric Selected percentiles

(95% confidence interval)
 224 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

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Fourth National Report on Human Exposure to Environmental Chemicals 227

 Metals

Molybdenum

CAS No. 7439-98-7

General Information

Elemental molybdenum is a silver-white, hard metal widely 

used to add strength and hardness and retard corrosion in 

metal alloys. Compounds of molybdenum are also used as 

corrosion inhibitors, hydrogenation catalysts, lubricants, 

chemical reagents in hospital laboratories, and in pigments 

for ceramics, inks, and paints. More recently, semiconductor 

and battery industries have begun to use molybdenum. 

Molybdenum occurs in natural waters and may be present 

in concentrations of several hundred micrograms per liter or 

higher in ground and surface water near mining operations 

or ore deposits.

Molybdenum is a nutritionally essential trace element that 

enters the body primarily from dietary sources. In humans, 

molybdenum is a cofactor for three enzyme classes—

sulfite oxidase, aldehyde dehydrogenase, and xanthine 

oxidase (Kisker et al., 1997). The recommended dietary 

allowance for adult men and women is 45 μg/day (IOM, 

2001), and the average dietary daily intake of molybdenum 

is approximately 100 μg/day (IOM, 2001; WHO, 1996). 

Gastrointestinal absorption of molybdenum averages 88-

93% for dietary intakes of 22-1490 μg/day. Excretion occurs 

predominantly via the kidneys, which exert homeostatic 

regulation over molybdenum balance. At a daily oral 

molybdenum dose of 24 μg, urinary excretion over six days 

Urinary Molybdenum 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 45.9 (40.1-52.6) 50.7 (44.6-58.4) 84.9 (78.7-92.3) 135 (125-146) 180 (154-216) 2257

01-02 45.0 (42.1-48.0) 52.4 (48.9-55.5) 83.4 (79.1-88.7) 124 (117-130) 165 (145-176) 2690

03-04 39.7 (37.7-41.7) 44.5 (41.6-46.7) 78.5 (74.9-82.3) 111 (105-118) 138 (133-146) 2558

Age group 

6-11 years 99-00 78.2 (61.0-100) 84.8 (67.7-105) 126 (106-147) 178 (147-259) 267 (159-840) 310

01-02 63.3 (53.4-75.0) 69.2 (63.0-77.6) 109 (94.5-124) 169 (138-197) 197 (161-291) 368

03-04 62.2 (56.7-68.3) 71.3 (55.7-84.1) 108 (92.7-122) 138 (127-152) 181 (138-235) 290

12-19 years 99-00 54.3 (47.6-62.0) 60.6 (52.2-70.3) 93.3 (79.9-109) 146 (112-171) 188 (146-216) 648

01-02 60.6 (55.5-66.2) 65.7 (58.7-73.1) 97.1 (91.8-108) 145 (129-159) 179 (155-227) 762

03-04 52.5 (49.0-56.3) 59.6 (55.5-65.1) 87.3 (84.5-91.4) 118 (105-125) 143 (130-156) 725

20 years and older 99-00 41.7 (36.7-47.4) 46.6 (40.5-52.5) 76.7 (73.4-82.2) 126 (114-134) 168 (143-206) 1299

01-02 41.1 (38.3-44.1) 47.6 (43.7-51.2) 79.1 (71.9-83.6) 114 (103-124) 150 (130-166) 1560

03-04 35.9 (34.0-38.0) 40.3 (37.6-42.1) 71.5 (67.3-75.2) 105 (98.6-111) 133 (119-144) 1543

Gender 

Males 99-00 52.7 (45.7-60.7) 57.5 (48.5-68.4) 93.2 (83.8-106) 150 (128-187) 215 (161-278) 1121

01-02 51.0 (46.6-55.7) 56.9 (52.0-62.6) 88.5 (81.6-96.5) 130 (120-141) 169 (145-194) 1335

03-04 45.5 (43.3-47.8) 51.0 (48.1-55.4) 85.8 (82.8-90.7) 119 (112-130) 148 (136-163) 1281

Females 99-00 40.4 (34.8-46.8) 45.6 (40.4-52.0) 77.3 (71.0-85.7) 119 (105-138) 154 (132-180) 1136

01-02 39.9 (37.2-42.9) 45.8 (42.8-49.3) 78.4 (72.6-82.9) 115 (104-128) 158 (130-177) 1355

03-04 34.9 (32.2-37.7) 37.9 (33.5-41.6) 67.3 (64.6-72.2) 101 (97.3-108) 127 (114-139) 1277

Race/ethnicity 

Mexican Americans 99-00 47.0 (42.1-52.4) 53.2 (49.2-59.0) 80.6 (73.7-91.7) 121 (103-139) 152 (120-217) 780

01-02 49.3 (46.5-52.3) 55.7 (50.4-61.0) 86.4 (80.8-94.1) 133 (113-155) 177 (142-207) 683

03-04 47.0 (43.1-51.1) 54.4 (48.2-59.9) 82.9 (73.2-91.0) 121 (106-143) 152 (141-169) 618

Non-Hispanic blacks 99-00 57.7 (51.0-65.2) 62.2 (55.0-71.5) 97.8 (85.0-110) 153 (126-188) 206 (150-274) 546

01-02 53.2 (49.9-56.7) 60.3 (55.1-63.8) 90.0 (81.0-101) 132 (121-147) 166 (147-170) 667

03-04 46.0 (41.7-50.8) 46.2 (40.9-55.2) 82.3 (73.3-91.3) 117 (109-129) 156 (135-175) 723

Non-Hispanic whites 99-00 44.5 (37.0-53.4) 48.5 (41.1-59.8) 85.0 (76.7-96.5) 135 (119-154) 187 (146-223) 760

01-02 42.2 (38.5-46.2) 48.9 (44.2-53.2) 80.7 (71.9-85.8) 117 (108-129) 152 (134-180) 1132

03-04 37.1 (34.7-39.6) 41.3 (38.1-44.5) 75.2 (69.2-79.6) 107 (99.3-115) 130 (119-142) 1074

Limits of detection (LOD, see Data Analysis section) for survey years 99-00, 01-02, and 03-04 are 0.8, 0.8, and 1.5, respectively. 
 228 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

was 18% of the ingested dose; at daily oral doses of 95 μg 

and 428 μg, urinary excretion over six days rose to 50% 

and 67%, respectively, of the ingested dose (Turnlund et al., 

1995). In industry, dust and other fine particles produced 

during refining or shaping of molybdenum or molybdenumcontaining alloys are inhalational pathways of exposure.

Human health effects from molybdenum at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Molybdenum 

is generally considered to be of low human toxicity, and 

clinical or epidemiologic evidence of adverse effects is 

limited. Chronic exposure to very high levels may result 

in higher serum uric acid levels and a gout-like illness 

(Koval’skiy et al., 1961; U.S. EPA, 1993). Based on studies 

finding adverse reproductive effects in rats and mice, 

the Panel on Micronutrients of the Institute of Medicine 

identified a no observed adverse effect level (NOAEL) 

of 0.9 mg/kg/day and established a tolerable upper intake 

level of 0.03 mg/kg/day in humans (IOM, 2001). A long 

term inhalation bioassay of molybdenum trioxide in mice 

yielded “some evidence” of carcinogenicity (NTP, 1997). 

One case-control study suggested a possible link between 

occupational exposure to molybdenum and lung cancer 

(Droste et al., 1999), but available epidemiologic data 

are scant, and molybdenum has not been systematically 

evaluated for carcinogenicity by IARC.

Biomonitoring Information

Molybdenum is an essential element for health, and urinary 

levels reflect intake from all sources. Levels of molybdenum 

Urinary Molybdenum (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 43.2 (40.0-46.6) 41.6 (38.5-45.2) 63.5 (59.3-68.8) 108 (97.3-115) 144 (125-171) 2257

01-02 42.5 (39.9-45.2) 42.2 (40.1-45.2) 62.0 (58.4-66.4) 98.8 (90.1-109) 130 (120-149) 2689

03-04 39.4 (37.6-41.3) 39.2 (37.9-40.7) 58.3 (55.6-61.5) 89.0 (80.5-99.0) 120 (107-135) 2558

Age group 

6-11 years 99-00 85.9 (73.7-100) 79.3 (71.6-88.4) 122 (107-133) 173 (130-243) 214 (154-1040) 310

01-02 77.2 (73.1-81.5) 77.6 (71.8-84.5) 109 (99.4-120) 159 (129-170) 185 (165-219) 368

03-04 72.5 (65.2-80.7) 73.5 (65.1-79.9) 101 (84.9-117) 132 (107-158) 160 (129-257) 290

12-19 years 99-00 41.9 (39.3-44.6) 40.5 (37.7-44.4) 57.3 (51.5-62.5) 85.4 (67.4-107) 112 (78.4-185) 648

01-02 43.4 (40.8-46.1) 44.1 (40.8-47.2) 60.8 (57.6-63.7) 85.5 (79.7-93.8) 106 (94.8-118) 762

03-04 37.5 (35.4-39.8) 38.9 (36.9-41.8) 53.2 (50.3-56.1) 71.9 (64.6-76.9) 81.0 (74.3-102) 725

20 years and older 99-00 39.6 (36.9-42.6) 38.5 (36.1-41.0) 56.4 (53.5-60.7) 92.5 (83.1-100) 122 (116-147) 1299

01-02 39.3 (36.8-42.0) 39.6 (36.4-42.1) 57.2 (52.9-61.0) 86.7 (75.2-96.8) 123 (109-139) 1559

03-04 36.9 (35.0-38.9) 37.0 (35.7-38.4) 53.5 (50.0-56.9) 79.8 (75.9-87.5) 118 (101-134) 1543

Gender 

Males 99-00 40.8 (37.5-44.3) 38.5 (37.2-40.4) 62.4 (55.9-68.4) 101 (83.9-118) 131 (112-179) 1121

01-02 40.3 (37.1-43.8) 40.2 (36.3-43.3) 60.5 (54.8-66.3) 91.3 (83.4-106) 123 (107-155) 1334

03-04 38.3 (36.1-40.7) 37.8 (36.1-39.3) 56.3 (53.3-59.3) 85.7 (77.2-96.7) 118 (100-139) 1281

Females 99-00 45.5 (41.5-50.0) 44.1 (39.5-48.8) 64.4 (59.5-70.5) 112 (95.2-121) 152 (122-181) 1136

01-02 44.6 (42.2-47.1) 45.1 (42.2-46.9) 63.6 (59.5-69.4) 107 (92.5-119) 136 (117-169) 1355

03-04 40.5 (38.1-43.0) 41.1 (38.7-43.7) 61.4 (56.8-65.1) 90.1 (82.2-103) 122 (115-142) 1277

Race/ethnicity 

Mexican Americans 99-00 42.9 (40.6-45.4) 43.2 (40.9-45.6) 61.6 (57.2-65.5) 89.5 (80.0-103) 115 (93.7-137) 780

01-02 48.1 (44.3-52.2) 48.4 (44.8-52.3) 71.7 (66.4-76.0) 103 (90.0-120) 129 (109-155) 682

03-04 43.5 (40.5-46.8) 43.5 (41.0-46.2) 62.8 (56.8-67.2) 85.9 (79.5-97.0) 112 (97.0-133) 618

Non-Hispanic blacks 99-00 37.2 (33.4-41.6) 37.1 (33.0-41.2) 55.9 (49.6-63.3) 88.2 (69.1-112) 119 (88.3-141) 546

01-02 36.5 (34.1-39.0) 37.5 (35.1-38.9) 57.1 (49.7-62.4) 78.3 (71.5-92.0) 109 (81.1-127) 667

03-04 33.1 (30.5-35.9) 31.7 (30.1-34.7) 47.2 (43.7-52.1) 72.9 (64.6-78.4) 90.5 (78.4-118) 723

Non-Hispanic whites 99-00 44.5 (40.2-49.2) 42.1 (38.8-47.3) 65.3 (58.9-71.3) 116 (101-126) 172 (131-195) 760

01-02 42.5 (39.3-46.0) 41.9 (39.3-45.6) 61.2 (57.1-67.2) 104 (88.7-120) 138 (120-163) 1132

03-04 39.1 (37.2-41.1) 39.3 (37.7-40.8) 58.1 (54.6-61.4) 87.4 (78.9-96.7) 118 (106-134) 1074
Fourth National Report on Human Exposure to Environmental Chemicals 229

 Metals

in urine for the U.S. population were well characterized in 

NHANES 1999-2000 and 2001-2002 (CDC, 2005); these 

levels were comparable to those reported for adults in 

smaller European population surveys (Iversen et al., 1998; 

Minoia et al., 2002; White and Sabbioni, 1998). Urinary 

molybdenum concentrations in infants may be slightly 

lower than those in other age groups (Sievers et al., 2001).

Finding a measurable amount of molybdenum in the urine 

does not mean that the level of molybdenum causes an 

adverse health effect. Biomonitoring studies on levels of 

molybdenum can provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels of 

molybdenum than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

References

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Droste JHJ, Weyler JJ, Van Meerbeeck JP, Vermeire PA, van 

Sprundel MP. Occupational risk factors of lung cancer: a hospital 

based case-control study. Occup Environ Med 1999; 56:322-327. 

Institute of Medicine (IOM). Standing Committee on the 

Scientific Evaluation of Dietary Reference Intakes, Food and 

Nutrition Board. Dietary reference intakes for vitamin A, vitamin 

K, arsenic, boron, chromium, copper, iodine, iron, manganese, 

molybdenum, nickel, silicon, vanadium, and zinc: a report of the 

Panel on Micronutrients. Washington, (DC): National Academy 

Press; 2001. pp. 420-441. Available at URL: http://books.nap.

edu/openbook.php?record_id=10026&page=420. 4/14/09

Iversen BS, Menne C, White MA, Kristiansen J, Christensen 

JM, Sabbioni E. Inductively coupled plasma mass spectrometric 

determination of molybdenum in urine from a Danish population. 

Analyst 1998;123(1):81-85.

Kisker C, Schindelin H, Rees DC. Molybdenum-cofactorcontaining enzymes: structure and mechanism. Ann Rev Biochem 

1997;66:233-267.

Koval’skiy GA, Yarovaya GA, Shmavonyan DM. Changes 

of purine metabolism in man and animals under conditions of 

molybdenum biogeochemical provinces. Zhurnal Obshchey 

Biologii 1961;22(3):179-191.

Minoia C, Gatti A, Aprea C, Ronchi A, Sciarra G, Turci R, et 

al. Inductively coupled plasma mass spectrometric determination 

of molybdenum in urine. Rapid Comm Mass Spectrom 2002; 

16:1313-1319.

National Toxicology Program (NTP). TR-462. Toxicology 

and carcinogenesis studies of molybdenum trioxide (CAS No. 

1313-27-5) in F344 Rats and B6C3F1 Mice (inhalation studies) 

1997 [online]. Available at URL: http://ntp.niehs.nih.gov/index.

cfm?objectid=070A72C6-E9C1-AE67-4BFAB97AD0F427E8. 

4/14/09

Sievers E, Schleyerbach U, Schaub J. Molybdenum in infancy: 

methodical investigation of urinary excretion. J Trace Elem Med 

Biol 2001;15(2-3):149-154.

Turnlund JR, Keyes WR, Peiffer GL. Molybdenum absorption, 

excretion, and retention studied with stable isotopes in young 

men at five intakes of dietary molybdenum. Am J Clin Nutr 

1995;62(4):790-796.

U.S. Environmental Protection Agency (U.S. EPA). Molybdenum 

1993 [online]. Available at URL: http://www.epa.gov/iris/

subst/0425.htm. 4/14/09

White MA, Sabbioni E. Trace element reference values in 

tissues from inhabitants of the European Union. X. A study of 13 

elements in blood and urine of a United Kingdom population. Sci 

Total Environ 1998;216:253-270.

World Health Organization (WHO). Molybdenum. In: Trace 

elements in human nutrition and health. Geneva: WHO, 1996. 

pp. 144-154.
 230 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Platinum

CAS No. 7440-06-4

General Information

Platinum is a silver-gray, lustrous metal found naturally 

in extremely low amounts in the earth’s crust and is 

typically associated with sulfide-ore bodies of nickel, 

copper, and iron. Important properties of platinum are 

resistance to corrosion, strength at high temperatures, and 

high catalytic activity. Platinum compounds are used in 

electrodes, jewelry, dental alloys, thick-film circuits printed 

on ceramic substrates, as oxidation catalysts in chemical 

manufacturing, and as drugs (e.g., cisplatin, carboplatin) in 

the treatment of cancer. Platinum-rhodium and platinumpalladium crystals are used as catalysts in petroleum 

refining and in vehicular catalytic converters to control 

exhaust emissions. Platinum-rhodium compounds are also 

used in glass and glass-fiber manufacture and in hightemperature thermocouples. Higher environmental soil 

concentrations of platinum from vehicular emissions have 

been found near roadways (Farago et al., 1998); however, 

the ambient air concentrations of platinum associated 

with its use in automotive engine catalytic converters are 

estimated to be thousands of times lower than occupational 

exposure limits.

Human health effects from platinum at low environmental 

Urinary Platinum 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * < LOD < LOD < LOD < LOD 2465

01-02 * < LOD < LOD < LOD < LOD 2690

03-04 * < LOD < LOD < LOD < LOD 2558

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 340

01-02 * < LOD < LOD < LOD < LOD 368

03-04 * < LOD < LOD < LOD < LOD 290

12-19 years 99-00 * < LOD < LOD < LOD < LOD 719

01-02 * < LOD < LOD < LOD < LOD 762

03-04 * < LOD < LOD < LOD < LOD 725

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1406

01-02 * < LOD < LOD < LOD < LOD 1560

03-04 * < LOD < LOD < LOD < LOD 1543

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 1227

01-02 * < LOD < LOD < LOD < LOD 1335

03-04 * < LOD < LOD < LOD < LOD 1281

Females 99-00 * < LOD < LOD < LOD < LOD 1238

01-02 * < LOD < LOD < LOD < LOD 1355

03-04 * < LOD < LOD < LOD < LOD 1277

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 884

01-02 * < LOD < LOD < LOD < LOD 683

03-04 * < LOD < LOD < LOD < LOD 618

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 568

01-02 * < LOD < LOD < LOD < LOD 667

03-04 * < LOD < LOD < LOD < LOD 723

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 822

01-02 * < LOD < LOD < LOD < LOD 1132

03-04 * < LOD < LOD < LOD < LOD 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.04, 0.04, and 0.07, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 231

 Metals

doses or at biomonitored levels from low environmental 

exposures are unknown. Toxicity is determined by the 

type of compound (e.g., metallic, inorganic salt, or 

organometallic), route of exposure (e.g., intravenous 

medicinal use, inhalational, cutaneous, oral), and duration 

of exposure. Platinum metal is biologically inert, whereas 

soluble platinum compounds (e.g., halogenated salts) 

encountered in occupational settings can cause platinum salt 

hypersensitivity with symptoms that include bronchitis and 

asthma after inhalational exposure and contact dermatitis 

after skin exposure. Animals exposed to cholorplatinate salts 

used in industry have demonstrated severe hypersensitivity 

with asthma-like symptoms and anaphylactic shock (Parrot 

et al., 1969; Saindelle et al., 1969). Platinum metal and 

insoluble salts can produce eye irritation. When ingested 

or inhaled, platinum metal and insoluble salts are very 

poorly absorbed (<1% of a dose) and cleared from the body 

within a week after a single dose. Most absorbed platinum 

accumulates in the kidneys and is excreted in urine (Moore 

et al., 1975a, 1975b). The pharmaceutical cisplatin is an 

animal carcinogen and reasonably anticipated to be a human 

carcinogen as determined by NTP. The carcinogenicity of 

other platinum compounds remains uncertain. Workplace 

air standards for external exposure are established for 

soluble salts of platinum by OSHA and ACGIH, or 

recommended for the metal form by NIOSH (Czerczak and 

Gromiec, 2000). Information about external exposure (i.e.,

environmental levels) and health effects is available from

Urinary Platinum (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 * < LOD < LOD < LOD < LOD 2465

01-02 * < LOD < LOD < LOD < LOD 2689

03-04 * < LOD < LOD < LOD < LOD 2558

Age group 

6-11 years 99-00 * < LOD < LOD < LOD < LOD 340

01-02 * < LOD < LOD < LOD < LOD 368

03-04 * < LOD < LOD < LOD < LOD 290

12-19 years 99-00 * < LOD < LOD < LOD < LOD 719

01-02 * < LOD < LOD < LOD < LOD 762

03-04 * < LOD < LOD < LOD < LOD 725

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1406

01-02 * < LOD < LOD < LOD < LOD 1559

03-04 * < LOD < LOD < LOD < LOD 1543

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 1227

01-02 * < LOD < LOD < LOD < LOD 1334

03-04 * < LOD < LOD < LOD < LOD 1281

Females 99-00 * < LOD < LOD < LOD < LOD 1238

01-02 * < LOD < LOD < LOD < LOD 1355

03-04 * < LOD < LOD < LOD < LOD 1277

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 884

01-02 * < LOD < LOD < LOD < LOD 682

03-04 * < LOD < LOD < LOD < LOD 618

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 568

01-02 * < LOD < LOD < LOD < LOD 667

03-04 * < LOD < LOD < LOD < LOD 723

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 822

01-02 * < LOD < LOD < LOD < LOD 1132

03-04 * < LOD < LOD < LOD < LOD 1074

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 232 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

the International Programme on Chemical Safety at http://

www.inchem.org/documents/ehc/ehc/ehc125.htm.

Biomonitoring Information

Urinary platinum levels reflect recent exposure. Levels of 

platinum in urine for the U.S. population were below the 

limit of detection (0.04 μg/L) in this Report. Several studies 

have shown that background concentrations in general 

populations were usually less than 0.005 μg/L (Iavicoli 

et al., 2004; Wilhelm et al., 2004) or less than 0.01 μg/L 

(Becker et al., 2003; Herr et al., 2003; Schierl et al., 1998). 

One study found that traffic-control officers had no 

greater urinary platinum concentrations than office-based 

control subjects (Iavicoli et al., 2004). Gold-platinum 

dental restorations were correlated with increased urinary 

platinum concentrations, which elevate urinary platinum 

by five to twelve-fold (Begerow et al., 1999; Herr et al., 

2003; Schierl, 2001). Platinum-industry and precious-metal 

workers had urinary concentrations about one-thousand 

times higher than general populations (Schierl et al., 1998). 

Modest (ten-fold or less) elevations in urinary platinum 

concentrations were associated with handling of cisplatin 

and carboplatin by pharmacy and other hospital personnel 

(Ensslin et al., 1997; Pethran et al., 2003).

Finding a measurable amount of platinum in the urine does 

not mean that the level of platinum causes an adverse health 

effect. Biomonitoring studies on levels of platinum provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels of platinum than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German 

environmental survey 1998 (GerES III): environmental pollutants 

in the urine of the German population. International Journal of 

Hygiene and Environmental Health 2003; 206:15-24.

Begerow J, Neuendorf J, Turfeld M, Raab W, Duneman 

L:Long-term urinary platinum, palladium, and gold excretion of 

patients after insertion of noble-metal dental alloys. Biomarkers 

1999;4(1):27-36.

Czerczak S, Gromiec JP. Nickel, ruthenium, rhodium, palladium, 

osmium, and platinum. In: Bingham E, Cohrssen B, Powell CH, 

eds. Patty’s Toxicology. 5th ed. New York: John Wiley & Sons; 

2000. pp. 289-380.

Ensslin AS, Huber R, Pethran A, Rommelt H, Schierl R, Kulka 

U, et al. Biological monitoring of hospital pharmacy personnel 

occupationally exposed to cytostatic drugs: urinary excretion 

and cytogenetic studies. Int Arch Occup Environ Health 

1997;70(3):205-208.

Farago ME, Kavanagh P, Blanks R, Kelly J, Kazantzis G, 

Thornton I, et al. Platinum concentrations in urban road dust 

and soil, and in blood and urine in the United Kingdom. Analyst 

1998;123(3):451-454.

Herr CE, Jankofsky M, Angerer J, Kuster W, Stilianakis NI, Gieler 

U, et al. Influences on human internal exposure to environmental 

platinum. J Expo Anal Environ Epidemiol 2003;13(1):24-30.

Iavicoli I, Bocca B, Petrucci F, Senofonte O, Carelli G, Alimonti 

A, et al. Biomonitoring of traffic police officers exposed to 

airborne platinum. Occup Environ Med 2004;61(7):636-9.

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 125. Platinum. 1991 [online]. 

Available at URL: http://www.inchem.org/documents/ehc/ehc/

ehc125.htm. 3/31/08

Moore W Jr, Hysell D, Crocker W, Stara J: Biological fate of a 

single administration of 191Pt in rats following different routes 

of exposure. Environ Res 1975a;9:152-158.

Moore W Jr, Hysell D, Hall L, Campbell K, Stara J: Preliminary 

studies on the toxicity and metabolism of palladium and platinum. 

Environ Health Perspect 1975b;10:63-71.

Parrot JL, Hebert R, Saindelle A, Ruff F: Platinum and platinosis. 

Allergy and histamine release due to some platinum salts. Arch 

Environ Health:1969;19:685-691.

Pethran A, Schierl R, Hauff K, Grimm CH, Boos KS, Nowak 

D. Uptake of antineoplastic agents in pharmacy and hospital 

personnel. Part 1: monitoring of urinary concentrations. Int Arch 

Occup Environ Health 2003;76(1):5-10.

Saindelle A, Ruff F: Histamine release by sodium cholorplatinate. 

Br J Pharmacol 1969;35:313-321.

Schierl R. Urinary platinum levels associated with dental gold 

alloys. Arch Environ Health 2001;56(3):283-286.

Schierl R, Fries HG, van de Weyer C, Fruhmann G. Urinary 

excretion of platinum from platinum-industry workers. Occup 

Environ Med 1998;55(2):138-140.

Wilhelm M, Ewers U, Schulz C. Revised and new reference 

values for some trace elements in blood and urine for human 

biomonitoring in environmental medicine. Int J Hyg Environ 

Health 2004;207(1):69-73.
Fourth National Report on Human Exposure to Environmental Chemicals 233

 Metals

Thallium

CAS No. 7440-28-0

General Information

Elemental thallium is a blue-white metal found in small 

amounts in soil and in sulfide-based minerals. In the past, 

thallium was obtained as a by-product of smelting other 

metals; however, it has not been specifically mined or 

refined in the United States since 1984. It is still used in 

relatively small amounts in pharmaceutical and electronics 

manufacturing, the latter being the current major industrial 

consumer of thallium in this country. In the United States, 

thallium has been restricted from use in rodenticides and 

depilatory cosmetics.

Thallium exposure occurs primarily from industrial 

processes such as coal-burning and smelting. From these 

and other sources, thallium is produced in a fine particulate 

form that can be absorbed through inhalation or ingestion. 

Thallium disappears from the blood with a half-life of 

several days, representing distribution into other tissues. 

In addition, thallium readily crosses the placenta and also 

distributes into breast milk. Elimination from the body 

tissues occurs slowly through urine and feces (Blanchardon 

et al., 2005).

Human health effects from thallium at low environmental 

Urinary Thallium 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .176 (.162-.192) .200 (.180-.220) .290 (.270-.330) .400 (.370-.420) .450 (.430-.480) 2413

01-02 .165 (.154-.177) .190 (.180-.200) .280 (.260-.290) .370 (.350-.390) .440 (.410-.470) 2653

03-04 .155 (.145-.165) .170 (.160-.180) .270 (.250-.290) .370 (.340-.400) .440 (.410-.490) 2558

Age group 

6-11 years 99-00 .201 (.167-.243) .210 (.150-.280) .310 (.250-.350) .410 (.330-.450) .450 (.350-.590) 336

01-02 .172 (.147-.202) .200 (.160-.220) .290 (.230-.330) .350 (.340-.370) .390 (.360-.430) 362

03-04 .191 (.170-.215) .190 (.170-.230) .300 (.250-.370) .430 (.360-.500) .510 (.430-.690) 290

12-19 years 99-00 .202 (.181-.225) .220 (.200-.240) .300 (.270-.340) .410 (.390-.430) .470 (.430-.510) 697

01-02 .200 (.182-.220) .220 (.190-.250) .310 (.290-.320) .370 (.350-.420) .470 (.400-.500) 746

03-04 .201 (.185-.218) .220 (.210-.240) .310 (.290-.320) .410 (.360-.470) .500 (.420-.560) 725

20 years and older 99-00 .170 (.157-.183) .190 (.180-.210) .290 (.260-.320) .400 (.370-.420) .450 (.420-.480) 1380

01-02 .159 (.147-.173) .190 (.170-.200) .270 (.250-.290) .380 (.350-.400) .440 (.410-.490) 1545

03-04 .145 (.134-.156) .160 (.150-.170) .250 (.240-.270) .360 (.330-.390) .420 (.390-.460) 1543

Gender 

Males 99-00 .197 (.179-.217) .220 (.200-.240) .320 (.280-.350) .400 (.370-.440) .450 (.420-.520) 1200

01-02 .184 (.173-.196) .210 (.200-.230) .290 (.280-.300) .380 (.360-.400) .430 (.400-.470) 1313

03-04 .167 (.156-.178) .190 (.180-.200) .280 (.260-.300) .370 (.340-.400) .430 (.400-.480) 1281

Females 99-00 .159 (.145-.175) .180 (.150-.200) .270 (.250-.300) .390 (.350-.420) .460 (.410-.490) 1213

01-02 .149 (.137-.163) .160 (.150-.180) .260 (.230-.290) .370 (.330-.400) .440 (.400-.500) 1340

03-04 .144 (.133-.156) .160 (.140-.170) .250 (.230-.280) .370 (.330-.410) .450 (.410-.510) 1277

Race/ethnicity 

Mexican Americans 99-00 .172 (.150-.196) .200 (.160-.230) .270 (.250-.300) .370 (.320-.420) .450 (.370-.520) 861

01-02 .160 (.148-.173) .180 (.160-.200) .260 (.240-.270) .340 (.310-.360) .400 (.350-.440) 675

03-04 .171 (.160-.183) .200 (.170-.220) .280 (.260-.310) .360 (.340-.420) .450 (.390-.480) 618

Non-Hispanic blacks 99-00 .217 (.197-.239) .230 (.220-.260) .350 (.300-.390) .450 (.400-.520) .550 (.460-.630) 561

01-02 .202 (.187-.218) .220 (.200-.230) .300 (.270-.340) .410 (.380-.440) .520 (.440-.590) 657

03-04 .185 (.167-.206) .190 (.170-.220) .290 (.250-.330) .410 (.330-.490) .490 (.410-.640) 723

Non-Hispanic whites 99-00 .170 (.153-.188) .200 (.170-.220) .290 (.260-.330) .400 (.360-.420) .450 (.420-.480) 801

01-02 .159 (.147-.172) .180 (.170-.200) .270 (.250-.290) .360 (.330-.390) .430 (.390-.460) 1114

03-04 .146 (.135-.158) .160 (.150-.170) .260 (.240-.280) .360 (.330-.380) .410 (.380-.460) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.02, 0.02, and 0.02, respectively. 
 234 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

doses or at biomonitored levels from low environmental 

exposures are unknown. Thallium produces toxicity by 

replacing intracellular potassium in the body, although 

additional mechanisms of action are possible. Severe 

accidental thallium poisonings from ingesting of rat poisons 

that contained water-soluble thallium salt have occurred. 

Relatively high-dose intentional or accidental ingestion 

can result in gastrointestinal symptoms followed by multiorgan failure, neurologic injury, and death. Peripheral 

neuropathy and alopecia are well-documented effects of 

acute and chronic exposures. Chronic high-level exposures 

have been associated with weight loss, arthralgias, and 

polyneuropathy. (ATSDR, 1992)

Workplace air standards and guidelines for external exposure 

are established by OSHA and ACGIH, respectively, 

and a drinking water standard has been established by 

U.S. EPA. IARC and NTP consider the evidence for the 

carcinogenicity of thallium as inadequate or unclassifiable. 

Information about external exposure (i.e., environmental 

levels) and health effects is available from ATSDR at: 

http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Urinary thallium levels reflect recent exposure. Levels of

thallium in urine for the U.S. population have been well 

characterized in NHANES 1999-2000 and 2001-2002 

Urinary Thallium (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .166 (.159-.173) .168 (.162-.176) .224 (.217-.233) .297 (.273-.319) .366 (.338-.387) 2413

01-02 .156 (.151-.162) .156 (.148-.164) .215 (.208-.222) .287 (.278-.300) .349 (.337-.365) 2652

03-04 .154 (.149-.158) .153 (.146-.160) .214 (.203-.222) .286 (.274-.304) .350 (.328-.369) 2558

Age group 

6-11 years 99-00 .221 (.197-.248) .222 (.196-.236) .297 (.229-.356) .375 (.318-.469) .424 (.356-.600) 336

01-02 .211 (.198-.226) .207 (.198-.221) .286 (.260-.321) .370 (.333-.402) .412 (.389-.456) 362

03-04 .223 (.208-.238) .216 (.198-.229) .306 (.280-.346) .412 (.346-.458) .458 (.400-.532) 290

12-19 years 99-00 .153 (.146-.160) .154 (.146-.162) .205 (.191-.219) .258 (.231-.278) .321 (.265-.364) 697

01-02 .143 (.137-.150) .145 (.135-.152) .196 (.184-.207) .272 (.250-.289) .312 (.299-.333) 746

03-04 .143 (.135-.152) .146 (.131-.155) .194 (.179-.208) .254 (.234-.280) .304 (.271-.327) 725

20 years and older 99-00 .162 (.153-.171) .167 (.155-.176) .218 (.207-.230) .286 (.271-.300) .364 (.325-.389) 1380

01-02 .153 (.147-.159) .153 (.144-.161) .210 (.200-.217) .278 (.263-.293) .343 (.313-.362) 1544

03-04 .148 (.144-.153) .149 (.141-.156) .206 (.192-.215) .273 (.258-.289) .333 (.306-.353) 1543

Gender 

Males 99-00 .154 (.147-.161) .156 (.149-.164) .202 (.192-.214) .269 (.254-.297) .338 (.300-.364) 1200

01-02 .146 (.140-.153) .148 (.142-.157) .192 (.184-.204) .260 (.246-.278) .307 (.291-.342) 1312

03-04 .140 (.135-.146) .142 (.134-.149) .188 (.180-.198) .264 (.235-.286) .317 (.287-.350) 1281

Females 99-00 .178 (.167-.189) .182 (.169-.197) .244 (.226-.259) .317 (.281-.366) .380 (.333-.462) 1213

01-02 .167 (.158-.176) .167 (.153-.180) .233 (.217-.250) .313 (.282-.348) .378 (.348-.402) 1340

03-04 .167 (.162-.173) .166 (.157-.177) .235 (.222-.243) .313 (.286-.333) .368 (.340-.412) 1277

Race/ethnicity 

Mexican Americans 99-00 .158 (.147-.170) .160 (.148-.176) .213 (.200-.237) .282 (.266-.304) .343 (.306-.389) 861

01-02 .156 (.145-.169) .155 (.145-.167) .204 (.191-.221) .286 (.250-.317) .361 (.301-.424) 674

03-04 .159 (.148-.170) .157 (.143-.172) .211 (.187-.241) .293 (.273-.324) .369 (.326-.422) 618

Non-Hispanic blacks 99-00 .142 (.133-.152) .140 (.129-.151) .200 (.184-.214) .278 (.244-.307) .383 (.286-.462) 561

01-02 .138 (.128-.150) .136 (.125-.146) .194 (.170-.212) .256 (.238-.278) .328 (.271-.387) 657

03-04 .133 (.122-.145) .128 (.119-.143) .185 (.171-.200) .255 (.237-.269) .323 (.267-.377) 723

Non-Hispanic whites 99-00 .169 (.160-.179) .173 (.167-.181) .227 (.215-.240) .300 (.272-.329) .364 (.333-.377) 801

01-02 .161 (.155-.167) .161 (.153-.171) .222 (.214-.231) .292 (.278-.304) .348 (.330-.383) 1114

03-04 .154 (.148-.160) .153 (.143-.162) .214 (.200-.223) .283 (.271-.304) .333 (.313-.363) 1074
Fourth National Report on Human Exposure to Environmental Chemicals 235

 Metals

(CDC, 2005) and are shown with results from NHANES 

2003-2004 in this Report. These urine levels are generally 

comparable to levels observed in earlier studies of general 

populations (Brockhaus et al., 1981; Minoia et al., 1990; 

Paschal et al., 1998; Schaller et al., 1980; White and 

Sabbioni, 1998). Urinary concentrations of 100 μg/L in 

asymptomatic workers (500 times higher than median 

levels in the U.S. population) are thought to correspond 

to workplace exposures at the threshold limit value of 0.1 

mg/m3 (Marcus, 1985). Brockhaus et al. (1981) studied 

1,265 people living near a thallium-emitting cement plant 

in Germany. Nearby residents were exposed by eating 

garden plants that had been contaminated by the thallium. 

Seventy-eight percent of the urine specimens in that study 

contained greater than 1 μg/L, with concentrations ranging 

up to 76.5 μg/L. There was no increase in the prevalence 

of symptoms at levels less than 20 μg/L and only a slight 

increase in nonspecific symptoms greater than 20 μg/L.

Finding a measurable amount of thallium in urine does not 

mean that the level of thallium causes an adverse health 

effect. Biomonitoring studies on levels of thallium provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels of thallium than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for thallium. 1992 [online]. Available at 

URL: http://www.atsdr.cdc.gov/toxprofiles/tp54.html. 7/15/09

Blanchardon E, Challeton-de Vathaire C, Boisson P, Celier D, 

Martin J-C, Cassot G, et al. Long term retention and excretion 

of 201Tl in a patient after myocardial perfusion imaging. Radiat 

Prot Dosim. 2005;113(1):47-53.

Brockhaus A, Dolger R, Ewers U, Kramer U, Soddemann 

H, Wiegand H. Intake and health effects of thallium among 

a population living in the vicinity of a cement plant emitting 

thallium-containing dust. Int Arch Occup Environ Health 

1981;48(4):375-389.

Centers for Disease Control and Prevention. Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Marcus RL. Investigation of a working population exposed to 

thallium. J Soc Occup Med 1985;35(1):4-9.

Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini 

M, et al. Trace element reference values in tissues from 

inhabitants of the European community I. A study of 46 elements 

in urine, blood, and serum of Italian subjects. Sci Total Environ 

1990;95:89-105.

Paschal DC, Ting BG, Morrow JC, Pirkle JL, Jackson RJ, 

Sampson EJ, et al. Trace metals in urine of United States residents: 

reference range concentrations. Environ Res 1998;76(1):53-59.

Schaller KH, Manke G, Raithel HJ, Buhlmeyer G, Schmidt M, 

Valentin H. Investigations of thallium-exposed workers in cement 

factories. Int Arch Occup Environ Health 1980;47(3):223-231.

White MA, Sabbioni E. Trace element reference values in 

tissues from inhabitants of the European Union. X. A study of 13 

elements in blood and urine of a United Kingdom population. Sci 

Total Environ 1998;216:253-270.
 236 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

Tungsten

CAS No. 7440-33-7

General Information

Tungsten is a steel-gray to tin-white metal that occurs 

naturally in the earth’s crust, mainly as scheelite (CaWO4). 

Tungsten is used mainly for producing hard metals, which 

are used in rock drills and metal-cutting tools, and for 

producing ferrotungsten, which is used in the steel industry. 

Tungsten compounds are used as lubricating agents, 

filaments for incandescent lamps, bronzes in pigments, and 

as catalysts in the petroleum industry.

Most background environmental exposures to tungsten 

are from the soluble forms such as tungstate salts that may 

occur in drinking water. Occupational exposure is from 

dusts released during grinding or drilling of hard metals. 

Human health effects from tungsten at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Little information is available on 

the toxicity of tungsten. Although workers occupationally 

exposed to tungsten carbide may develop serious lung 

disease (“hard metal disease”), their illness may stem 

from exposure to cobalt mixed with tungsten carbide 

rather than to tungsten alone. Evidence is lacking for the 

carcinogenicity of tungsten, and it has not been classified 

with respect to its carcinogenicity by either IARC or NTP. 

Urinary Tungsten 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .093 (.087-.100) .090 (.080-.090) .180 (.160-.190) .320 (.280-.370) .500 (.430-.550) 2338

01-02 .082 (.073-.092) .070 (.060-.090) .160 (.140-.180) .300 (.260-.350) .460 (.370-.560) 2652

03-04 .071 (.064-.078) .070 (.060-.080) .130 (.120-.140) .270 (.230-.300) .400 (.330-.480) 2558

Age group 

6-11 years 99-00 .158 (.123-.204) .160 (.120-.220) .270 (.220-.350) .510 (.380-.560) .620 (.510-.950) 320

01-02 .137 (.110-.170) .140 (.110-.170) .260 (.200-.350) .460 (.360-.690) .770 (.510-1.53) 363

03-04 .130 (.111-.151) .140 (.120-.150) .240 (.190-.290) .410 (.290-.500) .500 (.370-.630) 290

12-19 years 99-00 .113 (.097-.132) .110 (.090-.130) .210 (.180-.250) .360 (.310-.440) .530 (.380-.800) 679

01-02 .113 (.095-.135) .110 (.090-.130) .210 (.180-.260) .400 (.310-.520) .570 (.430-.790) 744

03-04 .105 (.090-.122) .100 (.090-.120) .190 (.160-.230) .350 (.290-.460) .530 (.350-1.00) 725

20 years and older 99-00 .084 (.078-.091) .080 (.070-.090) .160 (.130-.180) .280 (.260-.320) .450 (.360-.520) 1339

01-02 .073 (.065-.082) .060 (.050-.070) .140 (.110-.160) .260 (.210-.310) .380 (.310-.490) 1545

03-04 .062 (.056-.068) .060 (.050-.070) .110 (.100-.120) .210 (.180-.250) .360 (.270-.430) 1543

Gender 

Males 99-00 .107 (.096-.120) .100 (.090-.120) .210 (.190-.230) .390 (.310-.470) .530 (.470-.650) 1160

01-02 .088 (.074-.105) .080 (.060-.100) .170 (.140-.220) .330 (.260-.390) .490 (.380-.580) 1307

03-04 .081 (.071-.093) .080 (.070-.090) .140 (.130-.170) .300 (.250-.340) .430 (.340-.560) 1281

Females 99-00 .082 (.077-.087) .070 (.060-.080) .150 (.130-.160) .270 (.240-.300) .400 (.320-.470) 1178

01-02 .076 (.069-.084) .060 (.060-.080) .150 (.120-.170) .280 (.230-.330) .430 (.340-.560) 1345

03-04 .062 (.056-.069) .060 (.050-.070) .110 (.100-.120) .220 (.190-.250) .370 (.270-.460) 1277

Race/ethnicity 

Mexican Americans 99-00 .113 (.095-.133) .110 (.090-.130) .200 (.160-.250) .400 (.300-.520) .550 (.420-.830) 790

01-02 .101 (.093-.109) .100 (.090-.110) .190 (.170-.210) .370 (.310-.430) .570 (.450-.670) 680

03-04 .086 (.073-.100) .080 (.070-.100) .170 (.120-.220) .360 (.230-.620) .640 (.410-.800) 618

Non-Hispanic blacks 99-00 .113 (.101-.126) .100 (.090-.130) .210 (.180-.250) .370 (.290-.460) .560 (.420-.810) 562

01-02 .096 (.080-.116) .090 (.070-.120) .160 (.130-.250) .310 (.270-.400) .460 (.400-.590) 649

03-04 .092 (.082-.104) .090 (.080-.110) .160 (.150-.180) .300 (.250-.330) .470 (.340-.550) 723

Non-Hispanic whites 99-00 .092 (.084-.100) .080 (.070-.100) .180 (.160-.200) .320 (.270-.380) .470 (.380-.550) 802

01-02 .076 (.066-.088) .060 (.050-.080) .150 (.120-.180) .290 (.230-.360) .430 (.330-.620) 1117

03-04 .065 (.058-.073) .060 (.060-.070) .120 (.100-.130) .230 (.190-.290) .380 (.320-.410) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.04, 0.04, and 0.04, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 237

 Metals

Workplace air standards for external exposure have been 

established by ACGIH and recommended by NIOSH.

Biomonitoring Information

Levels of urinary tungsten reflect recent exposure. A 

nonrandom subsample from NHANES III demonstrated 

slightly higher values than those found in NHANES 1999-

2000, 2001-2002, and 2003-2004 (Paschal et al., 1998), 

possibly due to methodologic, population, or exposure 

differences. A study of 14 unexposed adults yielded values 

similar to those in this Report (Schramel et al., 1997). In 

a Nevada community where tungsten was measured and 

found at increased levels in drinking water, the residents’ 

median urinary levels were as much as 15-fold higher than 

median levels in the U.S. population (CDC, 2003, 2005).

Workers involved in grinding operations that released 

tungsten metal into the air had elevated urinary levels that 

were more than 900 times higher than the overall geometric 

mean of the U.S. population in the NHANES 1999-2000 

(Kraus et al., 2001). Using neutron activation analysis to 

measure urinary tungsten, Nicolaou et al. (1987) found 

that a control group of non-metal workers had mean levels 

that were similar to the 95th percentiles in this Report,

whereas the tungsten-worker group had mean urine levels 

35 times higher. Patients with medically-inserted tungsten 

embolization coils showed elevated tungsten levels in 

Urinary Tungsten (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .087 (.080-.095) .080 (.075-.086) .146 (.136-.158) .270 (.206-.333) .383 (.302-.459) 2338

01-02 .078 (.069-.087) .074 (.064-.084) .138 (.122-.154) .255 (.216-.300) .359 (.315-.436) 2651

03-04 .070 (.063-.078) .065 (.059-.074) .117 (.107-.133) .215 (.179-.253) .333 (.255-.439) 2558

Age group 

6-11 years 99-00 .174 (.150-.201) .169 (.136-.198) .293 (.216-.333) .439 (.331-.667) .667 (.452-.880) 320

01-02 .168 (.144-.197) .158 (.139-.190) .275 (.231-.326) .412 (.333-.554) .634 (.436-1.28) 363

03-04 .151 (.131-.174) .144 (.119-.167) .250 (.205-.283) .333 (.278-.484) .484 (.333-.739) 290

12-19 years 99-00 .084 (.078-.091) .079 (.074-.084) .138 (.124-.158) .231 (.180-.287) .339 (.237-.465) 679

01-02 .081 (.071-.092) .081 (.072-.091) .148 (.122-.167) .250 (.208-.301) .359 (.272-.431) 744

03-04 .075 (.065-.086) .071 (.061-.082) .122 (.098-.148) .197 (.167-.308) .379 (.197-.582) 725

20 years and older 99-00 .080 (.072-.089) .075 (.067-.082) .130 (.116-.146) .218 (.179-.301) .347 (.245-.426) 1339

01-02 .070 (.063-.079) .067 (.058-.075) .119 (.099-.139) .216 (.176-.267) .333 (.253-.431) 1544

03-04 .063 (.057-.071) .059 (.053-.065) .105 (.094-.117) .181 (.155-.215) .279 (.217-.370) 1543

Gender 

Males 99-00 .083 (.074-.094) .073 (.063-.086) .146 (.126-.165) .279 (.198-.386) .439 (.329-.605) 1160

01-02 .071 (.060-.083) .065 (.056-.077) .125 (.098-.153) .255 (.203-.306) .364 (.300-.431) 1306

03-04 .068 (.059-.079) .062 (.054-.071) .111 (.098-.133) .216 (.170-.284) .341 (.240-.500) 1281

Females 99-00 .091 (.085-.098) .084 (.080-.091) .145 (.136-.158) .265 (.200-.301) .339 (.300-.381) 1178

01-02 .085 (.077-.094) .083 (.075-.091) .143 (.130-.161) .258 (.216-.317) .353 (.317-.538) 1345

03-04 .072 (.065-.079) .069 (.063-.078) .121 (.108-.138) .211 (.176-.237) .333 (.261-.439) 1277

Race/ethnicity 

Mexican Americans 99-00 .106 (.093-.120) .100 (.086-.116) .184 (.152-.214) .329 (.267-.392) .497 (.354-.727) 790

01-02 .098 (.090-.108) .089 (.081-.100) .164 (.143-.187) .294 (.258-.375) .555 (.410-.797) 679

03-04 .079 (.065-.096) .073 (.054-.093) .136 (.103-.197) .300 (.233-.426) .482 (.344-.823) 618

Non-Hispanic blacks 99-00 .073 (.064-.083) .071 (.061-.081) .124 (.109-.154) .201 (.188-.222) .360 (.217-.465) 562

01-02 .066 (.056-.077) .060 (.049-.079) .109 (.090-.125) .199 (.153-.285) .340 (.250-.414) 649

03-04 .066 (.059-.074) .067 (.055-.075) .105 (.095-.120) .186 (.150-.224) .317 (.214-.358) 723

Non-Hispanic whites 99-00 .091 (.083-.100) .082 (.077-.088) .150 (.136-.169) .279 (.200-.354) .385 (.302-.462) 802

01-02 .078 (.068-.088) .073 (.061-.085) .139 (.121-.157) .253 (.209-.308) .353 (.286-.453) 1117

03-04 .069 (.060-.078) .063 (.057-.071) .116 (.104-.133) .199 (.167-.237) .299 (.222-.439) 1074
 238 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

blood, urine, and hair (Bachthaler et al., 2004). Urinary 

tungsten levels in many patients were hundreds-fold higher 

than observed in this Report.

Finding a measurable amount of tungsten in the urine does 

not mean that the level of tungsten causes an adverse health 

effect. Biomonitoring studies on levels of tungsten provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels of tungsten than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Bachthaler M, Lenhart M, Paetzel C, Feuerbach S, Link J, 

Manke C. Corrosion of tungsten coils after peripheral vascular 

embolization therapy: influence on outcome and tungsten load. 

Catheter Cardiovasc Interv 2004;62:380-384.

Centers for Disease Control and Prevention. National Center 

for Environmental Health. Cancer Clusters. Churchill County 

(Fallon). Nevada Exposure Asssessment. [online] 2003. Available 

at URL: http://www.cdc.gov/nceh/clusters/Fallon/study.htm. 

4/15/09

Centers for Disease Control and Prevention. Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Kraus T, Schramel P, Schaller KH, Zobelein P, Weber A, Angerer 

J. Exposure assessment in the hard metal manufacturing industry 

with special regard to tungsten and its compounds. Occup Environ 

Med 2001;58(10):631-634.

Nicolaou G, Pietra R, Sabioni E, Mosconi G, Cassina G, Seghizzi 

P. Multielement determination of metals in biological specimens 

of hard-metal workers: a study carried out by neutron activation 

analysis. J Trace Elem Electrolytes Health Dis 1987;(2):73-77.

Paschal DC, Ting BG, Morrow JC, Pirkle JL, Jackson RJ, 

Sampson EJ, et al. Trace metals in urine of United States residents: 

reference range concentrations. Environ Res 1998;76(1):53-59.

Schramel P, Wendler I, Angerer J. The determination of metals 

(antimony, bismuth, lead, cadmium, mercury, palladium, 

platinum, tellurium, thallium, tin and tungsten) in urine samples 

by inductively coupled plasma-mass spectrometry. Int Arch 

Occup Environ Health 1997;69(3):219-223.
Fourth National Report on Human Exposure to Environmental Chemicals 239

 Metals

Uranium

CAS No. 7440-61-1

General Information

Uranium is a silver-white metal that is extremely dense 

and weakly radioactive. It usually occurs as an oxide and 

is extracted from ores containing less than 1% natural 

uranium. Natural uranium is a mixture of three isotopes: 

238U (greater than 99%), 235U (about 0.72%), and 234U. 

Uranium has many commercial uses, including nuclear 

weapons, nuclear fuel, in some ceramics, and as an aid in 

electron microscopy and photography. Depleted uranium 

(DU) refers to uranium in which the proportions of 235U 

and 234U isotopes have been reduced compared with the 

proportion in natural uranium. Since the 1990’s, DU has 

been used by the military in armor-piercing ammunition 

and as a component of protective armor for tanks.

Variable concentrations of uranium occur naturally in 

drinking water sources. Thus, the primary exposure 

sources for nonoccupationally exposed persons are 

dietary (especially root vegetables) and drinking water. 

In workplaces that involve uranium mining, milling, or 

processing, human exposure occurs primarily by inhaling 

dust and other small particles. Exposure to DU may occur 

in military personnel from retention internal shrapnel that 

contains DU or exposure to dust generated from ammunition 

Urinary Uranium 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .008 (.007-.009) .007 (.006-.008) .013 (.010-.017) .027 (.021-.038) .046 (.037-.056) 2464

01-02 .009 (.007-.010) .008 (.007-.009) .014 (.012-.018) .030 (.023-.039) .046 (.034-.062) 2690

03-04 .008 (.007-.008) .007 (.006-.007) .011 (.010-.013) .021 (.017-.026) .031 (.026-.037) 2557

Age group 

6-11 years 99-00 .009 (.007-.011) .007 (.006-.009) .013 (.009-.022) .032 (.019-.048) .048 (.033-.066) 340

01-02 .008 (.007-.010) .008 (.006-.010) .014 (.010-.020) .026 (.020-.036) .040 (.025-.049) 368

03-04 .008 (.007-.009) .007 (.006-.009) .012 (.009-.016) .020 (.016-.026) .028 (.020-.039) 289

12-19 years 99-00 .009 (.008-.011) .009 (.008-.010) .015 (.012-.018) .026 (.020-.043) .044 (.028-.072) 719

01-02 .010 (.008-.012) .010 (.008-.012) .017 (.013-.023) .030 (.022-.042) .042 (.027-.088) 762

03-04 .010 (.009-.011) .009 (.008-.010) .015 (.012-.018) .028 (.023-.036) .038 (.036-.053) 725

20 years and older 99-00 .008 (.006-.009) .007 (.005-.008) .013 (.010-.017) .027 (.021-.040) .046 (.036-.056) 1405

01-02 .009 (.007-.010) .008 (.007-.009) .014 (.012-.017) .031 (.022-.040) .046 (.034-.065) 1560

03-04 * .006 (.005-.007) .011 (.009-.012) .019 (.016-.026) .029 (.024-.038) 1543

Gender 

Males 99-00 .009 (.008-.011) .008 (.007-.010) .015 (.012-.021) .036 (.024-.046) .053 (.040-.067) 1227

01-02 .009 (.008-.011) .009 (.007-.010) .015 (.013-.021) .033 (.024-.045) .047 (.035-.065) 1335

03-04 .008 (.007-.009) .007 (.006-.008) .013 (.011-.016) .023 (.019-.027) .031 (.027-.035) 1280

Females 99-00 .007 (.006-.008) .006 (.005-.007) .012 (.009-.015) .023 (.016-.033) .036 (.026-.050) 1237

01-02 .008 (.007-.010) .008 (.006-.009) .014 (.011-.017) .027 (.019-.037) .041 (.029-.063) 1355

03-04 * .006 (.005-.007) .010 (.009-.011) .018 (.013-.027) .031 (.022-.039) 1277

Race/ethnicity 

Mexican Americans 99-00 .017 (.012-.023) .016 (.011-.021) .033 (.020-.054) .060 (.040-.127) .114 (.054-.279) 883

01-02 .013 (.010-.016) .012 (.009-.016) .022 (.017-.030) .040 (.031-.054) .055 (.046-.069) 683

03-04 .014 (.011-.017) .013 (.009-.018) .024 (.017-.034) .041 (.028-.073) .064 (.039-.158) 618

Non-Hispanic blacks 99-00 .009 (.007-.011) .008 (.006-.010) .014 (.010-.020) .028 (.018-.049) .052 (.030-.067) 568

01-02 .008 (.007-.009) .008 (.007-.009) .012 (.011-.015) .021 (.017-.027) .030 (.023-.037) 667

03-04 .008 (.008-.009) .007 (.007-.008) .012 (.011-.013) .021 (.017-.027) .031 (.023-.045) 722

Non-Hispanic whites 99-00 .007 (.006-.009) .007 (.006-.007) .012 (.009-.016) .023 (.017-.037) .043 (.027-.051) 822

01-02 .008 (.007-.009) .007 (.006-.009) .013 (.011-.016) .026 (.019-.035) .037 (.029-.050) 1132

03-04 * .006 (.005-.007) .010 (.009-.012) .018 (.015-.023) .027 (.020-.036) 1074

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.004, 0.004, and 0.005, respectively. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 240 Fourth National Report on Human Exposure to Environmental Chemicals 

Metals

impact.

Soluble forms of uranium salts are poorly absorbed in 

the gastrointestinal tract. Depending upon the specific 

compound and solubility, 0.1%-6% of an ingested dose 

may be absorbed. Inhaled uranium-containing particles are 

retained in the lungs, where limited absorption occurs (less 

than 5%). In cases of retained DU shrapnel, the shrapnel 

acts as a source of chronic, low level exposure. After long 

term or repeated exposure, kidneys, liver, and bones can 

accumulate uranium with the largest amounts being stored 

in bones (Li et al., 2005). Uranium is eliminated in feces 

and urine; about 50% of the absorbed dose is eliminated in 

the urine within the first 24 hours. After exposure to soluble 

uranium salts, the initial half-life of uranium is about 15 days 

(Bhattacharyya et al., 1992), which represents distribution 

and excretion, with much slower elimination from bone. 

After inhalation, the half-life of insoluble uranium in the 

lungs is several years (Durakovic et al., 2003).

Human health effects from uranium at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Radiation risks from exposure to 

natural uranium are very low. Health effects from uranium 

exposure result from chemical toxicity to the kidney, which 

can occur occasionally from high occupational exposure. 

Studies of persons with chronic exposure to soluble 

uranium salts in drinking water have not shown kidney 

Urinary Uranium (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 .007 (.006-.009) .007 (.006-.009) .013 (.010-.016) .024 (.019-.030) .034 (.027-.053) 2464

01-02 .008 (.007-.010) .007 (.006-.009) .014 (.011-.018) .026 (.020-.034) .040 (.028-.058) 2689

03-04 .008 (.007-.008) .007 (.006-.008) .012 (.010-.014) .021 (.017-.025) .029 (.023-.039) 2557

Age group 

6-11 years 99-00 .009 (.007-.012) .008 (.006-.011) .015 (.010-.024) .030 (.016-.044) .037 (.030-.077) 340

01-02 .010 (.008-.011) .010 (.008-.012) .015 (.013-.019) .027 (.018-.032) .033 (.027-.048) 368

03-04 .009 (.008-.010) .008 (.007-.010) .013 (.011-.017) .024 (.016-.039) .033 (.022-.050) 289

12-19 years 99-00 .007 (.006-.008) .006 (.005-.008) .010 (.009-.014) .020 (.014-.030) .030 (.019-.074) 719

01-02 .007 (.006-.008) .007 (.006-.008) .012 (.009-.016) .020 (.015-.026) .026 (.020-.042) 762

03-04 .007 (.006-.008) .006 (.005-.007) .010 (.008-.013) .019 (.015-.027) .034 (.022-.041) 725

20 years and older 99-00 .007 (.006-.009) .007 (.006-.009) .013 (.010-.016) .024 (.019-.029) .034 (.025-.051) 1405

01-02 .008 (.007-.010) .007 (.006-.009) .014 (.011-.019) .027 (.020-.039) .043 (.030-.063) 1559

03-04 * .007 (.006-.008) .012 (.010-.014) .020 (.017-.024) .028 (.022-.038) 1543

Gender 

Males 99-00 .007 (.006-.009) .006 (.005-.008) .011 (.009-.015) .021 (.017-.028) .035 (.024-.056) 1227

01-02 .007 (.006-.008) .007 (.006-.008) .012 (.010-.015) .022 (.018-.028) .033 (.025-.047) 1334

03-04 .007 (.006-.008) .006 (.006-.007) .010 (.009-.012) .019 (.015-.024) .026 (.019-.039) 1280

Females 99-00 .008 (.007-.010) .007 (.006-.010) .013 (.010-.017) .025 (.019-.033) .034 (.027-.054) 1237

01-02 .009 (.008-.011) .009 (.007-.011) .016 (.012-.021) .029 (.021-.042) .045 (.031-.067) 1355

03-04 * .008 (.007-.009) .013 (.011-.016) .022 (.018-.028) .031 (.025-.041) 1277

Race/ethnicity 

Mexican Americans 99-00 .015 (.011-.022) .015 (.011-.020) .029 (.016-.058) .059 (.027-.146) .100 (.042-.270) 883

01-02 .012 (.010-.016) .012 (.009-.016) .021 (.015-.028) .033 (.024-.053) .050 (.034-.080) 682

03-04 .013 (.010-.016) .013 (.009-.017) .022 (.016-.029) .035 (.026-.051) .051 (.034-.061) 618

Non-Hispanic blacks 99-00 .006 (.004-.007) .005 (.004-.006) .008 (.006-.013) .017 (.011-.029) .028 (.018-.048) 568

01-02 .005 (.005-.006) .005 (.005-.006) .008 (.007-.010) .013 (.011-.014) .017 (.014-.029) 667

03-04 .006 (.005-.006) .005 (.005-.006) .009 (.008-.009) .013 (.012-.015) .018 (.014-.024) 722

Non-Hispanic whites 99-00 .007 (.006-.009) .007 (.006-.009) .012 (.010-.015) .021 (.017-.027) .030 (.024-.050) 822

01-02 .008 (.007-.009) .007 (.006-.009) .013 (.011-.016) .025 (.018-.032) .034 (.025-.051) 1132

03-04 * .007 (.006-.008) .011 (.010-.013) .019 (.015-.024) .027 (.020-.040) 1074

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 241

 Metals

injury associated with elevated urinary uranium levels 

(Kurttio et al., 2006; McDiarmid et al., 2006). IARC and 

NTP have no ratings for uranium human carcinogenicity.

Workplace air standards and guidelines for external 

exposure to soluble and insoluble uranium compounds 

have been established by OSHA and ACGIH, respectively. 

Drinking water and other environmental standards have 

been established by U.S. EPA. Information about external 

exposure (i.e., environmental levels) and health effects 

is available from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html.

Biomonitoring Information

Levels of urinary uranium reflect recent and accumulated 

exposure. A previous nonrandom subsample from NHANES 

III (n = 499) (Ting et al., 1999) and other small populations 

have shown urinary concentrations that are similar to those 

in NHANES 1999-2000, 2001-2002, and 2003-2004 (Dang 

et al.,1992; Galletti, 2003; Karpas et al.,1996; Tolmachev et 

al., 2006). Older studies have demonstrated urinary uranium 

concentrations that are consistent with levels in the U.S. 

population, in that the levels were below their respective 

detection limits (Byrne et al., 1991; Hamilton et al., 1994; 

Komaromy-Hiller et al., 2000). In a study of 105 persons 

exposed to natural uranium in well water, urinary levels of 

uranium were as high as 9.55 μg/L (median 0.162 μg/L) 

(Orloff et al., 2004). Eighty-five percent of those levels 

were above the 95th percentile of the NHANES 1999-2000 

population. In two studies of a Finnish population with high 

natural uranium concentrations in their drinking water, the 

median urinary concentration was 0.078 μg/L (ranging up to 

5.65 μg/L), and no consistent effects on multiple endpoints 

of kidney function were found. (Kurttio et al., 2002, 2006). 

The U.S. Nuclear Regulatory Commission (NRC) has 

set an action level of 15 μg/L urinary uranium to protect 

people who are occupationally exposed (U.S. NRC, 1978). 

Recent studies of veterans have been conducted to examine 

concerns about DU exposure during military conflicts. A 

cohort of 46 U.S. soldiers evaluated before, during, and 

after deployment had geometric mean urinary uranium 

concentrations that were less than the NHANES 1999-2000 

and 2001-2002 geometric means at all three time periods, 

although slightly increased during and after deployment, 

(May et al., 2004). In 17 U.S. soldiers who had been injured 

and had embedded DU shrapnel for as long as eight years, 

the median urinary uranium concentration was 2.61 μg/g 

creatinine. In the same study, 28 soldiers who may have 

been exposed to DU by inhalation, ingestion, or wound 

contamination, but in whom no shrapnel was embedded, 

had a mean urinary uranium concentration of 0.066 μg/g 

creatinine (Gwiazda et al., 2004). In a much larger study 

of 446 Gulf War veterans who were concerned about past 

exposure to DU, the geometric mean urinary uranium 

concentration was 0.011 μg/L (McDiarmid et al., 2004). 

Follow up of 32 veterans with embedded shrapnel showed 

that increased urinary uranium levels persisted more 

than 12 years after the first exposure (McDiarmid et al., 

2006). Six workers in a depleted uranium program showed 

concentrations of 0.110 to 45 μg/L (Ejnik et al., 2000). 

Urinary uranium measurements in 103 Canadian military 

personnel showed mean urinary levels slightly less than 

geometric mean in this Report (Ough et al., 2002).

Finding a measurable amount of uranium in urine does not 

mean that the level of uranium causes an adverse health 

effect. Biomonitoring studies on levels of uranium provide 

physicians and public health officials with reference values 

so that they can determine whether people have been 

exposed to higher levels of uranium than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

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BA, Stradling GN, Volf V. Guidebook for the treatment of 

accidental internal radionuclide contamination of workers. In: 

Gerber GB, Thomas RG, eds. Radiation protection dosimetry. 

Vol. 41 (1). Kent (England): Nuclear Technology Publishing; 

1992. pp. 1-49.

Byrne AR, Benedik L. Uranium content of blood, urine and hair of 

exposed and non-exposed persons determined by radiochemical 

neutron activation analysis, with emphasis on quality control. Sci 

Total Environ 1991;107:143-157.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Dang HS, Pullat VR, Pillai KC. Determining the normal 

concentration of uranium in urine and application of the data to 

its biokinetics. Health Phys 1992;62:562-566.

Durakovic A, Horan P, Dietz LA, Zimmerman I. Estimate of the 

time zero lung burden of depleted uranium in Persian Gulf War 

veterans by the 24-hour urinary excretion and exponential decay 

analysis. Mil Med 2003;168(8):600-605.

Ejnik JW, Carmichael AJ, Hamilton MM, McDiarmid M, Squibb 

K, Boyd P, et al. Determination of the isotopic composition 

of uranium in urine by inductively coupled plasma mass 

spectrometry. Health Phys 2000;78:143-146.
 242 Fourth National Report on Human Exposure to Environmental Chemicals 

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Galletti M, D’Annibale L, Pinto V, Cremisini C. Uranium daily 

intake and urinary excretion: a preliminary study in Italy. Health 

Phys 2003;85:228-235.

Gwiazda RH, Squibb K, McDiarmid M, Smith D. Detection of 

depleted uranium in urine of veterans from the 1991 Gulf War. 

Health Phys 2004;86:12-18.

Hamilton EI, Sabbioni E, Van der Venne MT. Element reference 

values in tissues from inhabitants of the European community. 

VI. Review of elements in blood, plasma and urine and a 

critical evaluation of reference values for the United Kingdom 

population. Sci Total Environ 1994;158:165-190.

Karpas Z, Halicz L, Roiz J, Marko R, Katorza E, Lorber A, et 

al. Inductively coupled plasma mass spectrometry as a simple, 

rapid, and inexpensive method for determination of uranium 

in urine and fresh water: comparison with LIF. Health Phys 

1996;71(6):879-85.

Komaromy-Hiller G, Ash KO, Costa R, Howerton K. Comparison 

of representative ranges based on U.S. patient population and 

literature reference intervals for urinary trace elements. Clin 

Chim Acta 2000;296(1-2):71-90.

Kurttio P, Auvinen A, Salonen L, Saha H, Pekkanen J, Makelainen 

I, et al. Renal effects of uranium in drinking water. Environ Health 

Perspect 2002;110(4):337-342.

Kurttio P, Harmionen A, Saha H, Salonen L, Karpas Z, 

Komulainen H, Auvinen A. Kidney toxicity of ingested uranium 

from drinking water. Am J Kidney Dis 2006;47(6):972-982.

Li WB, Roth P, Wahl W, Oeh U, Hollriegl V, Paretzke HG. 

Biokinetic modeling of uranium in man after injection and 

ingestion. Radiat Environ Biophys 2005;44:29-40.

May LM, Heller J, Kalinsky V, Ejnik J, Cordero S, Oberbroekling 

KJ, et al. Military deployment human exposure assessment: urine 

total and isotopic uranium sampling results. J Toxicol Environ 

Health A 2004;67(8-10):697-714.

McDiarmid MA, Squibb K, Engelhardt SM. Biologic monitoring 

for urinary uranium in Gulf War I veterans. Health Phys 

2004;87:51-56.

McDiarmid MA, Englehardt SA, Oliver M, Gucer P, Wilson PD, 

Kane R, et al. Biological monitoring and surveillance results of 

Gulf War I veterans exposed to depleted uranium. Int Arch Occup 

Environ Health 2006;79(1):11-21.

Orloff KG, Mistry K, Charp P, Metcalf S, Marino R, Shelly T, 

et al. Human exposure to uranium in groundwater. Environ Res 

2004;94:319-326.

Ough EA, Lewis BM, Andrews WS, Bennett LG, Hancock RG, 

Scott K. An examination of uranium levels in Canadian forces 

personnel who served in the Gulf War and Kosovo. Health Phys 

2002;82(4): 527-532.

Ting BG, Paschal DC, Jarrett JM, Pirkle JL, Jackson RJ, Sampson 

EJ, et al. Uranium and thorium in urine of United States residents: 

reference range concentrations. Environ Res 1999;81:45-51.

Tolmachev S, Kuwabara J, Noguchi H. concentration and 

daily excretion of uranium in urine of Japanese. Health Phys 

2006;91(2):144-153.

U.S. Nuclear Regulatory Commission (U.S. NRC). U.S. Nuclear 

Regulatory Commission (NRC) Guide 8.22–Bioassay at uranium 

mills. Washington (DC): NRC; July 1978.
Fourth National Report on Human Exposure to Environmental Chemicals 243

 Perchlorate 

Perchlorate

CAS No. 7601-90-3

General Information

Perchlorate is an inorganic chemical containing one chlorine 

and four oxygen atoms. It is normally found and produced 

as the anion of a sodium, potassium, or ammonium salt. 

Perchlorate is stable under most environmental and 

physiological conditions, but has strong oxidant properties 

in the presence of concentrated acids, certain catalytic 

metals, and reducing agents. The ammonium salt of the 

perchlorate ion has been manufactured in the military 

defense and aerospace industries primarily for use as an 

oxidizer in solid propellant systems for rockets and missiles. 

Other manufactured uses include fireworks, matches, and 

limited applications in pharmaceutics, laboratory analysis, 

leather tanning, fabric dyeing, and electroplating. In 

addition, small amounts of perchlorate can form naturally 

in the atmosphere (Dasgupta et al., 2006) and accumulate 

in nitrate-rich mineral deposits mined for use in fertilizers 

(Urbansky, 2002).

Perchlorate was added to the U.S. EPA’s Contaminant 

Candidate List (CCL) for drinking water in 1998 following 

discoveries of its presence in drinking water supplies 

throughout the southwestern United States (U.S.EPA, 

1998). Perchlorate has been characterized as a mobile and 

persistent ground and surface water contaminant. Drinking 

water, milk, and certain plants with high water content 

(e.g., lettuce) can be the main sources of intake for humans 

(FDA, 2007). Perchlorate is excreted unchanged from the 

human body with an estimated elimination half-life of about 

7.5 hours and has a small estimated volume of distribution 

(Crump and Gibbs, 2005).

Animal and human studies have shown that perchlorate 

can inhibit thyroid hormone production (NAS, 2005). 

Large doses of perchlorate have been used as a medicine to 

treat hyperthyroidism and to diagnose disorders related to 

thyroid or iodine metabolism. Inhibition of iodine uptake by 

competition for the sodium/iodide symporter in the thyroid 

can be estimated in humans by measuring radioiodine uptake 

Urinary Perchlorate 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 3.54 (3.29-3.81) 3.70 (3.50-4.00) 6.30 (5.80-6.90) 10.0 (9.10-11.0) 14.0 (11.0-17.0) 2820

03-04 3.22 (2.93-3.55) 3.30 (2.90-3.80) 5.50 (5.00-6.40) 9.50 (8.40-11.0) 13.0 (12.0-15.0) 2522

Age group 

6-11 years 01-02 4.93 (4.22-5.76) 5.20 (4.40-6.40) 8.10 (6.90-9.80) 12.0 (9.30-19.0) 19.0 (12.0-23.0) 374

03-04 4.32 (3.67-5.09) 4.60 (4.00-5.20) 7.90 (5.70-9.50) 13.0 (8.81-16.0) 16.0 (11.0-29.0) 314

12-19 years 01-02 3.80 (3.44-4.20) 4.40 (3.80-4.80) 6.80 (6.30-7.30) 10.0 (8.90-11.0) 13.0 (11.0-17.0) 828

03-04 3.62 (3.19-4.12) 3.80 (3.20-4.40) 6.40 (5.50-7.10) 9.80 (7.90-12.0) 13.0 (10.0-18.0) 721

20 years and older 01-02 3.35 (3.08-3.65) 3.50 (3.20-3.70) 5.90 (5.30-6.60) 10.0 (8.70-11.0) 13.0 (11.0-17.0) 1618

03-04 3.05 (2.75-3.38) 3.20 (2.70-3.60) 5.20 (4.70-6.10) 9.10 (7.90-10.0) 12.0 (11.0-14.0) 1487

Gender 

Males 01-02 4.19 (3.93-4.46) 4.40 (4.20-4.60) 7.10 (6.40-7.90) 11.0 (9.70-12.0) 14.0 (11.0-19.0) 1335

03-04 3.75 (3.39-4.16) 3.90 (3.40-4.40) 6.40 (5.60-7.50) 11.0 (9.20-12.0) 14.0 (13.0-17.0) 1229

Females 01-02 3.01 (2.74-3.31) 3.10 (2.70-3.40) 5.40 (5.00-6.00) 9.20 (8.20-11.0) 13.0 (11.0-17.0) 1485

03-04 2.79 (2.49-3.11) 2.90 (2.50-3.20) 4.90 (4.40-5.50) 8.20 (6.90-9.84) 11.0 (8.80-15.0) 1293

Race/ethnicity 

Mexican Americans 01-02 4.02 (3.47-4.66) 4.40 (3.70-5.00) 7.10 (5.80-8.40) 12.0 (9.40-13.0) 14.0 (12.0-18.0) 708

03-04 3.76 (3.45-4.11) 3.96 (3.50-4.40) 6.20 (5.30-7.50) 11.0 (9.10-12.0) 15.0 (12.0-17.0) 617

Non-Hispanic blacks 01-02 3.51 (3.07-4.03) 3.70 (3.10-4.10) 5.90 (5.10-7.00) 9.20 (7.80-12.0) 15.0 (11.0-20.0) 681

03-04 3.21 (2.90-3.56) 3.20 (2.87-3.50) 5.40 (4.60-6.30) 8.60 (7.50-11.0) 13.0 (9.30-17.0) 652

Non-Hispanic whites 01-02 3.51 (3.18-3.88) 3.70 (3.40-4.10) 6.30 (5.70-7.10) 10.0 (8.90-11.0) 14.0 (11.0-18.0) 1228

03-04 3.26 (2.89-3.68) 3.30 (2.80-4.00) 5.60 (4.90-6.80) 9.40 (8.10-11.0) 13.0 (11.0-15.0) 1092

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.05 and 0.05. 

2001-2002 performed on surplus samples (variable unavailable of NHANES website) 
 244 Fourth National Report on Human Exposure to Environmental Chemicals 

Perchlorate

inhibition (RUI). Short term human studies of the effect 

of perchlorate on RUI have been used for risk estimation 

(Greer et al., 2002; Lawrence et al. 2001, 2002; NAS, 2005; 

U.S.EPA, 2005). In these small short-term experimental 

studies on males and studies of male perchlorate workers 

with doses or estimated exposures thousands-fold higher 

than known environmental exposures, up to 68% RUI has 

been demonstrated, but without effects on serum levels of 

thyroid stimulating hormone or thyroxine (Braverman et 

al., 2005; Greer et al., 2002). However, in a representative 

sample of U.S. women with urinary levels of iodine less 

than 100 micrograms per day, urinary perchlorate at 

environmental exposure levels were inversely associated 

with thyroxine levels and positively associated with levels 

of thyroid stimulating hormone (Blount et al., 2006; 

Steinmaus et al., 2007).

During gestation and infancy, it is known that maternal and 

congenital hypothyroidism adversely effects neurological 

development and decreases learning capability. In the U.S., 

congenital hypothyroidism is a condition for which nearly 

all newborn blood is screened. Ecologic studies from 

screening programs with elevated perchlorate in the regional 

drinking water have indicated no increased prevalence of 

abnormal neonatal screening tests for this disorder in these 

regions (Kelsh et al., 2003; Lamm and Doemland, 1999; 

Li et al., 2000). Also, altered thyroid function was not 

found in Chilean pregnant women or their newborns with 

mean urinary perchlorate levels about 40-fold higher than 

average U.S. levels, although iodine intake was higher than 

U.S. levels and sufficient in most participants (Tellez et al., 

2005). Many factors may be important in consideration 

of perchlorate action on the thyroid: dose; dietary iodine 

intake; gender; age; menopausal status; chronicity of 

exposure; and the presence of other substances known 

to affect thyroid function (e.g., nitrate, thiocyanate, 

medications).

Though it produces follicular cell thyroid tumors in animal 

studies at goitrogenic doses, perchlorate is negative in 

most genotoxic assays (U.S.EPA, 2005), suggesting its 

tumorgenic effect is a result of a chronic increase in thyroid 

stimulating hormone indirectly resulting from iodine 

uptake inhibition. Follicular cell thyroid tumors would 

Urinary Perchlorate (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 3.56 (3.34-3.80) 3.39 (3.18-3.66) 5.61 (5.29-6.00) 9.36 (8.19-10.3) 12.7 (11.0-14.3) 2818

03-04 3.14 (2.89-3.41) 3.00 (2.80-3.30) 4.90 (4.50-5.30) 8.40 (7.20-9.50) 12.0 (11.0-14.0) 2504

Age group 

6-11 years 01-02 5.71 (5.22-6.25) 5.83 (5.19-6.25) 8.33 (7.41-9.74) 13.1 (11.1-16.0) 17.5 (13.1-22.6) 374

03-04 5.24 (4.61-5.96) 5.10 (4.70-5.50) 7.20 (6.40-10.0) 13.0 (8.90-20.0) 20.0 (11.0-44.0) 313

12-19 years 01-02 2.95 (2.64-3.29) 2.89 (2.56-3.39) 4.50 (3.97-5.26) 7.12 (6.60-8.10) 9.87 (7.46-13.4) 827

03-04 2.70 (2.45-2.98) 2.70 (2.50-3.00) 4.20 (3.70-4.50) 6.30 (5.10-7.50) 8.00 (6.90-11.0) 715

20 years and older 01-02 3.46 (3.20-3.73) 3.26 (3.04-3.58) 5.37 (4.93-5.91) 9.09 (7.61-10.2) 12.3 (10.1-14.3) 1617

03-04 3.03 (2.76-3.32) 2.90 (2.60-3.20) 4.70 (4.30-5.10) 8.10 (6.90-9.40) 11.0 (9.60-15.0) 1476

Gender 

Males 01-02 3.40 (3.20-3.60) 3.25 (3.04-3.47) 5.35 (4.93-5.86) 8.80 (7.52-9.87) 11.4 (10.1-13.0) 1335

03-04 3.07 (2.81-3.35) 2.90 (2.70-3.20) 4.80 (4.30-5.30) 7.30 (6.50-9.70) 12.0 (9.70-15.0) 1220

Females 01-02 3.72 (3.39-4.09) 3.60 (3.20-4.10) 5.99 (5.33-6.67) 10.0 (8.15-12.1) 13.4 (11.4-16.0) 1483

03-04 3.21 (2.87-3.59) 3.10 (2.80-3.40) 5.00 (4.60-5.60) 8.90 (7.00-11.0) 12.0 (9.90-15.0) 1284

Race/ethnicity 

Mexican Americans 01-02 3.77 (3.22-4.40) 3.51 (3.02-4.44) 6.05 (4.93-7.64) 10.4 (8.37-13.0) 14.4 (11.6-17.4) 708

03-04 3.42 (3.16-3.70) 3.30 (3.00-3.50) 5.40 (4.60-6.10) 9.20 (7.60-11.0) 13.0 (11.0-19.0) 616

Non-Hispanic blacks 01-02 2.53 (2.24-2.87) 2.54 (2.12-2.84) 4.08 (3.51-4.93) 6.87 (5.93-8.43) 10.1 (8.33-12.2) 680

03-04 2.22 (2.00-2.45) 2.10 (1.90-2.30) 3.40 (3.10-3.90) 6.20 (4.60-8.00) 8.50 (6.60-11.0) 648

Non-Hispanic whites 01-02 3.76 (3.46-4.08) 3.54 (3.22-4.02) 5.82 (5.44-6.25) 9.52 (8.30-10.5) 12.8 (11.3-14.6) 1227

03-04 3.35 (2.99-3.75) 3.20 (2.90-3.50) 5.10 (4.60-5.60) 8.80 (7.20-10.0) 12.0 (10.0-17.0) 1080

2001-2002 performed on surplus samples (variable unavailable of NHANES website) 
Fourth National Report on Human Exposure to Environmental Chemicals 245

 Perchlorate 

be unlikely to occur without overt perturbation of thyroid 

homeostasis. Additional information about exposure and 

health effects is available from the U.S.EPA at: http://www.

epa.gov/safewater/ccl/perchlorate/perchlorate.html and 

from ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Urinary perchlorate levels reflect recent exposure. Blount 

et al. (2007) analyzed a subsample of NHANES 2001-2002 

which demonstrated detectable perchlorate in all urinary 

samples and showed slightly higher levels in children as 

compared to adults. When these NHANES 2001-2002 

urinary levels of perchlorate are used to calculate daily 

oral intakes for the U.S. population, most of the population 

is considered to be below the U.S. EPA reference dose 

(Blount et al., 2007). The levels seen in NHANES 2003-

2004 show a similar pattern to NHANES 2001-2002. 

Compared to a previous study of pregnant women in three 

Chilean communities with varying perchlorate levels in 

the drinking water, the women in the community with the 

highest drinking water levels had mean urinary perchlorate 

levels about 40 times greater than the geometric mean 

for participants in NHANES 2001-2002 aged 20 years 

and older (Tellez et al., 2005). Also, the 95th percentile of 

NHANES 2001-2002 participants aged 20 years and older 

have urinary perchlorate levels that are several thousand 

times less than urinary levels measured during occupational 

exposure of perchlorate workers (Braverman et al., 2005).

Finding a measurable amount of perchlorate in urine does 

not mean that the level of perchlorate causes an adverse 

health effect. Biomonitoring studies of urinary perchlorate 

provide physicians and public health officials with 

reference values so that they can determine whether or not 

people have been exposed to higher levels of perchlorate 

than levels found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

References 

Blount BC, Pirkle JL, Osterloh JD, Valentin-Blasini L, Caldwell 

KL. Urinary perchlorate and thyroid hormone levels in adolescent 

and adult men and women living in the United States. Environ 

Health Perspect 2006;114(12):1865-1871.

Blount BC, Valentin-Blasini L, Osterloh JD, Mauldin JP, Pirkle 

JL. Perchlorate Exposure of the US Population, 2001-2002. J 

Expo Sci Environ Epidemiol 2007;17(4):400-407.

Braverman LE, He X, Pino S, Cross M, Magnani B, Lamm SH, 

et al. The effect of perchlorate, thiocyanate, and nitrate on thyroid 

function in workers exposed to perchlorate long-term. J Clin 

Endocrinol Metab 2005;90(2):700-706.

Crump KS, Gibbs JP. Benchmark calculations for perchlorate from 

three human cohorts. Environ Health Perspect 2005;113(8):1001-

1008.

Dasgupta PK, Dyke JV, Kirk AB, Jackson WA. Perchlorate in 

the United States. Analysis of relative source contributions to the 

food chain. Environ Sci Technol 2006;40(21):6608-6614.

Food and Drug Administration (FDA). CFSAN/Office of Plant 

& Dairy Foods. Preliminary Estimation of Perchlorate Dietary 

Exposure Based on FDA 2004/2005 Exploratory Data. May 

2007. Available at URL: http://www.fda.gov/Food/FoodSafety/

FoodContaminantsAdulteration/ChemicalContaminants/

Perchlorate/ucm077653.htm. Page Last Updated: 05/28/2009. 

6/2/09

Greer MA, Goodman G, Pleus RC, Greer SE. Health effects 

assessment for environmental perchlorate contamination: the 

dose response for inhibition of thyroidal radioiodine uptake in 

humans. Environ Health Perspect 2002;110(9):927-937. Erratum 

in: Environ Health Perspect 2005;113(11):A732.

Kelsh MA, Buffler PA, Daaboul JJ, Rutherford GW, Lau EC, 

Barnard JC, et al. Primary congenital hypothyroidism, newborn 

thyroid function, and environmental perchlorate exposure among 

residents of a Southern California community. J Occup Environ 

Med 2003;45(10):1116-1127. Erratum in: J Occup Environ Med 

2004;46(5):509.

Lamm SH, Doemland M. Has perchlorate in drinking water 

increased the rate of congenital hypothyroidism? J Occup Environ 

Med 1999;41(5):409-411.

Lawrence J, Lamm S, Braverman LE. Low dose perchlorate (3 

mg daily) and thyroid function. Thyroid 2001;11(3):295.

Lawrence JE, Lamm SH, Pino S, Richman K, Braverman 

LE. The effect of short-term low-dose perchlorate on various 

aspects of thyroid function. Thyroid 2000;10(8):659-663. 

Li Z, Li FX, Byrd D, Deyhle GM, Sesser DE, Skeels MR, et 

al. Neonatal thyroxine level and perchlorate in drinking water. J 

Occup Environ Med 2000;42(2):200-205.

National Academy of Sciences (NAS). Health Implications of 

Perchlorate Ingestion. National Research Council of the National 

Academies. Washington (DC): National Academy Press; 2005.

Steinmaus C, Miller MD, Howd R. Impact of smoking and 

thiocyanate on perchlorate and thyroid hormone associations in 

the 2001-2002 national health and nutrition examination survey. 

Environ Health Perspect 2007;115(9):1333-1338.

Tellez RT, Chacon PM, Abarca CR, Blount BC, Landingham 

CB, Crump KS, et al. Long-term environmental exposure to 

perchlorate through drinking water and thyroid function during 
 246 Fourth National Report on Human Exposure to Environmental Chemicals 

Perchlorate

pregnancy and the neonatal period. Thyroid 2005;15(9):963-975. 

U.S. Environmental Protection Agency (U.S. EPA). Perchlorate. 

Integrated Risk Information System (IRIS). Revised 2/11/05. 

Available from URL: http://cfpub.epa.gov/iris/quickview.

cfm?substance_nmbr=1007.1/15/06

U.S. Environmental Protection Agency (U.S. EPA). Drinking 

Water Contaminant Candidate List. Doc. No. EPA/600/F-98/002 

Washington (DC). 1988.

Urbansky TF. Perchlorate as an environmental contaminant. 

Environ Sci Pollut Res Int 2002;9(3):187-192.
Fourth National Report on Human Exposure to Environmental Chemicals 247

 Perfluorochemicals 

Perfluorochemicals

General Information

The perfluorochemicals (PFCs) are molecules in which 

all bonds of the alkyl chain are carbon-fluorine bonds 

except for the terminal functional group. Discussed here 

are perfluoroalkyl acids, amides, and alcohols which are 

by-products, end products, or processing aids used in 

the synthesis of fluoropolymers. Fluoropolymers have 

applications in waterproofing and protective coatings 

of clothes, furniture, and other products; and also as 

constituents of floor polish, adhesives, fire retardant foam, 

and insulation of electrical wire. A major application of 

one important fluoropolymer, polytetrafluoroethylene, 

has been the heat-resistant non-stick coatings used on 

cooking ware and other protected surfaces. Because of 

their properties, fluoropolymer products are used in a 

wide range of industries including aerospace, automotive, 

building/construction, chemical processing, electrical and 

electronics, semiconductor, and textiles. There are many 

other fluorocarbon type chemicals which are not addressed 

here, such as perfluorochemical telomers, finalized 

perfluorochemical polymer products, chlorofluorocarbons 

and investigational blood substitutes.

Perfluorooctanoic acid (PFOA) has been manufactured 

since the 1950s, primarily as its ammonium salt, as a 

solubilization aid in the synthesis of polytetrafluoroethylene. 

PFOA is usually not a residual contaminant in non-stick 

surfaces made of polytetrafluoroethylene. Worldwide 

annual production of PFOA was estimated to be 260 metric 

tons in 1999 (Prevedouros et al., 2006). Production rates and 

emission rates have fallen since 2002 after conversion to a 

new synthesis process. Other perfluoroalkyl carboxylates 

of various chain lengths were also formed in the process 

used prior to 2002. However, current manufacturing 

practices reduce the formation of these by exclusively 

using fluorotelomers (Prevedouros et al., 2006).

Perfluorooctanesulfonyl fluoride (POSF) was synthesized 

as a polymerization starting material. POSF-based 

polymers have been used in a wide variety of products 

such as waterproofing, textiles, and fire protection. 

Other PFCs (including small amounts of PFOA) 

can also form as side-reaction by-products in the 

synthesis of POSF (e.g., perfluorooctane sulfonamide, 

PFOSA), or form as degradation products during its 

reaction to create the intermediate reacting monomers, 

N-methylperfluorooctanesulfonamidoethanol (MeFOSE) 

and N-ethylperfluorooctanesulfonamidoethanol (EtFOSE), 

or form in the final product (e.g., perfluorooctane 

sulfonate, PFOS) (Hekster et al., 2003; Olsen et al., 

2005; U.S. EPA, 2003). MeFOSE and EtFOSE have 

been used in food packaging and textile treatments, 

and their oxidation products, N-methylperfluorooctanesulfonamidoacetic acid (Me-PFOSA-AcOH) and 

N-ethylperfluorooctanesulfonamidoacetic acid (EtPFOSA-AcOH), respectively, may be markers of food or 

consumer exposures. In addition, several pathways (during 

manufacturing) can lead to formation of PFOS or other 

sulfonyl-containing PFCs as residual contaminants in the 

final polymer products. Perfluorohexane sulfonate (PFHxS) 

has also been used to synthesize the fluoropolymers 

used in firefighting foams and some carpet treatments. 

U.S. manufacture of POSF-based products began ending 

in about 2000. Global production that year for POSF 

materials was 3700 metric tons (Prevedouros et al., 2006). 

Perfluorononanoic acid (PFNA) was an impurity in the 

process that produces PFOS.

The PFCs have limited water solubility, low volatility (as 

salts or ionized) and can remain in the environment and 

bioconcentrate in animals (e.g., some fish bioconcentrate 

Perfluorinated Chemicals in this Report

Perfluorinated Compounds CAS number Abbreviation

Serum Perfluorobutane Sulfonic Acid PFBuS

Serum Perfluorodecanoic Acid 335-76-2 PFDeA

Serum Perfluorododecanoic Acid 307-55-1 PFDoA

Serum Perfluoroheptanoic Acid 375-85-9 PFHpA

Serum Perfluorohexane Sulfonic Acid 355-46-4 PFHxS

Serum Perfluorononanoic Acid 375-95-1 PFNA

Serum Perfluorooctanoic Acid 335-67-1 PFOA

Serum Perfluorooctane Sulfonic Acid 1763-23-1 PFOS

Serum Perfluorooctane Sulfonamide 754-91-6 PFOSA

Serum 2-(N -Ethyl-Perfluorooctane sulfonamido) Acetic Acid Et-PFOSA-AcOH

Serum 2-(N -Methyl-perfluorooctane sulfonamido) Acetic Acid Me-PFOSA-AcOH

Serum Perfluoroundecanoic Acid 2058-94-8 PFUA
 248 Fourth National Report on Human Exposure to Environmental Chemicals 

Perfluorochemicals 

PFOS greater than 2000-fold over aquatic levels). PFOS 

and PFOA levels in archived bird eggs from Sweden have 

increased thirtyfold from 1968 to 2003 (Holmstrom et al., 

2005). PFCs have been identified in surface coastal and 

ocean waters (Yamashita et al., 2005), in a wide variety 

of marine and land animals (Kannan et al., 2005; Keller 

et al., 2005; Taniyasu et al., 2003), and in human blood 

and semen (Calafat et al., 2006a; Guruge et al., 2005; 

Kannan et al., 2004; Olsen et al., 2003a and 2004a). In 

some cases, environmental breakdown products of the 

telomers used to make fluoropolymers or the metabolic 

products of fluorochemicals in the body can produce 

PFCs that are measured human blood. For instance, the 

8-2 telomer, heptadecafluoro-1-decanol, may metabolize 

or degrade to PFOA (Dinglasan et al., 2004). It is unclear 

if environmentally degraded telomer products are a major 

source of other PFCs.

All sources of human exposure are uncertain, but probably 

include dietary sources (Kannan et al., 2004; Prevedouros et 

al., 2006; Tittlemier et al., 2007). PFOA (and probably other 

perfluoroalkyl acids) exist in the anionic state at physiologic 

and environmental pHs and their distribution in the body is 

determined, in part, by high protein binding in plasma and 

other proteins. Unlike many organohalogen contaminant 

chemicals, the perfluoroalkyl acids (PFOA and PFOS) do 

not tend to accumulate in fat tissue, but still can have long 

residence times in the body. PFOA is mostly excreted in the 

urine in animal studies, but limited observations in humans 

suggest that only one-fifth of the total body clearance is 

renal (Harada et al., 2005). The elimination half-life of 

PFOA in humans is roughly estimated to be 3.5 years and 

for PFOS, approximately 4.8 years (Olsen et al., 2007a). 

Excepting PFOS and PFOA, there is limited information on 

the sources, environmental fate, human toxicokinetics, or 

effects of other PFCs. The PFCs often measured in human 

serum are listed in the table.

Human health effects from PFCs at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. The ammonium salt of PFOA has 

been tested at high doses in mammalian animal studies 

and produced altered weights of the liver, kidney, thymus 

and spleen; hepatotoxicity; endocrine and immune effects; 

and in offspring, growth retardation and delayed sexual 

maturation (Kennedy et al., 2004; Lau et al., 2004; U.S. 

EPA, 2003). Both PFOA and perfluorodecanoic acid have 

been shown to reduce androgen levels in laboratory animal 

studies (Biegel et al., 1995; Bookstaff et al., 1990). PFOA 

preparations used in many studies may also contain a small 

percentage of other chain length perfluoroalkyl acids (i.e., 

C5, C6, C7). The liver toxicity of several PFCs is evident 

by vacuolization and lipid accumulation in both rodent and 

monkey livers (Seacat et al., 2002; Lau et al., 2004) and may 

be attributable to the ability of PFCs to affect intracellular 

lipid binding proteins, peroxisomal proliferation, and 

β-oxidation of lipids (Kudo et al., 2000, 2003; Vanden 

Heuvel et al., 1993). Some of the effects in animals may 

be mediated through peroxisomal proliferation, including 

immunologic effects and tumor induction, but the relevance 

of peroxisomal pathways in humans is unclear (Kennedy et 

al., 2004). PFOA has been reported to cause liver, pancreas, 

Serum Perfluorobutane sulfonic acid (PFBuS) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD < LOD < LOD < LOD 2094 

Age group 

12-19 years 03-04 * < LOD < LOD < LOD < LOD 640

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1454 

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1053 

Females 03-04 * < LOD < LOD < LOD < LOD 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 485

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 538

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 249

 Perfluorochemicals 

and testicular tumors in high dose animal testing (Biegel 

et al., 2001; Cook et al., 1992; Kennedy et al., 2004). 

Effects on serum liver enzymes in limited observational 

studies of human occupational exposures are unclear. Two 

recent cross-sectional human studies observed a negative 

correlation of birth weight with serum levels of PFOA 

(Apelberg et al., 2007; Fei et al., 2007).

Due to marked intergender differences in the elimination 

of PFOA in rats and substantial differences in the half-life 

of PFOA in rats, monkeys, and humans, the potential to 

estimate risks to humans from animal doses is uncertain. 

However, animal and human serum PFOA levels have been 

compared: serum levels associated with toxic effects in 

animals are 66-11,108 times higher than background serum 

levels in humans (Butenoff et al., 2004; U.S. EPA, 2003). 

A study of workers chronically exposed to primarily PFOA 

showed no biochemical evidence of hepatotoxicity or 

hormonal changes (adrenal, reproductive, thyroidal), and 

there was no clear evidence of excess all-cause or diseasespecific mortality, or increased cancer rates (Alexander et 

al., 2003; Olsen et al., 1999; U.S. EPA, 2003).

Serum PFOS levels associated with toxicity in test 

animals were 310-1550 fold higher than 95 percent of 

the levels found in a study of adults (Olsen et al., 2003a,

2005). Animal studies of PFOS have demonstrated 

weight loss, hepatotoxicity, and changes in thyroid 

hormone concentrations (Grasty et al., 2003; Thibodeaux 

et al., 2003; Lau et al., 2004). At doses causing maternal 

toxicity, developmental and teratogenic effects were 

demonstrated in offspring. At high but non-toxic maternal 

doses of PFOS, development in offspring was stunted and 

hypothyroxinemia was observed. Late gestational exposure 

to PFOS in animal studies has also demonstrated early 

neonatal lethality, possibly related to lung immaturity (Lau 

et al., 2003). PFOA, PFOS, and other PFCs have not been 

classified as to human carcinogenicity by IARC or NTP.

Biomonitoring Information

Serum levels of PFCs (particularly PFOA and PFOS) tend 

to reflect cumulative exposure over several years. Twelve 

different PFCs were measured in the sera of NHANES 

2003-2004 participants. Roughly similar levels of PFCs in 

serum have also been measured previously in other samples 

of the U.S. population. In such studies, PFOS, PFOA, 

perfluorohexanesulfonate (PFHxS), and perfluorononanoic 

acid (PFNA) are detectable in a high percentage of the 

participants and PFOS levels are generally 3-10 times 

higher than PFOA levels (Calafat et al., 2007a, 2007b; 

Olsen et al., 2003a, 2005). Analysis of the NHANES 2003-

2004 subsample demonstrated higher levels of PFOA and 

PFOS in males and a slight increase in levels of PFOS with 

age (Calafat et al., 2007b). Slightly higher levels of PFOS 

and PFOA in males than females have been noted in several 

other studies (Calafat et al., 2007a; Harada et al., 2004; 

Olsen et al., 2003a). In comparing three separate reports on 

adults, elderly and children, the median PFCs values tend 

to be roughly similar in these age categories (Olsen et al., 

2003a, 2004a, 2004b), and no substantial age trends were 

seen within adults ages 20-69 (Olsen et al., 2003a).

Serum Perfluorodecanoic acid (PFDeA) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD .300 (<LOD-.500) .600 (.400-1.10) .900 (.500-1.80) 2094 

Age group 

12-19 years 03-04 * < LOD < LOD .500 (<LOD-1.00) .800 (.300-1.20) 640

20 years and older 03-04 * < LOD .400 (<LOD-.500) .700 (.400-1.00) .900 (.500-1.80) 1454 

Gender 

Males 03-04 * < LOD .400 (<LOD-.500) .800 (.400-1.40) 1.10 (.600-2.10) 1053 

Females 03-04 * < LOD .300 (<LOD-.400) .500 (.400-.800) .800 (.500-1.20) 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD .500 (.400-.500) .600 (.500-.800) 485

Non-Hispanic blacks 03-04 * < LOD .400 (<LOD-.700) .800 (.400-1.50) 1.00 (.500-3.10) 538

Non-Hispanic whites 03-04 * < LOD .300 (<LOD-.500) .600 (.400-1.00) .900 (.500-1.80) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.3. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 250 Fourth National Report on Human Exposure to Environmental Chemicals 

Perfluorochemicals 

In a study of 598 blood donors aged 20-69 (Olsen et al., 

2003a), surprisingly little variance in across five widelydispersed U.S. cities was seen in median PFC levels. PFOS 

and PFOA were shown to be highly correlated in that study 

and also in NHANES 2003-2004 (Calafat et al., 2007b), 

possibly due to PFOA being a by-product in POSF-related 

production. The median levels of various PFCs in Olsen 

et al. (2003a) were similar to those of pooled samples 

(1990 through 2002) of the U.S. population (Calafat et al., 

2006a). Olsen et al (2005) also showed that PFCs serum 

concentrations increased from 1974 to 1989 in 58 paired 

samples: 25% for PFOS, 162% for PFOA, and 204% for 

Et-PFOSA-AcOH. Recently, Olsen et al. (2007b) reported 

reductions in PFOS and PFOA concentrations for a group 

of Red Cross blood donors in the United States from 2000 

to 2005.

Serum levels of PFCs, particularly PFOS, appear to be 

higher in the U.S. than in some other countries: about 

two to threefold higher than in Columbia, Brazil, Poland, 

Belgium, Malaysia, Korea and Japan; and about eight to 

sixteenfold higher than in Italy and India (Kannan et al., 

2004); and more than thirtyfold higher than in Peru (Calafat 

et al., 2006b). Notably, the sample sizes were small in these 

studies. In Japan, PFOS levels tended to vary within regions 

of the country ranging from U.S. median levels to about 

fivefold lower levels (Harada et al., 2004). PFC levels for the 

U.S. population, representing environmental exposures, are 

much lower than those reported for occupational exposure. 

In monitored workers employed at a POSF production 

facility with no biochemical or clinically observable effects, 

median levels of PFOS and PFOA were over 40 to 300-fold 

higher, respectively (Olsen et al., 2003b).

Finding a measurable amount of PFCs in serum does 

not mean that the levels of PFCs cause an adverse health 

effect. Biomonitoring studies of serum PFCs can provide 

physicians and public health officials with reference values 

so that they can determine whether or not people have 

been exposed to higher levels of PFCs than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.
Fourth National Report on Human Exposure to Environmental Chemicals 251

 Perfluorochemicals 

Serum Perfluorododecanoic acid (PFDoA) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD < LOD < LOD < LOD 2094 

Age group 

12-19 years 03-04 * < LOD < LOD < LOD < LOD 640

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1454 

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1053 

Females 03-04 * < LOD < LOD < LOD < LOD 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 485

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 538

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.0. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum Perfluoroheptanoic acid (PFHpA) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD < LOD < LOD .400 (<LOD-.500) 2094 

Age group 

12-19 years 03-04 * < LOD < LOD .400 (<LOD-.600) .600 (.500-.900) 640

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1454 

Gender 

Males 03-04 * < LOD < LOD < LOD .300 (<LOD-.400) 1053 

Females 03-04 * < LOD < LOD < LOD .400 (.300-.600) 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD .500 (<LOD-.900) 485

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 538

Non-Hispanic whites 03-04 * < LOD < LOD < LOD .300 (<LOD-.500) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.3. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 252 Fourth National Report on Human Exposure to Environmental Chemicals 

Perfluorochemicals 

Serum Perfluorohexane sulfonic acid (PFHxS) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 1.93 (1.73-2.16) 1.90 (1.70-2.10) 3.30 (2.80-3.90) 5.90 (4.80-7.20) 8.30 (7.10-9.70) 2094 

Age group 

12-19 years 03-04 2.44 (2.05-2.90) 2.40 (1.80-3.20) 4.90 (4.00-6.30) 9.50 (6.80-12.5) 13.3 (9.90-19.6) 640

20 years and older 03-04 1.86 (1.67-2.08) 1.80 (1.60-2.10) 3.00 (2.60-3.60) 5.50 (4.50-6.70) 7.60 (6.30-9.40) 1454 

Gender 

Males 03-04 2.17 (1.87-2.51) 2.10 (1.80-2.40) 3.40 (2.80-4.50) 6.10 (4.60-8.10) 8.50 (6.50-10.5) 1053 

Females 03-04 1.72 (1.56-1.91) 1.60 (1.40-1.80) 2.90 (2.50-3.50) 5.80 (4.60-7.10) 8.20 (6.70-10.0) 1041 

Race/ethnicity 

Mexican Americans 03-04 1.42 (1.17-1.72) 1.50 (1.20-1.70) 2.30 (1.90-2.90) 4.30 (3.10-5.10) 5.50 (4.00-8.90) 485

Non-Hispanic blacks 03-04 1.92 (1.62-2.26) 1.90 (1.60-2.20) 3.50 (2.80-4.60) 6.00 (5.00-7.10) 8.30 (6.30-12.0) 538

Non-Hispanic whites 03-04 2.01 (1.77-2.27) 1.90 (1.70-2.20) 3.30 (2.80-4.10) 6.10 (4.70-7.80) 8.20 (6.90-10.1) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.3. 

Serum Perfluorononanoic acid (PFNA) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 .966 (.816-1.14) 1.00 (.900-1.10) 1.50 (1.20-1.80) 2.30 (1.60-4.30) 3.20 (1.80-7.70) 2094 

Age group 

12-19 years 03-04 .852 (.697-1.04) .800 (.700-1.00) 1.20 (1.00-1.60) 1.90 (1.20-3.70) 2.80 (1.30-6.30) 640

20 years and older 03-04 .984 (.835-1.16) 1.00 (.900-1.10) 1.50 (1.20-1.80) 2.40 (1.60-4.40) 3.40 (1.80-8.40) 1454 

Gender 

Males 03-04 1.09 (.912-1.30) 1.10 (.900-1.20) 1.60 (1.40-1.90) 2.40 (1.70-5.00) 4.00 (1.80-8.70) 1053 

Females 03-04 .861 (.721-1.03) .900 (.800-1.00) 1.30 (1.00-1.70) 2.20 (1.40-3.40) 3.00 (1.70-6.10) 1041 

Race/ethnicity 

Mexican Americans 03-04 .689 (.586-.809) .700 (.600-.900) 1.10 (.900-1.40) 1.60 (1.30-2.00) 2.00 (1.60-2.80) 485

Non-Hispanic blacks 03-04 1.14 (.834-1.54) 1.10 (.900-1.40) 1.70 (1.20-2.90) 3.20 (1.50-6.50) 4.70 (2.10-9.30) 538

Non-Hispanic whites 03-04 .963 (.826-1.12) .900 (.900-1.10) 1.50 (1.20-1.70) 2.30 (1.60-3.60) 3.00 (1.80-6.20) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.1. 
Fourth National Report on Human Exposure to Environmental Chemicals 253

 Perfluorochemicals 

Serum Perfluorooctane sulfonic acid (PFOS) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 20.7 (19.2-22.3) 21.2 (19.8-22.4) 30.0 (27.5-33.0) 41.3 (35.6-50.0) 54.6 (44.0-66.5) 2094 

Age group 

12-19 years 03-04 19.3 (17.5-21.4) 19.9 (17.8-22.0) 27.1 (23.7-30.2) 36.5 (28.6-45.6) 42.6 (35.1-52.1) 640

20 years and older 03-04 20.9 (19.3-22.5) 21.4 (19.8-22.8) 30.4 (28.1-33.0) 42.7 (35.7-53.3) 57.8 (45.7-69.4) 1454 

Gender 

Males 03-04 23.2 (21.1-25.6) 23.9 (22.4-25.5) 32.2 (28.8-35.9) 45.3 (35.5-62.7) 62.7 (43.8-81.8) 1053 

Females 03-04 18.4 (17.0-20.0) 18.2 (16.9-19.8) 27.4 (23.8-30.2) 39.8 (34.4-42.6) 46.6 (42.3-61.5) 1041 

Race/ethnicity 

Mexican Americans 03-04 14.7 (13.0-16.6) 15.9 (13.4-17.9) 21.2 (18.7-23.5) 28.1 (24.1-35.0) 35.5 (28.9-38.5) 485

Non-Hispanic blacks 03-04 21.6 (19.1-24.4) 22.1 (19.6-24.9) 32.3 (28.1-36.2) 43.8 (37.2-57.3) 57.7 (43.8-78.4) 538

Non-Hispanic whites 03-04 21.4 (19.9-23.1) 22.0 (20.5-23.0) 30.2 (27.7-33.3) 41.7 (35.7-49.6) 56.3 (44.0-70.0) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.4. 

Serum Perfluorooctanoic acid (PFOA) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 3.95 (3.65-4.27) 4.10 (3.80-4.40) 5.80 (5.30-6.40) 7.80 (6.70-9.60) 9.80 (7.40-14.1) 2094 

Age group 

12-19 years 03-04 3.89 (3.47-4.35) 4.00 (3.50-4.50) 5.40 (4.60-6.10) 7.00 (5.60-9.20) 8.60 (5.90-12.6) 640

20 years and older 03-04 3.96 (3.67-4.27) 4.10 (3.90-4.40) 5.90 (5.40-6.50) 7.80 (6.80-9.60) 9.90 (7.60-14.2) 1454 

Gender 

Males 03-04 4.47 (4.07-4.91) 4.60 (4.30-5.00) 6.30 (5.70-7.20) 8.40 (6.80-12.5) 10.7 (7.40-17.5) 1053 

Females 03-04 3.50 (3.21-3.82) 3.60 (3.30-3.90) 5.20 (4.70-5.80) 7.10 (6.30-8.20) 8.60 (7.40-10.6) 1041 

Race/ethnicity 

Mexican Americans 03-04 3.11 (2.84-3.40) 3.30 (3.10-3.70) 4.50 (4.20-5.20) 6.70 (5.70-7.30) 7.60 (6.70-10.5) 485

Non-Hispanic blacks 03-04 3.37 (2.99-3.79) 3.70 (3.20-4.20) 5.20 (4.40-6.30) 7.70 (5.30-11.6) 9.60 (6.50-13.9) 538

Non-Hispanic whites 03-04 4.18 (3.85-4.53) 4.30 (3.90-4.70) 6.00 (5.50-6.70) 7.90 (7.20-9.20) 9.90 (7.60-13.3) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.1. 
 254 Fourth National Report on Human Exposure to Environmental Chemicals 

Perfluorochemicals 

Serum 2-(N-Ethyl-perfluorooctane sulfonamido) acetic acid (Et-PFOSA-AcOH) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD < LOD < LOD < LOD 2094 

Age group 

12-19 years 03-04 * < LOD < LOD < LOD < LOD 640

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1454 

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 1053 

Females 03-04 * < LOD < LOD < LOD < LOD 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 485

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD .400 (<LOD-.500) 538

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum Perfluorooctane sulfonamide (PFOSA) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD < LOD .300 (.200-.300) .300 (.300-.400) 2094 

Age group 

12-19 years 03-04 * < LOD < LOD .300 (.200-.300) .300 (.200-.500) 640

20 years and older 03-04 * < LOD < LOD .300 (.200-.300) .300 (.300-.400) 1454 

Gender 

Males 03-04 * < LOD < LOD .300 (.200-.300) .300 (.200-.500) 1053 

Females 03-04 * < LOD < LOD .300 (.200-.300) .300 (.300-.500) 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD .200 (<LOD-.300) 485

Non-Hispanic blacks 03-04 * < LOD < LOD .300 (.200-.300) .300 (.200-.500) 538

Non-Hispanic whites 03-04 * < LOD < LOD .300 (.200-.300) .300 (.300-.500) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.2. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 255

 Perfluorochemicals 

Serum Perfluoroundecanoic acid (PFUA) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD < LOD < LOD .600 (<LOD-1.30) 2094 

Age group 

12-19 years 03-04 * < LOD < LOD < LOD .300 (<LOD-1.10) 640

20 years and older 03-04 * < LOD < LOD .300 (<LOD-.600) .600 (<LOD-1.40) 1454 

Gender 

Males 03-04 * < LOD < LOD .400 (<LOD-1.00) .700 (<LOD-2.30) 1053 

Females 03-04 * < LOD < LOD < LOD .400 (<LOD-.700) 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 485

Non-Hispanic blacks 03-04 * < LOD < LOD .600 (<LOD-1.40) .900 (.300-2.90) 538

Non-Hispanic whites 03-04 * < LOD < LOD < LOD .500 (<LOD-.900) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.3. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2-(N-Methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) 

Geometric mean and selected percentiles of serum concentrations (in μg/L) for the U.S. population from the National Health and

Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 * < LOD .700 (<LOD-.700) 1.00 (.900-1.10) 1.30 (1.10-1.50) 2094 

Age group 

12-19 years 03-04 * < LOD .700 (<LOD-.800) 1.10 (.900-1.30) 1.50 (1.20-1.80) 640

20 years and older 03-04 * < LOD .700 (<LOD-.700) 1.00 (.900-1.10) 1.20 (1.10-1.60) 1454 

Gender 

Males 03-04 * < LOD .700 (<LOD-.700) 1.10 (.900-1.20) 1.30 (1.10-1.70) 1053 

Females 03-04 * < LOD .600 (<LOD-.700) 1.00 (.900-1.10) 1.10 (1.00-1.80) 1041 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD .700 (<LOD-.900) .900 (<LOD-1.30) 485

Non-Hispanic blacks 03-04 * < LOD .800 (<LOD-.900) 1.10 (.900-1.40) 1.50 (1.10-1.80) 538

Non-Hispanic whites 03-04 * < LOD .700 (<LOD-.800) 1.00 (.900-1.10) 1.30 (1.10-1.60) 962

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.6. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 256 Fourth National Report on Human Exposure to Environmental Chemicals 

Perfluorochemicals 

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 258 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Phthalates

General Information

Phthalates are industrial chemicals that are added to plastics 

to impart flexibility and resilience and are often referred to 

as plasticizers. Phthalates are also used as solubilizing and 

stabilizing agents in other applications. There are numerous 

products that contain phthalates: adhesives; automotive 

plastics; detergents; lubricating oils; some medical devices 

and pharmaceuticals; plastic raincoats; solvents; vinyl tiles 

and flooring; and personal-care products, such as soap, 

shampoo, deodorants, lotions, fragrances, hair spray, and 

nail polish. Phthalates are often used in polyvinyl chloride 

type plastics, such as plastic bags, garden hoses, inflatable 

recreational toys, blood product storage bags, intravenous 

medical tubing, and toys (ATSDR, 2001, 2002). Because 

they are not chemically bound to the plastics to which they 

are added, phthalates can be released into the environment 

during use or disposal of the product. Various phthalate 

esters have been measured in specific foods, indoor and 

ambient air, indoor dust, water sources, and sediments 

(Clark et al., 2003).

People are exposed through ingestion, inhalation, and, to 

a lesser extent, dermal contact with products that contain 

phthalates. For the general population, dietary sources have 

been considered as the major exposure route, followed by 

inhaling indoor air. Infants may have relatively greater 

exposures from ingesting indoor dust containing some 

phthalates (Clark et al., 2003). Human milk can be a 

source of phthalate exposure for nursing infants (Calafat 

et al., 2004; Mortensen et al., 2005). The intravenous or 

parenteral exposure route can be important in patients 

undergoing medical procedures involving devices or 

materials containing phthalates. In settings where workers 

may be exposed to higher air phthalate concentrations than 

the general population, urinary metabolite and air phthalate 

concentrations are roughly correlated (Liss et al., 1985; 

Nielsen et al., 1985; Pan et al., 2006).

Phthalates are metabolized and excreted quickly and do not 

accumulate in the body (Anderson et al., 2001). Ingested 

phthalate diesters are initially hydrolyzed in the intestine 

to the corresponding monoesters, which are then absorbed 

(Albro et al., 1982; Albro and Lavenhar, 1989). Absorbed 

monoester metabolites are usually oxidized in the body 

and, in humans, excreted in urine largely as glucuronide 

conjugates (Albro et al., 1982; Dirven et al., 1993). The 

table shows the phthalate diesters, corresponding monoester 

metabolites, and other oxidized metabolites included in this 

Report.

Human health effects from phthalates at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Phthalates have low acute 

animal toxicity. In chronic rodent studies, several of the 

phthalates produced testicular injury, liver injury, liver 

cancer, and teratogenicity, but these effects either have not 

been demonstrated when tested in non-human primates or 

are yet to be studied. In vitro studies showed that certain 

phthalates can bind to estrogen receptors and may have 

weak estrogenic or anti-estrogenic activity (Coldham et al., 

1997; Harris et al., 1997; Jobling et al., 1995), but in vivo

studies did not support phthalates having estrogenic effects 

(Milligan et al., 1998; Okubo et al., 2003; Parks et al., 

2000; Zacharewski et al., 1998); however, not all phthalates 

Phthalates and Urinary Metabolites in this Report

Phthalate name (CAS number) Abbreviation Urinary metabolite (CAS number) Abbreviation 

Benzylbutyl phthalate (85-68-7) BzBP Mono-benzyl phthalate (2528-16-7) MBzP

(some mono-n-butyl phthalate) 

Dibutyl phthalates (84-74-2) DBP Mono-isobutyl phthalate MiBP 

 Mono-n-butyl phthalate (131-70-4) MnBP 

Dicyclohexyl phthalate (84-61-7) DCHP Mono-cyclohexyl phthalate (7517-36-4) MCHP

Diethyl phthalate (84-66-2) DEP Mono-ethyl phthalate (2306-33-4) MEP 

Di-2-ethylhexyl phthalate (117-81-7) DEHP Mono-2-ethylhexyl phthalate (4376-20-9) MEHP

Mono-(2-ethyl-5-hydroxyhexyl) phthalate MEHHP

Mono-(2-ethyl-5-oxohexyl) phthalate MEOHP

Mono-(2-ethyl-5-carboxypentyl) phthalate MECPP

(40809-41-4) 

Di-isononyl phthalate (28553-12-0) DiNP Mono-isononyl phthalate MiNP 

Dimethyl phthalate (131-11-3) DMP Mono-methyl phthalate (4376-18-5) MMP

Di-n-octyl phthalate (117-84-0) DOP Mono-(3-carboxypropyl) phthalate MCPP

 Mono-n-octyl phthalate (5393-19-1) MOP 
Fourth National Report on Human Exposure to Environmental Chemicals 259

 Phthalates 

and metabolites have been tested. In animals, phthalates 

produced anti-androgenic effects by reducing testosterone 

production and, at very high levels, reducing estrogen 

production, effects that may be mediated by inhibiting 

testicular and ovarian steroidogenesis. High doses of di2-ethylhexyl phthalate (DEHP), dibutyl phthalate (DBP), 

and benzylbutyl phthalate (BzBP) during the fetal period 

produced lowered testosterone levels, testicular atrophy, and 

Sertoli cell abnormalities in the male animals and, at higher 

doses, ovarian abnormalities in the female animals (Jarfelt 

et al., 2005; Lovekamp-Swan and Davis, 2003; McKee 

et al., 2004; NTP-CERHR, 2000a, 2000b, 2000c, 2006). 

Phthalate urinary metabolite levels in men evaluated at an 

infertility clinic were associated with several measures of 

sperm function and morphology (Duty et al., 2004; Hauser 

et al., 2007), but similar findings were not present in young 

Swedish men with comparable or higher median levels of 

urinary metabolites (Jonsson et al., 2005).

The monoester metabolites are thought to mediate toxic 

effects for some of the phthalates, but there are known 

species-related differences in the hydrolysis of diester 

phthalates, efficiency of intestinal absorption, and extent of 

metabolite conjugation to glucuronide (Albro et al., 1982; 

Kessler et al., 2004; Rhodes et al., 1986). These differences 

may contribute to species-specific differences in toxicity 

(ATSDR, 2001, 2002). Also, phthalates have been shown to 

induce peroxisomal proliferation in rodents, which may be 

a pathway to the development of liver toxicity and cancers 

in these animals. However, peroxisomal proliferation may 

not be a relevant pathway in humans (Rusyn et al., 2006).

The National Toxicology Program’s Center for the 

Evaluation of Risks to Human Reproduction (NTPCERHR) has reviewed the developmental and reproductive 

effects of specific phthalates (http://cerhr.niehs.nih.gov/

reports/index.html). Information about external exposure 

(i.e., environmental levels) and health effects is also 

available for some phthalates from ATSDR at: http://www.

atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Urinary levels of phthalate metabolites reflect recent 

exposure to the parent phthalate diester. The proportions 

of each metabolite for a given phthalate may vary by 

differing routes of exposure (Liss et al., 1985; Peck and 

Albro, 1982). Variation occurs from person to person in 

the proportions or amounts of a metabolite excreted after 

similar doses (Anderson et al., 2001); variation also occurs 

in the same person during repetitive monitoring (Fromme 

et al., 2007; Hauser et al., 2004; Hoppin et al., 2002). 

Population estimates of concentrations of specific phthalate 

metabolites may differ by age, gender, and race/ethnicity 

(Silva et al., 2004).

Finding a measurable amount of one or more phthalate 

metabolites in urine does not mean that the levels of the 

metabolites or the parent phthalate cause an adverse 

health effect. Biomonitoring studies on levels of phthalate 

metabolites provide physicians and public health officials 

with reference values so that they can determine whether 

people have been exposed to higher levels of phthalates 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

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 Phthalates 

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 262 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Benzylbutyl Phthalate

CAS No. 85-68-7

General Information

Benzylbutyl phthalate (BzBP) is a solvent and additive 

used in products such as adhesives, vinyl tile, sealants, 

car care products, and to a lesser extent, some personal 

care products. BzBP can be released into the environment 

during its production and, because it is not bound to 

products in which it is incorporated, it can be released into 

the ambient air during use or disposal of the products. Food 

crops take up BzBP, and diet is the major source for general 

population exposure. People exposed to BzBP will excrete 

mono-benzyl phthalate (MBzP) and small amounts of 

mono-n-butyl phthalate in their urine. High dose BzBP and 

its monoester metabolites, including MBzP, can produce 

developmental and reproductive toxicity in rodents, 

particularly male animals (McKee et al., 2004; NTPCERHR, 2000). IARC considers BzBP not classifiable with 

respect to human carcinogenicity.

Biomonitoring Information

The median levels of MBzP in NHANES subsamples from 

1999-2000, 2001-2002, and 2003-2004 were generally 

similar those reported in U.S. residents (Blount et al., 

2000), in a small sample of pregnant women in New 

Urinary Mono-benzyl phthalate (MBzP) 

Metabolite of Benzylbutyl phthalate (BzBP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 15.3 (13.7-17.1) 17.0 (15.3-18.9) 35.4 (32.6-39.7) 67.1 (55.3-82.4) 103 (94.6-116) 2541

01-02 15.1 (13.9-16.3) 15.8 (14.8-17.4) 38.0 (34.5-41.2) 80.8 (71.3-88.2) 122 (102-142) 2782

03-04 13.7 (12.7-14.9) 14.3 (12.8-16.4) 32.3 (30.1-35.0) 66.5 (57.3-75.6) 101 (85.3-125) 2605

Age group 

6-11 years 99-00 39.4 (32.9-47.2) 40.3 (33.8-48.6) 82.0 (55.8-98.1) 129 (98.1-214) 214 (108-399) 328

01-02 33.4 (29.1-38.4) 37.0 (26.6-43.4) 68.5 (61.6-92.8) 166 (116-191) 235 (183-330) 393

03-04 33.9 (28.2-40.6) 35.0 (30.1-39.8) 63.8 (50.4-92.4) 145 (110-213) 255 (146-365) 342

12-19 years 99-00 25.6 (21.9-30.0) 28.3 (22.3-34.8) 51.2 (43.7-58.5) 88.5 (67.2-115) 125 (93.7-170) 752

01-02 23.2 (19.9-27.2) 24.9 (21.2-31.0) 55.5 (47.4-62.9) 113 (91.8-133) 169 (134-198) 742

03-04 22.1 (19.4-25.1) 24.9 (22.3-27.2) 49.9 (39.8-64.6) 89.8 (71.1-120) 152 (99.9-190) 729

20 years and older 99-00 12.4 (10.9-14.2) 13.8 (12.1-15.6) 29.2 (25.2-33.1) 52.0 (43.9-62.5) 86.3 (54.7-119) 1461

01-02 12.7 (11.7-13.9) 13.9 (12.8-14.9) 31.8 (28.5-33.5) 65.4 (53.8-76.3) 99.7 (82.8-121) 1647

03-04 11.4 (10.3-12.7) 12.1 (10.8-13.5) 27.0 (23.6-29.4) 54.2 (47.1-61.5) 79.5 (66.5-94.8) 1534

Gender 

Males 99-00 16.2 (14.1-18.6) 17.7 (15.2-20.0) 35.4 (31.5-40.3) 69.4 (59.9-87.2) 108 (96.3-130) 1215

01-02 15.6 (13.6-17.9) 16.0 (14.6-18.5) 37.0 (33.1-43.0) 78.4 (63.5-97.4) 122 (88.2-183) 1371

03-04 14.6 (13.2-16.2) 15.1 (13.2-17.5) 32.3 (29.5-35.6) 65.6 (53.6-79.6) 101 (78.6-132) 1250

Females 99-00 14.6 (12.7-16.6) 16.1 (14.2-19.2) 35.8 (30.8-41.4) 63.7 (53.7-82.4) 103 (84.2-116) 1326

01-02 14.6 (13.1-16.3) 15.4 (13.8-17.9) 38.1 (32.3-43.8) 81.4 (68.3-91.6) 122 (102-143) 1411

03-04 13.0 (11.8-14.2) 13.3 (12.1-15.6) 33.3 (29.5-36.2) 67.1 (58.8-72.4) 101 (84.4-120) 1355

Race/ethnicity 

Mexican Americans 99-00 13.9 (12.1-16.1) 15.7 (13.4-16.9) 33.0 (27.5-36.1) 67.5 (55.5-84.0) 98.8 (80.6-150) 814

01-02 13.2 (10.8-16.2) 14.8 (10.8-18.5) 29.5 (26.2-38.1) 70.4 (53.0-85.4) 94.7 (70.3-161) 677

03-04 14.9 (13.2-16.7) 15.5 (13.5-18.3) 32.4 (27.7-35.4) 71.4 (48.6-92.3) 99.8 (86.5-145) 652

Non-Hispanic blacks 99-00 23.0 (20.7-25.5) 23.1 (20.5-25.6) 49.3 (44.0-55.6) 94.7 (80.0-130) 138 (106-241) 603

01-02 23.8 (21.0-26.9) 24.2 (19.9-28.0) 50.6 (41.5-62.9) 101 (86.4-127) 143 (127-179) 703

03-04 18.9 (16.3-21.8) 20.0 (15.4-24.6) 43.8 (38.9-49.0) 80.9 (70.0-106) 120 (99.7-172) 699

Non-Hispanic whites 99-00 14.3 (12.7-16.1) 16.1 (14.3-18.6) 34.0 (30.6-38.4) 58.7 (51.3-74.1) 103 (74.1-116) 912

01-02 14.0 (12.7-15.4) 14.6 (13.4-15.6) 35.6 (32.2-39.5) 76.6 (66.1-90.3) 122 (93.2-155) 1216

03-04 12.9 (11.5-14.3) 13.2 (11.7-16.0) 30.5 (27.8-35.1) 63.8 (53.6-72.4) 91.5 (76.3-122) 1088

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.8, 0.3, and 0.1, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 263

 Phthalates 

York City (Adibi et al., 2003), in men attending a Boston 

infertility clinic (Duty et al., 2004; Hauser et al., 2007), 

in young Swedish men (Jonsson et al., 2005), and in a 

small sample of German residents (Koch et al., 2003). In 

an annual sample of German university students, median 

urine levels of MBzP were about one-half the median levels 

in NHANES subsamples from 1999-2002 (Wittassek et 

al., 2007). A small study of African-American women in 

Washington, DC reported median urinary MBzP levels that 

were about twice the levels of adults and females reported 

in NHANES 1999-2002 (CDC, 2005; Hoppin et al., 2002). 

Limited studies in children younger than 2 years old 

have found median and geometric mean urine MBzP that 

were similar to children aged 6-11 years in the NHANES 

subsamples (Brock et al., 2002; Weuve et al., 2006). In 

NHANES 1999-2000, the adjusted geometric mean levels 

of urinary MBzP were significantly higher in several 

subgroups: children compared to adolescents and adults; 

adolescents compared with adults; and females compared 

to males (Silva et al., 2004).

Finding a measurable amount of MBzP in the urine does 

not mean that the levels of MBzP or the parent compound 

cause an adverse health effect. Biomonitoring studies on 

levels of urinary MBzP provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels of BzBP 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

Urinary Mono-benzyl phthalate (MBzP) (creatinine corrected) 

Metabolite of Benzylbutyl phthalate (BzBP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 14.0 (13.0-15.0) 13.3 (12.8-14.3) 25.1 (23.4-27.2) 50.1 (41.5-58.8) 77.4 (69.6-86.3) 2541

01-02 14.1 (13.2-15.1) 13.5 (12.7-14.4) 26.6 (24.7-29.1) 54.8 (49.1-58.5) 90.4 (74.4-102) 2782

03-04 12.9 (12.2-13.7) 12.6 (11.2-13.6) 24.6 (22.2-26.4) 46.0 (41.0-51.5) 70.0 (62.4-79.9) 2605

Age group 

6-11 years 99-00 40.0 (33.6-47.6) 38.6 (30.2-51.3) 73.5 (56.6-99.2) 104 (89.4-142) 142 (99.8-173) 328

01-02 38.1 (34.4-42.1) 37.4 (33.8-42.2) 67.9 (55.8-80.4) 134 (116-176) 195 (121-305) 393

03-04 35.8 (30.5-42.1) 32.2 (27.9-40.5) 60.8 (50.1-79.4) 136 (85.5-213) 229 (99.7-397) 342

12-19 years 99-00 17.3 (15.4-19.4) 17.1 (14.6-20.3) 28.3 (24.3-34.8) 49.7 (38.8-69.3) 70.0 (49.6-81.9) 752

01-02 17.9 (15.7-20.5) 18.1 (15.7-20.8) 33.9 (29.3-38.6) 67.7 (55.8-85.9) 100 (80.7-123) 742

03-04 16.6 (15.4-17.8) 16.9 (15.4-18.2) 30.1 (25.1-35.5) 52.2 (40.7-61.8) 77.7 (54.9-115) 729

20 years and older 99-00 11.8 (10.7-12.9) 12.1 (11.1-12.9) 20.1 (18.4-23.3) 34.6 (30.6-40.9) 57.2 (41.3-73.9) 1461

01-02 12.0 (11.2-12.9) 11.8 (11.1-12.5) 21.6 (19.9-23.7) 42.3 (35.8-48.3) 64.9 (54.2-78.3) 1647

03-04 11.0 (10.3-11.7) 10.5 (9.69-11.6) 19.7 (18.2-21.4) 36.6 (34.8-39.1) 55.8 (46.9-62.4) 1534

Gender 

Males 99-00 12.7 (11.8-13.6) 12.4 (11.6-13.0) 23.7 (21.5-26.1) 44.5 (35.5-57.0) 73.5 (48.5-99.8) 1215

01-02 12.7 (11.4-14.2) 11.9 (10.9-13.2) 24.1 (21.0-26.4) 49.1 (43.7-56.1) 80.3 (60.9-104) 1371

03-04 11.5 (10.6-12.4) 11.1 (9.73-12.5) 21.1 (19.5-23.6) 39.4 (34.2-49.7) 62.9 (51.9-83.1) 1250

Females 99-00 15.3 (13.8-16.8) 14.7 (13.3-16.0) 25.9 (24.1-29.3) 56.4 (46.8-60.6) 80.4 (60.2-117) 1326

01-02 15.6 (14.2-17.3) 15.1 (13.9-16.5) 29.4 (25.8-34.1) 58.5 (49.9-69.4) 95.8 (69.4-116) 1411

03-04 14.4 (13.4-15.6) 13.9 (12.8-15.1) 27.9 (24.7-31.4) 51.9 (43.4-60.3) 73.4 (63.7-90.2) 1355

Race/ethnicity 

Mexican Americans 99-00 12.6 (11.4-14.0) 11.9 (10.9-13.2) 24.1 (21.5-26.5) 46.5 (42.0-53.8) 68.2 (56.4-93.8) 814

01-02 12.4 (10.7-14.4) 11.9 (9.95-14.9) 23.7 (19.5-29.0) 46.6 (36.5-61.6) 71.6 (51.1-120) 677

03-04 13.4 (11.7-15.4) 12.5 (11.5-13.4) 24.1 (21.0-27.8) 53.0 (38.3-64.8) 77.8 (57.1-125) 652

Non-Hispanic blacks 99-00 14.8 (13.5-16.3) 13.7 (12.2-15.2) 26.9 (22.5-31.8) 56.3 (39.5-76.0) 86.8 (64.4-99.8) 603

01-02 16.7 (14.7-19.0) 15.7 (13.7-19.3) 33.4 (26.5-38.0) 60.1 (53.7-69.4) 108 (75.6-116) 703

03-04 13.4 (11.8-15.3) 13.6 (11.6-15.6) 24.1 (21.9-28.7) 50.0 (41.2-57.8) 74.7 (59.0-90.5) 699

Non-Hispanic whites 99-00 14.0 (12.7-15.3) 13.4 (12.9-14.8) 25.3 (23.1-27.4) 53.3 (38.8-64.8) 78.0 (67.4-90.3) 912

01-02 13.8 (12.8-14.9) 13.0 (12.1-14.3) 25.7 (23.8-27.9) 53.1 (46.5-58.5) 89.2 (69.0-109) 1216

03-04 12.7 (11.8-13.7) 12.5 (10.8-13.8) 24.4 (21.6-26.7) 41.9 (39.0-48.8) 65.6 (57.5-79.5) 1088
 264 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

References

Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, 

Jacek R, et al. Prenatal exposures to phthalates among women 

in New York City and Krakow, Poland. Environ Health Perspect 

2003;111(14):1719-1722.

Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, 

Sampson EJ, et al. Levels of seven urinary phthalate metabolites 

in a human reference population. Environ Health Perspect 

2000;108(10):979-982.

Brock JW, Caudill SP, Silva MJ, Needham LL, Hilborn ED. 

Phthalate monoesters levels in the urine of young children. Bull 

Environ Contam Toxicol 2002;68:309-314.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Duty SM, Calafat AM, Silva MJ, Brock JW, Ryan L, Chen Z, et al. 

The relationship between environmental exposure to phthalates 

and computer-aided sperm analysis motion parameters. J Androl 

2004;25(2):293-302.

Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, et 

al. DNA damage in human sperm is related to urinary levels of 

phthalate monoester and oxidative metabolites. Hum Reprod 

2007;22(3):688-695.

Hoppin JA, Brock JW, Davis BJ, Baird DD. Reproducibility 

of urinary phthalate metabolites in first morning urine samples. 

Environ Health Perspect 2002;110(5):515-518.

Jonsson BAG, Richthoff J, Rylander L, Giwercman A, Hagmar 

L. Urinary phthalate metabolites and biomarkers of reproductive 

function in young men. Epidemiol 2005;16(4):487-493.

Koch HM, Rossbach B, Drexler H, Angerer J. Internal exposure 

of the general population to DEHP and other phthalates - 

determination of secondary and primary phthalate monoester 

metabolites in urine. Environ Res 2003;93:177-185.

McKee RH, Butala JH, David RM, Gans G. NTP center for the 

evaluation of risks to human reproduction reports on phthalates: 

addressing the data gaps [review]. Reprod Toxicol 2004;18(1):1-

22.

NTP-CERHR. National Toxicology Program-Center for the 

Evaluation of Risks to Human Reproduction. Monograph on 

the Potential Human Reproductive and Developmental Effects 

of Butyl Benzyl Phthalate (BBP). Research Triangle Park (NC). 

2000 [online]. Available at URL: http://cerhr.niehs.nih.gov/

chemicals/phthalates/bb-phthalate/bbp-eval.html. 4/20/09

Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, 

et al. Urinary levels of seven phthalate metabolites in the U.S. 

population from the National Health and Nutrition Examination 

Survey (NHANES) 1999-2000 [published erratum appears in 

Environ Health Perspect 2004; 112(5):A270]. Environ Health 

Perspect 2004;112(3):331-338.

Weuve J, Sanchez GN, Calafat AM, Schettler T, Green RA, Hu 

H, et al. Exposure to phthalates in neonatal intensive care unit 

infants: urinary concentrations of monoesters and oxidative 

metabolites. Environ Health Perspect 2006;114(9):1424-1431.

Wittassek M, Wiesmuller GA, Koch HM, Eckard R, Dobler 

L, Helm D, et al. Internal phthalate exposure over the last two 

decades—a retrospective human biomonitoring study. Int J Hyg 

Environ Health 2007;210(3-4):319-333.
Fourth National Report on Human Exposure to Environmental Chemicals 265

 Phthalates 

Di-n-butyl Phthalate

CAS No. 84-74-2

Di-isobutyl Phthalate

CAS No. 84-69-5

General Information

Dibutyl phthalates (both di-n-butyl and di-isobutyl 

phthalates, referred to as DBP) are industrial solvents or 

additives used in many personal care products such as 

nail polish and cosmetics, and also in some printing inks, 

pharmaceutical coatings, and insecticides. People exposed 

to dibutyl phthalates will excrete mono-n-butyl phthalate 

(MnBP) and mono-isobutyl phthalate (MiBP) in their 

urine. When total DBP metabolites have been measured, 

they have been referred to as monobutyl phthalate (MBP). 

Small amounts of mono-3-carboxypropyl phthalate are also 

produced from di-n-butyl phthalate. In addition, exposure 

to benzylbutyl phthalate (BzBP) will also result in small 

amounts of mono-n-butyl phthalate appearing in the urine. 

Following oral administration of DBP to humans, about 

65% to 80% of a dose is eliminated in urine within 24 hours, 

mostly as MnBP (Anderson et al., 2001). DBP can produce 

reproductive toxicity in male rodents (McKee et al., 2004; 

NTP-CERHR, 2000). OSHA has established a workplace 

air standard for external exposure to DBP; NIOSH and 

ACGIH have established guidelines for workplace air 

exposure to di-n-butyl phthalate. Neither IARC nor NTP 

has evaluated dibutyl phthalates with respect to human 

carcinogenicity.

Biomonitoring Information

Median concentrations reported in the NHANES 1999-

2000, 2001-2002 and 2003-2004 subsamples were similar 

to MBP levels reported in U.S. residents (Blount et al., 

2000; CDC, 2005), in men attending a Boston infertility 

clinic (Duty et al., 2004; Hauser et al., 2007), in a small 

sample of pregnant women in New York City (Adibi et al., 

2003), and in a small sample of Japanese adults (Itoh et 

al., 2005). Median MBP levels in two European studies 

were about two to six times higher than median levels 

in this Report (Jonsson et al., 2005; Koch et al., 2003). 

Studies of children found age-related differences in urine 

MBP levels. Compared with the median for 6 to 11 year 

olds in NHANES 1999-2004 (CDC, 2005), the median 

Urinary Mono-isobutyl phthalate (MiBP) 

Metabolite of Di-isobutyl phthalate (DBP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 2.71 (2.49-2.94) 2.70 (2.40-3.00) 5.70 (5.30-6.10) 12.0 (11.4-12.7) 17.9 (16.3-19.8) 2782 

03-04 3.80 (3.40-4.25) 4.20 (3.70-4.80) 8.40 (7.40-9.50) 15.0 (13.1-17.3) 21.3 (18.6-26.0) 2605 

Age group 

6-11 years 01-02 4.22 (3.28-5.43) 4.40 (3.20-6.20) 10.7 (7.30-13.4) 18.6 (14.2-22.0) 23.4 (20.4-27.8) 393

03-04 6.56 (5.24-8.22) 7.00 (5.10-9.10) 12.8 (9.40-17.7) 24.3 (19.6-34.5) 40.6 (29.3-48.5) 342

12-19 years 01-02 3.48 (2.90-4.17) 3.80 (2.90-4.40) 7.40 (6.00-9.00) 14.5 (11.7-18.6) 22.3 (16.2-33.4) 742

03-04 4.55 (3.73-5.55) 5.60 (4.50-6.30) 10.1 (8.00-11.4) 17.1 (13.3-20.9) 22.7 (18.5-29.1) 729

20 years and older 01-02 2.46 (2.30-2.63) 2.40 (2.20-2.70) 5.10 (4.80-5.50) 10.6 (9.40-12.0) 16.3 (13.6-18.5) 1647 

03-04 3.46 (3.11-3.84) 3.90 (3.40-4.30) 7.50 (6.70-8.50) 13.3 (11.5-16.5) 19.9 (16.0-25.0) 1534 

Gender 

Males 01-02 2.73 (2.50-2.97) 2.80 (2.40-3.20) 5.60 (5.00-6.10) 11.6 (10.1-12.6) 16.6 (13.6-20.1) 1371 

03-04 4.07 (3.56-4.66) 4.30 (3.80-5.10) 9.20 (7.50-10.2) 16.0 (13.3-18.5) 22.7 (17.3-30.3) 1250 

Females 01-02 2.68 (2.44-2.96) 2.60 (2.30-3.00) 5.80 (5.30-6.50) 12.6 (11.0-14.7) 18.7 (16.3-24.0) 1411 

03-04 3.56 (3.19-3.97) 4.10 (3.50-4.50) 8.00 (7.10-9.10) 14.2 (12.5-16.6) 20.5 (17.9-23.0) 1355 

Race/ethnicity 

Mexican Americans 01-02 3.26 (2.72-3.91) 3.40 (2.70-4.30) 7.20 (6.20-9.30) 12.2 (11.2-14.7) 18.4 (14.1-25.6) 677

03-04 4.81 (3.85-6.02) 5.10 (4.00-6.70) 10.2 (8.20-12.6) 18.3 (13.5-24.5) 26.0 (19.0-38.5) 652

Non-Hispanic blacks 01-02 4.90 (4.46-5.37) 5.30 (4.60-6.00) 10.7 (9.20-12.0) 18.3 (16.1-20.1) 25.5 (20.7-31.3) 703

03-04 6.67 (5.97-7.46) 6.90 (6.30-7.50) 12.6 (10.9-14.7) 25.7 (17.7-31.0) 33.5 (27.3-43.9) 699

Non-Hispanic whites 01-02 2.33 (2.10-2.59) 2.30 (1.90-2.60) 4.90 (4.40-5.30) 9.60 (8.30-11.6) 15.6 (13.0-18.6) 1216 

03-04 3.17 (2.82-3.56) 3.50 (3.00-4.00) 6.80 (5.90-7.90) 12.5 (10.6-14.5) 17.6 (14.7-20.8) 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 1.0 and 0.3. 
 266 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

for neonates was lower (by about half) and the median for 

toddlers was higher (by about sixfold) (Brock et al., 2002; 

Weuve et al., 2006). In an analysis of NHANES 1999-2000, 

the adjusted geometric mean levels of urinary MBP were 

significantly higher in children aged 6 to 11 years than in 

either adolescents or adults (Silva et al., 2004). Differences 

in urinary MBP population estimates by gender have also 

been shown (Silva et al., 2004). An analysis of NHANES 

2001-2002 showed similar age- and gender- related 

differences in the adjusted geometric mean levels of urinary 

MiBP and MnBP (CDC, 2005).

Studies measuring urinary MnBP have reported variable 

median values compared to the NHANES 2001-2002 and 

2003-2004 subsamples, ranging from more than one-tenth 

the NHANES median (Itoh et al., 2005), to about two 

to fourfold higher (Fromme et al., 2007). Between 1998 

and 2003, samples from German university students had 

consistently higher median urine levels of MnBP and 

MiBP, up to four and 13 fold, respectively, than adults in 

NHANES subsamples during the same time period. Over 

this time, the students’ median values for MiBP levels 

remained relatively unchanged, while MnBP declined 

(Wittassek et al., 2007).

Finding a measurable amount of MnBP or MiBP in urine 

does not mean that these levels or the parent compound 

cause an adverse health effect. Biomonitoring studies on 

levels of MnBP and MiBP provide physicians and public 

health officials with reference values so that they can 

determine whether people have been exposed to higher 

levels of dibutyl phthalates than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Urinary Mono-isobutyl phthalate (MiBP) (creatinine corrected) 

Metabolite of Di-isobutyl phthalate (DBP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 2.54 (2.36-2.73) 2.46 (2.26-2.68) 4.54 (4.20-4.86) 8.02 (7.78-8.66) 12.0 (10.8-13.5) 2782 

03-04 3.57 (3.18-4.00) 3.57 (3.15-4.08) 6.21 (5.36-7.17) 10.9 (9.47-12.7) 15.4 (12.8-18.6) 2605 

Age group 

6-11 years 01-02 4.81 (3.89-5.94) 5.18 (4.13-6.32) 9.20 (7.03-11.7) 15.2 (11.1-24.3) 24.3 (13.9-40.3) 393

03-04 6.94 (5.79-8.31) 7.03 (5.29-8.95) 11.8 (9.56-15.1) 18.6 (15.1-25.1) 28.7 (21.8-36.9) 342

12-19 years 01-02 2.68 (2.29-3.15) 2.83 (2.39-3.33) 4.79 (4.04-5.51) 7.62 (6.18-10.2) 12.8 (8.76-15.6) 742

03-04 3.41 (2.86-4.05) 3.69 (2.99-4.31) 5.75 (4.69-7.04) 9.32 (7.17-12.0) 13.5 (9.52-20.1) 729

20 years and older 01-02 2.33 (2.20-2.46) 2.26 (2.08-2.43) 3.89 (3.65-4.25) 7.31 (7.00-7.78) 10.6 (9.46-11.3) 1647 

03-04 3.32 (3.00-3.68) 3.33 (3.00-3.81) 5.59 (4.93-6.51) 9.84 (8.65-11.2) 13.5 (11.4-16.0) 1534 

Gender 

Males 01-02 2.22 (2.09-2.35) 2.18 (1.97-2.37) 3.76 (3.58-4.11) 7.38 (6.64-7.95) 11.1 (10.1-12.5) 1371 

03-04 3.20 (2.80-3.66) 3.19 (2.74-3.56) 5.84 (4.79-6.56) 10.0 (8.27-12.2) 13.9 (11.5-19.1) 1250 

Females 01-02 2.88 (2.61-3.18) 2.85 (2.52-3.18) 5.14 (4.67-5.89) 8.66 (8.02-10.1) 13.7 (11.1-15.0) 1411 

03-04 3.96 (3.56-4.42) 4.00 (3.57-4.45) 6.73 (5.64-7.80) 11.6 (10.2-13.0) 15.7 (13.0-18.7) 1355 

Race/ethnicity 

Mexican Americans 01-02 3.07 (2.58-3.66) 2.98 (2.53-3.82) 5.82 (4.91-6.99) 10.6 (8.28-13.3) 16.0 (12.6-19.4) 677

03-04 4.34 (3.47-5.43) 4.47 (3.53-5.24) 7.75 (6.33-9.69) 13.1 (11.9-16.8) 23.3 (17.9-26.1) 652

Non-Hispanic blacks 01-02 3.44 (3.20-3.69) 3.52 (2.95-3.81) 6.11 (5.03-7.04) 10.6 (8.94-12.4) 15.6 (12.6-19.7) 703

03-04 4.74 (4.07-5.51) 4.65 (4.10-5.30) 7.81 (6.38-10.0) 15.2 (10.8-18.4) 19.9 (15.7-28.7) 699

Non-Hispanic whites 01-02 2.31 (2.11-2.52) 2.20 (2.01-2.43) 3.80 (3.53-4.39) 7.30 (6.72-7.78) 10.7 (9.62-12.6) 1216 

03-04 3.13 (2.76-3.54) 3.17 (2.76-3.72) 5.28 (4.55-6.21) 8.92 (7.64-10.3) 11.8 (10.2-15.1) 1088 
Fourth National Report on Human Exposure to Environmental Chemicals 267

 Phthalates 

Urinary Mono-n-butyl phthalate (MnBP) 

Metabolite of Dibutyl phthalate (DBP) and Benzylbutyl phthalate (BzBP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00* 24.6 (22.1-27.4) 26.0 (23.6-29.2) 51.6 (44.5-60.3) 98.6 (90.2-114) 150 (121-169) 2541 

01-02 18.9 (17.4-20.6) 20.4 (19.2-21.8) 40.4 (36.5-44.2) 73.6 (65.3-85.6) 108 (94.1-122) 2782 

03-04 21.1 (19.8-22.5) 23.2 (21.2-24.8) 42.7 (38.5-47.2) 80.7 (70.2-93.9) 122 (104-137) 2605 

Age group 

6-11 years 99-00* 41.4 (35.6-48.0) 40.0 (36.2-49.2) 75.5 (59.1-92.8) 124 (98.4-159) 166 (127-279) 328 

01-02 31.1 (26.6-36.5) 32.4 (25.6-37.1) 62.1 (51.3-76.9) 107 (84.3-136) 159 (110-290) 393 

03-04 36.3 (30.7-42.9) 36.7 (28.5-47.5) 71.3 (56.9-87.2) 137 (107-162) 191 (150-243) 342 

12-19 years 99-00* 36.0 (30.8-42.1) 36.3 (30.6-44.9) 68.6 (55.9-79.7) 119 (90.2-159) 165 (121-227) 752 

01-02 25.1 (21.6-29.2) 26.7 (22.0-32.7) 52.6 (48.4-60.4) 92.4 (72.7-121) 148 (106-185) 742 

03-04 26.7 (24.1-29.5) 28.2 (25.2-33.1) 52.0 (45.3-60.9) 97.5 (74.7-116) 134 (110-158) 729 

20 years and older 99-00* 21.6 (19.0-24.5) 23.1 (19.7-26.1) 46.3 (36.9-53.6) 95.0 (78.7-111) 143 (117-161) 1461 

01-02 17.0 (15.4-18.8) 19.1 (17.1-20.4) 35.1 (31.6-40.2) 64.8 (57.3-79.7) 95.4 (84.6-113) 1647 

03-04 19.0 (17.7-20.5) 20.7 (18.9-22.9) 38.4 (35.7-42.7) 74.7 (64.1-82.6) 108 (90.7-127) 1534 

Gender 

Males 99-00* 22.0 (20.1-24.1) 23.2 (20.4-26.3) 43.1 (36.6-49.5) 84.4 (71.3-96.2) 116 (97.8-132) 1215 

01-02 17.7 (16.0-19.6) 19.3 (17.3-21.0) 34.5 (30.3-40.6) 62.1 (54.1-75.5) 95.2 (75.5-117) 1371 

03-04 20.0 (18.1-22.0) 21.1 (19.0-24.0) 39.4 (35.5-43.4) 65.5 (59.0-73.0) 95.9 (79.8-111) 1250 

Females 99-00* 27.3 (23.6-31.5) 30.0 (25.9-33.3) 59.7 (51.6-69.6) 120 (98.3-145) 167 (143-223) 1326 

01-02 20.2 (18.2-22.4) 21.7 (19.7-24.3) 46.7 (43.1-51.1) 85.0 (72.7-92.5) 121 (106-136) 1411 

03-04 22.2 (21.2-23.3) 24.4 (23.4-25.8) 47.3 (42.7-53.0) 95.9 (79.9-114) 137 (122-156) 1355 

Race/ethnicity 

Mexican Americans 99-00* 23.4 (21.8-25.1) 26.3 (23.9-28.1) 48.1 (41.2-56.7) 92.2 (78.9-101) 117 (104-131) 814 

01-02 20.1 (16.6-24.5) 23.1 (18.0-26.5) 42.1 (34.0-51.5) 77.1 (62.9-92.5) 112 (84.6-143) 677 

03-04 24.1 (19.8-29.5) 26.9 (20.2-32.0) 47.4 (38.0-58.5) 85.6 (61.7-117) 127 (99.8-165) 652 

Non-Hispanic blacks 99-00* 37.0 (31.9-42.9) 38.7 (33.4-44.5) 78.2 (58.7-91.8) 118 (108-143) 167 (143-197) 603 

01-02 29.6 (26.6-33.1) 31.5 (28.7-34.1) 58.3 (51.2-63.4) 93.2 (79.5-121) 138 (110-184) 703 

03-04 30.1 (28.4-31.9) 31.5 (29.7-34.1) 64.1 (58.3-67.1) 106 (94.8-119) 144 (115-168) 699 

Non-Hispanic whites 99-00* 21.8 (19.3-24.6) 23.2 (19.5-27.5) 46.3 (37.5-53.3) 90.2 (74.7-106) 142 (111-161) 912 

01-02 17.6 (16.0-19.3) 19.2 (17.0-21.0) 36.6 (32.4-42.6) 69.2 (59.2-87.6) 107 (89.8-123) 1216 

03-04 18.9 (17.6-20.3) 20.7 (18.9-22.8) 38.4 (35.5-42.7) 71.3 (60.1-80.0) 101 (90.7-124) 1088 

Limits of detection (LOD, see Data Analysis section) for survey years 99-00, 01-02, and 03-04 are 0.9, 1.1, and 0.4, respectively. 

*In the 1999-2000 survey period, concentrations of mono-isobutyl phthalate and mono-n-butyl phthalate were measured together and expressed as a combined value, referred to as monobutyl 

phthalate (MBP). 
 268 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Urinary Mono-n-butyl phthalate (MnBP) (creatinine corrected) 

Metabolite of Dibutyl phthalate (DBP) and Benzylbutyl phthalate (BzBP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00* 22.4 (20.6-24.4) 21.9 (19.8-24.3) 38.9 (35.0-41.8) 68.3 (60.3-78.3) 97.7 (81.4-131) 2541 

01-02 17.8 (16.7-19.0) 17.4 (16.3-18.4) 30.3 (28.1-32.3) 52.4 (47.4-61.0) 81.3 (71.0-92.5) 2782 

03-04 19.8 (18.5-21.2) 19.3 (17.7-20.8) 33.9 (30.9-38.5) 59.0 (52.9-68.1) 91.6 (74.1-115) 2605 

Age group 

6-11 years 99-00* 41.9 (37.4-47.1) 39.1 (34.3-49.0) 65.9 (56.7-80.0) 108 (71.2-179) 159 (102-263) 328 

01-02 35.4 (31.7-39.6) 35.1 (29.3-38.9) 55.4 (50.1-62.3) 84.0 (69.0-113) 147 (93.8-235) 393 

03-04 38.4 (33.8-43.6) 39.0 (34.7-42.6) 59.3 (52.9-68.1) 104 (83.6-119) 137 (108-198) 342 

12-19 years 99-00* 24.3 (21.2-27.8) 23.7 (20.6-27.4) 37.6 (31.6-43.8) 63.3 (52.4-76.4) 88.1 (61.5-142) 752 

01-02 19.4 (17.3-21.7) 20.3 (17.5-22.3) 34.9 (30.5-37.9) 53.4 (45.2-73.9) 89.7 (60.3-106) 742 

03-04 20.0 (18.7-21.3) 19.8 (18.2-21.7) 30.7 (27.9-34.8) 52.7 (43.4-65.4) 74.4 (56.0-90.9) 729 

20 years and older 99-00* 20.4 (18.6-22.4) 19.5 (18.1-21.4) 34.9 (30.3-40.0) 62.4 (53.4-72.1) 91.0 (70.4-135) 1461 

01-02 16.1 (15.0-17.3) 15.5 (14.2-16.5) 26.3 (24.2-28.6) 44.2 (38.7-51.1) 71.6 (61.2-85.6) 1647 

03-04 18.3 (17.0-19.6) 17.7 (16.6-19.2) 31.0 (27.4-34.0) 53.3 (46.5-64.2) 83.8 (65.3-114) 1534 

Gender 

Males 99-00* 17.3 (16.1-18.6) 17.0 (15.5-18.8) 28.6 (25.8-32.1) 49.3 (42.6-53.5) 64.7 (57.3-71.5) 1215 

01-02 14.4 (13.5-15.4) 13.7 (12.9-14.9) 22.9 (20.8-24.6) 39.9 (35.6-44.0) 60.0 (50.5-76.2) 1371 

03-04 15.7 (14.5-16.9) 14.8 (13.6-16.0) 25.4 (23.6-28.1) 41.4 (37.0-47.5) 59.4 (50.3-81.5) 1250 

Females 99-00* 28.6 (25.3-32.3) 28.8 (25.5-30.5) 50.6 (41.9-56.3) 84.3 (69.2-106) 134 (93.6-155) 1326 

01-02 21.7 (19.6-23.9) 21.6 (19.7-23.6) 35.8 (33.0-38.7) 64.9 (58.9-70.2) 91.5 (81.4-103) 1411 

03-04 24.8 (22.9-26.8) 24.1 (21.6-26.8) 42.9 (39.2-48.9) 74.9 (64.2-86.6) 117 (83.6-139) 1355 

Race/ethnicity 

Mexican Americans 99-00* 21.2 (19.3-23.3) 20.0 (18.2-22.9) 40.1 (32.6-44.3) 63.6 (57.5-70.1) 82.9 (73.9-100) 814 

01-02 19.0 (16.2-22.2) 19.2 (16.3-21.9) 33.7 (28.3-39.6) 61.0 (43.9-84.0) 86.7 (60.6-128) 677 

03-04 21.8 (17.7-26.8) 20.4 (17.4-24.0) 37.6 (29.6-50.1) 75.3 (55.6-92.0) 96.3 (76.4-164) 652 

Non-Hispanic blacks 99-00* 23.9 (21.3-26.8) 25.0 (20.7-28.1) 42.2 (35.9-49.6) 70.0 (61.1-83.9) 96.2 (83.9-105) 603 

01-02 20.8 (18.8-23.1) 20.2 (19.2-22.8) 34.5 (30.9-36.8) 62.8 (50.6-74.6) 85.6 (72.1-99.0) 703 

03-04 21.4 (19.5-23.4) 22.0 (19.6-24.8) 35.4 (31.6-42.7) 65.7 (54.0-75.3) 94.0 (71.1-128) 699 

Non-Hispanic whites 99-00* 21.3 (19.1-23.8) 20.5 (18.6-23.2) 36.4 (31.5-41.0) 67.1 (56.7-78.4) 97.7 (73.5-142) 912 

01-02 17.4 (16.2-18.6) 16.5 (15.3-17.8) 29.0 (26.6-32.2) 51.1 (46.0-60.0) 81.4 (68.1-99.0) 1216 

03-04 18.6 (17.3-20.1) 17.9 (16.7-19.8) 31.6 (27.7-37.8) 53.3 (48.2-61.5) 81.5 (64.2-108) 1088 

*In the 1999-2000 survey period, concentrations of mono-isobutyl phthalate and mono-n-butyl phthalate were measured together and expressed as a combined value. 
Fourth National Report on Human Exposure to Environmental Chemicals 269

 Phthalates 

References

Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, 

Jacek R, et al. Prenatal exposures to phthalates among women 

in New York City and Krakow, Poland. Environ Health Perspect 

2003;111(14):1719-1722.

Anderson WA, Castle L, Scotter MJ, Massey RC, Springall C. 

A biomarker approach to measuring human dietary exposure to 

certain phthalate diesters. Food Addit Contam 2001;18(12):1068-

1074.

Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, 

Sampson EJ, et al. Levels of seven urinary phthalate metabolites 

in a human reference population. Environ Health Perspect 

2000;108(10)979-982.

Brock JW, Caudill SP, Silva MJ, Needham LL, Hilborn ED. 

Phthalate monoesters levels in the urine of young children. Bull 

Environ Contam Toxicol 2002;68:309-314.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Duty SM, Calafat AM, Silva MJ, Brock JW, Ryan L, Chen Z, et al. 

The relationship between environmental exposure to phthalates 

and computer-aided sperm analysis motion parameters. J Androl 

2004;25(2):293-302.

Fromme H, Bolte G, Koch HM, Angerer J, Boehmer S, Drexler 

H, et al. Occurrence and daily variation of phthalate metabolites 

in the urine of an adult population. Int J Hyg Environ Health 

2007;210:21-33.

Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, et 

al. DNA damage in human sperm is related to urinary levels of 

phthalate monoester and oxidative metabolites. Hum Reprod 

2007;22(3):688-695.

Itoh H, Yoshida K, Masunaga S. Evaluation of the effect ofa

governmental control of human exposure to two phthalates in 

Japan using a urinary biomarker approach. Int J Hyg Environ 

Health 2005;208:237-245.

Jonsson BAG, Richthoff J, Rylander L, Giwercman A, Hagmar 

L. Urinary phthalate metabolites and biomarkers of reproductive 

function in young men. Epidemiol 2005;16(4):487-493.

Koch HM, Rossbach B, Drexler H, Angerer J. Internal exposure 

of the general population to DEHP and other phthalates - 

determination of secondary and primary phthalate monoester 

metabolites in urine. Environ Res 2003;93:177-185.

McKee RH, Butala JH, David RM, Gans G. NTP center for the 

evaluation of risks to human reproduction reports on phthalates: 

addressing the data gaps [review]. Reprod Toxicol 2004;18(1):1-

22.

NTP-CERHR. National Toxicology Program-Center for the 

Evaluation of Risks to Human Reproduction. Monograph on the 

Potential Human Reproductive and Developmental Effects of 

Di-n-Butyl Phthalate (DBP). Research Triangle Park (NC). 2000 

[online]. Available at URL: http://cerhr.niehs.nih.gov/chemicals/

phthalates/dbp/dbp-eval.html. 4/20/09

Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, 

et al. Urinary levels of seven phthalate metabolites in the U.S. 

population from the National Health and Nutrition Examination 

Survey (NHANES) 1999-2000 [published erratum appears in 

Environ Health Perspect 2004; 112(5):A270]. Environ Health 

Perspect 2004;112(3):331-338.

Weuve J, Sanchez GN, Calafat AM, Schettler T, Green RA, Hu 

H, et al. Exposure to phthalates in neonatal intensive care unit 

infants: urinary concentrations of monoesters and oxidative 

metabolites. Environ Health Perspect 2006;114(9):1424-1431.

Wittassek M, Wiesmuller GA, Koch HM, Eckard R, Dobler 

L, Helm D, et al. Internal phthalate exposure over the last two 

decades—a retrospective human biomonitoring study. Int J Hyg 

Environ Health 2007;210(3-4):319-33.
 270 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Dicyclohexyl Phthalate

CAS No. 84-61-7

General Information

Dicyclohexyl phthalate (DCHP) is used to stabilize some 

rubbers, resins, and polymers, including nitrocellulose, 

polyvinyl acetate, and polyvinyl chloride. People exposed 

to DCHP will excrete mono-cyclohexyl phthalate (MCHP) 

in their urine. Neither IARC nor NTP has evaluated DCHP 

with respect to human carcinogenicity.

Biomonitoring Information

Urinary levels of MCHP are infrequently measured and the 

limited population-based surveys available to date have 

reported most levels below the limit of detection. In this 

Report, only levels at or above the 90th percentile could be 

characterized.

Finding a measurable amount of MCHP in urine does not 

mean that the levels of MCHP or the parent compound 

cause an adverse health effect. Biomonitoring studies on 

levels of urinary MCHP provide physicians and public 

health officials with reference values so that they can 

determine whether people have been exposed to higher 

levels of DHCP than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

Urinary Mono-cyclohexyl phthalate (MCHP) 

Metabolite of Dicyclohexyl phthalate (DCHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 1.10 (<LOD-1.70) 2541 

01-02 * < LOD < LOD .400 (.300-.500) .500 (.400-.600) 2782 

03-04 * < LOD < LOD < LOD .300 (.200-.400) 2605 

Age group 

6-11 years 99-00 * < LOD < LOD 1.00 (<LOD-1.10) 1.70 (1.00-3.80) 328

01-02 * < LOD < LOD .400 (.300-.500) .600 (.500-.700) 393

03-04 * < LOD < LOD .300 (<LOD-.400) .500 (.300-.500) 342

12-19 years 99-00 * < LOD < LOD 1.00 (<LOD-1.50) 1.70 (1.00-2.50) 752

01-02 * < LOD < LOD .400 (.300-.500) .500 (.400-.600) 742

03-04 * < LOD < LOD .200 (<LOD-.300) .400 (.300-.600) 729

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1461 

01-02 * < LOD < LOD .400 (<LOD-.500) .500 (.400-.600) 1647 

03-04 * < LOD < LOD < LOD .300 (.200-.300) 1534 

Gender 

Males 99-00 * < LOD < LOD < LOD 1.10 (<LOD-2.00) 1215 

01-02 * < LOD < LOD .400 (.300-.500) .500 (.400-.600) 1371 

03-04 * < LOD < LOD < LOD .300 (.300-.400) 1250 

Females 99-00 * < LOD < LOD < LOD 1.10 (<LOD-1.90) 1326 

01-02 * < LOD < LOD .400 (<LOD-.400) .500 (.400-.500) 1411 

03-04 * < LOD < LOD < LOD .300 (.200-.500) 1355 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 814

01-02 * < LOD < LOD .400 (<LOD-.500) .500 (.300-.700) 677

03-04 * < LOD < LOD < LOD .300 (.200-.500) 652

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 1.10 (.900-1.20) 603

01-02 * < LOD < LOD .400 (.300-.500) .500 (.400-.700) 703

03-04 * < LOD < LOD .300 (.200-.300) .400 (.300-.500) 699

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 1.00 (<LOD-1.70) 912

01-02 * < LOD < LOD .400 (<LOD-.400) .500 (.400-.600) 1216 

03-04 * < LOD < LOD < LOD .300 (.200-.400) 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.9, 0.3, and 0.2, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 271

 Phthalates 

Urinary Mono-cyclohexyl phthalate (MCHP) (creatinine corrected) 

Metabolite of Dicyclohexyl phthalate (DCHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 3.00 (<LOD-3.33) 2541 

01-02 * < LOD < LOD .610 (.530-.690) .910 (.770-1.00) 2782 

03-04 * < LOD < LOD < LOD .450 (.400-.500) 2605 

Age group 

6-11 years 99-00 * < LOD < LOD 1.54 (<LOD-2.34) 2.82 (1.54-6.44) 328

01-02 * < LOD < LOD .690 (.510-.740) .940 (.690-1.17) 393

03-04 * < LOD < LOD .370 (<LOD-.530) .530 (.350-.830) 342

12-19 years 99-00 * < LOD < LOD 1.22 (<LOD-1.54) 1.67 (1.36-1.82) 752

01-02 * < LOD < LOD .470 (.380-.660) .770 (.530-1.18) 742

03-04 * < LOD < LOD .220 (<LOD-.270) .380 (.240-.620) 729

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1461 

01-02 * < LOD < LOD .630 (<LOD-.690) .910 (.770-1.05) 1647 

03-04 * < LOD < LOD < LOD .450 (.400-.500) 1534 

Gender 

Males 99-00 * < LOD < LOD < LOD 2.14 (<LOD-3.16) 1215 

01-02 * < LOD < LOD .510 (.420-.660) .880 (.670-1.06) 1371 

03-04 * < LOD < LOD < LOD .330 (.290-.500) 1250 

Females 99-00 * < LOD < LOD < LOD 3.33 (<LOD-3.53) 1326 

01-02 * < LOD < LOD .670 (<LOD-.770) .910 (.800-1.10) 1411 

03-04 * < LOD < LOD < LOD .500 (.420-.590) 1355 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 814

01-02 * < LOD < LOD .590 (<LOD-.690) .950 (.790-1.11) 677

03-04 * < LOD < LOD < LOD .390 (.310-.560) 652

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 1.43 (1.12-1.74) 603

01-02 * < LOD < LOD .410 (.360-.490) .590 (.500-.710) 703

03-04 * < LOD < LOD .250 (.170-.310) .330 (.260-.470) 699

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 3.16 (<LOD-3.53) 912

01-02 * < LOD < LOD .630 (<LOD-.740) .910 (.770-1.06) 1216 

03-04 * < LOD < LOD < LOD .480 (.420-.530) 1088 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 272 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Diethyl Phthalate

CAS No. 84-66-2

General Information

Diethyl phthalate (DEP) is a solvent used in many consumer 

products, particularly those containing fragrances. Products 

that may contain DEP include perfumes, colognes, 

deodorants, soaps, shampoos, and hand lotions. People 

exposed to DEP eliminate mono-ethyl phthalate (MEP) in 

their urine. Workplace air guidelines for external exposure 

to DEP have been established by ACGIH and NIOSH. 

Neither IARC nor NTP has evaluated DEP with respect to 

human carcinogenicity.

Biomonitoring Information

MEP levels in the NHANES 1999-2000, 2001-2002, and 

2003-2004 subsamples were similar to median or geometric 

mean levels in small samples of pregnant women in New 

York City (Adibi et al., 2003) and African-American women 

in Washington, DC (Hoppin et al., 2002), and also in men 

attending a Boston infertility clinic (Hauser et al., 2007). 

In contrast, a sample of young Swedish males entering 

the military had median urinary MEP levels that were 

somewhat higher than males in the NHANES subsamples. 

A small study of children less than 2 years old reported 

mean urine MEP levels that were about twice as high as 

levels in children (aged 6-11 years) in NHANES 2001-

Urinary Mono-ethyl phthalate (MEP) 

Metabolite of Diethyl phthalate (DEP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 179 (156-204) 164 (136-201) 454 (370-538) 1260 (1010-1480) 2840 (2150-3770) 2536

01-02 178 (159-199) 169 (141-194) 465 (415-527) 1230 (1040-1440) 2500 (1860-3220) 2782

03-04 193 (169-220) 174 (151-208) 502 (457-555) 1380 (1170-1750) 2700 (2160-3310) 2605

Age group 

6-11 years 99-00 91.3 (74.8-111) 75.4 (62.1-93.7) 197 (129-249) 378 (290-730) 756 (379-1070) 328

01-02 85.1 (71.2-102) 71.9 (61.9-92.5) 183 (142-217) 451 (315-636) 808 (572-1090) 393

03-04 95.3 (82.3-110) 81.7 (70.3-103) 196 (170-241) 521 (295-571) 827 (542-1440) 342

12-19 years 99-00 211 (160-278) 193 (141-256) 564 (419-818) 1510 (1050-2150) 3260 (1550-4420) 752

01-02 197 (159-243) 184 (148-227) 479 (387-651) 1260 (983-1480) 2070 (1470-3050) 742

03-04 225 (187-270) 221 (165-294) 557 (432-695) 1250 (973-1560) 2310 (1360-3310) 729

20 years and older 99-00 190 (164-219) 180 (140-221) 482 (390-590) 1340 (1010-1660) 3480 (2230-4640) 1456

01-02 191 (171-214) 181 (152-212) 498 (441-567) 1350 (1060-1660) 2720 (2160-3670) 1647

03-04 205 (176-238) 188 (158-219) 533 (471-629) 1590 (1220-2070) 2980 (2250-3800) 1534

Gender 

Males 99-00 179 (149-215) 154 (119-197) 523 (372-650) 1440 (1020-2280) 3500 (2130-4560) 1214

01-02 182 (157-211) 171 (139-199) 502 (419-603) 1450 (1060-2110) 3100 (2110-4390) 1371

03-04 197 (173-224) 171 (148-201) 536 (449-654) 1520 (1210-2070) 2910 (2210-3480) 1250

Females 99-00 178 (154-206) 174 (138-210) 425 (350-508) 988 (880-1230) 2230 (1370-3880) 1322

01-02 174 (153-198) 167 (139-194) 427 (387-498) 1050 (879-1310) 1860 (1490-2500) 1411

03-04 189 (160-225) 182 (138-219) 478 (392-564) 1260 (969-1640) 2590 (1800-3420) 1355

Race/ethnicity 

Mexican Americans 99-00 181 (157-209) 174 (146-210) 441 (390-541) 1280 (851-1510) 1720 (1460-2130) 813

01-02 226 (195-262) 220 (190-264) 530 (444-660) 1490 (1050-2110) 2630 (1540-4460) 677

03-04 267 (239-298) 249 (212-307) 597 (523-688) 1640 (1320-2180) 3050 (2230-4300) 652

Non-Hispanic blacks 99-00 322 (275-377) 306 (256-350) 789 (635-949) 1890 (1410-2270) 3610 (2130-4640) 603

01-02 352 (324-384) 357 (290-407) 853 (709-1090) 2160 (1620-2470) 3540 (2810-5070) 703

03-04 357 (310-412) 306 (253-414) 948 (769-1150) 2500 (1840-2980) 4370 (2780-5910) 699

Non-Hispanic whites 99-00 152 (133-175) 134 (108-157) 367 (287-482) 986 (798-1340) 2470 (1590-3880) 908

01-02 158 (141-178) 147 (119-177) 413 (366-451) 1020 (905-1230) 2320 (1560-2720) 1216

03-04 167 (145-193) 148 (125-175) 418 (366-477) 1210 (954-1480) 2250 (1590-3290) 1088

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 1.2, 0.9, and 0.4, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 273

 Phthalates 

2002 (Brock et al., 2002). Median MEP levels found in a 

small sample of German residents (Koch et al., 2003) were 

slightly lower than levels found in NHANES 2001-2002.

In an analysis of NHANES 1999-2000, the adjusted 

geometric mean levels of urinary MEP were lower in 

the group aged 6-11 years than in either of the other age 

groups. This age-related trend is opposite the direction 

seen for other phthalates. Other population estimates also 

differed by sex and race ethnicity (Silva et al., 2004). 

Analysis of NHANES 2001-2002 showed similar findings, 

with adjusted geometric mean levels of urinary MEP that 

increased with age (CDC, 2005).

Finding a measurable amount of MEP in urine does not 

mean that the levels of MEP or the parent compound cause 

an adverse health effect. Biomonitoring studies on levels 

of MEP provide physicians and public health officials with 

reference values so that they can determine whether people 

have been exposed to higher levels of DEP than are found 

in the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Urinary Mono-ethyl phthalate (MEP) (creatinine corrected) 

Metabolite of Diethyl phthalate (DEP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 163 (149-178) 141 (129-157) 360 (307-422) 905 (753-1180) 1950 (1670-2310) 2536

01-02 167 (150-185) 148 (133-162) 388 (330-435) 969 (805-1180) 1840 (1450-2200) 2782

03-04 181 (163-202) 153 (137-177) 452 (386-504) 1110 (889-1290) 2040 (1640-2540) 2605

Age group 

6-11 years 99-00 92.6 (77.9-110) 79.6 (65.7-110) 165 (127-208) 341 (219-554) 625 (400-784) 328

01-02 96.9 (82.5-114) 81.2 (66.3-105) 177 (135-224) 512 (290-802) 843 (512-1320) 393

03-04 101 (87.0-117) 87.0 (66.5-113) 180 (145-203) 470 (310-596) 719 (470-1330) 342

12-19 years 99-00 142 (119-169) 122 (93.0-156) 364 (275-495) 879 (676-1260) 1760 (1000-2000) 752

01-02 152 (126-184) 140 (111-180) 330 (249-409) 808 (590-1100) 1330 (868-1840) 742

03-04 168 (141-201) 150 (123-184) 363 (292-485) 791 (589-1080) 1470 (987-2220) 729

20 years and older 99-00 179 (161-199) 154 (136-177) 390 (336-452) 1010 (803-1460) 2170 (1790-3350) 1456

01-02 181 (164-200) 160 (146-182) 419 (363-486) 1060 (884-1320) 2120 (1520-2790) 1647

03-04 197 (174-223) 177 (147-202) 512 (423-632) 1230 (989-1610) 2290 (1770-3200) 1534

Gender 

Males 99-00 141 (124-159) 120 (107-134) 324 (249-415) 1000 (693-1480) 1950 (1460-2900) 1214

01-02 148 (130-168) 126 (110-147) 352 (282-425) 1100 (839-1480) 2120 (1490-3030) 1371

03-04 154 (139-171) 127 (108-150) 390 (341-465) 1070 (852-1360) 2000 (1610-2410) 1250

Females 99-00 187 (165-211) 158 (142-179) 377 (307-495) 822 (697-1170) 1930 (1170-3410) 1322

01-02 187 (166-210) 171 (148-188) 407 (355-473) 860 (712-1100) 1430 (1190-2010) 1411

03-04 211 (180-248) 181 (148-217) 508 (379-634) 1120 (889-1400) 2250 (1440-3330) 1355

Race/ethnicity 

Mexican Americans 99-00 164 (142-190) 154 (136-174) 382 (314-472) 814 (673-974) 1330 (974-1920) 813

01-02 213 (182-249) 199 (164-242) 461 (396-572) 1080 (860-1650) 1940 (1410-2630) 677

03-04 241 (213-271) 233 (202-270) 533 (417-665) 1230 (956-1610) 2270 (1810-3140) 652

Non-Hispanic blacks 99-00 208 (183-236) 196 (166-228) 443 (390-505) 1030 (762-1700) 1920 (1230-2590) 603

01-02 247 (226-271) 227 (185-270) 557 (478-618) 1240 (961-1480) 2090 (1550-2800) 703

03-04 254 (225-287) 212 (188-246) 619 (476-791) 1530 (1200-1970) 2590 (2160-3500) 699

Non-Hispanic whites 99-00 149 (135-165) 128 (111-142) 313 (239-387) 856 (655-1390) 1950 (1480-2740) 908

01-02 157 (142-173) 136 (124-150) 338 (288-402) 919 (712-1160) 1590 (1320-2170) 1216

03-04 165 (144-189) 135 (120-158) 386 (338-485) 989 (831-1330) 1920 (1400-2780) 1088
 274 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

References

Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, 

Jacek R, et al. Prenatal exposures to phthalates among women 

in New York City and Krakow, Poland. Environ Health Perspect 

2003;111(14):1719-1722.

Brock JW, Caudill SP, Silva MJ, Needham LL, Hilborn ED. 

Phthalate monoesters levels in the urine of young children. Bull 

Environ Contam Toxicol 2002;68:309-314.

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, et 

al. DNA damage in human sperm is related to urinary levels of 

phthalate monoester and oxidative metabolites. Hum Reprod 

2007;22(3):688-695.

Hoppin JA, Brock JW, Davis BJ, Baird DD. Reproducibility 

of urinary phthalate metabolites in first morning urine samples. 

Environ Health Perspect 2002;110(5):515-518.

Koch HM, Rossbach B, Drexler H, Angerer J. Internal exposure 

of the general population to DEHP and other phthalates - 

determination of secondary and primary phthalate monoester 

metabolites in urine. Environ Res 2003;93:177-185.

Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, 

et al. Urinary levels of seven phthalate metabolites in the U.S. 

population from the National Health and Nutrition Examination 

Survey (NHANES) 1999-2000 [published erratum appears in 

Environ Health Perspect 2004; 112(5):A270]. Environ Health 

Perspect 2004;112(3):331-338.
Fourth National Report on Human Exposure to Environmental Chemicals 275

 Phthalates 

Di-2-ethylhexyl Phthalate

CAS No. 117-81-7

General Information

Di-2-ethylhexyl phthalate (DEHP) is primarily used to 

produce flexibility in plastics, mainly polyvinyl chloride, 

which is used for many consumer products, toys, packaging 

film, and blood product storage and intravenous delivery 

systems. Concentrations in plastic materials may reach 

40% by weight. DEHP has been removed from or replaced 

in most toys and food packaging in the United States.

Following ingestion, DEHP is metabolized to more than 

30 metabolites which are rapidly eliminated in urine, 

and in humans, as glucuronide conjugates (Albro et al., 

1982; Albro and Lavenhar, 1989; ATSDR, 2002; Peck 

and Albro,1982). Four metabolites were measured in this 

Report: mono-(2-ethyl-5-hexyl) phthalate (MEHP), mono-

(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl5-carboxypentyl) phthalate (MECPP).

MEHP is primarily formed by the hydrolysis of DEHP in 

the gastrointestinal tract and then absorbed. DEHP present 

in medical devices and parenteral delivery systems results 

in the diester rather than the monoester form being directly 

introduced into the blood. After parenteral administration, 

Urinary Mono-2-ethylhexyl phthalate (MEHP) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 3.43 (3.19-3.69) 3.20 (3.00-3.60) 7.60 (6.80-8.40) 14.9 (13.5-17.4) 23.8 (19.2-28.6) 2541

01-02 4.27 (3.80-4.79) 4.20 (3.70-4.90) 9.80 (8.40-11.6) 23.0 (19.1-27.9) 39.2 (31.8-50.0) 2782

03-04 2.34 (2.10-2.62) 1.90 (1.70-2.40) 5.30 (4.50-6.60) 15.1 (11.4-20.6) 31.0 (21.4-42.0) 2605

Age group 

6-11 years 99-00 5.12 (4.42-5.92) 4.90 (3.70-6.40) 11.1 (8.30-13.6) 19.0 (13.8-36.1) 35.3 (15.6-130) 328

01-02 4.41 (3.90-5.00) 4.40 (4.10-5.30) 9.30 (7.90-11.7) 19.7 (14.6-25.9) 31.4 (21.8-47.9) 393

03-04 2.84 (2.10-3.84) 2.70 (1.80-4.10) 6.40 (4.40-9.60) 13.9 (7.80-27.6) 27.6 (11.3-64.7) 342

12-19 years 99-00 3.75 (3.24-4.35) 3.70 (2.90-4.60) 8.10 (6.40-9.40) 15.3 (11.4-20.5) 22.8 (19.1-29.2) 752

01-02 4.57 (3.96-5.27) 4.50 (3.70-5.10) 11.0 (9.50-14.4) 23.0 (17.7-32.7) 42.5 (25.9-57.5) 742

03-04 2.77 (2.25-3.41) 2.50 (2.00-3.00) 6.40 (4.50-8.60) 18.6 (10.2-35.6) 40.6 (20.7-58.4) 729

20 years and older 99-00 3.21 (2.94-3.51) 3.00 (2.70-3.40) 7.30 (6.40-8.00) 14.5 (12.1-17.0) 22.7 (17.5-27.0) 1461

01-02 4.20 (3.63-4.86) 4.10 (3.50-5.00) 9.50 (8.10-11.9) 23.5 (18.0-29.8) 39.5 (30.3-57.1) 1647

03-04 2.23 (2.03-2.44) 1.70 (1.50-2.00) 5.10 (4.50-6.00) 15.1 (10.9-19.7) 29.5 (20.4-40.0) 1534

Gender 

Males 99-00 3.68 (3.31-4.10) 3.40 (2.90-3.90) 8.00 (7.40-8.80) 16.0 (14.0-19.0) 25.3 (19.5-36.7) 1215

01-02 4.31 (3.84-4.83) 4.30 (3.70-5.10) 9.70 (8.30-11.2) 23.0 (16.9-29.8) 37.9 (29.9-48.4) 1371

03-04 2.56 (2.26-2.90) 2.20 (1.70-2.60) 6.00 (4.60-7.70) 17.2 (11.3-26.3) 33.3 (24.9-55.5) 1250

Females 99-00 3.21 (2.91-3.54) 3.10 (2.80-3.50) 7.10 (5.90-8.50) 13.6 (12.1-17.2) 21.9 (15.6-28.5) 1326

01-02 4.23 (3.67-4.86) 4.10 (3.50-5.00) 9.80 (8.40-12.2) 23.0 (19.5-28.4) 43.5 (31.4-53.7) 1411

03-04 2.15 (1.92-2.42) 1.80 (1.50-2.10) 4.90 (4.10-5.70) 13.2 (10.0-18.1) 27.8 (17.5-40.7) 1355

Race/ethnicity 

Mexican Americans 99-00 3.49 (3.16-3.85) 3.50 (3.10-3.90) 7.00 (5.70-8.60) 13.3 (10.7-18.7) 23.9 (17.4-27.3) 814

01-02 4.32 (3.75-4.98) 4.70 (3.80-5.70) 10.1 (8.50-11.4) 19.6 (16.6-23.0) 28.5 (24.2-39.9) 677

03-04 2.35 (1.87-2.96) 2.20 (1.50-3.00) 5.10 (4.30-6.60) 11.2 (7.50-16.5) 18.5 (11.6-38.2) 652

Non-Hispanic blacks 99-00 4.82 (3.92-5.93) 5.20 (4.10-5.80) 9.50 (7.60-11.4) 19.5 (12.9-26.5) 29.5 (18.6-60.3) 603

01-02 6.60 (5.57-7.82) 6.70 (5.40-8.10) 15.4 (13.0-18.7) 32.9 (26.5-41.4) 52.6 (41.0-84.0) 703

03-04 3.61 (3.07-4.23) 3.50 (3.00-4.00) 8.50 (7.10-11.4) 22.9 (16.5-28.6) 35.2 (29.3-49.1) 699

Non-Hispanic whites 99-00 3.16 (2.89-3.46) 2.80 (2.50-3.10) 7.40 (6.30-8.40) 14.5 (12.2-17.4) 22.4 (16.9-28.5) 912

01-02 3.85 (3.37-4.40) 3.70 (3.10-4.40) 8.70 (7.80-9.90) 20.9 (17.3-25.9) 37.9 (29.9-49.5) 1216

03-04 2.14 (1.92-2.39) 1.70 (1.40-1.90) 4.80 (4.00-5.80) 13.6 (9.50-20.0) 31.0 (18.1-48.9) 1088

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 1.2, 1.0, and 0.9, respectively. 
 276 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

hydrolysis of DEHP most likely also occurs in the blood, 

and subsequent metabolism is similar to that following 

ingestion (Koch et al., 2005a, 2005b, 2005c). MEOHP, 

MEHHP, and MECPP are produced by the oxidative 

metabolism of MEHP and are present at roughly three- to 

five-fold higher concentrations than MEHP in urine (Barr 

et al., 2003; Fromme et al., 2007; Koch et al., 2003).

MEHP is the putative toxic metabolite of DEHP. Liver 

toxicity, decreased testicular weight, and testicular 

atrophy have been observed in rodents fed high doses 

over a short term or with chronic dosing (McKee et al., 

2004; NTP-CERHR, 2000c, 2006). In contrast, marmoset 

monkeys fed high dose DEHP for longer than a year did 

not demonstrate testicular or liver toxicity (NTP-CERHR, 

2006). Very high doses of DEHP have suppressed estradiol 

production in female rats (Lovecamp-Swan and Davis, 

2003). The Food and Drug Administration determined that 

in adults, the amounts of DEHP or MEHP received from 

intravenous delivery systems or blood transfusions (DEHP 

is hydrolyzed to MEHP in stored blood) would result in 

short-term elevations similar to background levels (FDA, 

2001). However, critically ill neonates and infants receiving 

selected or multiple intensive procedures, such as exchange 

transfusions, extracorporeal membrane oxygenation, and 

parenteral nutrition, could receive higher exposures than 

the general population (Calafat et al., 2004; FDA, 2001; 

Loff et al., 2000; Weuve et al., 2006).

Urinary Mono-2-ethylhexyl phthalate (MEHP) (creatinine corrected) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 3.12 (2.95-3.31) 3.08 (2.82-3.27) 5.88 (5.38-6.25) 10.8 (9.62-12.5) 18.9 (15.0-21.8) 2541

01-02 4.00 (3.58-4.48) 3.90 (3.44-4.47) 7.94 (7.22-9.02) 18.0 (15.3-21.5) 32.8 (25.2-42.9) 2782

03-04 2.20 (2.01-2.41) 1.89 (1.68-2.19) 4.31 (3.84-4.74) 10.8 (8.72-13.8) 25.4 (16.7-34.7) 2605

Age group 

6-11 years 99-00 5.19 (4.55-5.93) 5.37 (4.52-5.95) 9.11 (8.06-11.4) 21.6 (11.5-41.9) 41.9 (13.5-86.2) 328

01-02 5.03 (4.47-5.65) 5.38 (4.51-6.21) 9.90 (7.87-11.5) 21.1 (13.8-28.8) 31.4 (24.3-40.7) 393

03-04 3.00 (2.30-3.93) 2.80 (1.93-4.09) 5.86 (4.69-7.70) 14.3 (8.54-24.4) 28.7 (14.1-45.3) 342

12-19 years 99-00 2.53 (2.14-2.99) 2.35 (2.05-2.76) 5.83 (4.38-6.29) 9.66 (7.41-11.5) 12.1 (10.5-17.3) 752

01-02 3.53 (3.09-4.03) 3.67 (2.89-4.48) 7.47 (6.51-8.67) 15.2 (11.7-21.9) 25.2 (17.7-32.8) 742

03-04 2.07 (1.74-2.48) 1.88 (1.60-2.23) 4.25 (3.19-5.62) 11.6 (6.83-23.2) 24.8 (11.6-37.9) 729

20 years and older 99-00 3.03 (2.83-3.25) 2.98 (2.73-3.23) 5.55 (4.90-6.06) 10.0 (8.60-12.9) 17.5 (13.8-22.1) 1461

01-02 3.97 (3.49-4.52) 3.82 (3.26-4.38) 7.79 (7.00-9.00) 18.3 (15.3-21.8) 34.5 (23.1-47.9) 1647

03-04 2.14 (1.98-2.31) 1.84 (1.63-2.08) 4.14 (3.78-4.40) 10.5 (8.38-12.9) 25.6 (15.9-36.3) 1534

Gender 

Males 99-00 2.89 (2.60-3.22) 2.76 (2.52-2.96) 5.58 (4.71-6.08) 10.3 (9.35-12.4) 21.6 (14.1-27.7) 1215

01-02 3.50 (3.08-3.99) 3.33 (2.83-3.90) 7.00 (6.49-7.77) 16.2 (12.8-20.9) 31.6 (20.5-49.4) 1371

03-04 2.01 (1.82-2.21) 1.71 (1.46-1.89) 4.14 (3.49-4.81) 10.4 (7.68-16.2) 23.3 (15.1-41.1) 1250

Females 99-00 3.36 (3.11-3.63) 3.33 (2.91-3.80) 6.15 (5.55-6.77) 11.1 (9.11-14.0) 17.3 (12.4-24.6) 1326

01-02 4.54 (4.02-5.13) 4.47 (3.85-5.14) 9.28 (7.94-10.3) 20.3 (16.6-24.4) 34.7 (27.1-42.0) 1411

03-04 2.40 (2.15-2.69) 2.16 (1.84-2.40) 4.40 (3.97-4.89) 10.9 (8.27-16.0) 27.0 (17.5-34.6) 1355

Race/ethnicity 

Mexican Americans 99-00 3.16 (2.72-3.68) 3.15 (2.52-3.81) 5.88 (4.86-7.24) 11.6 (9.63-13.1) 15.7 (12.6-23.1) 814

01-02 4.07 (3.60-4.61) 4.18 (3.82-4.90) 7.80 (6.64-9.49) 16.4 (13.6-18.9) 24.9 (19.8-28.7) 677

03-04 2.12 (1.74-2.59) 1.94 (1.50-2.42) 4.06 (3.29-4.93) 9.38 (5.72-15.4) 16.8 (9.86-38.6) 652

Non-Hispanic blacks 99-00 3.11 (2.59-3.73) 3.13 (2.50-3.61) 5.84 (4.43-7.32) 10.2 (8.05-15.6) 18.4 (11.6-35.2) 603

01-02 4.63 (3.96-5.42) 4.59 (3.97-5.02) 9.93 (7.95-12.4) 21.2 (16.0-33.2) 39.9 (27.7-48.1) 703

03-04 2.56 (2.24-2.92) 2.28 (2.02-2.78) 5.17 (4.48-6.83) 13.2 (10.5-16.2) 27.5 (18.4-36.0) 699

Non-Hispanic whites 99-00 3.09 (2.84-3.36) 3.08 (2.73-3.47) 5.87 (5.11-6.67) 10.6 (8.95-13.5) 20.0 (14.0-24.6) 912

01-02 3.81 (3.34-4.35) 3.67 (3.11-4.33) 7.78 (6.74-9.35) 17.0 (14.1-21.8) 32.8 (21.5-46.9) 1216

03-04 2.12 (1.91-2.35) 1.82 (1.60-2.13) 4.11 (3.49-4.42) 10.7 (7.42-15.1) 27.0 (15.1-37.4) 1088
Fourth National Report on Human Exposure to Environmental Chemicals 277

 Phthalates 

OSHA has established a workplace air standard for external 

exposure to DEHP; NIOSH and ACGIH have established 

guidelines for workplace air exposure to DEHP. IARC 

considers DEHP to be unclassifiable with respect to human 

carcinogenicity. NTP determined that DEHP is reasonably 

anticipated to be a human carcinogen.

Biomonitoring Information

The levels of MEHP reported in NHANES 1999-2000, 

2001-2002, and 2003-2004 appear roughly comparable 

to those reported previously in several small U.S. studies 

involving adults (Blount et al., 2000), pregnant women 

in New York City (Adibi et al., 2003), and low income 

African-American women in Washington, DC (Hoppin et 

al., 2002). In contrast, a sample of South Korean women had 

higher urine MEHP levels: the geometric mean was about 

ten times higher than for females in each of the NHANES 

survey periods (Koo and Lee, 2005; CDC, 2005). Median 

urine MEHP levels in a small group of Japanese adults, in 

a group of Swedish male military recruits, and in samples 

of men attending an infertility clinic were similar to median 

values for adults and males, respectively, in NHANES 

1999-2000 and 2001-2002 subsamples (Duty et al., 2004, 

2005; Itoh et al., 2005).

In another sample of men attending an infertility clinic, 

the median and 95th percentile values of urinary MEHP 

were similar, but MEHHP and MEOHP were about three 

to five times higher than comparable values found in males 

in two NHANES survey periods (1999-2000, 2001-2002) 

(CDC, 2005; Hauser et al., 2007). Compared with the U.S. 

population in this Report, urinary MEHP, MEOHP, and 

MEHHP levels were similar or up to twofold higher in a 

sample of German residents (Koch et al., 2003; Preuss et 

al., 2005) and German children (Becker et al., 2004; Koch 

et al., 2004). During 2001-2003, median levels of urinary 

MEOHP and MEHHP appeared to be similar in samples of 

German university students and the adults in this Report

(Wittasek et al., 2007).

In separate analyses of NHANES 1999-2000 and NHANES 

2001-2002, the adjusted geometric mean levels of urinary 

MEHP were significantly higher in children compared with 

adolescents and adults, and in females compared with males 

(CDC, 2005; Silva et al., 2004). South Korean children had 

geometric mean urine MEHP levels that were about three 

times higher than the U.S. children in this Report (Koo and 

Urinary Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 20.0 (17.8-22.5) 20.1 (17.8-22.4) 43.6 (38.0-49.7) 92.3 (77.0-108) 192 (131-256) 2782 

03-04 21.7 (19.3-24.4) 21.2 (18.7-24.1) 49.1 (40.5-56.9) 121 (91.3-164) 266 (165-383) 2605 

Age group 

6-11 years 01-02 33.6 (29.7-37.9) 32.9 (26.9-39.1) 66.9 (49.7-74.0) 127 (103-148) 216 (137-280) 393

03-04 36.9 (28.4-47.9) 36.5 (26.5-47.0) 77.4 (49.1-103) 164 (79.9-350) 318 (164-400) 342

12-19 years 01-02 24.9 (21.3-29.1) 25.3 (22.9-31.3) 50.6 (40.7-64.5) 107 (78.5-148) 216 (117-330) 742

03-04 28.3 (23.0-34.8) 29.8 (25.9-33.9) 56.9 (45.4-73.7) 157 (84.1-299) 317 (176-553) 729

20 years and older 01-02 18.1 (15.7-20.9) 17.8 (14.7-20.7) 39.8 (32.7-48.0) 86.2 (65.7-107) 175 (110-279) 1647 

03-04 19.5 (17.7-21.5) 18.4 (16.6-21.0) 41.9 (36.9-51.2) 107 (88.2-136) 225 (148-384) 1534 

Gender 

Males 01-02 22.0 (19.5-24.7) 21.2 (19.4-24.2) 48.0 (41.4-54.4) 94.2 (80.8-110) 212 (130-256) 1371 

03-04 24.1 (20.9-27.9) 22.9 (19.2-27.9) 51.0 (40.5-59.8) 133 (94.8-220) 317 (162-470) 1250 

Females 01-02 18.3 (15.7-21.4) 18.2 (14.9-22.1) 39.8 (34.3-46.0) 86.0 (69.4-115) 170 (119-273) 1411 

03-04 19.7 (17.4-22.2) 19.4 (16.7-22.8) 46.4 (37.5-54.4) 103 (84.1-148) 214 (140-318) 1355 

Race/ethnicity 

Mexican Americans 01-02 18.5 (16.2-21.1) 19.1 (16.3-21.6) 36.3 (31.6-44.0) 79.9 (66.4-93.9) 123 (100-161) 677

03-04 18.9 (15.4-23.4) 19.8 (17.6-22.3) 37.5 (30.0-45.6) 72.2 (52.4-115) 116 (71.6-327) 652

Non-Hispanic blacks 01-02 29.8 (26.1-34.1) 30.9 (27.2-34.3) 61.9 (52.6-69.4) 126 (108-157) 276 (157-339) 703

03-04 30.8 (26.8-35.5) 29.1 (25.3-32.3) 65.6 (53.7-76.3) 154 (113-178) 275 (174-401) 699

Non-Hispanic whites 01-02 19.1 (16.7-21.9) 19.2 (16.9-21.4) 41.7 (35.3-50.7) 91.1 (75.6-110) 212 (130-275) 1216 

03-04 20.8 (18.6-23.3) 19.7 (17.2-22.5) 47.5 (39.4-56.1) 120 (91.3-165) 270 (155-403) 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 1.0 and 0.3. 
 278 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Lee, 2005). Younger children eliminate higher proportions 

of urinary MEHHP and MEOHP relative to MEHP, with 

the difference increasing as age decreases; this may be the 

result of differences in metabolism and/or excretion (NTPCERHR, 2006). Studies of hospitalized neonates have 

reported urinary geometric mean levels of MEHP, MEOHP, 

and MEHHP that were two to five times higher, or more 

(depending on the intensity of DEHP-product exposure), 

than the geometric means of children in the NHANES 

subsamples for all three survey periods (Calafat et al., 2004; 

Weuve et al., 2006). Small studies of plasma and platelet 

donors have reported very high levels of MEHP, MEOHP, 

MEHHP and MECPP in urine collected shortly after these 

procedures (Koch et al., 2005b, 2005c).

Finding a measurable amount of one or more DEHP 

metabolites in urine does not mean that the levels of the 

metabolites or the parent compound cause an adverse health 

effect. Biomonitoring studies on levels of urinary DEHP 

metabolites provide physicians and public health officials 

with reference values so that they can determine whether 

people have been exposed to higher levels of DEHP than 

are found in the general population. Biomonitoring data can 

also help scientists plan and conduct research on exposure 

and health effects.

Urinary Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (creatinine corrected) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 18.8 (17.0-20.7) 16.6 (14.9-18.5) 32.2 (27.8-37.1) 71.1 (58.7-88.3) 143 (101-200) 2782 

03-04 20.4 (18.7-22.3) 17.7 (16.3-19.6) 35.8 (30.5-43.3) 93.5 (74.0-128) 182 (134-262) 2605 

Age group 

6-11 years 01-02 38.2 (34.3-42.6) 34.3 (29.9-38.9) 60.6 (51.9-76.4) 107 (96.3-147) 211 (122-313) 393

03-04 39.0 (31.1-48.9) 36.6 (25.3-49.3) 65.6 (49.8-91.3) 129 (77.1-253) 211 (123-708) 342

12-19 years 01-02 19.2 (17.0-21.8) 17.8 (15.6-20.0) 34.9 (29.2-42.7) 73.4 (58.4-80.7) 102 (86.6-160) 742

03-04 21.2 (18.1-24.7) 18.6 (16.9-21.7) 38.7 (29.7-53.4) 103 (62.7-209) 212 (100-358) 729

20 years and older 01-02 17.1 (15.2-19.3) 15.0 (13.3-16.7) 27.7 (23.2-34.0) 63.7 (48.3-86.9) 137 (84.4-203) 1647 

03-04 18.8 (17.5-20.2) 16.3 (15.4-17.5) 31.6 (28.1-35.3) 83.8 (67.2-106) 171 (129-246) 1534 

Gender 

Males 01-02 17.9 (16.2-19.7) 15.4 (13.8-17.9) 32.2 (27.8-36.8) 73.4 (55.3-91.8) 137 (97.7-224) 1371 

03-04 18.9 (17.1-20.9) 17.1 (15.2-18.6) 32.7 (26.6-41.6) 93.4 (68.8-123) 193 (108-291) 1250 

Females 01-02 19.7 (17.3-22.4) 17.6 (15.4-19.5) 32.1 (26.8-38.6) 70.5 (57.8-93.7) 156 (93.7-201) 1411 

03-04 21.9 (19.7-24.5) 18.7 (16.8-20.9) 39.3 (33.8-46.9) 94.3 (72.8-136) 171 (146-261) 1355 

Race/ethnicity 

Mexican Americans 01-02 17.4 (15.9-19.1) 15.7 (14.4-17.5) 30.6 (26.0-34.7) 65.9 (50.6-83.9) 103 (75.5-128) 677

03-04 17.1 (14.3-20.4) 15.4 (13.2-17.7) 29.3 (23.8-36.8) 57.3 (45.7-97.6) 105 (70.1-195) 652

Non-Hispanic blacks 01-02 20.9 (18.8-23.3) 19.7 (17.5-21.8) 38.3 (32.1-46.0) 93.5 (69.2-123) 164 (130-183) 703

03-04 21.9 (20.1-23.8) 19.5 (17.3-22.6) 40.1 (35.8-45.3) 102 (75.5-122) 164 (133-269) 699

Non-Hispanic whites 01-02 18.9 (17.0-21.0) 16.3 (14.8-18.4) 32.1 (27.3-37.3) 70.8 (56.9-93.7) 177 (98.0-242) 1216 

03-04 20.5 (18.5-22.8) 17.8 (16.2-19.7) 35.3 (29.7-44.9) 96.2 (75.8-136) 211 (136-283) 1088 
Fourth National Report on Human Exposure to Environmental Chemicals 279

 Phthalates 

Urinary Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 13.5 (12.0-15.0) 14.0 (12.5-15.1) 29.6 (25.2-34.0) 59.9 (50.4-70.9) 120 (87.2-156) 2782 

03-04 14.5 (13.0-16.1) 14.4 (12.4-16.7) 31.4 (27.4-36.6) 76.7 (59.4-102) 157 (106-232) 2605 

Age group 

6-11 years 01-02 23.3 (20.9-26.1) 22.9 (18.5-28.1) 46.5 (38.1-52.0) 81.6 (64.7-109) 142 (93.9-178) 393

03-04 25.1 (19.6-32.3) 25.8 (19.3-31.4) 51.1 (32.1-76.5) 97.9 (58.8-197) 197 (97.6-261) 342

12-19 years 01-02 17.5 (15.1-20.3) 18.6 (16.2-20.7) 35.0 (27.7-42.1) 70.7 (52.2-104) 118 (74.0-174) 742

03-04 19.5 (16.0-23.7) 20.3 (18.4-23.5) 37.8 (32.6-44.6) 110 (54.6-168) 212 (103-326) 729

20 years and older 01-02 12.0 (10.5-13.9) 12.3 (10.4-14.1) 26.0 (21.6-32.1) 52.3 (41.8-68.3) 116 (74.9-160) 1647 

03-04 12.9 (11.8-14.1) 12.4 (10.9-14.5) 27.0 (25.0-30.9) 68.9 (55.0-86.5) 139 (92.7-216) 1534 

Gender 

Males 01-02 14.5 (13.0-16.2) 14.6 (13.1-16.2) 31.6 (25.6-34.7) 60.4 (52.3-71.4) 129 (84.4-167) 1371 

03-04 15.6 (13.6-17.9) 14.7 (12.7-18.1) 31.8 (27.2-39.5) 83.8 (59.4-134) 185 (96.2-277) 1250 

Females 01-02 12.5 (10.8-14.6) 13.1 (11.2-15.0) 28.1 (23.7-33.5) 57.5 (45.8-72.7) 115 (81.8-147) 1411 

03-04 13.4 (11.9-15.1) 13.7 (11.4-16.4) 29.5 (26.1-36.6) 68.6 (53.7-88.1) 143 (88.2-210) 1355 

Race/ethnicity 

Mexican Americans 01-02 13.1 (11.6-14.9) 13.4 (11.6-15.0) 25.5 (21.6-30.8) 56.6 (40.6-70.3) 77.3 (70.5-101) 677

03-04 12.8 (10.5-15.5) 13.6 (11.4-15.6) 25.3 (20.4-29.9) 46.6 (32.3-70.8) 76.0 (51.6-153) 652

Non-Hispanic blacks 01-02 19.6 (17.1-22.5) 20.1 (17.9-22.4) 39.0 (34.8-44.2) 80.5 (71.4-97.4) 153 (102-228) 703

03-04 20.2 (17.7-23.0) 20.1 (17.0-22.5) 40.0 (33.9-46.9) 92.6 (68.8-130) 173 (104-247) 699

Non-Hispanic whites 01-02 12.8 (11.2-14.6) 13.2 (11.6-14.6) 28.5 (23.6-34.0) 58.6 (48.8-70.9) 126 (83.7-172) 1216 

03-04 13.8 (12.4-15.4) 13.4 (11.3-16.3) 31.0 (27.0-36.3) 77.6 (59.4-102) 161 (98.7-241) 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 1.1 and 0.5. 
 280 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Urinary Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (creatinine corrected) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 12.6 (11.5-13.9) 11.2 (10.2-12.3) 21.3 (18.3-23.8) 45.2 (37.1-58.1) 87.0 (68.0-124) 2782 

03-04 13.6 (12.4-14.8) 12.1 (11.0-12.9) 24.3 (20.9-27.8) 63.0 (47.8-75.8) 118 (94.1-153) 2605 

Age group 

6-11 years 01-02 26.6 (24.0-29.4) 22.8 (20.3-25.0) 43.3 (33.6-47.1) 74.7 (69.0-91.9) 131 (83.0-183) 393

03-04 26.6 (21.4-33.0) 25.3 (17.8-32.4) 43.6 (34.2-63.2) 77.1 (63.0-118) 121 (76.3-435) 342

12-19 years 01-02 13.5 (12.0-15.2) 12.0 (10.8-14.3) 23.4 (20.0-28.5) 48.4 (39.2-54.9) 70.5 (55.0-97.2) 742

03-04 14.6 (12.6-16.9) 12.7 (11.6-14.4) 25.5 (20.7-33.8) 67.9 (42.3-143) 153 (61.8-209) 729

20 years and older 01-02 11.4 (10.2-12.8) 10.1 (8.89-11.4) 17.5 (15.2-21.8) 38.4 (30.5-52.5) 84.3 (53.3-128) 1647 

03-04 12.4 (11.5-13.3) 11.0 (10.0-12.0) 20.9 (18.6-22.8) 53.9 (40.7-70.2) 109 (88.6-130) 1534 

Gender 

Males 01-02 11.8 (10.7-13.0) 10.2 (8.93-11.7) 21.2 (18.5-23.3) 46.1 (35.3-58.7) 84.2 (69.6-104) 1371 

03-04 12.3 (11.1-13.5) 11.1 (10.0-12.0) 21.6 (17.6-26.9) 59.1 (45.4-72.0) 120 (72.0-162) 1250 

Females 01-02 13.5 (11.9-15.2) 12.0 (10.8-13.7) 21.5 (18.0-25.6) 44.8 (36.8-61.6) 92.3 (61.0-139) 1411 

03-04 14.9 (13.4-16.7) 12.7 (11.4-14.2) 26.6 (21.8-30.6) 65.6 (48.0-90.1) 118 (97.0-157) 1355 

Race/ethnicity 

Mexican Americans 01-02 12.4 (11.4-13.5) 11.0 (10.5-12.3) 20.9 (18.5-24.4) 44.6 (33.4-56.2) 65.9 (53.1-83.1) 677

03-04 11.5 (9.81-13.6) 10.7 (9.04-12.3) 18.8 (15.6-24.6) 39.1 (31.8-53.9) 63.0 (47.2-121) 652

Non-Hispanic blacks 01-02 13.8 (12.3-15.4) 13.1 (12.0-14.2) 23.9 (20.0-29.3) 58.3 (45.3-79.7) 101 (81.3-124) 703

03-04 14.3 (13.1-15.6) 13.3 (11.3-15.5) 24.8 (21.7-27.7) 61.2 (46.8-76.6) 105 (79.7-152) 699

Non-Hispanic whites 01-02 12.7 (11.4-14.0) 11.1 (9.90-12.3) 20.8 (18.0-23.9) 45.7 (35.9-64.9) 96.0 (68.5-161) 1216 

03-04 13.7 (12.2-15.3) 12.0 (10.5-12.9) 24.9 (20.7-28.6) 69.5 (51.4-95.3) 124 (90.3-182) 1088 
Fourth National Report on Human Exposure to Environmental Chemicals 281

 Phthalates 

Urinary Mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 34.7 (31.0-38.9) 33.0 (29.1-37.4) 71.8 (61.7-84.8) 168 (133-240) 339 (235-506) 2605 

Age group 

6-11 years 03-04 58.2 (44.7-75.6) 51.6 (39.2-67.6) 112 (71.4-182) 314 (124-524) 391 (238-781) 342

12-19 years 03-04 44.6 (36.8-54.0) 42.7 (38.4-47.6) 86.5 (67.3-108) 220 (120-397) 448 (235-808) 729

20 years and older 03-04 31.3 (28.6-34.4) 29.2 (26.2-33.0) 63.5 (56.5-73.9) 157 (130-187) 312 (199-457) 1534 

Gender 

Males 03-04 37.9 (33.1-43.5) 34.7 (30.0-39.5) 73.7 (60.8-91.9) 187 (133-300) 388 (222-660) 1250 

Females 03-04 31.9 (28.1-36.2) 31.3 (27.5-35.8) 69.3 (58.9-81.9) 154 (128-199) 312 (182-441) 1355 

Race/ethnicity 

Mexican Americans 03-04 31.9 (27.1-37.6) 31.5 (26.8-37.4) 57.4 (45.9-71.8) 116 (86.0-162) 175 (133-355) 652

Non-Hispanic blacks 03-04 42.6 (37.0-49.2) 38.3 (33.8-46.9) 82.5 (68.7-103) 191 (146-246) 339 (244-468) 699

Non-Hispanic whites 03-04 33.8 (30.1-37.9) 32.1 (27.6-37.5) 72.4 (62.0-87.7) 167 (133-240) 354 (220-560) 1088 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.3. 

Urinary Mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (creatinine corrected) 

Metabolite of Di-2-ethylhexyl phthalate (DEHP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 32.6 (29.6-36.0) 27.0 (24.3-30.6) 54.6 (48.0-63.5) 139 (109-186) 251 (192-356) 2605 

Age group 

6-11 years 03-04 61.5 (49.0-77.2) 52.2 (41.6-73.8) 104 (74.2-140) 210 (111-500) 372 (192-988) 342

12-19 years 03-04 33.4 (28.7-38.7) 27.1 (23.9-32.0) 55.0 (43.8-83.8) 168 (92.5-289) 294 (159-387) 729

20 years and older 03-04 30.1 (27.7-32.7) 25.1 (22.9-27.6) 49.1 (44.1-55.2) 126 (101-154) 237 (191-315) 1534 

Gender 

Males 03-04 29.8 (26.8-33.1) 23.5 (21.4-27.1) 50.7 (42.2-61.7) 132 (98.0-191) 248 (159-422) 1250 

Females 03-04 35.5 (31.6-40.0) 30.6 (26.4-35.5) 58.3 (48.8-71.8) 144 (108-192) 251 (192-349) 1355 

Race/ethnicity 

Mexican Americans 03-04 28.8 (25.4-32.6) 24.7 (22.4-26.3) 46.7 (39.0-56.3) 94.7 (73.2-137) 152 (118-238) 652

Non-Hispanic blacks 03-04 30.3 (27.7-33.2) 27.0 (23.2-30.7) 51.1 (41.6-64.0) 135 (100-161) 212 (173-252) 699

Non-Hispanic whites 03-04 33.4 (29.5-37.7) 27.0 (23.5-31.6) 56.8 (48.6-69.4) 145 (109-198) 294 (193-385) 1088 
 282 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

References

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toxprofiles/tp9.html. 4/20/09

Albro PW, Corbett JT, Schroeder JL, Jordan S, Matthews HB. 

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Albro PW and Lavenhar SR. Metabolism of di(2-ethylhexyl) 

phthalate. Drug Metab Rev 1989;21:13-34.

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Becker K, Seiwert M, Angerer J, Heger W, Koch HM, Nagorka 

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house dust. Int J Hyg Environ Health 2004;207(5):409-417.

Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, 

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exposure and reproductive hormones in adult men. Hum Reprod 

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devices. 2001 [online]. Available at URL: http://www.fda.gov/

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Fromme H, Bolte G, Koch HM, Angerer J, Boehmer S, Drexler 

H, et al. Occurrence and daily variation of phthalate metabolites 

in the urine of an adult population. Int J Hyg Environ Health 

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Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, et 

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of urinary phthalate metabolites in first morning urine samples. 

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Health 2005;208:237-245.

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ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and 

platelet donors. Int J Hyg Environ Health 2005c;208:489-498.

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1982;45:11-17.

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et al. Urinary levels of seven phthalate metabolites in the U.S. 

population from the National Health and Nutrition Examination 

Survey (NHANES) 1999-2000 [published erratum appears in 

Environ Health Perspect 2004; 112(5):A270]. Environ Health 

Perspect 2004;112(3):331-338.

Weuve J, Sanchez GN, Calafat AM, Schettler T, Green RA, Hu 

H, et al. Exposure to phthalates in neonatal intensive care unit 

infants: urinary concentrations of monoesters and oxidative 

metabolites. Environ Health Perspect 2006;114(9):1424-1431.

Wittassek M, Wiesmuller GA, Koch HM, Eckard R, Dobler 

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 284 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Di-isononyl Phthalate

CAS No. 28553-12-0

General Information

Di-isononyl phthalate (DiNP) is a mixture of phthalates 

with branched alkyl side chains of varying length (C8, 

C9, and C10). DiNP is primarily used to produce flexible 

plastics and has replaced di-2-ethylhexyl phthalate (DEHP) 

in some plastics, though not in medical products. DiNP 

is widely used in such products as toys, flooring, gloves, 

drinking straws, garden hoses, and in sealants used for 

food packaging. People exposed to DiNP will excrete small 

amounts of mono-isononyl phthalate (MiNP) and other 

secondary oxidative metabolites. Urinary MiNP represents 

only about 2% of a dose (Koch and Angerer, 2007; 

Silva et al., 2006a, 2006b). Because DiNP is a complex 

mixture, MiNP may not reflect exposure to all the chemical 

components.

DiNP administered to rodents produced liver and kidney 

toxicity, and may cause liver tumors by a mechanism 

involving peroxisomal proliferation. High dose DiNP was 

a developmental toxicant in rodents (NTP-CERHR, 2000). 

Although DiNP is considered an animal carcinogen, neither 

IARC nor NTP has evaluated DiNP with respect to human 

carcinogenicity.

Urinary Mono-isononyl phthalate (MiNP) 

Metabolite of Di-isononyl phthalate (DiNP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 3.50 (<LOD-13.8) 2541 

01-02 * < LOD < LOD < LOD < LOD 2782 

03-04 * < LOD < LOD < LOD 1.00 (<LOD-1.30) 2605 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD 6.20 (<LOD-22.5) 328

01-02 * < LOD < LOD < LOD < LOD 393

03-04 * < LOD < LOD 1.00 (<LOD-1.50) 1.70 (1.20-3.10) 342

12-19 years 99-00 * < LOD < LOD < LOD 2.30 (<LOD-20.3) 752

01-02 * < LOD < LOD < LOD .900 (<LOD-1.10) 742

03-04 * < LOD < LOD < LOD 1.40 (<LOD-1.80) 729

20 years and older 99-00 * < LOD < LOD < LOD 3.10 (<LOD-13.2) 1461 

01-02 * < LOD < LOD < LOD < LOD 1647 

03-04 * < LOD < LOD < LOD < LOD 1534 

Gender 

Males 99-00 * < LOD < LOD .800 (<LOD-5.40) 4.90 (<LOD-18.9) 1215 

01-02 * < LOD < LOD < LOD < LOD 1371 

03-04 * < LOD < LOD < LOD 1.00 (<LOD-1.80) 1250 

Females 99-00 * < LOD < LOD < LOD 2.50 (<LOD-6.80) 1326 

01-02 * < LOD < LOD < LOD .900 (<LOD-1.10) 1411 

03-04 * < LOD < LOD < LOD < LOD 1355 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 1.50 (<LOD-2.80) 814

01-02 * < LOD < LOD < LOD 1.00 (<LOD-1.40) 677

03-04 * < LOD < LOD < LOD < LOD 652

Non-Hispanic blacks 99-00 * < LOD < LOD 2.30 (<LOD-13.8) 6.80 (<LOD-30.2) 603

01-02 * < LOD < LOD < LOD 1.00 (<LOD-1.70) 703

03-04 * < LOD < LOD < LOD 1.30 (1.00-2.00) 699

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 3.50 (<LOD-16.0) 912

01-02 * < LOD < LOD < LOD < LOD 1216 

03-04 * < LOD < LOD < LOD < LOD 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.8, 0.8, and 1.0, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 285

 Phthalates 

Biomonitoring Information

MiNP was detected mainly at the 95th percentiles in this 

Report. A low detection rate was also reported in a small 

sample of African-American women in Washington, DC 

(Hoppin et al., 2002).

Finding a measurable amount of MiNP in urine does not 

mean that the levels of MiNP or the parent compound cause 

an adverse health effect. Biomonitoring studies on levels of 

MiNP provide physicians and public health officials with 

reference values so that they can determine whether people 

have been exposed to higher levels of DiNP than are found 

in the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Urinary Mono-isononyl phthalate (MiNP) (creatinine corrected) 

Metabolite of Di-isononyl phthalate (DiNP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 4.29 (<LOD-8.31) 2541 

01-02 * < LOD < LOD < LOD < LOD 2782 

03-04 * < LOD < LOD < LOD 2.92 (<LOD-3.18) 2605 

Age group 

6-11 years 99-00 * < LOD < LOD < LOD 6.00 (<LOD-14.2) 328

01-02 * < LOD < LOD < LOD < LOD 393

03-04 * < LOD < LOD 2.41 (<LOD-3.13) 3.27 (2.41-4.67) 342

12-19 years 99-00 * < LOD < LOD < LOD 2.00 (<LOD-7.65) 752

01-02 * < LOD < LOD < LOD 2.07 (<LOD-3.33) 742

03-04 * < LOD < LOD < LOD 1.97 (<LOD-2.59) 729

20 years and older 99-00 * < LOD < LOD < LOD 4.62 (<LOD-8.07) 1461 

01-02 * < LOD < LOD < LOD < LOD 1647 

03-04 * < LOD < LOD < LOD < LOD 1534 

Gender 

Males 99-00 * < LOD < LOD 2.00 (<LOD-3.71) 4.24 (<LOD-10.2) 1215 

01-02 * < LOD < LOD < LOD < LOD 1371 

03-04 * < LOD < LOD < LOD 2.31 (<LOD-2.95) 1250 

Females 99-00 * < LOD < LOD < LOD 4.29 (<LOD-7.65) 1326 

01-02 * < LOD < LOD < LOD 2.73 (<LOD-2.86) 1411 

03-04 * < LOD < LOD < LOD < LOD 1355 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 3.53 (<LOD-5.00) 814

01-02 * < LOD < LOD < LOD 2.40 (<LOD-2.73) 677

03-04 * < LOD < LOD < LOD < LOD 652

Non-Hispanic blacks 99-00 * < LOD < LOD 2.03 (<LOD-5.31) 4.29 (<LOD-14.3) 603

01-02 * < LOD < LOD < LOD 1.76 (<LOD-2.14) 703

03-04 * < LOD < LOD < LOD 2.19 (1.67-2.50) 699

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 5.45 (<LOD-10.0) 912

01-02 * < LOD < LOD < LOD < LOD 1216 

03-04 * < LOD < LOD < LOD < LOD 1088 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 286 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

References

Hoppin JA, Brock JW, Davis BJ, Baird DD. Reproducibility 

of urinary phthalate metabolites in first morning urine samples. 

Environ Health Perspect 2002;110(5):515-518.

Koch HM, Angerer J. Di-iso-nonylphthalate (DINP) metabolites 

in human urine after a single oral dose of deuterium-labelled 

DINP. Int J Hyg Environ Health 2007;79:210:9-19.

NTP-CERHR. National Toxicology Program-Center for the 

Evaluation of Risks to Human Reproduction. Monograph on the 

Potential Human Reproductive and Developmental Effects of Din-octyl Phthalate (DnOP). Research Triangle Park (NC). 2000 

[online]. Available at URL: http://cerhr.niehs.nih.gov/chemicals/

phthalates/dnop/dnop-eval.html. 6/2/09

Silva MJ, Kato K, Wolf C, Samandar El, Silva SS, Gray EL, et 

al. Urinary biomarkers of di-isononyl phthalate in rats. Toxicol 

2006a;223:101-112.

Silva MJ, Reidy JA, Preu Jr JL, Needham LL, Calafat AM. 

Oxidative metabolites of diisononyl phthalate as biomarkers 

for human exposure assessment. Environ Health Perspect 

2006b;114(8):1158-1161.
Fourth National Report on Human Exposure to Environmental Chemicals 287

 Phthalates 

Dimethyl Phthalate

CAS No.131-11-3

General Information

Dimethyl phthalate (DMP) is used in manufacturing solid 

rocket propellant and consumer products such as insect 

repellents and plastics. People exposed to DMP will 

excrete mono-methyl phthalate (MMP) in their urine. A 

workplace air standard for external exposure to DMP has 

been established by OSHA, and guidelines established by 

ACGIH and NIOSH. Neither IARC nor NTP has evaluated 

DBP with respect to human carcinogenicity.

Biomonitoring Information

In NHANES 2001-2002 and 2003-2004, the urinary levels 

of MMP were similar. Among men attending a Boston 

infertility clinic, at least 75% had detectable urine MMP 

levels, and the median value was similar to the median 

urine MMP levels for both males and adults in this Report

(Hauser et al., 2007). Analysis of the NHANES 2001-

2002 levels showed that adjusted geometric mean levels 

of urinary MMP were higher in children aged 6-11 years 

than either groups aged 12-19 years or 20 years and older. 

Females had higher levels than males (CDC, 2005).

Finding a measurable amount of MMP in urine does not 

mean that the levels of MMP or the parent compound cause 

an adverse health effect. Biomonitoring studies on levels of 

urinary MMP provide physicians and public health officials 

with reference values so that they can determine whether 

people have been exposed to higher levels of DMP than are 

found in the general population. Biomonitoring data can 

also help scientists plan and conduct research on exposure 

and health effects.

Urinary Mono-methyl phthalate (MMP) 

Metabolite of Dimethyl phthalate (DMP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 1.15 (.985-1.34) 1.50 (1.30-1.80) 3.30 (2.90-3.70) 6.00 (5.10-7.50) 9.80 (8.00-12.5) 2782 

03-04 * 1.30 (<LOD-1.70) 3.90 (3.00-4.90) 9.70 (7.70-12.2) 16.3 (12.0-20.4) 2605 

Age group 

6-11 years 01-02 1.45 (1.13-1.87) 1.90 (1.40-2.80) 4.00 (3.40-4.90) 7.20 (6.00-8.00) 11.8 (7.60-20.8) 393

03-04 2.10 (1.67-2.63) 1.70 (1.20-2.40) 4.30 (2.80-6.40) 9.50 (6.40-18.8) 18.8 (9.40-33.4) 342

12-19 years 01-02 1.59 (1.28-1.96) 2.10 (1.80-2.50) 3.90 (3.30-4.70) 8.50 (5.30-10.5) 13.0 (9.60-17.8) 742

03-04 * 1.50 (1.00-2.20) 4.40 (3.00-7.00) 13.3 (7.40-20.9) 21.8 (17.8-31.5) 729

20 years and older 01-02 1.06 (.904-1.25) 1.40 (1.10-1.60) 3.10 (2.50-3.50) 5.60 (4.60-7.10) 9.20 (7.40-12.3) 1647 

03-04 * 1.20 (<LOD-1.50) 3.80 (2.80-4.90) 9.30 (7.10-11.8) 14.3 (10.8-19.9) 1534 

Gender 

Males 01-02 1.17 (.962-1.43) 1.50 (1.30-1.90) 3.30 (2.90-4.00) 5.90 (4.80-7.90) 9.20 (7.10-13.5) 1371 

03-04 * 1.30 (1.00-1.80) 4.00 (3.20-5.20) 10.0 (7.30-13.5) 17.7 (11.8-20.4) 1250 

Females 01-02 1.13 (.973-1.31) 1.40 (1.10-1.70) 3.30 (2.80-3.70) 6.40 (5.00-7.80) 10.3 (8.20-16.2) 1411 

03-04 * 1.20 (<LOD-1.60) 3.60 (2.80-4.70) 9.50 (7.70-12.2) 15.3 (11.7-22.9) 1355 

Race/ethnicity 

Mexican Americans 01-02 1.21 (1.02-1.45) 1.60 (1.30-1.70) 3.30 (2.70-4.00) 5.60 (4.70-7.30) 8.60 (6.40-15.2) 677

03-04 * 1.40 (1.10-1.80) 4.00 (2.50-6.30) 9.60 (7.30-13.4) 15.0 (11.4-18.8) 652

Non-Hispanic blacks 01-02 1.64 (1.37-1.98) 2.10 (1.70-2.70) 4.40 (3.60-5.10) 8.30 (6.20-10.1) 11.0 (9.50-13.4) 703

03-04 2.16 (1.64-2.84) 1.70 (1.00-2.80) 5.10 (3.70-7.00) 11.4 (7.30-17.3) 17.8 (10.2-39.4) 699

Non-Hispanic whites 01-02 1.08 (.906-1.29) 1.40 (1.10-1.70) 3.20 (2.50-3.60) 5.60 (4.70-6.70) 9.70 (7.10-14.0) 1216 

03-04 * 1.20 (<LOD-1.60) 3.60 (2.80-4.80) 9.70 (7.50-12.2) 16.5 (12.0-20.4) 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.2 and 1.0. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 288 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Urinary Mono-methyl phthalate (MMP) (creatinine corrected) 

Metabolite of Dimethyl phthalate (DMP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 1.08 (.936-1.25) 1.33 (1.13-1.55) 2.62 (2.36-2.97) 5.00 (3.97-6.02) 8.00 (6.07-11.0) 2782 

03-04 * 1.53 (<LOD-1.79) 3.45 (2.76-4.37) 7.95 (5.83-11.8) 13.5 (11.3-18.1) 2605 

Age group 

6-11 years 01-02 1.65 (1.28-2.14) 2.32 (1.72-2.86) 3.97 (3.27-4.71) 7.20 (5.99-9.41) 13.2 (7.60-22.5) 393

03-04 2.22 (1.75-2.81) 1.88 (1.49-2.60) 4.96 (2.81-6.49) 9.67 (6.15-14.6) 16.2 (12.1-34.5) 342

12-19 years 01-02 1.23 (1.01-1.48) 1.51 (1.32-1.82) 2.84 (2.52-3.33) 5.36 (3.68-6.39) 7.27 (5.64-11.4) 742

03-04 * 1.34 (1.12-1.73) 3.19 (2.26-4.43) 7.84 (4.95-12.1) 13.3 (9.49-19.1) 729

20 years and older 01-02 1.00 (.868-1.16) 1.21 (1.05-1.40) 2.44 (2.14-2.68) 4.53 (3.49-6.02) 7.72 (5.52-11.4) 1647 

03-04 * 1.52 (<LOD-1.79) 3.39 (2.69-4.31) 7.69 (5.40-11.8) 13.3 (10.1-18.9) 1534 

Gender 

Males 01-02 .954 (.794-1.15) 1.17 (1.02-1.40) 2.37 (2.03-2.75) 4.18 (3.45-5.64) 6.42 (4.94-9.59) 1371 

03-04 * 1.35 (1.15-1.52) 2.95 (2.26-4.09) 7.11 (5.00-10.2) 11.8 (9.05-13.3) 1250 

Females 01-02 1.21 (1.06-1.38) 1.45 (1.23-1.82) 2.87 (2.58-3.06) 5.56 (4.55-7.14) 10.0 (7.20-15.3) 1411 

03-04 * 1.83 (<LOD-2.10) 3.87 (3.04-4.96) 9.41 (6.41-13.6) 16.5 (12.5-23.5) 1355 

Race/ethnicity 

Mexican Americans 01-02 1.14 (.975-1.34) 1.48 (1.30-1.63) 2.50 (2.20-2.94) 4.19 (3.77-5.76) 8.47 (5.58-12.5) 677

03-04 * 1.36 (1.15-1.71) 3.56 (2.45-4.90) 7.53 (5.62-9.64) 12.5 (9.44-16.9) 652

Non-Hispanic blacks 01-02 1.15 (.949-1.40) 1.39 (1.29-1.67) 2.70 (2.36-2.95) 4.87 (4.21-5.93) 8.09 (5.86-11.0) 703

03-04 1.53 (1.21-1.94) 1.40 (1.07-1.75) 3.14 (2.26-4.37) 7.50 (4.29-14.6) 13.7 (7.70-20.7) 699

Non-Hispanic whites 01-02 1.07 (.914-1.26) 1.30 (1.05-1.58) 2.62 (2.32-2.99) 5.22 (3.68-6.82) 8.26 (6.07-12.6) 1216 

03-04 * 1.56 (<LOD-1.89) 3.50 (2.71-4.67) 8.10 (6.00-11.9) 13.6 (11.3-18.9) 1088 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 289

 Phthalates 

References

Centers for Disease Control and Prevention (CDC). Third National 

Report on Human Exposure to Environmental Chemicals. Atlanta 

(GA). 2005.

Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, et 

al. DNA damage in human sperm is related to urinary levels of 

phthalate monoester and oxidative metabolites. Hum Reprod 

2007;22(3):688-695.
 290 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Di-n-octyl Phthalate

CAS No. 117-84-0

General Information

Di-n-octyl phthalate (DOP) is added to polyvinyl chloride 

resins used in diverse products including floorings, carpet 

tiles, vinyl gloves, garden hoses, wire and cable insulation, 

and adhesives. In addition, DOP may be added to polyvinyl 

chloride with food applications, such as package sealants 

and bottle cap liners. People exposed to DOP will excrete 

primarily mono-3-carboxypropyl phthalate (MCPP) and 

smaller amounts of mono-n-octyl phthalate (MOP) and 

other oxidative metabolites in their urine. In rodent studies, 

oral DOP produces liver and thyroid toxicity (NTPCERHR, 2000). Neither IARC nor NTP has evaluated DOP 

with respect to human carcinogenicity.

Biomonitoring Information

In NHANES 1999-2000, MOP was only detectable at the 

90th and 95th percentiles, and less frequently detected 

in the 2001-2002 and 2003-2004 survey periods. A low 

detection rate was reported in small samples of German 

residents (Koch et al., 2003) and of African-American 

women in Washington, DC (Hoppin et al., 2002). MCPP 

levels measured in NHANES 2001-2002 and 2003-2004 

subsamples had overall median values that were roughly 

similar to a smaller sample of U.S. adults (Calafat et al., 

2006).

Finding a measurable amount of MCPP or MOP in urine 

does not mean that the levels of MCPP or MOP or the parent 

compound cause an adverse health effect. Biomonitoring 

studies on levels of MCPP and MOP provide physicians 

and public health officials with reference values so that 

they can determine whether people have been exposed 

to higher levels of DOP than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Urinary Mono-(3-carboxypropyl) phthalate (MCPP) 

Metabolite of Di-n-octyl phthalate (DOP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 2.75 (2.49-3.04) 3.10 (2.80-3.30) 5.70 (5.10-6.40) 10.0 (8.90-11.3) 14.6 (12.7-17.5) 2782 

03-04 2.91 (2.79-3.04) 3.10 (3.00-3.30) 5.70 (5.20-6.10) 10.2 (9.20-11.8) 15.3 (13.8-16.2) 2605 

Age group 

6-11 years 01-02 6.11 (5.46-6.84) 6.70 (5.40-7.50) 11.8 (10.2-13.3) 20.1 (17.8-23.1) 24.7 (22.2-31.6) 393

03-04 6.86 (5.80-8.11) 7.10 (6.00-8.90) 12.7 (10.4-16.4) 22.0 (17.2-27.7) 29.2 (22.3-36.6) 342

12-19 years 01-02 3.71 (3.18-4.33) 4.00 (3.40-4.70) 7.10 (6.10-8.10) 11.5 (9.50-12.7) 14.1 (11.8-19.0) 742

03-04 3.72 (3.33-4.15) 4.10 (3.50-4.60) 7.20 (5.80-8.40) 11.0 (9.50-13.6) 15.4 (13.4-17.9) 729

20 years and older 01-02 2.37 (2.11-2.66) 2.60 (2.20-3.00) 4.80 (4.30-5.40) 8.10 (7.20-9.50) 12.0 (10.1-14.2) 1647 

03-04 2.53 (2.41-2.66) 2.80 (2.60-2.90) 4.90 (4.50-5.20) 8.10 (7.50-8.90) 13.2 (10.8-14.3) 1534 

Gender 

Males 01-02 2.89 (2.64-3.17) 3.10 (2.80-3.40) 5.70 (5.00-6.80) 9.90 (8.70-12.0) 14.2 (12.4-18.1) 1371 

03-04 3.25 (3.01-3.52) 3.30 (3.00-3.60) 6.00 (5.60-6.80) 11.8 (10.1-13.6) 16.0 (14.2-20.0) 1250 

Females 01-02 2.62 (2.29-2.99) 3.00 (2.50-3.30) 5.70 (5.00-6.30) 10.0 (8.50-11.5) 14.7 (11.2-20.3) 1411 

03-04 2.63 (2.44-2.83) 3.00 (2.60-3.20) 5.20 (4.70-5.80) 9.20 (8.20-10.3) 13.4 (11.0-16.2) 1355 

Race/ethnicity 

Mexican Americans 01-02 2.67 (2.26-3.16) 3.00 (2.30-3.50) 5.30 (4.40-5.90) 9.20 (7.30-12.4) 13.6 (10.4-18.7) 677

03-04 3.08 (2.86-3.32) 3.10 (2.80-3.40) 5.50 (4.80-6.10) 9.90 (7.90-12.6) 13.7 (11.5-19.8) 652

Non-Hispanic blacks 01-02 3.09 (2.81-3.40) 3.30 (2.90-3.60) 6.30 (5.50-6.50) 10.9 (9.10-13.0) 15.1 (13.5-22.4) 703

03-04 3.30 (3.01-3.62) 3.20 (2.90-3.60) 6.10 (5.50-6.90) 11.6 (9.30-13.4) 20.1 (13.6-25.5) 699

Non-Hispanic whites 01-02 2.72 (2.40-3.08) 3.00 (2.60-3.30) 5.80 (4.80-6.80) 10.3 (8.90-11.9) 15.8 (12.6-19.5) 1216 

03-04 2.87 (2.73-3.02) 3.10 (2.90-3.30) 5.60 (5.00-6.00) 10.1 (9.10-12.0) 15.2 (13.4-16.1) 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.4 and 0.2. 
Fourth National Report on Human Exposure to Environmental Chemicals 291

 Phthalates 

Urinary Mono-(3-carboxypropyl) phthalate (MCPP) (creatinine corrected) 

Metabolite of Di-n-octyl phthalate (DOP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 2.58 (2.35-2.83) 2.47 (2.25-2.76) 4.08 (3.87-4.48) 7.24 (6.58-8.00) 11.4 (10.0-12.5) 2782 

03-04 2.74 (2.56-2.93) 2.60 (2.42-2.79) 4.39 (3.94-4.86) 7.70 (6.65-8.60) 10.7 (9.53-11.9) 2605 

Age group 

6-11 years 01-02 6.96 (6.29-7.70) 7.08 (5.83-7.87) 11.2 (9.15-14.0) 20.7 (15.5-22.3) 26.4 (20.7-27.0) 393

03-04 7.25 (6.43-8.18) 7.06 (5.93-7.59) 11.2 (9.38-12.4) 19.1 (14.4-25.6) 26.9 (19.3-29.0) 342

12-19 years 01-02 2.86 (2.52-3.25) 2.94 (2.50-3.36) 4.59 (4.03-5.23) 6.69 (6.30-7.25) 9.55 (8.03-10.7) 742

03-04 2.78 (2.54-3.05) 2.75 (2.53-2.99) 4.55 (4.05-5.15) 6.61 (6.15-7.20) 8.24 (7.00-10.2) 729

20 years and older 01-02 2.24 (2.03-2.47) 2.20 (2.00-2.40) 3.51 (3.11-3.95) 5.39 (4.82-6.18) 7.71 (6.71-9.28) 1647 

03-04 2.43 (2.27-2.61) 2.38 (2.19-2.56) 3.70 (3.33-4.08) 6.09 (5.38-7.06) 8.79 (7.84-9.56) 1534 

Gender 

Males 01-02 2.35 (2.17-2.56) 2.20 (2.02-2.42) 3.76 (3.45-4.20) 7.17 (6.27-8.06) 11.5 (9.28-15.1) 1371 

03-04 2.55 (2.39-2.72) 2.36 (2.22-2.47) 4.14 (3.52-4.86) 7.84 (6.80-8.79) 11.6 (10.2-13.5) 1250 

Females 01-02 2.81 (2.48-3.18) 2.76 (2.46-3.02) 4.39 (3.97-4.92) 7.66 (6.17-8.69) 11.0 (8.62-15.9) 1411 

03-04 2.93 (2.68-3.20) 2.89 (2.58-3.23) 4.53 (4.09-5.00) 7.58 (6.44-8.57) 10.0 (8.60-11.6) 1355 

Race/ethnicity 

Mexican Americans 01-02 2.52 (2.21-2.88) 2.37 (2.07-2.73) 4.29 (3.73-5.00) 7.36 (5.58-10.3) 11.4 (8.36-14.5) 677

03-04 2.78 (2.56-3.02) 2.63 (2.30-2.96) 4.32 (3.66-4.96) 8.14 (6.72-10.3) 12.8 (9.37-17.1) 652

Non-Hispanic blacks 01-02 2.17 (2.02-2.33) 2.07 (1.88-2.28) 3.68 (3.25-4.07) 6.73 (5.46-7.70) 10.0 (8.27-13.1) 703

03-04 2.34 (2.13-2.58) 2.17 (1.99-2.45) 3.96 (3.33-4.43) 6.93 (6.03-8.80) 13.4 (9.32-15.9) 699

Non-Hispanic whites 01-02 2.69 (2.42-3.00) 2.57 (2.25-2.94) 4.19 (3.87-4.79) 7.63 (6.58-8.45) 11.8 (10.0-14.7) 1216 

03-04 2.83 (2.60-3.09) 2.65 (2.43-2.96) 4.55 (3.90-5.16) 7.79 (6.59-8.79) 10.6 (9.43-11.3) 1088 
 292 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

Urinary Mono-n-octyl phthalate (MOP) 

Metabolite of Di-n-octyl phthalate (DOP) 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 1.60 (1.20-2.00) 2.90 (2.30-3.40) 2541 

01-02 * < LOD < LOD < LOD < LOD 2782 

03-04 * < LOD < LOD < LOD < LOD 2605 

Age group 

6-11 years 99-00 * < LOD < LOD 2.20 (.900-3.50) 3.20 (1.70-5.00) 328

01-02 * < LOD < LOD < LOD < LOD 393

03-04 * < LOD < LOD < LOD < LOD 342

12-19 years 99-00 * < LOD < LOD 1.70 (.900-2.50) 2.80 (2.00-4.20) 752

01-02 * < LOD < LOD < LOD < LOD 742

03-04 * < LOD < LOD < LOD < LOD 729

20 years and older 99-00 * < LOD < LOD 1.50 (1.10-1.90) 2.90 (2.10-3.50) 1461 

01-02 * < LOD < LOD < LOD < LOD 1647 

03-04 * < LOD < LOD < LOD < LOD 1534 

Gender 

Males 99-00 * < LOD < LOD 1.60 (1.10-2.20) 2.80 (2.00-3.50) 1215 

01-02 * < LOD < LOD < LOD < LOD 1371 

03-04 * < LOD < LOD < LOD < LOD 1250 

Females 99-00 * < LOD < LOD 1.50 (1.20-2.10) 3.10 (2.20-3.80) 1326 

01-02 * < LOD < LOD < LOD < LOD 1411 

03-04 * < LOD < LOD < LOD < LOD 1355 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD 1.10 (<LOD-1.40) 1.60 (1.40-2.60) 814

01-02 * < LOD < LOD < LOD < LOD 677

03-04 * < LOD < LOD < LOD < LOD 652

Non-Hispanic blacks 99-00 * < LOD < LOD 1.90 (<LOD-3.00) 3.00 (2.20-4.10) 603

01-02 * < LOD < LOD < LOD < LOD 703

03-04 * < LOD < LOD < LOD < LOD 699

Non-Hispanic whites 99-00 * < LOD < LOD 1.60 (1.20-2.10) 3.00 (2.30-3.50) 912

01-02 * < LOD < LOD < LOD < LOD 1216 

03-04 * < LOD < LOD < LOD < LOD 1088 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.9, 1.0, and 1.0, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 293

 Phthalates 

Urinary Mono-n-octyl phthalate (MOP) (creatinine corrected) 

Metabolite of Di-n-octyl phthalate (DOP) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 2.40 (2.07-2.61) 3.53 (2.95-4.29) 2541 

01-02 * < LOD < LOD < LOD < LOD 2782 

03-04 * < LOD < LOD < LOD < LOD 2605 

Age group 

6-11 years 99-00 * < LOD < LOD 2.22 (1.60-3.75) 3.75 (1.97-10.3) 328

01-02 * < LOD < LOD < LOD < LOD 393

03-04 * < LOD < LOD < LOD < LOD 342

12-19 years 99-00 * < LOD < LOD 1.49 (1.29-1.71) 1.88 (1.54-3.33) 752

01-02 * < LOD < LOD < LOD < LOD 742

03-04 * < LOD < LOD < LOD < LOD 729

20 years and older 99-00 * < LOD < LOD 2.60 (2.07-2.91) 3.53 (3.00-4.62) 1461 

01-02 * < LOD < LOD < LOD < LOD 1647 

03-04 * < LOD < LOD < LOD < LOD 1534 

Gender 

Males 99-00 * < LOD < LOD 1.82 (1.54-2.07) 2.56 (1.94-3.45) 1215 

01-02 * < LOD < LOD < LOD < LOD 1371 

03-04 * < LOD < LOD < LOD < LOD 1250 

Females 99-00 * < LOD < LOD 3.00 (2.50-3.55) 4.29 (3.33-6.23) 1326 

01-02 * < LOD < LOD < LOD < LOD 1411 

03-04 * < LOD < LOD < LOD < LOD 1355 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD 1.82 (<LOD-2.80) 3.33 (2.60-4.00) 814

01-02 * < LOD < LOD < LOD < LOD 677

03-04 * < LOD < LOD < LOD < LOD 652

Non-Hispanic blacks 99-00 * < LOD < LOD 1.36 (<LOD-1.94) 2.22 (1.50-3.27) 603

01-02 * < LOD < LOD < LOD < LOD 703

03-04 * < LOD < LOD < LOD < LOD 699

Non-Hispanic whites 99-00 * < LOD < LOD 2.61 (2.14-3.08) 3.64 (3.15-5.00) 912

01-02 * < LOD < LOD < LOD < LOD 1216 

03-04 * < LOD < LOD < LOD < LOD 1088 

< LOD means less than the limit of detection for the urine levels not corrected for creatinine. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 294 Fourth National Report on Human Exposure to Environmental Chemicals 

Phthalates

References

Calafat AM, Silva MJ, Reidy JA, Gray LE, Samander E, Preau Jr 

JL, et al. Mono-(3-carboxypropyl)phthalate, a metabolite of din-octyl phthalate. J Toxicol Environ Health Part A 2006;69:215-

227.

Hoppin JA, Brock JW, Davis BJ, Baird DD. Reproducibility 

of urinary phthalate metabolites in first morning urine samples. 

Environ Health Perspect 2002;110(5):515-518.

Koch HM, Rossbach B, Drexler H, Angerer J. Internal exposure 

of the general population to DEHP and other phthalates - 

determination of secondary and primary phthalate monoester 

metabolites in urine. Environ Res 2003;93:177-185.

NTP-CERHR. National Toxicology Program-Center for the 

Evaluation of Risks to Human Reproduction. Monograph on the 

Potential Human Reproductive and Developmental Effects of Diisononyl Phthalate (DiOP). Research Triangle Park (NC). 2000 

[online]. Available at URL: http://cerhr.niehs.nih.gov/chemicals/

phthalates/dinp/dinp-eval.html. 6/2/09
Fourth National Report on Human Exposure to Environmental Chemicals 295

 Phytoestrogens

Phytoestrogens

General Informatgraceion

Phytoestrogens are naturally occurring polycyclic phenols 

found in certain plants. These are chemicals that may 

have weak estrogenic effects when they are ingested and 

metabolized. Two important groups of phytoestrogens are 

isoflavones and lignans. The table shows the phytoestrogen 

classes, examples, and some human urinary metabolites.

The isoflavones considered here include formononetin, 

daidzein, biochanin A, genistein, O-desmethylangolensin, 

and equol. Plant sources of isoflavones include legumes, 

with the largest contribution coming from soy-based foods. 

Because soy flour and soy protein isolates may be added 

to processed meats, meat substitutes, breads, and protein 

food bars, these items can be a major source of isoflavones 

(Grace et al., 2004; Lampe et al., 1999). However, the 

isoflavone content of soy protein preparations can vary 

widely and is affected by production techniques (Erdman 

et al., 2004). Daidzein and genistein are the main soy 

isoflavones. Kudzu root, used in some dietary supplements, 

also contains appreciable amounts of daidzein. Naringenin, 

a precursor to genistein, is found in some citrus fruits. 

Formononetin and biochanin A are methylated isoflavones 

found in clovers, which may be used in red clover dietary 

supplements; these isoflavones are metabolized in the body 

to daidzein and genistein, respectively.

Ingested daidzein is further metabolized to 

O-desmethylangolensin and to equol by intestinal bacteria. 

Equol, but not O-desmethylangolensin, has estrogenic 

activity. About 30% of adults can be characterized as equol 

producers and demonstrate higher serum equol levels after 

daidzein consumption (Cassidy et al., 2006; Setchell et al., 

2003). This ability to produce equol may be related to an 

individual’s intestinal microflora and influenced by dietary 

habits (Rowland et al., 2000). The relevance of equolproducer status to potential health related effects is unclear 

(Vafeiadou et al., 2006).

Lignans include matairesinol and secoisolariciresinol, 

which are transformed by intestinal bacteria into the 

estrogenic compounds enterolactone and enterodiol, 

respectively (Cornwell et al., 2004; Rowland et al., 2003). 

Enterodiol may also interconvert with enterolactone. 

Lignans are found in flax seeds, whole wheat flour, tea, 

some fruits, and other cereal grains. Other phytoestrogens 

of interest are resveratrol and trans-resveratrol, found in 

grape skins, wine, and peanuts.

Diet is the source of human exposure to phytoestrogens. 

The absorption and metabolism of phytoestrogens 

demonstrate large interindividual variability, which may 

relate to differences in both human pharmacokinetics and 

metabolism by intestinal bacteria. Phytoestrogens are 

ingested in their naturally occurring beta-glycosidic forms. 

The beta-glycosidic forms are hydrolyzed to their aglycones 

in the intestine, absorbed, and then glucuronidated in the 

intestinal wall and liver (Doerge et al., 2000; Rowland et 

al., 2003). The glucuronidated metabolites of isoflavones 

predominate in blood and urine (Rozman et al., 2006a;

Setchell et al., 2001).

The isoflavones are excreted from the body about 24 hours 

after ingestion, mainly in urine and, to a lesser extent, in 

feces. Urinary concentrations of daidzein and genistein did 

not correlate well with the ingested doses, possibly due 

to limited absorption of these isoflavones at higher doses 

(Setchell et al., 2003a). In contrast, plasma and urine lignan 

concentrations after flax seed consumption increased in 

a dose-dependent manner (Nesbitt et al., 1999). Equol 

excretion may depend on diet, the type of intestinal bacteria 

present, and individual genetic factors (Rowland et al., 

2000; Setchell et al., 2002; Setchell and Cassidy, 1999).

Phytoestrogens and Urinary Metabolites in this Report

Phytoestrogen Class Phytoestrogen or Metabolite (CAS number) 

Isoflavones

Daidzein (486-66-8) 

 O-Desmethylangolensin (21255-69-6) 

 Equol (531-95-3) 

Genistein (466-72-0) 

Lignans Enterolactone (78473-71-9) 

Enterodiol (80226-00-2) 
 296 Fourth National Report on Human Exposure to Environmental Chemicals 

Phytoestrogens 

After hydrolysis to the aglycone forms, phytoestrogens 

can weakly bind to estrogen-beta receptors (ER-beta) 

which are expressed in arteries and smooth muscle. 

Individual phytoestrogens may be either estrogen agonists 

or antagonists. Equol has more potent estrogenic activity 

than its precursor, daidzein. Equol also has been shown 

to have antiandrogenic activity in animals (Lund et al., 

2004; Magee and Rowland, 2004). Genistein binds ERbeta with greater affinity than equol (Doerge and Sheehan, 

2002). Although far less potent, phytoestrogens can be 

present in concentrations 100 to 1000 times greater than 

the endogenously produced estrogens. Soy-based infant 

formula can result in plasma concentrations of isoflavones 

in infants that are 13,000-22,000 times higher than 

endogenous estrogen concentrations in infants (Setchell et 

al., 1997). Phytoestrogens may also act through pathways 

other than the interaction with estrogen receptors. These 

actions include inhibiting the transformation of estrone 

to estradiol, inhibiting enzymes important for steroid 

biosynthesis and cell growth, and having antioxidant and 

anti-angiogenesis activities. (Adlercreutz et al., 1995a; 

Dixon and Ferreira, 2002; Sirtori et al., 2005). Numerous 

studies of either dietary soy or phytoestrogens and health 

outcomes have demonstrated inconsistent or inconclusive 

results. Consensus reviews of these studies suggest that 

no evidence clearly shows that dietary phytoestrogens 

significantly reduce cardiovascular disease risk, reduce 

postmenopausal vasomotor symptoms, improve bone 

Urinary Daidzein 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 75.1 (61.9-91.1) 69.8 (57.8-82.6) 229 (184-298) 538 (471-702) 1320 (1020-1540) 2553

01-02 51.7 (46.6-57.5) 52.3 (48.9-57.4) 192 (151-226) 577 (447-725) 1250 (863-1640) 2794

03-04 66.7 (60.4-73.7) 62.0 (54.1-69.7) 195 (171-219) 590 (500-675) 1070 (893-1330) 2594

Age group 

6-11 years 99-00 90.5 (75.1-109) 101 (70.3-138) 257 (172-430) 510 (437-840) 1130 (657-1740) 330

01-02 84.9 (71.6-101) 72.7 (56.3-97.0) 261 (155-385) 605 (437-989) 1060 (645-1500) 396

03-04 84.9 (71.6-101) 66.8 (55.4-92.8) 229 (151-314) 574 (371-654) 818 (625-1060) 341

12-19 years 99-00 123 (91.4-166) 124 (85.6-168) 326 (227-454) 833 (445-1490) 1460 (861-2410) 753

01-02 69.3 (52.6-91.3) 70.2 (52.5-87.5) 255 (185-344) 774 (573-984) 1360 (922-1950) 744

03-04 89.0 (75.2-105) 78.0 (59.0-104) 248 (197-332) 808 (500-968) 1200 (900-1790) 729

20 years and older 99-00 67.6 (55.4-82.4) 60.9 (49.3-74.1) 215 (167-239) 518 (459-573) 1320 (978-1540) 1470

01-02 46.4 (41.4-52.0) 49.1 (40.8-53.4) 176 (133-216) 520 (396-703) 1210 (771-1900) 1654

03-04 61.9 (55.2-69.4) 57.9 (48.7-68.5) 180 (150-214) 554 (416-695) 1110 (857-1360) 1524

Gender 

Males 99-00 88.9 (71.4-111) 80.6 (66.6-112) 262 (198-355) 587 (501-989) 1540 (989-2080) 1220

01-02 49.8 (42.8-57.9) 50.8 (46.0-55.0) 190 (137-240) 498 (386-694) 920 (717-1380) 1375

03-04 73.8 (63.4-85.9) 65.2 (56.1-76.4) 214 (156-311) 709 (535-900) 1200 (969-1380) 1244

Females 99-00 64.1 (52.9-77.6) 57.8 (45.0-73.2) 199 (150-244) 476 (389-722) 1220 (566-1700) 1333

01-02 53.6 (48.1-59.8) 55.7 (49.8-62.7) 199 (149-234) 642 (511-816) 1470 (1170-1980) 1419

03-04 60.7 (53.6-68.8) 57.4 (49.1-67.6) 175 (159-201) 466 (381-622) 884 (654-1380) 1350

Race/ethnicity 

Mexican Americans 99-00 78.9 (59.8-104) 66.2 (48.4-87.1) 254 (170-402) 806 (534-1020) 1360 (968-2780) 816

01-02 39.2 (28.5-54.0) 39.9 (28.8-59.9) 169 (100-291) 515 (388-669) 896 (613-1480) 679

03-04 57.4 (50.2-65.7) 45.5 (35.2-53.3) 178 (130-236) 686 (487-934) 1390 (934-1650) 653

Non-Hispanic blacks 99-00 91.9 (71.9-118) 103 (81.6-133) 286 (243-377) 553 (459-824) 1190 (640-1900) 607

01-02 66.1 (48.2-90.7) 72.9 (52.8-97.3) 255 (182-393) 757 (448-1400) 1410 (757-2480) 706

03-04 75.0 (56.1-100) 66.0 (50.7-86.6) 241 (151-340) 622 (408-875) 1190 (660-2300) 699

Non-Hispanic whites 99-00 74.4 (61.5-89.9) 66.9 (56.2-78.2) 216 (157-298) 512 (438-745) 1360 (989-1710) 917

01-02 48.6 (43.8-54.0) 49.8 (42.8-54.2) 171 (137-204) 504 (389-658) 1140 (774-1620) 1222

03-04 65.8 (58.6-74.0) 62.0 (52.8-71.9) 191 (165-215) 572 (416-722) 1070 (823-1330) 1079

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.5, 1.6, and 1.6, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 297

 Phytoestrogens

mineral density, or reduce cancer risk (Cornwell et al., 

2004; Messina et al., 2006; NAMS, 2000; Nedrow et al., 

2006; Sacks et al., 2006; Sirtori et al., 2005).

Adverse effects on fertility have been observed in animals 

that graze on red clover. Results of chronic feeding studies in 

pregnant animals suggest that high doses of phytoestrogens 

alter the fetal hormonal environment (Cornwell et al., 2004). 

Studies of children who had been fed soy-based formula 

as infants and who were followed through adolescence 

(Klein, 1998) and young adulthood (Strom et al., 2001) 

found no adverse reproductive or endocrine effects. In vitro

and animal studies suggest that soy isoflavones may have 

immunologic and thyroid effects (Doerge and Sheehan, 

2002; Sirtori et al., 2005). The Center for the Evaluation 

of Risks to Human Reproduction (CERHR) of the 

National Toxicology Program reviewed developmental and 

reproductive toxicity of both soy formula and genistein and 

concluded that available data were inadequate to determine 

whether soy formula has developmental or reproductive 

toxicity (Rozman et al., 2006a). The expert review panel 

expressed negligible concern for adverse effects in the 

general population consuming dietary sources of genistein 

(Rozman et al., 2006b).

Biomonitoring Information

The concentrations of urinary phytoestrogens observed 

Urinary Daidzein (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 68.5 (55.9-83.9) 65.1 (52.8-80.8) 204 (156-249) 560 (471-629) 944 (836-1150) 2553

01-02 48.5 (43.7-54.0) 48.3 (43.1-56.5) 166 (140-196) 500 (391-608) 957 (801-1180) 2794

03-04 62.5 (58.3-67.0) 56.1 (50.0-63.6) 164 (144-187) 502 (429-591) 1060 (825-1150) 2594

Age group 

6-11 years 99-00 92.6 (76.3-112) 93.1 (71.2-114) 251 (157-324) 552 (363-838) 1070 (781-2150) 330

01-02 96.4 (79.0-118) 85.9 (60.3-127) 275 (159-395) 655 (452-733) 938 (683-1140) 396

03-04 90.4 (77.2-106) 72.8 (58.2-99.5) 201 (152-240) 454 (329-638) 702 (526-1200) 341

12-19 years 99-00 83.1 (58.4-118) 85.6 (53.8-126) 207 (138-386) 628 (295-1060) 1000 (628-2380) 753

01-02 53.4 (40.8-70.0) 50.9 (38.3-77.6) 181 (142-248) 549 (385-718) 1030 (622-1360) 744

03-04 66.6 (55.7-79.6) 56.4 (43.9-74.6) 179 (151-217) 517 (370-753) 877 (617-1240) 729

20 years and older 99-00 63.8 (51.5-79.1) 59.3 (48.7-75.0) 194 (151-234) 554 (471-624) 908 (783-1180) 1470

01-02 43.9 (39.4-48.9) 43.8 (37.4-53.3) 153 (125-186) 428 (348-590) 946 (728-1220) 1654

03-04 59.2 (54.3-64.5) 51.7 (46.4-62.6) 155 (131-185) 501 (404-658) 1090 (808-1240) 1524

Gender 

Males 99-00 69.7 (54.7-88.8) 70.2 (51.3-84.3) 198 (147-276) 623 (494-836) 1050 (884-1290) 1220

01-02 40.5 (34.8-47.1) 41.7 (34.5-47.9) 139 (107-179) 348 (260-553) 788 (585-947) 1375

03-04 57.7 (49.4-67.3) 48.9 (41.6-58.3) 160 (126-205) 467 (368-600) 919 (665-1200) 1244

Females 99-00 67.4 (54.8-82.9) 62.6 (51.1-80.9) 207 (152-250) 509 (356-624) 850 (610-1410) 1333

01-02 57.6 (50.8-65.2) 59.5 (48.1-73.4) 191 (159-227) 615 (536-722) 1180 (924-1430) 1419

03-04 67.4 (60.8-74.9) 65.1 (54.6-73.4) 165 (143-191) 564 (409-699) 1090 (757-1370) 1350

Race/ethnicity 

Mexican Americans 99-00 72.5 (59.1-88.9) 64.2 (47.1-91.1) 243 (176-310) 677 (468-1080) 1380 (753-2690) 816

01-02 36.9 (27.8-49.0) 37.1 (24.8-57.9) 146 (101-225) 441 (307-596) 722 (565-1160) 679

03-04 51.8 (45.0-59.6) 47.7 (35.9-58.3) 159 (117-209) 502 (354-686) 1130 (779-1390) 653

Non-Hispanic blacks 99-00 59.1 (46.5-75.1) 67.6 (52.1-87.1) 172 (134-207) 381 (316-533) 802 (562-1010) 607

01-02 46.4 (33.7-63.8) 49.8 (35.5-69.7) 169 (104-249) 504 (263-773) 939 (542-1530) 706

03-04 53.1 (42.5-66.4) 44.7 (28.6-72.1) 147 (121-191) 415 (275-538) 727 (538-1040) 699

Non-Hispanic whites 99-00 72.8 (60.3-88.0) 67.5 (55.3-81.5) 207 (160-249) 560 (442-659) 908 (742-1350) 917

01-02 48.1 (43.4-53.3) 47.0 (42.1-56.0) 163 (137-191) 463 (375-627) 957 (805-1220) 1222

03-04 64.9 (59.8-70.3) 58.2 (50.4-66.3) 165 (138-204) 516 (385-667) 1090 (786-1250) 1079
 298 Fourth National Report on Human Exposure to Environmental Chemicals 

Phytoestrogens 

in the NHANES 1999-2000, 2000-2001, and 2003-2004 

subsamples generally reflect a diet consumed in the 

U.S. that is lower in isoflavones than in lignans. This is 

consistent with a Western diet in which whole grains and 

cereals, rather than soybean products, contribute the bulk 

of phytoestrogens (CDC, 2005). Enterolactone levels 

were highest, followed by daidzein, enterodiol, genistein, 

equol, and O-desmethylangolensin. Isoflavone levels at 

the higher percentiles may reflect dietary supplementation 

with soy products. The relationship between the dose and 

urinary excretion is linear for many phytoestrogens, except 

for equol (Karr et al., 1997; Slavin et al., 1998). Because 

excretory half-lives are reported to be in the range of 

3-10 hours (Lu et al., 1995; Setchell et al., 2001), urinary 

concentrations reflect recent consumption.

Levels of lignans (enterolactone, enterodiol) in the 

NHANES 1999-2000, 2001-2002, and 2003-2004 

subsamples appeared broadly similar to levels found in 

studies of postmenopausal women in the United Kingdom 

(Grace et al., 2004); men and women in the U. S. (ValentinBlasini et al., 2003); men and women in Minnesota (Lampe 

et al., 1999); postmenopausal Dutch women (den Tonkelaar 

et al., 2001); young African-American, Latina, and Japanese 

women in the San Francisco Bay Area (Horn-Ross et 

al., 1997); Japanese men and women (Adlercreutz et al., 

1991; Uehara et al., 2000a); premenopausal omnivorous 

women in Boston (Adlercreutz et al., 1986); and healthy 

Urinary O-Desmethylangolensin 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 4.39 (3.37-5.73) 4.98 (3.65-6.77) 22.7 (18.7-30.1) 100 (74.8-141) 222 (182-250) 2271

01-02 4.08 (3.53-4.73) 3.30 (2.70-4.20) 19.8 (16.7-24.6) 96.0 (70.1-135) 260 (161-437) 2794

03-04 4.91 (4.34-5.55) 4.60 (4.00-5.20) 23.6 (18.6-27.2) 95.9 (70.7-122) 230 (185-342) 2581

Age group 

6-11 years 99-00 5.60 (3.85-8.15) 7.52 (3.43-15.2) 36.2 (20.3-45.0) 78.7 (43.4-191) 176 (74.8-264) 287

01-02 6.19 (4.51-8.49) 5.90 (3.80-9.30) 26.9 (15.7-52.1) 122 (61.5-215) 281 (161-466) 396

03-04 6.33 (4.30-9.30) 6.10 (3.50-10.6) 24.0 (17.0-33.8) 70.8 (51.4-122) 138 (80.9-256) 341

12-19 years 99-00 6.04 (3.76-9.70) 7.60 (5.13-13.5) 36.6 (22.0-57.3) 107 (63.4-165) 194 (107-238) 667

01-02 5.92 (4.46-7.87) 5.20 (3.70-7.60) 33.6 (18.0-56.8) 125 (91.2-172) 299 (172-435) 744

03-04 6.37 (4.95-8.18) 5.30 (3.80-8.10) 33.9 (18.2-50.5) 110 (82.2-198) 257 (175-415) 729

20 years and older 99-00 4.05 (3.12-5.26) 4.46 (3.31-5.64) 19.8 (16.0-26.5) 101 (80.8-150) 228 (179-259) 1317

01-02 3.65 (3.08-4.32) 2.80 (2.30-3.70) 17.0 (13.9-22.4) 81.5 (63.0-128) 260 (135-526) 1654

03-04 4.56 (4.02-5.17) 4.40 (3.60-4.90) 22.0 (17.8-25.6) 94.0 (67.6-131) 230 (187-398) 1511

Gender 

Males 99-00 4.97 (3.71-6.66) 5.62 (4.12-8.73) 29.1 (19.8-42.9) 121 (74.1-190) 235 (177-332) 1087

01-02 3.81 (3.08-4.71) 3.30 (2.60-4.50) 17.4 (13.2-24.6) 82.8 (58.4-116) 194 (123-324) 1375

03-04 4.90 (3.93-6.12) 4.60 (3.40-5.50) 23.0 (16.6-30.1) 92.9 (70.7-129) 222 (159-332) 1240

Females 99-00 3.92 (2.97-5.16) 4.22 (3.18-5.51) 19.4 (14.1-26.1) 83.8 (61.1-114) 192 (123-250) 1184

01-02 4.36 (3.64-5.23) 3.40 (2.50-4.60) 21.3 (16.8-29.2) 107 (70.6-199) 394 (230-746) 1419

03-04 4.91 (4.26-5.66) 4.60 (3.90-5.50) 23.9 (18.1-27.4) 99.3 (63.5-155) 283 (160-433) 1341

Race/ethnicity 

Mexican Americans 99-00 2.41 (1.55-3.73) 2.14 (1.31-3.37) 21.0 (10.6-30.5) 97.6 (59.7-140) 191 (122-320) 721

01-02 2.44 (1.51-3.94) 1.40 (.500-3.40) 13.1 (5.80-27.6) 66.4 (33.5-102) 152 (75.8-265) 679

03-04 2.54 (1.86-3.48) 1.90 (1.00-3.40) 14.4 (9.00-18.1) 62.3 (40.3-99.5) 146 (99.5-254) 652

Non-Hispanic blacks 99-00 5.74 (4.55-7.24) 8.71 (5.82-10.9) 33.5 (22.1-52.4) 108 (78.3-156) 192 (149-255) 538

01-02 5.35 (4.00-7.14) 5.30 (2.90-7.30) 32.7 (22.0-52.4) 128 (75.9-216) 308 (150-436) 706

03-04 5.49 (4.05-7.46) 4.20 (3.30-6.10) 26.1 (13.4-49.0) 117 (86.2-166) 221 (177-354) 698

Non-Hispanic whites 99-00 4.50 (3.26-6.22) 4.99 (3.43-7.10) 22.5 (17.1-34.4) 103 (72.0-152) 228 (177-259) 826

01-02 4.13 (3.43-4.96) 3.40 (2.60-4.40) 17.9 (15.5-23.8) 98.7 (67.4-153) 260 (153-526) 1222

03-04 5.27 (4.63-5.99) 5.30 (4.40-6.00) 24.2 (18.8-28.5) 99.5 (67.6-149) 246 (183-409) 1070

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.2, 0.4, and 0.4, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 299

 Phytoestrogens

postmenopausal Finnish women who were omnivores and 

vegetarians (Uehara et al., 2000a,b). Vegetarian women 

in Boston and Helsinki (Adlercreutz et al., 1986), men 

and women consuming an experimental cruciferous diet 

(Kirkman et al., 1995), and Boston women consuming a 

macrobiotic diet excreted significantly higher urinary levels 

of these lignans (Hutchins, 1995a). Urinary enterolactone 

and enterodiol levels have been reported to vary by age, 

gender, race/ethnicity, and income (Valentin-Blasini et al., 

2003). Men were shown to have higher urinary mean levels 

of the isoflavones and higher levels of total phytoestrogens 

when compared with women (Lampe et al., 1999).

Levels of isoflavones (daidzein, genistein, equol, and 

Urinary O-Desmethylangolensin (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 4.03 (2.97-5.45) 4.44 (3.10-6.34) 21.8 (15.3-31.6) 90.4 (62.9-122) 167 (140-218) 2271

01-02 3.83 (3.32-4.43) 3.24 (2.55-4.12) 18.9 (16.1-23.3) 85.2 (65.1-117) 281 (149-412) 2794

03-04 4.58 (4.20-5.01) 4.09 (3.53-4.59) 19.6 (17.4-22.6) 92.9 (76.5-120) 201 (183-261) 2581

Age group 

6-11 years 99-00 6.00 (4.04-8.91) 7.15 (3.94-16.6) 28.8 (14.3-45.0) 83.3 (45.0-167) 179 (88.2-262) 287

01-02 7.03 (5.05-9.77) 6.49 (4.24-11.6) 29.9 (16.3-54.1) 101 (75.3-199) 305 (134-464) 396

03-04 6.73 (4.55-9.97) 5.97 (4.09-8.28) 27.7 (15.6-42.3) 86.1 (45.2-135) 149 (84.3-189) 341

12-19 years 99-00 4.13 (2.33-7.35) 5.71 (2.82-11.5) 26.0 (14.7-44.4) 71.4 (40.8-122) 122 (75.2-262) 667

01-02 4.57 (3.44-6.07) 3.88 (2.82-5.32) 26.0 (18.0-35.9) 95.0 (61.4-129) 259 (129-331) 744

03-04 4.76 (3.71-6.11) 4.26 (3.13-5.97) 22.9 (14.3-39.2) 86.4 (49.0-149) 185 (101-261) 729

20 years and older 99-00 3.82 (2.84-5.13) 3.90 (2.69-5.73) 20.2 (12.9-29.2) 96.5 (61.8-133) 172 (140-252) 1317

01-02 3.46 (2.95-4.04) 2.74 (2.03-3.64) 16.8 (13.7-20.3) 78.9 (58.2-124) 281 (143-467) 1654

03-04 4.35 (3.96-4.78) 3.75 (3.23-4.35) 18.7 (15.7-22.6) 95.2 (76.5-131) 228 (192-284) 1511

Gender 

Males 99-00 3.95 (2.79-5.58) 4.50 (2.88-6.50) 24.5 (13.8-40.5) 96.5 (62.4-122) 210 (125-265) 1087

01-02 3.10 (2.48-3.86) 2.87 (2.00-3.96) 15.0 (10.4-19.7) 60.7 (41.5-90.2) 154 (96.4-301) 1375

03-04 3.83 (3.10-4.73) 3.33 (2.41-4.35) 15.6 (13.9-19.0) 76.2 (51.1-99.5) 193 (124-255) 1240

Females 99-00 4.10 (3.00-5.61) 4.17 (2.91-6.34) 20.4 (14.4-27.2) 86.0 (49.1-145) 155 (100-205) 1184

01-02 4.68 (3.87-5.68) 3.74 (2.77-4.88) 26.8 (18.7-34.0) 111 (70.3-205) 399 (175-739) 1419

03-04 5.45 (4.71-6.30) 4.81 (4.09-5.92) 24.3 (19.6-28.9) 106 (78.5-163) 255 (193-343) 1341

Race/ethnicity 

Mexican Americans 99-00 2.19 (1.49-3.24) 1.88 (1.15-3.10) 16.6 (11.3-25.8) 71.2 (52.3-113) 136 (90.5-251) 721

01-02 2.30 (1.48-3.57) 1.45 (.770-3.37) 11.8 (4.91-23.6) 46.7 (31.4-87.8) 108 (54.7-218) 679

03-04 2.30 (1.68-3.15) 1.65 (.850-3.06) 13.2 (6.63-21.2) 51.6 (36.9-75.4) 125 (84.1-165) 652

Non-Hispanic blacks 99-00 3.65 (2.90-4.60) 5.22 (3.58-6.75) 23.8 (17.6-32.1) 67.1 (52.1-79.7) 116 (81.9-239) 538

01-02 3.75 (2.76-5.10) 3.56 (2.14-5.48) 22.8 (14.5-30.4) 78.5 (46.5-175) 218 (98.5-339) 706

03-04 3.89 (3.03-4.99) 3.12 (1.96-4.96) 17.0 (11.3-26.7) 80.0 (58.6-104) 159 (120-255) 698

Non-Hispanic whites 99-00 4.42 (3.12-6.27) 4.68 (3.05-7.23) 22.3 (15.3-37.9) 102 (57.6-148) 177 (140-215) 826

01-02 4.08 (3.41-4.89) 3.51 (2.45-4.57) 21.2 (16.3-27.4) 96.4 (69.8-126) 300 (153-464) 1222

03-04 5.18 (4.70-5.70) 4.58 (3.89-5.39) 21.6 (17.4-27.7) 103 (77.7-149) 225 (185-272) 1070

O-desmethylangolensin) in the NHANES 1999-2004 

subsamples appeared broadly similar to those seen in young 

Caucasian, African-American, Latino, and Japanese women 

in the San Francisco Bay area (CDC, 2005; Horn-Ross et 

al., 1997); men and women in the United States (ValentinBlasini et al., 2003; Lampe et al., 1999); Caucasian and 

Filipino women living in Hawaii (Maskarinec et al., 1998); 

postmenopausal women from Holland (den Tonkelaar et 

al., 2001) and the United Kingdom (Grace et al., 2004); 

omnivorous and vegetarian Helsinki women (Uehara et al., 

2000 a,b); and premenopausal omnivorous Boston women 

(Hutchins, 1995a,b).

Isoflavone levels seen in the NHANES 1999-2004 
 300 Fourth National Report on Human Exposure to Environmental Chemicals 

Phytoestrogens 

subsamples were 4 to 50 times lower than levels observed 

in Japanese men and women (Adlercreutz et al., 1991; 

CDC, 2005; Uehara et al., 2000a); Japanese women 

(Arai et al., 2000); postmenopausal Chinese women 

(Zheng et al., 1999); Singaporean women (Chen et al., 

1999; Seow et al., 1998); and Japanese women living in 

Hawaii (Maskarinec et al., 1998). Genistein and daidzein 

levels in NHANES 1999-2004 subsamples were twice as 

high as levels reported in people consuming a carotenoid 

diet, but lower than levels found in people consuming a 

cruciferous diet; O-desmethylangolensin levels were seven 

times lower (Kirkman et al., 1995). Levels of genistein, 

daidzein, and O-desmethylangolensin in urine of people 

consuming a soy diet were 6 to 100 times higher than levels 

found in NHANES 1999-2004 subsamples (CDC, 2005). 

Supplementing an omnivorous U.S. diet over a three month 

period with 60 grams of soy powder for female subjects 

increased isoflavone levels by more than thirteen-fold. 

(Albertazzi et al., 1999). Among U.S. adults, non-Hispanic 

whites were reported to have higher urinary isoflavone 

levels than non-Hispanic blacks or Hispanics (ValentinBlasini et al., 2003).

Finding a measurable amount of one or more phytoestrogen 

metabolites in urine does not mean that the levels of the 

metabolites or the parent phytoestrogen cause an adverse 

health effect. Biomonitoring studies on the levels of 

phytoestrogen metabolites provide physicians and public 

Urinary Enterodiol 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 26.6 (21.9-32.3) 34.0 (29.4-38.7) 78.8 (62.6-95.5) 165 (135-215) 266 (215-335) 2527

01-02 35.7 (32.5-39.3) 39.4 (36.3-43.4) 89.2 (80.7-96.9) 181 (162-205) 253 (223-308) 2794

03-04 39.5 (36.1-43.3) 44.9 (40.6-50.3) 106 (97.2-115) 242 (212-264) 367 (311-423) 2594

Age group 

6-11 years 99-00 26.5 (17.1-41.0) 29.4 (21.2-44.2) 78.7 (44.2-109) 215 (91.1-279) 276 (131-458) 327

01-02 33.6 (29.8-37.8) 35.5 (29.4-43.7) 78.1 (63.8-87.0) 152 (113-171) 203 (167-327) 396

03-04 42.0 (34.5-51.1) 42.1 (34.4-49.2) 91.4 (74.4-110) 199 (126-289) 312 (217-525) 341

12-19 years 99-00 29.8 (23.8-37.2) 34.0 (27.4-42.0) 84.4 (59.1-101) 166 (112-234) 253 (182-337) 744

01-02 35.3 (30.5-40.9) 37.7 (34.8-43.4) 84.2 (72.1-96.9) 165 (128-206) 238 (169-343) 744

03-04 45.1 (39.4-51.6) 46.3 (38.7-56.9) 99.5 (84.9-109) 191 (161-269) 325 (275-415) 729

20 years and older 99-00 26.1 (21.8-31.3) 34.3 (29.8-38.7) 78.3 (63.5-94.8) 160 (132-196) 263 (189-335) 1456

01-02 36.1 (31.8-41.0) 40.4 (36.0-45.7) 91.2 (79.3-105) 190 (161-220) 256 (224-312) 1654

03-04 38.4 (34.2-43.0) 44.9 (40.1-51.9) 112 (98.8-125) 255 (215-274) 398 (320-448) 1524

Gender 

Males 99-00 25.3 (19.5-32.7) 33.0 (28.0-38.0) 72.6 (54.7-94.3) 149 (109-219) 258 (169-286) 1206

01-02 35.2 (31.8-39.1) 40.5 (36.8-44.8) 90.6 (82.3-103) 184 (158-198) 263 (223-338) 1375

03-04 39.7 (36.2-43.6) 45.1 (40.5-51.1) 102 (92.9-115) 231 (186-266) 361 (268-460) 1244

Females 99-00 27.9 (23.4-33.3) 36.0 (29.9-40.3) 84.4 (71.8-97.9) 177 (146-219) 280 (219-375) 1321

01-02 36.2 (32.2-40.7) 38.5 (35.3-43.4) 87.0 (75.6-98.5) 175 (152-212) 248 (220-283) 1419

03-04 39.3 (33.8-45.5) 44.9 (38.3-53.0) 110 (97.3-124) 250 (203-294) 398 (309-464) 1350

Race/ethnicity 

Mexican Americans 99-00 21.7 (19.5-24.1) 28.0 (24.7-34.7) 70.4 (60.8-78.8) 143 (117-169) 213 (169-256) 791

01-02 30.5 (25.7-36.3) 34.0 (29.0-39.2) 75.9 (58.8-89.7) 159 (119-202) 244 (192-298) 679

03-04 33.1 (26.4-41.6) 38.7 (31.2-47.6) 95.2 (78.1-115) 198 (125-307) 307 (186-480) 653

Non-Hispanic blacks 99-00 25.8 (21.7-30.7) 31.2 (24.4-35.9) 66.0 (50.2-86.7) 157 (122-193) 260 (185-336) 608

01-02 35.0 (28.9-42.3) 38.7 (33.2-49.2) 83.7 (70.0-103) 169 (132-191) 225 (175-339) 706

03-04 40.4 (34.9-46.7) 47.1 (40.4-53.7) 100 (81.3-123) 212 (157-254) 293 (232-417) 699

Non-Hispanic whites 99-00 29.2 (24.0-35.4) 37.6 (31.3-43.8) 85.8 (68.3-99.4) 171 (138-228) 270 (187-375) 915

01-02 35.6 (31.8-40.0) 40.4 (36.1-44.7) 89.6 (78.5-101) 175 (153-198) 254 (214-337) 1222

03-04 39.8 (35.5-44.7) 45.8 (38.9-54.9) 109 (95.8-126) 255 (206-267) 365 (294-424) 1079

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.8, 1.5, and 1.5, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 301

 Phytoestrogens

Urinary Enterodiol (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 24.2 (20.3-28.9) 29.9 (25.0-34.7) 70.5 (59.6-82.1) 146 (124-177) 240 (199-320) 2527

01-02 33.5 (30.7-36.7) 37.6 (33.0-42.1) 79.2 (72.6-87.3) 149 (136-164) 224 (197-250) 2794

03-04 37.0 (33.6-40.7) 41.7 (37.9-45.4) 95.9 (85.6-106) 194 (171-213) 294 (247-368) 2594

Age group 

6-11 years 99-00 27.0 (18.6-39.3) 33.7 (21.8-43.7) 62.7 (43.0-108) 168 (81.6-290) 290 (150-411) 327

01-02 38.1 (32.5-44.7) 39.3 (30.8-53.1) 78.3 (66.6-103) 188 (147-244) 304 (242-389) 396

03-04 44.7 (37.4-53.5) 46.6 (38.5-58.3) 93.3 (73.9-125) 177 (128-205) 215 (181-413) 341

12-19 years 99-00 20.1 (16.7-24.2) 24.1 (19.6-30.1) 55.1 (42.6-71.7) 99.5 (91.5-116) 158 (121-177) 744

01-02 27.2 (23.3-31.8) 28.7 (24.9-34.9) 62.7 (54.9-71.0) 104 (84.2-139) 152 (111-225) 744

03-04 33.8 (30.3-37.7) 34.8 (33.2-38.8) 67.6 (64.1-73.9) 130 (107-164) 221 (138-324) 729

20 years and older 99-00 24.7 (20.6-29.5) 30.6 (26.0-34.8) 73.0 (62.5-84.5) 157 (129-184) 242 (199-344) 1456

01-02 34.2 (30.3-38.5) 39.6 (32.5-45.3) 84.1 (73.8-93.3) 152 (136-169) 224 (193-250) 1654

03-04 36.7 (32.5-41.4) 42.0 (37.1-47.8) 103 (91.8-111) 205 (173-239) 327 (256-431) 1524

Gender 

Males 99-00 19.8 (15.4-25.4) 25.4 (20.0-31.4) 55.1 (46.4-64.2) 122 (94.6-168) 199 (145-282) 1206

01-02 28.7 (26.0-31.7) 31.4 (27.0-36.8) 71.3 (64.2-78.0) 136 (114-160) 212 (179-259) 1375

03-04 31.1 (27.5-35.0) 34.8 (32.3-38.5) 78.0 (68.8-92.7) 165 (128-211) 249 (187-361) 1244

Females 99-00 29.3 (25.0-34.4) 35.4 (29.5-41.6) 85.2 (74.5-92.3) 165 (141-201) 321 (226-370) 1321

01-02 38.9 (34.9-43.3) 43.9 (39.3-48.7) 88.3 (74.7-102) 157 (139-174) 235 (180-304) 1419

03-04 43.6 (38.3-49.7) 49.0 (43.4-57.7) 109 (98.8-123) 215 (178-270) 377 (278-443) 1350

Race/ethnicity 

Mexican Americans 99-00 19.6 (17.3-22.2) 23.5 (19.7-28.7) 60.6 (49.8-77.7) 134 (114-154) 193 (154-227) 791

01-02 28.7 (24.5-33.7) 31.0 (27.0-37.3) 64.1 (55.0-77.5) 133 (94.4-183) 223 (143-337) 679

03-04 29.9 (23.8-37.4) 34.0 (26.5-42.8) 74.1 (62.0-101) 176 (118-234) 241 (189-364) 653

Non-Hispanic blacks 99-00 16.6 (13.9-19.7) 18.8 (14.4-22.9) 47.3 (37.7-55.8) 113 (85.9-145) 169 (131-272) 608

01-02 24.5 (19.7-30.6) 27.0 (22.6-33.4) 57.5 (48.2-73.2) 117 (92.2-143) 157 (118-246) 706

03-04 28.6 (24.5-33.4) 30.4 (26.1-36.1) 68.3 (53.4-87.5) 126 (96.3-191) 203 (153-227) 699

Non-Hispanic whites 99-00 28.6 (24.3-33.6) 34.4 (28.9-39.3) 75.8 (65.3-87.2) 163 (130-197) 252 (203-363) 915

01-02 35.3 (31.6-39.4) 40.9 (34.3-46.8) 83.3 (74.7-90.3) 152 (136-173) 225 (189-275) 1222

03-04 39.3 (34.4-44.8) 45.5 (38.4-53.0) 105 (90.2-116) 202 (168-234) 299 (244-374) 1079

health officials with reference values so that they can 

determine whether people have been exposed to higher 

levels of phytoestrogens than those found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.
 302 Fourth National Report on Human Exposure to Environmental Chemicals 

Phytoestrogens 

Urinary Enterolactone 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 239 (200-286) 315 (245-381) 726 (595-879) 1970 (1440-2370) 2800 (2500-3140) 2548

01-02 259 (233-287) 350 (314-389) 807 (739-873) 1590 (1440-1820) 2720 (1870-3430) 2794

03-04 298 (265-334) 395 (331-464) 900 (819-969) 1790 (1560-2040) 2620 (2360-2880) 2594

Age group 

6-11 years 99-00 308 (219-432) 356 (243-474) 721 (520-1320) 1730 (973-2840) 2840 (1700-3590) 331

01-02 288 (245-339) 329 (271-412) 680 (566-794) 1380 (929-1620) 2200 (1420-2550) 396

03-04 384 (287-513) 414 (299-567) 926 (589-1190) 1660 (1140-2280) 2360 (1700-3440) 341

12-19 years 99-00 250 (191-327) 317 (242-410) 672 (454-888) 1760 (973-2480) 2920 (1950-4330) 746

01-02 267 (231-308) 321 (255-399) 729 (617-856) 1480 (1230-1800) 2180 (1560-3440) 744

03-04 314 (267-369) 400 (333-468) 866 (736-1050) 1690 (1410-2080) 2620 (2000-2890) 729

20 years and older 99-00 230 (193-274) 310 (242-375) 734 (599-888) 2000 (1490-2390) 2790 (2510-3540) 1471

01-02 254 (223-289) 357 (314-397) 835 (760-914) 1660 (1460-1890) 2840 (1890-3610) 1654

03-04 286 (253-324) 394 (311-465) 900 (824-960) 1820 (1560-2060) 2630 (2350-3100) 1524

Gender 

Males 99-00 254 (212-304) 351 (266-418) 778 (579-1050) 2000 (1580-2400) 2730 (2430-3350) 1219

01-02 262 (233-295) 340 (314-387) 873 (769-957) 1810 (1490-2470) 3050 (1990-4070) 1375

03-04 314 (280-351) 425 (376-477) 938 (840-1060) 1760 (1540-2050) 2620 (2060-3230) 1244

Females 99-00 226 (180-284) 287 (236-339) 684 (560-799) 1890 (1200-2460) 2830 (2100-4330) 1329

01-02 255 (226-288) 357 (298-397) 759 (680-840) 1450 (1190-1700) 2200 (1710-2950) 1419

03-04 283 (233-343) 371 (278-465) 859 (706-984) 1810 (1440-2170) 2630 (2210-3440) 1350

Race/ethnicity 

Mexican Americans 99-00 212 (169-265) 281 (230-335) 631 (539-732) 1650 (950-2210) 2690 (2380-3350) 813

01-02 275 (221-342) 347 (312-395) 778 (671-913) 1520 (1090-1920) 2340 (1610-2990) 679

03-04 275 (239-316) 376 (316-435) 849 (744-958) 1560 (1320-1860) 2240 (1860-3100) 653

Non-Hispanic blacks 99-00 262 (196-349) 363 (293-440) 759 (629-925) 1730 (1000-2420) 2500 (1870-3280) 605

01-02 278 (226-342) 418 (341-479) 769 (686-853) 1450 (1160-1840) 2000 (1540-2420) 706

03-04 328 (285-378) 437 (362-526) 942 (768-1110) 1580 (1360-1820) 2280 (1880-2640) 699

Non-Hispanic whites 99-00 247 (196-311) 317 (240-403) 752 (616-955) 2040 (1600-2450) 3000 (2460-3880) 917

01-02 267 (235-303) 357 (307-397) 834 (750-923) 1630 (1420-1890) 2780 (1820-3740) 1222

03-04 299 (254-352) 396 (299-488) 900 (789-996) 1810 (1510-2140) 2680 (2310-3230) 1079

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.6, 1.9, and 1.9, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 303

 Phytoestrogens

Urinary Enterolactone (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 218 (184-260) 284 (247-336) 733 (613-869) 1580 (1290-1830) 2250 (1860-2830) 2548

01-02 243 (220-268) 324 (293-360) 756 (668-858) 1430 (1250-1580) 2120 (1720-2450) 2794

03-04 279 (245-317) 371 (324-430) 810 (697-911) 1590 (1350-1910) 2400 (2000-2890) 2594

Age group 

6-11 years 99-00 315 (238-416) 384 (266-435) 704 (495-1110) 1580 (1110-2010) 2100 (1580-3040) 331

01-02 327 (274-391) 349 (263-478) 738 (603-994) 1420 (1140-1800) 2020 (1420-2940) 396

03-04 409 (310-540) 470 (354-632) 904 (669-1150) 1480 (1090-2420) 2300 (1480-2690) 341

12-19 years 99-00 169 (133-214) 210 (172-264) 486 (371-615) 1150 (742-1540) 1850 (1310-2350) 746

01-02 206 (178-239) 255 (223-293) 619 (466-753) 1110 (869-1480) 1500 (1140-2080) 744

03-04 235 (202-273) 285 (255-307) 631 (533-744) 1230 (993-1350) 1510 (1240-2230) 729

20 years and older 99-00 217 (181-261) 288 (249-350) 785 (653-923) 1640 (1330-1890) 2310 (1890-3110) 1471

01-02 240 (213-271) 331 (300-375) 786 (672-915) 1460 (1300-1630) 2180 (1890-2470) 1654

03-04 274 (236-318) 377 (316-448) 823 (697-937) 1700 (1430-1980) 2480 (2040-3100) 1524

Gender 

Males 99-00 199 (170-234) 263 (228-309) 664 (490-828) 1380 (1200-1710) 2030 (1780-2480) 1219

01-02 213 (191-238) 287 (255-316) 682 (601-764) 1350 (1090-1580) 1980 (1570-2550) 1375

03-04 245 (215-280) 330 (288-372) 729 (676-808) 1330 (1160-1580) 2040 (1590-2380) 1244

Females 99-00 238 (191-297) 303 (260-379) 819 (662-968) 1720 (1390-2010) 2550 (1940-3390) 1329

01-02 274 (241-312) 356 (313-407) 833 (710-1000) 1490 (1320-1670) 2150 (1890-2410) 1419

03-04 314 (257-385) 414 (327-510) 866 (704-1090) 1840 (1460-2280) 2840 (2220-3910) 1350

Race/ethnicity 

Mexican Americans 99-00 194 (165-228) 254 (225-282) 605 (519-695) 1340 (969-1740) 2100 (1620-2790) 813

01-02 259 (213-314) 362 (296-409) 730 (586-905) 1240 (1010-1490) 1630 (1240-2540) 679

03-04 248 (217-282) 350 (310-403) 724 (657-826) 1320 (1020-1560) 1820 (1460-2170) 653

Non-Hispanic blacks 99-00 168 (125-226) 214 (173-274) 546 (411-732) 1130 (874-1450) 1590 (1120-2560) 605

01-02 195 (155-245) 302 (257-331) 562 (470-629) 985 (821-1130) 1490 (1080-1730) 706

03-04 233 (197-274) 303 (276-347) 621 (512-707) 1050 (917-1350) 1550 (1170-2220) 699

Non-Hispanic whites 99-00 241 (194-300) 323 (279-388) 828 (674-997) 1780 (1390-2020) 2490 (1930-3340) 917

01-02 264 (232-301) 339 (299-393) 833 (719-944) 1530 (1340-1880) 2410 (1940-2800) 1222

03-04 294 (246-353) 399 (326-488) 836 (707-980) 1660 (1330-2040) 2500 (1990-3350) 1079
 304 Fourth National Report on Human Exposure to Environmental Chemicals 

Phytoestrogens 

Urinary Equol 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 8.37 (7.21-9.72) 8.02 (6.27-9.90) 17.2 (15.2-19.8) 35.0 (28.9-41.6) 53.7 (40.1-74.2) 2182

01-02 9.17 (7.76-10.8) 9.00 (7.40-10.5) 19.6 (16.6-23.5) 42.1 (34.3-51.5) 73.5 (53.6-89.2) 2794

03-04 8.02 (7.07-9.10) 8.00 (6.80-9.40) 18.2 (15.2-20.8) 36.6 (31.3-40.0) 64.9 (45.4-97.9) 2590

Age group 

6-11 years 99-00 10.5 (7.65-14.3) 11.7 (5.43-18.6) 24.9 (17.5-29.5) 34.4 (29.5-53.3) 56.1 (30.1-149) 272

01-02 12.2 (10.2-14.6) 13.7 (11.1-16.2) 26.2 (17.9-37.9) 50.4 (35.0-84.3) 85.4 (50.4-159) 396

03-04 12.4 (9.71-15.8) 12.1 (8.40-17.8) 24.4 (20.1-31.2) 46.7 (33.5-82.3) 85.8 (44.9-118) 341

12-19 years 99-00 10.9 (8.64-13.8) 10.8 (8.52-13.4) 22.3 (16.0-34.9) 42.9 (34.1-71.3) 71.6 (48.1-210) 657

01-02 10.2 (8.50-12.1) 10.5 (8.20-12.5) 20.5 (16.8-24.8) 43.1 (30.1-56.1) 70.0 (46.3-99.2) 744

03-04 10.6 (8.97-12.4) 10.5 (8.70-12.2) 22.6 (19.3-26.4) 39.9 (34.8-45.1) 61.9 (45.1-113) 729

20 years and older 99-00 7.79 (6.79-8.94) 7.43 (5.71-8.85) 16.0 (13.6-18.1) 33.1 (24.4-39.7) 52.2 (36.3-93.9) 1253

01-02 8.70 (7.29-10.4) 8.00 (6.20-10.2) 18.6 (15.0-22.3) 41.3 (34.1-47.4) 73.5 (53.9-89.0) 1654

03-04 7.28 (6.37-8.33) 7.20 (6.00-8.70) 16.0 (14.2-19.2) 33.9 (28.2-38.9) 63.0 (41.3-121) 1520

Gender 

Males 99-00 9.15 (7.37-11.4) 8.44 (6.36-11.2) 19.0 (15.9-24.0) 35.6 (29.2-54.8) 71.3 (39.7-166) 1042

01-02 9.41 (7.99-11.1) 9.20 (7.70-10.8) 20.1 (16.7-26.1) 43.1 (32.4-53.1) 61.7 (51.8-81.5) 1375

03-04 8.56 (7.54-9.72) 8.70 (7.20-10.2) 19.0 (15.9-21.6) 38.0 (31.9-44.2) 72.6 (45.4-100) 1240

Females 99-00 7.70 (6.79-8.75) 7.57 (5.79-9.04) 15.6 (12.7-18.9) 33.6 (26.7-37.7) 48.2 (37.1-62.9) 1140

01-02 8.94 (7.38-10.8) 8.60 (6.70-10.7) 19.0 (15.6-22.9) 41.6 (33.3-51.5) 79.8 (56.6-122) 1419

03-04 7.55 (6.44-8.84) 7.30 (6.20-9.00) 16.9 (14.7-19.8) 33.8 (28.3-40.0) 60.3 (42.5-116) 1350

Race/ethnicity 

Mexican Americans 99-00 5.24 (4.77-5.76) 4.51 (3.65-5.18) 9.48 (7.96-10.3) 18.5 (14.5-22.6) 30.9 (21.6-48.4) 726

01-02 7.22 (6.04-8.62) 6.50 (4.40-9.10) 14.2 (11.3-20.1) 31.4 (21.1-41.0) 42.4 (38.1-60.2) 679

03-04 6.08 (5.08-7.28) 5.70 (4.70-6.80) 12.5 (9.80-15.4) 26.1 (18.1-39.7) 43.6 (34.3-88.2) 653

Non-Hispanic blacks 99-00 6.73 (5.20-8.71) 6.24 (3.86-10.0) 15.1 (12.7-17.6) 27.6 (19.4-35.6) 36.4 (28.9-49.4) 514

01-02 7.15 (6.06-8.43) 6.10 (4.70-7.60) 14.7 (12.0-18.7) 30.9 (22.8-41.9) 45.7 (36.1-90.5) 706

03-04 7.35 (6.16-8.79) 7.90 (6.00-9.60) 16.5 (14.2-18.3) 32.0 (25.1-37.5) 47.0 (37.8-68.2) 696

Non-Hispanic whites 99-00 9.26 (7.80-11.0) 8.98 (6.73-11.9) 19.0 (16.1-22.8) 36.2 (30.1-45.4) 56.1 (42.1-89.4) 758

01-02 9.91 (7.95-12.4) 10.0 (7.30-12.6) 22.0 (17.4-27.4) 44.4 (35.1-57.5) 74.4 (55.1-107) 1222

03-04 8.52 (7.26-10.0) 8.80 (7.10-10.3) 19.3 (15.4-23.0) 37.7 (31.7-44.2) 73.1 (46.7-120) 1078

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 3.0, 3.3, and 3.3, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 305

 Phytoestrogens

Urinary Equol (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 7.70 (6.82-8.70) 7.96 (6.87-9.35) 16.2 (13.2-18.6) 30.6 (26.9-35.1) 50.3 (41.8-67.3) 2182

01-02 8.60 (7.26-10.2) 7.98 (6.62-9.76) 17.6 (14.8-21.8) 37.8 (30.3-46.3) 62.6 (50.0-85.0) 2794

03-04 7.52 (6.83-8.29) 7.29 (6.56-8.18) 14.6 (13.3-15.7) 27.8 (24.7-31.9) 50.6 (39.9-75.1) 2590

Age group 

6-11 years 99-00 10.3 (7.83-13.5) 11.4 (7.46-16.3) 22.6 (14.7-27.2) 32.7 (25.5-46.0) 47.8 (32.7-150) 272

01-02 13.9 (11.2-17.2) 14.0 (10.6-17.0) 28.8 (19.6-39.8) 54.4 (34.9-99.8) 88.2 (56.8-186) 396

03-04 13.2 (10.9-15.9) 13.2 (9.19-17.5) 24.2 (20.6-28.0) 41.6 (35.2-64.1) 93.5 (45.4-117) 341

12-19 years 99-00 7.61 (6.17-9.39) 8.02 (6.72-9.29) 14.0 (11.4-20.4) 27.5 (20.8-38.3) 47.4 (27.5-149) 657

01-02 7.83 (6.68-9.17) 7.77 (6.29-9.13) 17.4 (14.9-19.2) 31.9 (25.3-41.7) 54.3 (33.0-76.7) 744

03-04 7.91 (6.59-9.49) 8.11 (6.80-9.09) 14.5 (11.8-17.5) 30.1 (21.0-38.2) 40.6 (32.6-66.9) 729

20 years and older 99-00 7.45 (6.60-8.41) 7.63 (6.34-9.22) 15.3 (12.7-17.7) 30.8 (25.0-37.2) 53.2 (41.2-71.8) 1253

01-02 8.23 (6.93-9.79) 7.52 (5.97-9.56) 16.6 (14.0-20.8) 36.4 (29.3-42.9) 58.7 (47.9-85.0) 1654

03-04 6.98 (6.30-7.73) 6.76 (6.05-7.65) 13.6 (12.5-14.9) 24.6 (21.9-29.4) 42.8 (35.7-81.6) 1520

Gender 

Males 99-00 7.01 (5.93-8.29) 7.31 (5.63-8.78) 13.8 (11.7-17.6) 29.3 (21.4-41.8) 54.1 (35.8-81.0) 1042

01-02 7.66 (6.39-9.18) 7.43 (5.81-9.16) 16.2 (14.0-19.4) 32.9 (27.9-40.4) 54.3 (37.8-67.1) 1375

03-04 6.71 (6.02-7.47) 6.63 (5.78-7.29) 13.3 (11.9-15.5) 25.7 (23.1-30.3) 51.1 (37.1-76.7) 1240

Females 99-00 8.41 (7.33-9.66) 8.71 (7.33-10.1) 17.7 (15.1-20.0) 31.6 (27.5-37.2) 46.3 (41.0-56.5) 1140

01-02 9.60 (7.99-11.5) 8.66 (6.97-10.6) 19.2 (15.7-23.7) 41.7 (32.3-55.9) 85.0 (61.7-115) 1419

03-04 8.38 (7.39-9.51) 8.29 (7.03-9.28) 15.1 (14.0-16.6) 30.6 (25.0-32.5) 45.4 (38.7-102) 1350

Race/ethnicity 

Mexican Americans 99-00 4.89 (4.36-5.47) 4.73 (3.90-5.27) 8.85 (8.18-9.91) 22.3 (16.5-26.8) 37.1 (25.3-57.6) 726

01-02 6.79 (5.82-7.92) 6.81 (5.55-8.04) 14.9 (11.7-17.8) 29.1 (22.9-36.0) 41.3 (31.4-47.1) 679

03-04 5.48 (4.60-6.54) 4.72 (3.95-5.78) 10.1 (7.76-13.4) 24.4 (17.2-30.9) 35.6 (27.6-102) 653

Non-Hispanic blacks 99-00 4.36 (3.41-5.57) 4.57 (2.94-6.23) 10.2 (7.96-12.0) 17.1 (14.8-19.8) 26.0 (19.6-32.0) 514

01-02 5.01 (4.26-5.89) 4.48 (3.80-5.42) 11.0 (8.80-13.0) 22.7 (16.5-29.3) 35.4 (24.8-46.7) 706

03-04 5.23 (4.44-6.16) 5.28 (4.67-6.09) 10.3 (8.61-12.3) 20.2 (17.1-23.9) 29.4 (23.9-42.3) 696

Non-Hispanic whites 99-00 9.13 (7.85-10.6) 9.51 (7.63-11.2) 18.0 (15.2-21.6) 35.4 (29.5-41.3) 56.5 (46.0-73.0) 758

01-02 9.81 (7.93-12.1) 9.17 (7.06-12.2) 19.8 (15.4-25.6) 41.3 (30.7-55.9) 66.4 (56.8-85.0) 1222

03-04 8.40 (7.50-9.41) 8.17 (7.13-9.19) 15.6 (14.1-17.1) 30.6 (25.0-32.8) 56.8 (38.0-107) 1078
 306 Fourth National Report on Human Exposure to Environmental Chemicals 

Phytoestrogens 

Urinary Genistein 

Geometric mean and selected percentiles of urine concentrations (in μg/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 24.4 (19.7-30.3) 27.0 (22.5-32.8) 93.6 (75.8-118) 284 (244-331) 563 (413-709) 2557

01-02 33.0 (30.1-36.2) 29.0 (26.8-31.8) 92.5 (77.9-109) 306 (240-372) 619 (523-719) 2794

03-04 31.1 (29.0-33.3) 26.2 (23.9-29.7) 87.8 (78.8-102) 286 (239-313) 528 (402-610) 2594

Age group 

6-11 years 99-00 27.6 (21.1-36.1) 31.9 (18.1-42.6) 104 (67.6-151) 220 (151-315) 376 (272-725) 331

01-02 39.2 (33.4-46.0) 31.7 (25.8-39.6) 94.1 (62.3-158) 258 (190-426) 502 (258-830) 396

03-04 33.6 (27.8-40.6) 29.3 (23.1-37.8) 79.4 (56.7-111) 193 (146-274) 351 (207-376) 341

12-19 years 99-00 43.7 (34.2-55.7) 45.4 (34.3-60.5) 138 (93.7-179) 319 (245-464) 547 (321-777) 754

01-02 34.1 (27.2-42.8) 29.0 (26.1-32.9) 90.6 (71.5-113) 278 (216-363) 470 (360-687) 744

03-04 34.7 (29.3-41.0) 29.0 (23.4-37.6) 111 (69.3-141) 304 (206-376) 530 (358-671) 729

20 years and older 99-00 21.9 (17.6-27.2) 24.0 (21.7-28.4) 86.2 (67.5-108) 293 (235-343) 566 (412-744) 1472

01-02 32.1 (28.8-35.8) 28.8 (25.4-33.4) 93.4 (77.3-110) 312 (235-389) 627 (537-790) 1654

03-04 30.2 (27.8-32.8) 25.9 (22.3-29.8) 87.8 (77.9-103) 296 (239-321) 557 (412-653) 1524

Gender 

Males 99-00 29.8 (22.2-40.0) 31.9 (26.3-37.2) 108 (79.1-151) 335 (257-440) 709 (437-981) 1222

01-02 32.2 (27.9-37.2) 29.5 (25.4-33.7) 91.2 (73.4-103) 239 (190-331) 474 (335-719) 1375

03-04 33.7 (29.6-38.4) 27.3 (23.4-33.0) 92.6 (68.6-124) 310 (228-351) 562 (443-653) 1244

Females 99-00 20.3 (17.0-24.2) 23.1 (20.1-26.3) 84.7 (59.6-105) 242 (203-288) 446 (339-619) 1335

01-02 33.7 (30.9-36.8) 28.7 (26.0-32.3) 97.0 (79.9-118) 387 (253-500) 666 (598-807) 1419

03-04 28.7 (25.5-32.4) 25.0 (22.4-28.4) 85.0 (71.2-106) 256 (218-308) 467 (356-620) 1350

Race/ethnicity 

Mexican Americans 99-00 31.1 (25.1-38.5) 30.0 (25.1-37.3) 117 (83.9-179) 328 (248-479) 573 (419-1180) 819

01-02 28.3 (22.0-36.4) 25.6 (19.6-32.5) 74.8 (48.8-111) 225 (174-314) 424 (323-523) 679

03-04 31.1 (27.5-35.2) 25.2 (19.1-32.6) 83.2 (63.6-120) 319 (252-537) 653 (537-851) 653

Non-Hispanic blacks 99-00 26.7 (19.2-37.0) 32.9 (24.4-41.5) 103 (84.8-137) 257 (213-367) 495 (329-926) 608

01-02 37.6 (27.4-51.6) 35.3 (23.6-49.5) 95.5 (71.1-142) 378 (192-530) 598 (375-1120) 706

03-04 32.3 (24.0-43.4) 27.4 (18.8-44.9) 84.8 (60.5-113) 279 (163-412) 514 (323-852) 699

Non-Hispanic whites 99-00 23.6 (19.1-29.3) 25.6 (21.7-32.0) 91.4 (68.0-122) 288 (227-353) 566 (395-734) 917

01-02 30.9 (27.8-34.4) 27.6 (24.6-30.8) 89.7 (71.1-105) 278 (226-365) 626 (485-755) 1222

03-04 30.8 (28.2-33.6) 26.2 (22.6-31.0) 93.6 (78.8-112) 279 (225-313) 504 (376-610) 1079

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 0.3, 0.8, and 0.8, respectively. 
Fourth National Report on Human Exposure to Environmental Chemicals 307

 Phytoestrogens

Urinary Genistein (creatinine corrected) 

Geometric mean and selected percentiles of urine concentrations (in μg/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 99-00 22.3 (17.7-28.1) 23.8 (18.8-28.9) 84.7 (67.2-105) 222 (182-279) 381 (334-497) 2557

01-02 30.9 (28.5-33.6) 25.9 (23.4-29.2) 83.3 (72.2-96.3) 256 (211-296) 427 (375-490) 2794

03-04 29.1 (27.3-31.0) 24.6 (21.3-27.5) 77.7 (67.3-90.9) 231 (203-279) 510 (388-619) 2594

Age group 

6-11 years 99-00 28.3 (21.1-37.9) 27.8 (15.8-41.3) 94.3 (60.5-145) 209 (148-317) 490 (279-895) 331

01-02 44.5 (37.0-53.5) 37.9 (29.7-49.0) 112 (76.5-146) 252 (173-371) 504 (252-713) 396

03-04 35.8 (29.7-43.0) 35.4 (24.9-43.2) 78.6 (60.9-119) 172 (130-243) 297 (168-618) 341

12-19 years 99-00 29.4 (22.3-38.8) 32.0 (23.8-41.6) 83.2 (64.1-104) 184 (130-295) 336 (184-816) 754

01-02 26.3 (21.3-32.5) 21.0 (17.8-26.5) 66.2 (47.9-91.5) 200 (149-298) 321 (261-435) 744

03-04 25.9 (21.8-30.9) 21.8 (17.0-29.1) 65.6 (51.0-83.1) 201 (145-313) 366 (297-455) 729

20 years and older 99-00 20.6 (16.3-26.2) 21.6 (17.7-26.2) 83.1 (64.9-107) 234 (190-287) 381 (325-562) 1472

01-02 30.4 (27.6-33.4) 24.8 (21.9-30.0) 83.2 (68.5-99.0) 269 (208-328) 435 (374-518) 1654

03-04 28.9 (26.7-31.3) 24.0 (20.1-27.5) 78.5 (66.1-92.9) 253 (209-302) 542 (399-673) 1524

Gender 

Males 99-00 23.3 (16.8-32.3) 23.8 (17.5-32.2) 86.2 (64.7-115) 236 (178-330) 523 (323-889) 1222

01-02 26.2 (23.1-29.8) 22.1 (19.4-26.0) 67.6 (57.4-78.1) 186 (144-237) 350 (278-418) 1375

03-04 26.4 (22.8-30.5) 21.5 (17.3-26.2) 70.1 (51.1-90.5) 203 (159-235) 415 (346-600) 1244

Females 99-00 21.3 (17.5-26.0) 23.2 (17.5-29.3) 83.1 (57.2-106) 211 (154-283) 357 (283-398) 1335

01-02 36.2 (32.8-39.9) 29.6 (25.2-34.3) 107 (88.4-129) 321 (269-355) 547 (427-729) 1419

03-04 31.9 (28.7-35.5) 27.1 (23.6-31.6) 87.1 (71.1-102) 278 (209-324) 548 (363-763) 1350

Race/ethnicity 

Mexican Americans 99-00 28.4 (23.3-34.7) 27.9 (22.5-35.0) 109 (91.5-137) 257 (209-380) 562 (257-981) 819

01-02 26.6 (21.6-32.9) 21.0 (16.1-28.9) 61.6 (50.6-76.8) 205 (147-270) 372 (271-479) 679

03-04 28.0 (24.8-31.8) 23.5 (18.5-28.1) 69.2 (52.3-92.8) 254 (187-390) 608 (417-764) 653

Non-Hispanic blacks 99-00 17.1 (12.4-23.7) 19.5 (15.7-26.1) 59.5 (43.1-93.7) 179 (132-245) 299 (222-446) 608

01-02 26.4 (19.3-36.1) 22.7 (16.4-33.6) 69.4 (42.2-115) 217 (139-317) 384 (217-747) 706

03-04 22.8 (18.1-28.8) 19.6 (14.3-27.1) 55.0 (39.6-78.1) 182 (107-240) 311 (210-514) 699

Non-Hispanic whites 99-00 23.2 (18.5-29.0) 24.9 (19.0-31.7) 86.1 (68.4-105) 232 (178-295) 381 (325-523) 917

01-02 30.6 (28.2-33.2) 25.4 (22.7-29.5) 82.0 (68.3-96.3) 248 (207-320) 427 (365-518) 1222

03-04 30.4 (27.9-33.0) 26.2 (21.5-31.4) 79.6 (69.1-99.6) 238 (195-321) 534 (352-688) 1079
 308 Fourth National Report on Human Exposure to Environmental Chemicals 

Phytoestrogens 

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Fourth National Report on Human Exposure to Environmental Chemicals 311

 Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

Polybrominated Diphenyl Ethers and 

2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

General Information

Polybrominated diphenyl ethers (PBDEs) are a class of 

synthetic chemicals first produced commercially in the 1970s. 

They are added to products such as foam padding, textiles, 

or plastics to retard combustion. 2,2’,4,4’,5,5’-hexabromobiphenyl (BB-153) is a brominated biphenyl that was used 

as a flame retardant in the U.S. until the 1970s. Its use 

was phased out following an accidental contamination of 

cattle feed in the state of Michigan with the contamination 

extending to other animals, the environment, and into 

humans (Fries, 1985).

Three major commercial mixtures of PBDEs have been 

produced and used. These are named for the average number 

of bromines attached to the diphenyl ether structure, e.g., 

pentaBDE. The pentaBDE technical mixture contains 50-

60% of PBDE congeners with five bromines, 24-38% with 

four bromines (tetraBDEs) and 4-8% with six bromines 

(hexaBDE), though reports on mixtures vary (Alaee et 

al., 2003; Birnbaum and Staskal, 2004; OECD, 1994). 

Commercial pentaBDEs are often added to polyurethane 

foams used in mattresses, upholstered furniture, and carpet 

padding. OctaBDE technical mixtures contain 10-12% of 

PBDE congeners with six bromines, 43-44% with seven 

bromines, 31-35% with eight bromines and 10-11% with 

nine bromines. OctaBDE mixtures are added to acrylonitrilebutadiene-styrene used in computer and appliance casings, 

and also to some polyolefins and nylon. DecaBDE is the 

most widely used PBDE globally and greater than 97% of 

its content includes PBDEs with ten bromines. It is added to 

polystyrene, polybutylene, nylon, polypropylene, and other 

thermoelastic polymers used in adhesives, wire insulation, 

casings for televisions and computers, and in some nonclothing textiles (OECD, 1994; Sjödin et al., 2003; WSDH, 

2004). PBDEs are often combined with antimony trioxide 

to enhance the fire protection offered by the PBDEs. 

For example, protected polypropylene can contain 23% 

decaBDE and 8% antimony trioxide by weight. PBDE 

content in protected products varies from 3-33% (Gill et 

al., 2004).

PBDE production makes up about 25% of all fire retardant 

production. In 2000, global production was 67,000 metric 

tons annually with about 80% of the total being decaBDE 

(Birnbaum and Staskal, 2004; WSDH, 2004). Most of 

the pentaBDE produced has been used within the U.S. 

About 40% and 44% of the global production of octaBDE 

and decaBDE were also used in the U.S. Since PBDEs 

are not chemically bound to the flame-retarded material, 

they can enter the environment from volatilization, 

leaching, or degradation of PBDE-containing products 

(Gill et al., 2004). Also, PBDEs can enter the environment 

from manufacturer-related releases. When thermally 

decomposed, PBDEs can produce polybrominated dibenzop-dioxins and dibenzofurans (Watanabe and Sakai, 2003). 

Manufacturers of pentaBDE and octaBDE in the U.S. were 

to have phased out production of these chemicals by 2004 

and U.S. EPA issued a rule to prevent new production 

(U.S. EPA, 2005). PBDEs are generally persistent in the 

environment and have been measured in aquatic sediments 

and aquatic and terrestrial animals, especially in fish where 

PBDEs are known to bioconcentrate. Several studies of 

stored biologic specimens have shown dramatic increases 

in PBDE concentrations over the last several decades, for 

example, in archived bird eggs (Norstrom et al., 2002).

Human exposure to PBDEs is thought to result from 

Polybrominated Diphenyl Ethers in this Report

Polybrominated Diphenyl Ether (IUPAC number) CAS Number 

Serum 2,2',4’-Tribromodiphenyl ether (BDE 17) 147217-75-2 

Serum 2,4,4’-Tribromodiphenyl ether (BDE 28) 41318-75-6 

Serum 2,2’,4,4’-Tetrabromodiphenyl ether (BDE 47) 5436-43-1 

Serum 2,3',4,4'-Tetrabromodiphenyl ether (BDE 66) 189084-61-5 

Serum 2,2’,3,4,4’-Pentabromodiphenyl ether (BDE 85) 182346-21-0 

Serum 2,2’,4,4’,5-Pentabromodiphenyl ether (BDE 99) 60328-60-9 

Serum 2,2’,4,4’,6-Pentabromodiphenyl ether (BDE 100) 189084-64-8 

Serum 2,2’,4,4’,5,5’-Hexabromodiphenyl ether (BDE 153) 68631-49-2 

Serum 2,2’,4,4’,5,6’-Hexabromodiphenyl ether (BDE 154) 207122-15-4 

Serum 2,2’,3,4,4’,5’,6-Heptabromodiphenyl ether (BDE 183) 207122-16-5 
 312 Fourth National Report on Human Exposure to Environmental Chemicals 

Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

dietary sources, including fish, fatty foods, and mother’s 

milk. However, oral ingestion from dust and leachates 

may be a larger source (Sjödin et al, 2004b), particularly 

for children (Jones-Otazo et al., 2005; Stapleton et al., 

2005). Once absorbed, PBDEs distribute into body fat. 

The metabolism and elimination of PBDEs in humans are 

not well characterized. One occupational study indicated 

that decaBDE has an elimination half-life of 11-18 days 

and the octaBDEs have half-lives ranging between 37-

91 days (Thuresson et al., 2006). In animals, PBDE 

elimination occurs primarily through fecal excretion with 

decaBDE being more rapidly eliminated than the other less 

brominated PBDEs (Gill et al., 2004; Hardy, 2002). Some 

PBDEs measured in human serum are listed in the table.

Human health effects from PBDEs at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. In animal studies, PBDEs have 

low acute toxicity, but have demonstrated effects on thyroid 

function, neurodevelopment, hepatic enzyme induction 

and hepatic injury in subchronic or chronic dosing studies 

(Birnbaum and Staskal, 2004; Branchi et al., 2002; Gill et 

al., 2004; Hallgren and Darnerud, 2002; Viberg et al., 2003 

and 2004; Zhou et al., 2002). Some developmental and 

behavioral effects may be mediated by the aforementioned 

effect on the thyroid, by alteration in cholinergic function 

(Branchi et al., 2003; Dufault et al., 2005), or by altered 

intracellular signaling within brain cells (Kodavanti et al., 

2005). The lesser brominated PBDEs have been reported to 

have fetotoxic and reproductive effects, to alter expression 

of estrogen-regulated genes and receptors, and to have antiandrogenic effects (Ceccatelli et al., 2006; Gill et al., 2004; 

Kuriyama et al., 2005; Stoker et al., 2005; Talsness et al., 

2005; WSDH, 2004). PentaBDE is considered more toxic 

than decaBDE and the most sensitive effects of pentaBDE 

in animal studies are neurodevelopmental and reproductive. 

In a study of electronics dismantlers, serum levels of 

PBDEs were not generally higher than in nonexposed 

workers and were not associated with changes in thyroid 

function (Julander et al., 2005). PBDEs are not considered 

genotoxic and are not classified by IARC and NTP with 

respect to human carcinogenicity. Additional information 

about external exposure (i.e., environmental levels) and 

health effects is available from ATSDR at: http://www.

atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Levels of PBDEs in serum reflect cumulative exposure 

over the recent months to years of exposure. The PBDE 

congeners measured for biomonitoring often include 

those containing three bromines (BDE-17, BDE-28), four 

bromines (BDE-47, BDE-66), five bromines (BDE-85, 

BDE-99, BDE-100), six bromines (BDE-153, BDE-154) 

and seven bromines (BDE-183). Analysis of the NHANES 

2003-2004 subsample showed detection of BDE-47 (a 

tetraBDE present in commercial pentaBDEs) in nearly all 

participants and detection of BDE-28, BDE-99, BDE-100, 

and BDE-153 in greater than 60 percent of participants 

(Sjödin et al., 2008). Levels of these PBDEs tended to be 

well-correlated with each other. Serum levels of BDE47, BDE-99, and BDE-153 were found to decrease with 

Serum 2,2',4-Tribromodiphenyl ether (BDE 17) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1992 

Age group 

12-19 years 03-04 * < LOD < LOD < LOD < LOD 607

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1385 

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 964

Females 03-04 * < LOD < LOD < LOD < LOD 1028 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 482

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 491

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 892

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.0. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 313

 Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

increasing age from 12-19 to 20-39 to 40-59 years, and 

then increase slightly in the 60 years and older age group. 

Slight differences by gender and race/ethnicity were also 

observed for several PBDEs (Sjödin et al., 2008).

From the 1970s to the late 1990s, levels of BDE-47 had 

increased in samples of breast milk and sera in Sweden and 

Norway, respectively (Meironyté et al., 1999; Thomsen et 

al., 2002). Also, in small samplings of residents in Japan 

and U.S., serum levels have been shown to increase by 

more than fivefold to twentyfold over the past two decades 

(Koizumi et al., 2005; Schecter et al., 2005; Sjödin et 

al., 2004a). Several small studies of U.S. residents have 

shown increasing levels of BDE-47 during recent decades 

that were 3-10 times higher than contemporary European 

residents (Petreas et al., 2003; Sjödin et al., 2003). Serum 

levels of PBDEs in the NHANES 2003-2004 subsample 

(Sjödin et al., 2008) also appeared generally higher than 

those reported for Japan, Sweden, and Norway (Koizumi et 

al., 2005; Thomsen et al., 2002; Thuresson et al., 2006). In 

most studies, BDE-47 demonstrates the highest levels of all 

the measured PBDEs.

Detection of BB-153 was also prevalent in the NHANES 

2003-2004 subsample and increased with age (Sjödin et al., 

2008). This age trend may be due to the longer time that 

BB-153 stays in the body or due to greater past exposures 

in older people. Mexican Americans and NHANES 

participants born in foreign countries had lower serum 

concentrations of BB-153 (Sjödin et al, 2008). Levels of 

BB-153 in NHANES 2003-2004 were about one-fourth to 

one-fortieth of the levels of BDE-47, depending on the age 

group. In human sera from Sweden, BB-153 was generally 

not detected as compared to detectable levels a small 

regional sample of U.S. residents (Sjödin et al., 2001).

Finding measurable amounts of PBDEs or BB-153 in 

serum does not mean that the levels of these chemicals 

cause an adverse health effect. Biomonitoring studies of 

serum PBDEs and BB-153 can provide physicians and 

public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of PBDEs or BB-153 than levels found in the general 

population. Biomonitoring data can also help scientists plan 

and conduct research on exposure and health effects.

Serum 2,4,4'-Tribromodiphenyl ether (BDE 28) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 1.19 (1.03-1.37) 1.10 (1.00-1.30) 2.20 (1.90-2.60) 4.80 (3.30-6.70) 8.00 (5.40-11.3) 1987 

Age group 

12-19 years 03-04 1.30 (1.15-1.46) 1.20 (1.10-1.50) 2.40 (2.00-2.60) 4.00 (2.90-5.60) 6.10 (4.00-9.40) 598

20 years and older 03-04 1.17 (1.01-1.37) 1.10 (.900-1.30) 2.20 (1.90-2.70) 5.00 (3.30-7.20) 8.20 (6.00-10.9) 1389 

Gender 

Males 03-04 1.21 (1.05-1.39) 1.10 (1.00-1.30) 2.30 (2.00-2.70) 5.10 (3.50-7.30) 8.20 (6.00-11.3) 964

Females 03-04 1.17 (.990-1.38) 1.10 (.900-1.40) 2.10 (1.80-2.60) 4.60 (3.00-6.90) 7.80 (4.70-11.8) 1023 

Race/ethnicity 

Mexican Americans 03-04 1.43 (1.29-1.59) 1.40 (1.20-1.50) 2.40 (2.00-2.90) 4.70 (3.70-5.50) 7.30 (5.60-8.30) 488

Non-Hispanic blacks 03-04 1.21 (1.03-1.42) 1.10 (.900-1.30) 2.20 (1.80-2.50) 5.30 (3.50-6.70) 8.40 (5.40-12.3) 470

Non-Hispanic whites 03-04 1.17 (.968-1.42) 1.10 (.900-1.30) 2.20 (1.80-2.70) 4.90 (3.00-8.00) 8.00 (4.50-13.6) 905

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.8. 
 314 Fourth National Report on Human Exposure to Environmental Chemicals 

Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

Serum 2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 20.5 (17.6-23.9) 19.2 (15.7-22.3) 41.1 (35.6-49.2) 85.1 (66.8-127) 163 (108-240) 2016 

Age group 

12-19 years 03-04 28.2 (24.6-32.3) 27.2 (22.1-33.6) 53.6 (44.9-63.6) 104 (82.4-145) 174 (115-211) 615

20 years and older 03-04 19.5 (16.5-23.1) 18.0 (14.6-21.6) 39.1 (32.8-47.0) 83.3 (63.0-127) 163 (102-240) 1401 

Gender 

Males 03-04 21.4 (18.1-25.3) 19.2 (15.8-24.0) 45.2 (37.3-54.9) 94.3 (66.8-148) 168 (112-382) 981

Females 03-04 19.6 (16.4-23.5) 19.1 (14.1-23.2) 38.4 (31.8-46.4) 79.5 (60.7-121) 155 (102-239) 1035 

Race/ethnicity 

Mexican Americans 03-04 25.5 (23.0-28.1) 23.6 (21.2-25.5) 47.1 (38.2-56.5) 87.2 (72.0-105) 151 (105-195) 478

Non-Hispanic blacks 03-04 24.3 (20.9-28.2) 21.4 (18.2-25.6) 47.5 (40.7-53.2) 116 (81.8-149) 242 (136-481) 499

Non-Hispanic whites 03-04 19.5 (16.1-23.7) 17.4 (14.4-22.2) 40.2 (33.1-51.9) 85.1 (60.3-142) 163 (90.2-283) 912

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 4.2. 

Serum 2,3',4,4'-Tetrabromodiphenyl ether (BDE 66) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD 1.30 (1.00-2.10) 1999 

Age group 

12-19 years 03-04 * < LOD < LOD < LOD 1.30 (<LOD-1.90) 606

20 years and older 03-04 * < LOD < LOD < LOD 1.30 (1.00-2.20) 1393 

Gender 

Males 03-04 * < LOD < LOD < LOD 1.40 (1.00-2.60) 970

Females 03-04 * < LOD < LOD < LOD 1.10 (<LOD-2.20) 1029 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD 1.20 (<LOD-1.60) 461

Non-Hispanic blacks 03-04 * < LOD < LOD 1.00 (<LOD-2.00) 2.40 (1.40-5.10) 496

Non-Hispanic whites 03-04 * < LOD < LOD < LOD 1.20 (<LOD-2.50) 914

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.0. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 315

 Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

Serum 2,2',3,4,4'-Pentabromodiphenyl ether (BDE 85) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD 4.10 (2.80-6.30) 2000 

Age group 

12-19 years 03-04 * < LOD < LOD 2.80 (<LOD-3.50) 4.00 (3.50-6.30) 610

20 years and older 03-04 * < LOD < LOD < LOD 4.10 (2.50-6.70) 1390 

Gender 

Males 03-04 * < LOD < LOD 2.40 (<LOD-3.30) 4.80 (3.10-8.40) 967

Females 03-04 * < LOD < LOD < LOD 3.60 (<LOD-5.20) 1033 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD 3.70 (2.80-4.80) 484

Non-Hispanic blacks 03-04 * < LOD < LOD 3.50 (2.50-4.40) 6.90 (3.10-18.0) 493

Non-Hispanic whites 03-04 * < LOD < LOD < LOD 3.90 (<LOD-7.50) 895

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 2.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2’,4,4’,5-Pentabromodiphenyl ether (BDE 99) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD 9.20 (7.50-11.1) 21.7 (17.0-29.1) 42.2 (33.3-54.8) 1985 

Age group 

12-19 years 03-04 6.88 (6.14-7.72) 5.70 (<LOD-7.70) 12.9 (11.4-15.7) 27.9 (19.6-37.9) 45.2 (35.9-56.8) 602

20 years and older 03-04 * < LOD 8.50 (7.10-10.5) 20.6 (15.5-28.8) 41.6 (30.8-57.3) 1383 

Gender 

Males 03-04 5.28 (<LOD-6.14) < LOD 10.0 (8.40-11.6) 24.5 (18.0-37.3) 45.5 (33.8-57.3) 964

Females 03-04 * < LOD 8.70 (6.60-10.6) 18.3 (14.7-28.8) 41.2 (22.9-60.3) 1021 

Race/ethnicity 

Mexican Americans 03-04 5.90 (5.45-6.39) 5.50 (<LOD-5.80) 10.8 (9.30-12.6) 20.0 (17.0-23.5) 30.8 (24.5-41.7) 478

Non-Hispanic blacks 03-04 6.22 (5.42-7.12) 5.00 (<LOD-5.70) 11.5 (9.60-13.1) 30.2 (21.5-42.2) 74.7 (30.2-155) 479

Non-Hispanic whites 03-04 * < LOD 8.90 (6.80-11.3) 21.7 (15.3-34.0) 43.6 (30.7-71.4) 903

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 5.0. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 316 Fourth National Report on Human Exposure to Environmental Chemicals 

Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

Serum 2,2',4,4',6-Pentabromodiphenyl ether (BDE 100) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 3.93 (3.42-4.51) 3.60 (3.10-4.10) 7.80 (6.80-9.00) 18.4 (15.4-22.0) 36.5 (24.6-54.0) 2040 

Age group 

12-19 years 03-04 5.17 (4.46-6.00) 4.90 (3.80-6.10) 9.50 (7.90-12.8) 19.3 (14.4-26.2) 34.3 (25.2-45.0) 622

20 years and older 03-04 3.77 (3.24-4.38) 3.30 (2.90-4.00) 7.40 (6.20-9.00) 18.3 (15.0-22.2) 36.6 (23.2-59.2) 1418 

Gender 

Males 03-04 4.16 (3.55-4.86) 3.80 (3.10-4.50) 8.50 (7.50-9.90) 18.5 (14.9-25.1) 44.1 (21.9-61.5) 994

Females 03-04 3.72 (3.15-4.40) 3.30 (2.80-4.10) 7.10 (6.00-8.00) 18.4 (14.4-23.1) 33.3 (23.3-46.0) 1046 

Race/ethnicity 

Mexican Americans 03-04 4.58 (4.03-5.22) 4.30 (3.80-5.20) 8.10 (6.80-9.10) 14.9 (11.4-20.3) 26.7 (20.3-36.2) 488

Non-Hispanic blacks 03-04 4.72 (4.01-5.55) 4.30 (3.30-5.20) 9.50 (7.80-10.9) 24.1 (16.6-34.3) 41.3 (26.0-79.2) 503

Non-Hispanic whites 03-04 3.78 (3.17-4.51) 3.30 (2.90-4.10) 7.70 (6.20-9.70) 18.6 (14.5-23.3) 40.5 (22.6-59.2) 921

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.4. 

Serum 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE 153) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 5.69 (5.11-6.34) 4.80 (4.20-5.30) 11.3 (9.90-12.8) 32.6 (27.9-40.3) 65.7 (54.9-88.4) 2039 

Age group 

12-19 years 03-04 8.05 (6.68-9.70) 7.50 (6.10-9.90) 15.3 (11.7-19.4) 31.0 (22.9-44.2) 52.9 (35.9-68.5) 621

20 years and older 03-04 5.41 (4.83-6.05) 4.40 (3.80-5.10) 10.6 (9.00-12.3) 32.8 (26.5-45.9) 73.3 (58.2-90.4) 1418 

Gender 

Males 03-04 6.85 (5.99-7.84) 5.50 (4.80-6.70) 12.7 (11.2-16.5) 49.3 (31.0-62.9) 88.4 (63.4-115) 994

Females 03-04 4.78 (4.20-5.43) 4.10 (3.40-5.00) 9.70 (7.40-11.9) 26.0 (20.2-31.6) 54.5 (34.6-62.9) 1045 

Race/ethnicity 

Mexican Americans 03-04 5.11 (4.32-6.06) 4.80 (4.20-5.40) 8.70 (6.50-11.0) 17.2 (13.0-25.3) 34.0 (18.3-55.1) 487

Non-Hispanic blacks 03-04 6.05 (5.35-6.83) 5.50 (4.80-6.20) 12.9 (9.90-17.5) 30.0 (21.0-44.2) 53.1 (36.8-63.3) 503

Non-Hispanic whites 03-04 5.85 (5.03-6.81) 4.90 (3.90-5.70) 11.9 (9.90-15.2) 39.0 (28.5-54.9) 75.9 (58.0-93.2) 921

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 2.2. 
Fourth National Report on Human Exposure to Environmental Chemicals 317

 Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

Serum 2,2',4,4',5,6'-Hexabromodiphenyl ether (BDE 154) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD .900 (.800-1.10) 2.10 (1.70-2.70) 4.20 (2.80-5.40) 2014 

Age group 

12-19 years 03-04 * < LOD 1.20 (1.00-1.40) 2.70 (2.00-3.00) 4.00 (3.00-4.80) 614

20 years and older 03-04 * < LOD .900 (.800-1.10) 2.00 (1.60-2.60) 4.20 (2.70-5.70) 1400 

Gender 

Males 03-04 * < LOD 1.00 (.800-1.20) 2.30 (1.80-3.00) 4.30 (3.20-6.50) 976

Females 03-04 * < LOD .900 (.800-1.00) 1.80 (1.40-2.80) 4.20 (2.50-5.70) 1038 

Race/ethnicity 

Mexican Americans 03-04 * < LOD 1.00 (.900-1.10) 1.80 (1.40-2.30) 3.90 (2.30-4.50) 477

Non-Hispanic blacks 03-04 * < LOD 1.20 (.900-1.40) 2.70 (2.30-4.40) 5.30 (3.10-8.70) 498

Non-Hispanic whites 03-04 * < LOD .900 (.800-1.10) 2.00 (1.50-2.80) 4.20 (2.50-6.70) 913

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.8. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2',3,4,4',5',6-Heptabromodiphenyl ether (BDE 183) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1993 

Age group 

12-19 years 03-04 * < LOD < LOD < LOD < LOD 604

20 years and older 03-04 * < LOD < LOD < LOD < LOD 1389 

Gender 

Males 03-04 * < LOD < LOD < LOD 1.70 (<LOD-2.60) 962

Females 03-04 * < LOD < LOD < LOD < LOD 1031 

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 484

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD 1.80 (<LOD-2.70) 482

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 901

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 1.7. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 318 Fourth National Report on Human Exposure to Environmental Chemicals 

Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

Serum 2,2',4,4',5,5'-Hexabromobiphenyl (BB 153) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 2.29 (1.82-2.87) 2.20 (2.00-2.60) 4.40 (3.40-6.30) 12.8 (6.60-25.5) 27.2 (11.7-60.9) 2032 

Age group 

12-19 years 03-04 * < LOD 1.10 (.900-1.60) 2.70 (2.00-3.00) 4.10 (2.90-4.70) 616

20 years and older 03-04 2.72 (2.14-3.47) 2.50 (2.20-2.80) 4.90 (3.60-7.90) 13.6 (7.20-34.6) 34.6 (12.8-66.8) 1416 

Gender 

Males 03-04 2.76 (2.21-3.45) 2.70 (2.30-3.20) 5.40 (3.90-8.50) 15.8 (9.30-27.8) 35.4 (13.5-70.3) 987

Females 03-04 1.92 (1.50-2.46) 2.00 (1.60-2.30) 3.60 (2.80-4.90) 9.70 (4.60-27.5) 23.9 (7.40-56.6) 1045 

Race/ethnicity 

Mexican Americans 03-04 1.11 (.917-1.33) 1.10 (<LOD-1.30) 2.60 (2.00-3.00) 6.00 (3.50-8.60) 10.0 (6.50-15.2) 484

Non-Hispanic blacks 03-04 2.35 (1.64-3.37) 2.10 (1.70-2.80) 4.80 (3.00-12.1) 13.9 (7.00-38.2) 29.7 (12.1-70.2) 503

Non-Hispanic whites 03-04 2.66 (2.06-3.42) 2.50 (2.20-2.80) 4.90 (3.40-7.80) 13.5 (6.60-36.4) 34.6 (11.6-70.3) 917

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.8. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 319

 Polybrominated Diphenyl Ethers and 2,2’,4,4’,5,5’-Hexabromobiphenyl (BB-153)

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SA. Polybrominated diphenyl ethers in house dust and clothes 

dryer lint. Environ Sci Technol 2005;39(4):925-931.

Stoker TE, Cooper RL, Lambright CS, Wilson VS, Furr J, Gray 

LE. In vivo and in vitro anti-androgenic effects of DE-71, a 

commercial polybrominated diphenyl ether (PBDE) mixture. 

Toxicol Appl Pharmacol 2005;207(1):78-88.

Talsness CE, Shakibaei M, Kuriyama SN, Grande SW, SternerKock A, Schnitker P, et al. Ultrastructural changes observed in rat 

ovaries following in utero and lactational exposure to low doses of 

a polybrominated flame retardant. Toxicol Lett 2005;157(3):189-

202.

Thomsen C, Lundanes E, Becher G. Brominated flame retardants 

in archived serum samples from Norway: a study on temporal 

trends and the role of age. Environ Sci Technol. 2002;36(7):1414-

1418.

Thuresson K, Hoglund P, Hagmar L, Sjödin A, Bergman A, 

Jakobsson K. Apparent half-lives of hepta- to decabrominated 

diphenyl ethers in human serum as determined in occupationally 

exposed workers. Environ Health Perspect 2006;114(2):176-181.

U.S. Environmental Protection Agency (U.S. EPA). 

Polybrominated diphenylethers (PBDEs) Significant New Use 

Rule (SNUR) Questions and Answers. 2005. Revised 1/12/06. 

Available from URL: http://www.epa.gov/oppt/pbde/pubs/qanda.

htm, 1/30/06

Viberg H, Fredriksson A, Eriksson P. Investigations of strain 

and/or gender differences in developmental neurotoxic effects 

of polybrominated diphenyl ethers in mice. Toxicol Sci 

2004;81(2):344-353.

Viberg H, Fredriksson A, Eriksson P. Neonatal exposure to 

polybrominated diphenyl ether (PBDE 153) disrupts spontaneous 

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hippocampal cholinergic receptors in adult mice. Toxicol Appl 

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Fourth National Report on Human Exposure to Environmental Chemicals 321

 Non-Dioxin-Like Polychlorinated Biphenyls

Non-Dioxin-Like Polychlorinated Biphenyls

(The coplanar and mono-ortho-substituted PCBs are 

discussed in the section titled “Dioxin-Like Chemicals: 

Polychlorinated Dibenzo-p-dioxins, Polychlorinated 

Dibenzofurans, and Coplanar and Mono-ortho-substituted 

Polychlorinated Biphenyls.”)

General Information

Polychlorinated biphenyls (PCBs) are a class of chlorinated 

aromatic hydrocarbon chemicals that once were used as 

heat-exchanger, transformer, and hydraulic fluids, and as 

additives to paints, oils, joint caulking, and floor tiles. Peak 

production occurred in the early 1970s, and production 

was banned in the United States after 1979. More than 1.5 

billion pounds of PCBs were manufactured in the United 

States prior to 1977. The continued concern about these 

chemicals is because of their persistence in the environment 

and accumulation in wildlife and the animal food chain.

Food is the main source of exposure for the general 

population. PCBs enter the food chain by a variety of 

routes, including migration into food from external 

sources, contamination of animal feeds, and accumulation 

in the fatty tissues of animals. PCBs are found at higher 

concentrations in fatty foods (e.g., dairy products and fish). 

The transfer of PCBs from mother to infant via breast 

milk is another important source of exposure. The lesserchlorinated PCBs are more volatile and indoor inhalational 

exposure from buildings containing caulking made with 

these PCBs prior to 1979 can increase background serum 

levels (Johansson et al., 2003; Kohler et al., 2005). Other 

sources of exposure in the general population include the 

release of these chemicals from PCB-containing waste 

sites and from fires involving transformers and capacitors. 

Additionally, the heat from fires can result in the production 

of polychlorinated dibenzofurans from PCBs. In certain 

Non-Dioxin-like Polychlorinated Biphenyls in this Report

Non-dioxin-like polychlorinated biphenyls (IUPAC 

number) CAS number 

Polychlorinated biphenyls (general class) 1336-36-3 

2,4,4'-Trichlorobiphenyl (PCB 28) 7012-37-5 

2,2',3,5'-Tetrachlorobiphenyl (PCB 44) 41464-39-5 

2,2',4,5'-Tetrachlorobiphenyl (PCB 49) 41464-40-8 

2,2',5,5'-Tetrachlorobiphenyl (PCB 52) 35693-99-3 

2,3',4,4'-Tetrachlorobiphenyl (PCB 66) 32598-10-0 

2,4,4',5-Tetrachlorobiphenyl (PCB 74) 32690-93-0 

2,2',3,4,5'-Pentachlorobiphenyl (PCB 87) 38380-02-8 

2,2',4,4',5-Pentachlorobiphenyl (PCB 99) 38380-01-7 

2,2',4,5,5'-Pentachlorobiphenyl (PCB 101) 37680-73-2 

2,3,3',4',6-Pentachlorobiphenyl (PCB 110) 38380-03-9 

2,2',3,3',4,4'-Hexachlorobiphenyl (PCB 128) 38380-07-3 

2,2',3,4,4',5'-Hexachlorobiphenyl (PCB 138) 35065-28-2 

2,3,3',4,4',6-Hexachlorobiphenyl (PCB 158) 74472-42-7 

2,2',3,4',5,5'-Hexachlorobiphenyl (PCB 146) 51908-16-8 

2,2',3,4',5',6-Hexachlorobiphenyl (PCB 149) 38380-04-0 

2,2',3,5,5',6-Hexachlorobiphenyl (PCB 151) 52663-63-5 

2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) 35065-27-1 

2,2',3,3',4,4',5-Heptachlorobiphenyl (PCB 170) 35065-30-6 

2,2',3,3',4,5,5'-Heptachlorobiphenyl (PCB 172) 52663-74-8 

2,2',3,3',4,5',6'-Heptachlorobiphenyl (PCB 177) 52663-70-4 

2,2',3,3',5,5',6-Heptachlorobiphenyl (PCB 178) 52663-67-9 

2,2',3,4,4',5,5'-Heptachlorobiphenyl (PCB 180) 35065-29-3 

2,2',3,4,4',5',6-Heptachlorobiphenyl (PCB 183) 52663-69-1 

2,2',3,4',5,5',6-Heptachlorobiphenyl (PCB 187) 52663-68-0 

2,2',3,3',4,4',5,5'-Octachlorobiphenyl (PCB 194) 35694-08-7 

2,2',3,3',4,4',5,6-Octachlorobiphenyl (PCB 195) 52663-78-2 

2,2',3,3',4,4',5,6'-Octachlorobiphenyl (PCB 196) 42740-50-1 

2,2',3,3',4,5,5',6'-Octachlorobiphenyl (PCB 199) 52663-75-9 

2,2',3,4,4',5,5',6-Octachlorobiphenyl (PCB 203) 52663-76-0 

2,2',3,3',4,4',5,5',6-Nonachlorobiphenyl (PCB 206) 40186-72-9 

2,2’3,3’4,4’5,5’6,6’-Decachlorobiphenyl (PCB 209) 2051-24-3 
 322 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

occupational settings, workers can be exposed to PCBs 

such as when repairing or manufacturing transformers, 

capacitors, and hydraulic systems, and when remediating 

hazardous-waste sites. Both U.S. FDA and OSHA have 

developed criteria on the allowable levels of these chemicals 

in foods and the workplace. The U.S. EPA has also set criteria 

for allowable levels in water and waste materials. The 

international Stockholm Convention on Persistent Organic 

Pollutants of 2001 establishes the most stringent guidelines 

to date regarding elimination, restriction and unintentional 

production of PCBs and selected organochlorine chemicals 

(Porta and Zumeta, 2002).

Exposure to these chemicals nearly always occurs as 

mixtures rather than from individual PCBs. The different 

types of PCB chemicals are known as congeners, which 

are compounds that are distinguished by the number of 

chlorine atoms and their location on the biphenyl structure. 

PCB congeners can be divided into the coplanar, the monoortho-substituted PCBs, and other non-dioxin-like PCBs. 

The significance of this designation is that the coplanar 

and some of the mono-ortho-substituted PCBs have 

dioxin-like toxicologic effects. Structural nomenclature 

is available at: http://www.epa.gov/oswer/riskassessment/

pdf/1340-erasc-003.pdf. The non-dioxin-like PCBs and 

their metabolites do not interact substantially with the aryl 

hydrocarbon receptor (AhR) and may act through different 

pathways than the dioxin-like chemicals, so their effects 

are not represented in the use of toxic equivalency factors 

(TEFs) (Carpenter, 2006). The non-dioxin-like PCBs 

measured in this Report are listed in the table.

Human health effects that have been reported after 

investigations of occupational and accidental exposures to 

high levels of PCBs include elevations of serum hepatic 

enzymes, dermal changes, inconsistent associations with 

serum lipid levels, and some types of cancer (e.g., liver, 

biliary) (ATSDR, 2000; Carpenter, 2006; Charles et al., 

2001; Negri et al., 2003). Animal studies have demonstrated 

varied effects of PCBs including neurotoxicity, immune 

suppression, altered thyroid and reproductive function, 

and liver cancer (Carpenter, 2006; U.S.EPA, 2008). 

Effects of PCBs in humans are difficult to study due 

to coexposures to the dioxin-like chemicals and other 

organochlorine chemicals. (Also see the section titled: 

“Dioxin-Like Chemicals: Polychlorinated Dibenzo-pdioxins, Polychlorinated Dibenzofurans, and the Coplanar 

and Mono-ortho-substituted Polychlorinated Biphenyls”).

Transplacental transfer of PCBs after maternal 

Serum 2,4,4'-Trichlorobiphenyl (PCB 28) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years# (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1849 

03-04 4.90 (4.60-5.22) 4.96 (4.65-5.26) 6.79 (6.40-7.31) 9.39 (8.70-10.1) 11.3 (10.7-11.8) 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 647 

03-04 5.02 (4.48-5.63) 4.88 (4.26-5.48) 7.20 (5.90-8.60) 10.2 (8.40-11.5) 11.7 (10.7-13.3) 590 

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1202 

03-04 4.88 (4.61-5.17) 4.98 (4.67-5.26) 6.78 (6.40-7.25) 9.10 (8.70-9.87) 11.1 (10.6-11.8) 1276 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 886 

03-04 4.81 (4.47-5.16) 4.86 (4.45-5.20) 6.70 (6.07-7.50) 9.39 (8.34-10.4) 10.8 (10.5-11.4) 926 

Females 99-00 * < LOD < LOD < LOD < LOD 963 

03-04 4.99 (4.66-5.35) 5.07 (4.73-5.37) 6.90 (6.49-7.40) 9.37 (8.72-10.1) 11.6 (10.7-13.1) 940 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 618 

03-04 4.95 (4.55-5.38) 4.90 (4.40-5.70) 6.70 (6.07-7.90) 8.94 (8.17-9.70) 10.5 (9.02-14.7) 413 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 392 

03-04 4.95 (4.20-5.84) 5.03 (4.10-5.60) 7.20 (5.62-8.80) 10.2 (8.51-12.4) 13.1 (10.8-15.3) 459 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 687 

03-04 4.89 (4.58-5.22) 4.90 (4.61-5.26) 6.76 (6.33-7.32) 9.40 (8.70-10.3) 11.1 (10.6-11.8) 876 

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00 and 03-04 are 32.4 and 1.7. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

# Data not available for Survey years 2001-2002. 
Fourth National Report on Human Exposure to Environmental Chemicals 323

 Non-Dioxin-Like Polychlorinated Biphenyls

environmental exposure has been reported to be associated 

with altered psychomotor development in children and lower 

birth weight and size in newborns ( Hertz-Picciotto et al., 

2005; Jacobson and Jacobson, 1996; Koopman-Essenboom 

et al., 1996; Longnecker et al., 2003; Lundqvist et al., 2006; 

Sagiv et al., 2007; Sala et al., 2001), although other studies 

have either not confirmed these findings or found that such 

effects do not persist into toddler and school aged children 

(Gladen and Rogan, 1991; Gray et al., 2005; Hertz-Picciotto 

et al., 2005; Koopman-Essenboom et al., 1996; Wolff et al., 

2007). Many animal studies demonstrate that high dose 

PCB impairs neurodevelopment or their hydroxylated 

metabolites may interfere with thyroid hormone-dependent 

neurodevelopment (Kimura-Kuroda et al., 2007; Nguon et 

al., 2005; Purkey et al., 2004; Roegge et al., 2006).

The non-dioxin-like PCBs weakly interact with estrogen 

and thyroid receptors and with transport proteins, and the 

hydroxylated metabolites of PCBs may be more potent 

mediators of these actions (Azulmozhiraja et al., 2005; 

DeCastro et al., 2006; Langer et al., 2005; Purkey et al., 

2004; Kitamura etal., 2005; You et al., 2006). Variations 

in thyroid hormone levels have been associated with PCB 

exposures in human populations (Langer et al., 2007a; 

Meeker et al., 2007; Otake et al., 2007; Wang et al., 

2005). Though only limited investigation of estrogenic or 

reproductive effects has occurred in women, inconsistent 

associations of PCB levels with altered spermatogenesis 

and reproductive hormone levels have been reported in 

environmentally exposed men (Giwercman et al., 2006; 

Rignell-Hydbom et al., 2005; Toft et al., 2006).

PCBs are not considered directly genotoxic. They are 

classified as probable human carcinogens by IARC and 

are classified by NTP as reasonably anticipated to be 

carcinogens. Early studies associated workplace PCB 

exposures with increased deaths from cancer of the liver, 

gallbladder, biliary tract, gastrointestinal tract, brain and 

malignant melanoma (Knerr and Schrenk, 2006). Follow 

up studies of these earlier investigations have shown no 

increase in deaths or cancers, with the exception of liver 

cancer (Kimbrough et al., 2003; Prince et al., 2006; Ross, 

2004), though the contributions of dioxin-like chemicals 

or other organochlorines were unclear. Recent studies 

have associated PCB exposures with other cancers (De 

Roos et al., 2005; Engel et al., 2007; Prince et al., 2006). 

Information about external exposure (i.e., environmental 

levels) and health effects is available from ATSDR at: 

http://www.atsdr.cdc.gov/toxpro2.html and from the U.S. 

EPA at: http://www.epa.gov/iris.

Serum 2,4,4'-Trichlorobiphenyl (PCB 28) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years# (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1849 

03-04 .030 (.028-.032) .030 (.028-.032) .041 (.039-.043) .057 (.055-.060) .067 (.063-.071) 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 647 

03-04 .025 (.023-.028) .025 (.021-.028) .035 (.030-.042) .051 (.042-.061) .061 (.051-.070) 590 

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1202 

03-04 .031 (.029-.033) .031 (.029-.032) .042 (.040-.043) .058 (.055-.061) .067 (.063-.071) 1276 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 886 

03-04 .030 (.028-.032) .030 (.027-.032) .041 (.037-.044) .056 (.051-.061) .065 (.061-.070) 926 

Females 99-00 * < LOD < LOD < LOD < LOD 963 

03-04 .030 (.028-.032) .030 (.028-.032) .042 (.039-.044) .058 (.055-.061) .070 (.064-.075) 940 

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 618 

03-04 .030 (.028-.033) .031 (.027-.035) .041 (.036-.044) .053 (.048-.059) .063 (.054-.070) 413 

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 392 

03-04 .028 (.024-.033) .029 (.024-.033) .039 (.034-.047) .059 (.047-.070) .070 (.064-.082) 459 

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 687 

03-04 .030 (.028-.032) .030 (.028-.032) .041 (.039-.043) .058 (.055-.061) .068 (.062-.075) 876 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

# Data not available for Survey years 2001-2002. 
 324 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Biomonitoring Information

Measurement of serum PCBs generally reflect cumulative 

past exposure. Levels of non-dioxin-like PCBs in NHANES 

2003-2004 are observed to be roughly similar to the previous 

two NHANES survey periods. Many PCBs can remain in 

the body for years after exposure, though some of the PCBs 

with fewer chlorine atoms have short residence times. The 

levels of individual PCB congeners in the body may vary 

by exposure source and by differences in pharmacokinetics, 

i.e., those with longer half-lives accumulate to higher 

levels. Adult age-related accumulations in the non-dioxinlike PCBs have been observed in many studies (Apostoli 

et al., 2005; Park et al., 2007; Patterson et al., 1994). 

Breastfeeding is a major source of PCBs, with serum 

levels increasing after birth in breastfed infants and then 

decreasing in early adolescence due to dilution as body 

mass increases (Barr et al., 2006). Fish consumption from 

the Great Lakes region contributed a twofold to tenfold 

increase in the mean concentrations of non-dioxin-like 

PCBs over referent populations (Patterson et al., 1994; 

Turyk et al., 2006). Arctic native Alaskans who consumed 

locally-caught fish, meat, and eggs had mean serum levels 

of total PCB that were nearly three times higher than the 

adult NHANES 1999-2000 subsample (Carpenter et al., 

2005; CDC, 2005; Needham et al., 2005). Much higher 

levels due to contaminated fish intake have also been noted 

also in eastern Europe (Langer et al., 2007b).

The concentrations of the di-ortho-substituted PCBs are 

usually higher than the mono-ortho-substituted PCBs, 

which in turn are higher than the coplanar PCBs (CDC, 

2005; Glynn et al., 2000; Longnecker et al., 2000; Patterson 

et al., 1994). The most frequently detected di-orthochlorine-substituted PCBs in population studies are 138, 

153, and 180 (CDC, 2005; Heudorf et al., 2002; Patterson 

et al., 1994 and 2009; Turyk et al., 2006). These three 

congeners contributed a substantial portion of the total PCB 

concentration observed in pooled specimens representative 

of a New Zealand population (Bates et al., 2004); in a 

small population of Swedish men (Glynn et al., 2000), 

and in blood bank specimens from Canada (Longnecker 

et al., 2000). In the U.S representative subsample from 

NHANES 1999-2000, non-dioxin-like PCBs 138, 153, 

and 180 accounted for 65% of the measured total sum 

of PCBs (Needham et al., 2005) and for 78% of the total 

in a referent population of 311 Italian residents in 2001-

2003 (Apostoli et al., 2005). Non-dioxin-like PCBs with 

five, six, and seven chlorines attached comprised about 

80% of the total PCBs in human serum, or alternatively, 

PCBs 138, 153, 180, 187 and 118 composed 57% of the 

total PCB concentration in a small sample of South Korean 

residents and incineration workers (Park et al., 2007). In 

the sera of Yucheng victims analyzed 15 years after the 

rice oil contamination event (See the section “Dioxin-Like 

Chemicals” for further discussion.),73% of the total PCB 

concentration was contributed by PCBs 99, 138, 153, 156, 

170, 179, and 180 (Hsu et al., 2005). 

As has been shown for other organochlorines, median 

serum lipid-adjusted levels of PCB 153 declined by 38% 

from 1991 to 2001 in a small sample of Swedish men 

(Hagmar et al., 2006). In four biannual surveys covering the 

years 1996-2003, about 400 German fourth grade children 

were sampled each period and demonstrated a decrease of 

more than one-half in mean whole blood levels of PCBs 

138, 153, and 180 (Link et al., 2005). Lipid adjusted levels 

of the non-dioxin-like PCBs seen in the U.S representative 

subsample from NHANES 2001-2002 are generally lower 

than levels in selected populations during the 1980s to 

1990s (CDC, 2005; Glynn et al., 2000; Longnecker et al., 

2000; Patterson et al., 1994).

In a convenience sample of 624 urban Germans aged 0-65 

years conducted during 1998 (Heudorf et al., 2002), 95th

percentile levels for PCBs 138, 153, and 180 were similar or 

up to two-fold higher than 95th percentile levels in the U.S. 

NHANES 1999-2000 subsample (CDC, 2005). In contrast, 

a representative pooled sampling of New Zealand residents 

in 1996-1997 demonstrated slightly lower levels than for 

NHANES 1999-2000 (Bates et al., 2004). In two separate 

Italian studies of a regional reference population and a 

convenience sample in 2001-2003, median serum levels of 

PCBs 138, 153, and 180, as well as the sum of measurable 

PCBs, were about fivefold higher than NHANES 1999-

2000 (Apostoli et al., 2005; CDC, 2005; Needham et al., 

2005; Turci et al., 2006). Mean levels of PCBs 153 and 

180 in 753 adult native Americans were approximately 

similar to the 95th percentile for the overall adult NHANES 

2001-2002 population (CDC, 2005; DeCaprio et al., 2005). 

In some other countries, comparable population levels are 

ten or more times higher than those reported for NHANES 

subsamples from 1999-2000 and 2001-2002 (CDC, 

2005; Jursa et al.,2006; Petrik et al., 2006). In the sera of 

Yucheng victims analyzed at 15 years following the rice 

oil contamination event, mean serum lipid adjusted levels 

of PCBs 99, 153, 170, and 180 were several to eightfold 

higher than the 95th percentiles of NHANES 1999-2000 

(Hsu et al., 2005).

Finding a measurable amount of one or more PCBs in 

serum does not mean that the levels of the PCBs cause 

an adverse health effect. Biomonitoring studies of serum 

PCBs can provide physicians and public health officials 

with reference values so that they can determine whether 
Fourth National Report on Human Exposure to Environmental Chemicals 325

 Non-Dioxin-Like Polychlorinated Biphenyls

or not people have been exposed to higher levels of PCBs 

than levels found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.
 326 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2'3,5'-Tetrachlorobiphenyl (PCB 44) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 2.06 (1.93-2.19) 2.05 (1.90-2.20) 3.03 (2.90-3.20) 4.40 (4.10-4.86) 5.70 (5.40-6.10) 1890 

Age group 

12-19 years 03-04 2.45 (2.22-2.70) 2.44 (2.10-2.70) 3.68 (3.19-4.37) 5.78 (5.13-6.30) 7.99 (6.20-9.10) 597

20 years and older 03-04 2.00 (1.88-2.13) 2.00 (1.90-2.11) 2.97 (2.80-3.20) 4.27 (3.85-4.70) 5.44 (5.00-5.89) 1293 

Gender 

Males 03-04 2.12 (2.01-2.25) 2.12 (2.00-2.30) 3.11 (2.97-3.31) 4.52 (4.10-5.20) 5.89 (5.38-6.80) 942

Females 03-04 1.99 (1.82-2.18) 1.98 (1.80-2.20) 2.94 (2.72-3.21) 4.30 (3.77-5.05) 5.60 (5.00-6.20) 948

Race/ethnicity 

Mexican Americans 03-04 2.09 (1.88-2.31) 2.10 (1.90-2.39) 3.10 (2.52-3.73) 4.20 (3.30-6.10) 5.69 (3.80-7.40) 427

Non-Hispanic blacks 03-04 2.21 (1.94-2.52) 2.12 (1.80-2.56) 3.18 (2.72-3.94) 4.90 (3.90-6.32) 6.32 (5.01-9.62) 464

Non-Hispanic whites 03-04 2.03 (1.87-2.19) 2.01 (1.90-2.20) 3.07 (2.90-3.29) 4.40 (4.01-4.95) 5.70 (5.25-6.35) 877

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.4. 

Serum 2,2'3,5'-Tetrachlorobiphenyl (PCB 44) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 .013 (.012-.013) .013 (.012-.014) .018 (.017-.020) .026 (.024-.028) .032 (.030-.034) 1890 

Age group 

12-19 years 03-04 .012 (.011-.014) .013 (.011-.014) .019 (.016-.021) .029 (.024-.031) .037 (.030-.042) 597

20 years and older 03-04 .013 (.012-.013) .013 (.012-.014) .018 (.017-.020) .025 (.023-.027) .031 (.029-.034) 1293 

Gender 

Males 03-04 .013 (.012-.014) .013 (.012-.014) .018 (.017-.020) .026 (.024-.028) .034 (.030-.038) 942

Females 03-04 .012 (.011-.013) .012 (.011-.013) .018 (.016-.020) .025 (.023-.028) .030 (.028-.032) 948

Race/ethnicity 

Mexican Americans 03-04 .013 (.011-.014) .013 (.011-.014) .017 (.015-.020) .023 (.018-.031) .027 (.021-.049) 427

Non-Hispanic blacks 03-04 .013 (.011-.014) .012 (.010-.014) .018 (.015-.022) .026 (.021-.034) .035 (.026-.040) 464

Non-Hispanic whites 03-04 .012 (.012-.014) .012 (.011-.014) .019 (.017-.020) .026 (.024-.028) .032 (.029-.035) 877
Fourth National Report on Human Exposure to Environmental Chemicals 327

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',4,5'-Tetrachlorobiphenyl (PCB 49) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 1.29 (1.20-1.39) 1.35 (1.24-1.45) 1.90 (1.80-2.10) 2.80 (2.60-3.08) 3.53 (3.33-3.80) 1876 

Age group 

12-19 years 03-04 1.54 (1.37-1.72) 1.59 (1.33-1.80) 2.30 (2.00-2.84) 3.60 (3.10-4.13) 4.66 (3.80-5.73) 590

20 years and older 03-04 1.26 (1.17-1.35) 1.33 (1.22-1.40) 1.90 (1.78-2.03) 2.69 (2.50-2.80) 3.36 (3.15-3.63) 1286 

Gender 

Males 03-04 1.36 (1.27-1.45) 1.40 (1.30-1.50) 2.00 (1.90-2.20) 3.00 (2.60-3.23) 3.79 (3.36-4.10) 932

Females 03-04 1.23 (1.12-1.35) 1.30 (1.13-1.40) 1.80 (1.70-2.04) 2.66 (2.38-3.01) 3.39 (3.02-3.73) 944

Race/ethnicity 

Mexican Americans 03-04 1.33 (1.20-1.48) 1.46 (1.20-1.57) 2.00 (1.67-2.30) 2.70 (2.17-3.80) 3.56 (2.63-4.20) 426

Non-Hispanic blacks 03-04 1.40 (1.23-1.59) 1.40 (1.20-1.64) 2.06 (1.70-2.80) 3.23 (2.80-3.70) 3.88 (3.33-5.53) 453

Non-Hispanic whites 03-04 1.26 (1.15-1.38) 1.32 (1.20-1.40) 1.90 (1.78-2.11) 2.77 (2.50-3.10) 3.45 (3.20-3.90) 876

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.4. 

Serum 2,2',4,5'-Tetrachlorobiphenyl (PCB 49) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 .008 (.007-.008) .008 (.007-.009) .012 (.011-.012) .016 (.015-.017) .019 (.018-.021) 1876 

Age group 

12-19 years 03-04 .008 (.007-.009) .008 (.007-.009) .012 (.010-.013) .018 (.015-.019) .022 (.018-.025) 590

20 years and older 03-04 .008 (.007-.008) .008 (.007-.009) .012 (.011-.013) .015 (.015-.017) .019 (.018-.021) 1286 

Gender 

Males 03-04 .008 (.008-.009) .008 (.008-.009) .012 (.011-.013) .017 (.015-.018) .021 (.019-.022) 932

Females 03-04 .007 (.007-.008) .008 (.007-.008) .011 (.010-.012) .015 (.014-.017) .018 (.017-.019) 944

Race/ethnicity 

Mexican Americans 03-04 .008 (.007-.009) .008 (.007-.009) .011 (.010-.014) .015 (.012-.018) .018 (.015-.023) 426

Non-Hispanic blacks 03-04 .008 (.007-.009) .008 (.007-.009) .012 (.010-.014) .017 (.015-.020) .021 (.017-.026) 453

Non-Hispanic whites 03-04 .008 (.007-.009) .008 (.007-.009) .012 (.011-.013) .016 (.015-.017) .019 (.018-.021) 876
 328 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1912 

01-02 * < LOD < LOD < LOD 16.5 (14.3-17.2) 1537 

03-04 2.66 (2.43-2.91) 2.74 (2.50-3.00) 4.17 (3.72-4.60) 5.91 (5.40-6.67) 7.60 (7.01-8.00) 1897 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 664

01-02 * < LOD < LOD 16.2 (<LOD-23.8) 22.9 (16.9-32.3) 291

03-04 3.16 (2.81-3.56) 3.22 (2.60-3.96) 5.15 (4.46-5.79) 7.60 (6.55-8.33) 9.20 (7.80-12.5) 597

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1248 

01-02 * < LOD < LOD < LOD 16.0 (13.5-16.9) 1246 

03-04 2.59 (2.36-2.84) 2.70 (2.46-2.92) 4.06 (3.60-4.43) 5.70 (5.16-6.49) 7.15 (6.62-7.80) 1300 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 908

01-02 * < LOD < LOD < LOD 16.0 (<LOD-17.5) 716

03-04 2.75 (2.54-2.98) 2.80 (2.55-3.20) 4.36 (3.90-4.88) 5.94 (5.51-6.80) 7.80 (7.29-8.49) 946

Females 99-00 * < LOD < LOD < LOD < LOD 1004 

01-02 * < LOD < LOD < LOD 16.6 (14.0-18.2) 821

03-04 2.57 (2.30-2.87) 2.70 (2.40-2.96) 3.96 (3.52-4.30) 5.86 (4.96-6.67) 7.15 (6.57-8.10) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631

01-02 * < LOD < LOD < LOD 16.9 (<LOD-20.6) 366

03-04 2.88 (2.56-3.24) 3.00 (2.70-3.30) 4.41 (3.60-5.30) 6.00 (4.71-8.11) 7.83 (5.70-12.0) 426

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD < LOD < LOD 16.6 (<LOD-20.9) 282

03-04 2.74 (2.35-3.19) 2.58 (2.08-3.40) 4.11 (3.30-5.60) 6.92 (5.10-8.70) 8.70 (7.10-10.2) 464

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 716

01-02 * < LOD < LOD < LOD 16.6 (14.7-17.5) 773

03-04 2.60 (2.35-2.88) 2.70 (2.40-2.98) 4.17 (3.70-4.60) 5.79 (5.20-6.75) 7.37 (6.80-7.87) 885

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.5, 12.4, and 0.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 329

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1912 

01-02 * < LOD < LOD < LOD .090 (.080-.100) 1537 

03-04 .016 (.015-.018) .017 (.015-.019) .024 (.022-.028) .035 (.032-.037) .043 (.039-.046) 1897 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 664

01-02 * < LOD < LOD .080 (<LOD-.100) .100 (.080-.140) 291

03-04 .016 (.014-.018) .017 (.014-.019) .026 (.022-.029) .037 (.032-.041) .042 (.037-.056) 597

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1248 

01-02 * < LOD < LOD < LOD .090 (.080-.090) 1246 

03-04 .016 (.015-.018) .017 (.015-.019) .024 (.022-.028) .034 (.031-.036) .043 (.038-.045) 1300 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 908

01-02 * < LOD < LOD < LOD .090 (<LOD-.110) 716

03-04 .017 (.016-.018) .018 (.016-.020) .025 (.023-.029) .036 (.032-.039) .044 (.040-.048) 946

Females 99-00 * < LOD < LOD < LOD < LOD 1004 

01-02 * < LOD < LOD < LOD .090 (.080-.100) 821

03-04 .016 (.014-.017) .016 (.014-.018) .024 (.021-.028) .033 (.030-.036) .042 (.036-.046) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631

01-02 * < LOD < LOD < LOD .090 (<LOD-.110) 366

03-04 .018 (.016-.020) .018 (.016-.021) .025 (.022-.030) .035 (.028-.044) .044 (.032-.064) 426

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD < LOD < LOD .090 (<LOD-.110) 282

03-04 .016 (.014-.018) .015 (.012-.019) .022 (.019-.031) .035 (.029-.043) .043 (.035-.049) 464

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 716

01-02 * < LOD < LOD < LOD .090 (.080-.100) 773

03-04 .016 (.014-.018) .017 (.014-.019) .024 (.022-.028) .035 (.032-.037) .043 (.038-.047) 885

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 330 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,3',4,4'-Tetrachlorobiphenyl (PCB 66) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1931 

01-02 * < LOD < LOD < LOD < LOD 2250 

03-04 1.39 (1.32-1.47) 1.37 (1.30-1.40) 1.97 (1.90-2.10) 3.10 (2.94-3.26) 4.10 (3.90-4.55) 1898 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 671

01-02 * < LOD < LOD < LOD < LOD 724

03-04 1.24 (1.14-1.34) 1.20 (1.10-1.26) 1.76 (1.62-2.00) 2.40 (2.30-2.70) 3.25 (2.70-4.10) 598

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1260 

01-02 * < LOD < LOD < LOD < LOD 1526 

03-04 1.42 (1.34-1.49) 1.40 (1.30-1.43) 2.00 (1.90-2.12) 3.10 (2.97-3.40) 4.20 (3.90-4.71) 1300 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1047 

03-04 1.29 (1.20-1.39) 1.30 (1.20-1.38) 1.87 (1.72-2.01) 2.70 (2.50-3.00) 3.30 (2.96-3.82) 947

Females 99-00 * < LOD < LOD < LOD < LOD 1012 

01-02 * < LOD < LOD < LOD < LOD 1203 

03-04 1.50 (1.42-1.58) 1.41 (1.38-1.50) 2.10 (1.92-2.30) 3.70 (3.20-4.00) 5.08 (4.10-5.46) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD < LOD < LOD < LOD 548

03-04 1.19 (1.09-1.30) 1.14 (1.00-1.30) 1.60 (1.48-1.73) 2.23 (1.80-3.20) 3.20 (2.46-3.60) 427

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 414

01-02 * < LOD < LOD < LOD < LOD 495

03-04 1.50 (1.34-1.68) 1.38 (1.21-1.50) 2.31 (1.80-2.80) 3.80 (3.10-4.80) 5.46 (4.30-8.60) 464

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 723

01-02 * < LOD < LOD < LOD < LOD 1047 

03-04 1.39 (1.31-1.47) 1.39 (1.30-1.45) 1.96 (1.90-2.10) 3.01 (2.71-3.28) 4.09 (3.70-4.33) 885

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 12.4, and 0.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 331

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,3',4,4'-Tetrachlorobiphenyl (PCB 66) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1931 

01-02 * < LOD < LOD < LOD < LOD 2250 

03-04 .008 (.008-.009) .008 (.008-.009) .012 (.012-.013) .019 (.018-.021) .025 (.024-.030) 1898 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 671

01-02 * < LOD < LOD < LOD < LOD 724

03-04 .006 (.006-.007) .006 (.005-.007) .009 (.008-.010) .013 (.012-.014) .017 (.013-.019) 598

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1260 

01-02 * < LOD < LOD < LOD < LOD 1526 

03-04 .009 (.008-.009) .008 (.008-.009) .013 (.012-.013) .020 (.019-.022) .026 (.024-.032) 1300 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1047 

03-04 .008 (.007-.009) .008 (.007-.008) .011 (.010-.013) .017 (.016-.019) .020 (.019-.022) 947

Females 99-00 * < LOD < LOD < LOD < LOD 1012 

01-02 * < LOD < LOD < LOD < LOD 1203 

03-04 .009 (.009-.010) .009 (.008-.009) .013 (.012-.014) .022 (.021-.024) .032 (.026-.034) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD < LOD < LOD < LOD 548

03-04 .007 (.007-.008) .007 (.006-.008) .010 (.009-.011) .015 (.011-.018) .018 (.014-.020) 427

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 414

01-02 * < LOD < LOD < LOD < LOD 495

03-04 .009 (.008-.009) .008 (.007-.009) .013 (.011-.015) .022 (.019-.030) .036 (.024-.070) 464

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 723

01-02 * < LOD < LOD < LOD < LOD 1047 

03-04 .009 (.008-.009) .008 (.008-.009) .012 (.012-.013) .019 (.018-.022) .025 (.023-.030) 885

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 332 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,4,4',5-Tetrachlorobiphenyl (PCB 74) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 20.8 (17.9-23.4) 29.0 (24.5-32.3) 1924 

01-02 * < LOD 13.2 (11.0-15.7) 23.5 (20.2-27.7) 33.0 (26.9-38.7) 2307 

03-04 4.81 (4.63-4.99) 4.36 (3.90-4.88) 8.72 (8.30-9.28) 15.8 (14.7-17.7) 22.3 (19.7-25.5) 1898 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 671

01-02 * < LOD < LOD < LOD < LOD 758

03-04 2.20 (2.02-2.39) 2.20 (2.03-2.33) 2.98 (2.80-3.30) 4.19 (3.60-4.73) 5.32 (4.20-6.90) 598

20 years and older 99-00 * < LOD 12.6 (<LOD-14.4) 22.4 (19.5-25.6) 30.0 (26.2-35.8) 1253 

01-02 * < LOD 14.7 (12.4-17.1) 25.2 (21.4-28.9) 34.8 (28.8-41.4) 1549 

03-04 5.38 (5.16-5.62) 5.00 (4.60-5.50) 9.60 (8.90-10.6) 17.1 (15.7-18.5) 24.1 (20.8-27.7) 1300 

Gender 

Males 99-00 * < LOD < LOD 15.4 (13.0-17.8) 21.6 (18.3-24.4) 915

01-02 * < LOD 10.6 (<LOD-12.3) 20.2 (15.4-24.9) 28.8 (20.8-38.2) 1075 

03-04 4.06 (3.82-4.31) 3.62 (3.30-4.00) 6.71 (6.20-7.77) 12.4 (10.8-13.1) 15.8 (14.6-18.5) 947

Females 99-00 * < LOD 13.9 (<LOD-16.4) 24.6 (21.9-28.5) 31.9 (28.8-40.3) 1009 

01-02 * < LOD 15.8 (13.5-18.7) 26.1 (23.2-29.3) 35.9 (31.4-41.4) 1232 

03-04 5.65 (5.33-5.98) 5.38 (4.84-5.95) 10.9 (9.30-12.1) 19.1 (17.4-21.1) 27.4 (22.9-29.6) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 15.8 (12.8-18.2) 636

01-02 * < LOD < LOD 13.3 (<LOD-18.1) 19.6 (16.2-23.0) 567

03-04 2.43 (2.10-2.80) 2.12 (1.90-2.40) 3.34 (2.90-4.16) 6.10 (5.25-7.40) 10.4 (6.61-12.2) 427

Non-Hispanic blacks 99-00 * < LOD < LOD 29.0 (18.6-38.4) 43.8 (35.4-64.0) 411

01-02 * < LOD 12.0 (<LOD-14.2) 21.7 (16.4-26.9) 31.9 (24.5-41.0) 515

03-04 4.96 (4.21-5.83) 4.00 (3.45-4.65) 9.17 (6.80-12.4) 23.0 (14.6-35.1) 40.2 (23.0-68.2) 464

Non-Hispanic whites 99-00 * < LOD < LOD 21.6 (18.9-24.0) 29.0 (24.3-32.3) 719

01-02 * < LOD 14.7 (12.2-17.3) 25.8 (21.3-30.1) 35.9 (29.0-42.5) 1061 

03-04 5.23 (4.98-5.50) 4.91 (4.38-5.65) 9.30 (8.60-10.4) 16.1 (15.1-18.2) 21.9 (19.2-25.2) 885

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.8, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 333

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,4,4',5-Tetrachlorobiphenyl (PCB 74) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .140 (.120-.150) .180 (.160-.220) 1924 

01-02 * < LOD .090 (.070-.100) .150 (.140-.180) .210 (.180-.270) 2307 

03-04 .029 (.028-.031) .027 (.024-.029) .058 (.053-.062) .104 (.093-.121) .153 (.135-.171) 1898 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 671

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .011 (.010-.012) .011 (.010-.012) .015 (.014-.018) .021 (.019-.025) .026 (.021-.033) 598

20 years and older 99-00 * < LOD .080 (<LOD-.100) .150 (.140-.160) .200 (.170-.230) 1253 

01-02 * < LOD .100 (.080-.110) .170 (.140-.190) .230 (.200-.280) 1549 

03-04 .034 (.032-.035) .031 (.028-.033) .064 (.059-.068) .115 (.103-.128) .167 (.143-.186) 1300 

Gender 

Males 99-00 * < LOD < LOD .100 (.090-.120) .150 (.130-.170) 915

01-02 * < LOD .070 (<LOD-.080) .130 (.100-.170) .190 (.140-.250) 1075 

03-04 .025 (.023-.027) .023 (.021-.027) .043 (.040-.050) .077 (.067-.087) .103 (.092-.118) 947

Females 99-00 * < LOD .100 (<LOD-.110) .160 (.140-.180) .220 (.190-.250) 1009 

01-02 * < LOD .100 (.090-.110) .170 (.150-.190) .240 (.210-.290) 1232 

03-04 .034 (.032-.037) .031 (.027-.036) .071 (.062-.085) .130 (.120-.143) .186 (.154-.216) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD .110 (.080-.130) 636

01-02 * < LOD < LOD .090 (<LOD-.120) .140 (.110-.160) 567

03-04 .015 (.013-.017) .013 (.011-.016) .022 (.019-.026) .042 (.032-.054) .071 (.049-.097) 427

Non-Hispanic blacks 99-00 * < LOD < LOD .170 (.110-.250) .280 (.220-.420) 411

01-02 * < LOD .070 (<LOD-.080) .130 (.100-.170) .200 (.150-.250) 515

03-04 .028 (.024-.033) .022 (.019-.025) .055 (.038-.077) .153 (.090-.215) .236 (.143-.337) 464

Non-Hispanic whites 99-00 * < LOD < LOD .150 (.130-.160) .190 (.160-.210) 719

01-02 * < LOD .100 (.080-.110) .170 (.140-.200) .230 (.190-.280) 1061 

03-04 .032 (.030-.034) .030 (.027-.033) .064 (.058-.067) .113 (.096-.123) .153 (.131-.176) 885

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 334 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,5'-Pentachlorobiphenyl (PCB 87) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 .656 (.579-.744) .900 (.800-.980) 1.32 (1.24-1.46) 2.02 (1.90-2.17) 2.70 (2.40-3.03) 1892 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 .706 (.629-.792) .860 (.800-1.00) 1.56 (1.32-1.69) 2.25 (2.05-2.60) 3.44 (2.27-3.98) 596

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 .650 (.568-.742) .900 (.800-.970) 1.30 (1.22-1.40) 2.00 (1.85-2.17) 2.60 (2.35-2.91) 1296 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 .665 (.606-.730) .900 (.800-.970) 1.40 (1.30-1.50) 2.05 (1.90-2.27) 2.70 (2.33-3.08) 945

Females 01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 .648 (.545-.771) .870 (.780-1.00) 1.30 (1.20-1.41) 2.00 (1.84-2.23) 2.60 (2.35-3.08) 947

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 564

03-04 .693 (.569-.843) .840 (.700-1.00) 1.49 (1.14-1.70) 2.00 (1.64-2.40) 2.30 (2.00-3.10) 427

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 .824 (.723-.939) 1.05 (.950-1.10) 1.70 (1.32-2.10) 2.81 (2.48-3.09) 3.42 (3.00-4.14) 462

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 .625 (.531-.735) .830 (.780-.940) 1.30 (1.20-1.40) 1.97 (1.85-2.17) 2.49 (2.30-2.80) 882

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 335

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,5'-Pentachlorobiphenyl (PCB 87) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 .004 (.004-.005) .005 (.005-.006) .008 (.008-.009) .012 (.012-.013) .017 (.015-.017) 1892 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 .004 (.003-.004) .005 (.004-.005) .008 (.007-.008) .011 (.010-.013) .016 (.011-.021) 596

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 .004 (.004-.005) .006 (.005-.006) .008 (.008-.009) .012 (.011-.014) .017 (.014-.018) 1296 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 .004 (.004-.005) .006 (.005-.006) .009 (.008-.009) .013 (.012-.014) .017 (.015-.018) 945

Females 01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 .004 (.003-.005) .005 (.005-.006) .008 (.007-.009) .012 (.011-.013) .016 (.014-.017) 947

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 564

03-04 .004 (.003-.005) .005 (.004-.006) .008 (.007-.010) .011 (.009-.014) .014 (.011-.022) 427

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 .005 (.004-.005) .006 (.006-.006) .009 (.008-.012) .015 (.014-.017) .020 (.017-.027) 462

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 .004 (.003-.005) .005 (.005-.006) .008 (.007-.009) .012 (.011-.013) .016 (.014-.017) 882

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 336 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',4,4',5-Pentachlorobiphenyl (PCB 99) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 13.1 (<LOD-14.7) 19.1 (16.2-20.6) 1897 

01-02 * < LOD < LOD 17.6 (15.3-21.0) 26.3 (22.1-30.5) 2281 

03-04 4.16 (3.82-4.54) 3.79 (3.43-4.10) 6.53 (5.76-7.56) 13.0 (10.5-16.1) 18.0 (16.7-19.4) 1877 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 654

01-02 * < LOD < LOD < LOD < LOD 758

03-04 2.34 (2.08-2.64) 2.30 (2.05-2.60) 3.20 (2.80-3.86) 5.16 (3.80-6.12) 6.00 (4.77-10.0) 587

20 years and older 99-00 * < LOD < LOD 13.9 (<LOD-16.0) 20.0 (17.2-21.6) 1243 

01-02 * < LOD 10.8 (<LOD-12.3) 19.4 (16.7-22.3) 29.0 (23.5-32.1) 1523 

03-04 4.52 (4.14-4.94) 4.08 (3.75-4.45) 7.10 (6.08-8.53) 14.7 (10.9-17.0) 18.6 (17.1-21.3) 1290 

Gender 

Males 99-00 * < LOD < LOD < LOD 16.7 (13.8-20.5) 905

01-02 * < LOD < LOD 17.0 (13.8-21.0) 24.9 (19.8-30.1) 1061 

03-04 3.97 (3.64-4.33) 3.69 (3.31-4.00) 6.11 (5.44-7.00) 11.1 (9.40-14.3) 16.8 (12.9-19.0) 936

Females 99-00 * < LOD < LOD 13.9 (<LOD-16.2) 20.3 (17.3-23.5) 992

01-02 * < LOD < LOD 18.0 (15.8-22.2) 28.5 (22.5-33.2) 1220 

03-04 4.35 (3.94-4.81) 3.90 (3.43-4.70) 7.05 (6.00-8.46) 15.3 (11.5-17.3) 18.9 (17.5-22.8) 941

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 624

01-02 * < LOD < LOD < LOD 13.8 (10.7-17.4) 562

03-04 2.33 (2.08-2.62) 2.20 (1.90-2.47) 3.35 (2.80-4.02) 5.21 (4.50-6.10) 6.35 (5.53-7.55) 426

Non-Hispanic blacks 99-00 * < LOD < LOD 21.1 (17.0-31.1) 32.0 (22.9-57.4) 400

01-02 * < LOD 11.7 (10.6-13.1) 22.5 (18.8-25.8) 29.0 (23.0-37.2) 510

03-04 5.54 (4.53-6.77) 4.81 (3.80-5.80) 10.4 (7.20-15.3) 23.1 (16.7-29.7) 31.7 (24.2-49.1) 447

Non-Hispanic whites 99-00 * < LOD < LOD 12.5 (<LOD-14.5) 18.2 (14.3-20.8) 715

01-02 * < LOD < LOD 18.5 (15.3-22.3) 28.5 (22.1-32.4) 1046 

03-04 4.23 (3.80-4.72) 3.90 (3.40-4.44) 6.70 (5.70-8.00) 12.6 (9.73-15.8) 17.3 (15.5-18.1) 883

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.5, 10.5, and 0.6, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 337

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',4,4',5-Pentachlorobiphenyl (PCB 99) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .090 (<LOD-.100) .120 (.100-.150) 1897 

01-02 * < LOD < LOD .120 (.100-.140) .180 (.150-.210) 2281 

03-04 .025 (.023-.028) .024 (.021-.026) .042 (.038-.049) .082 (.067-.102) .119 (.102-.140) 1877 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 654

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .012 (.011-.013) .012 (.010-.013) .017 (.015-.019) .025 (.019-.032) .032 (.025-.045) 587

20 years and older 99-00 * < LOD < LOD .090 (<LOD-.100) .130 (.110-.150) 1243 

01-02 * < LOD .070 (<LOD-.080) .130 (.110-.160) .190 (.160-.210) 1523 

03-04 .028 (.026-.031) .026 (.024-.028) .046 (.041-.054) .093 (.073-.110) .127 (.110-.153) 1290 

Gender 

Males 99-00 * < LOD < LOD < LOD .110 (.090-.130) 905

01-02 * < LOD < LOD .110 (.090-.140) .160 (.120-.200) 1061 

03-04 .025 (.022-.027) .023 (.021-.025) .040 (.036-.045) .070 (.059-.090) .110 (.078-.132) 936

Females 99-00 * < LOD < LOD .100 (<LOD-.110) .130 (.100-.170) 992

01-02 * < LOD < LOD .130 (.110-.160) .200 (.160-.210) 1220 

03-04 .026 (.024-.029) .024 (.020-.028) .045 (.040-.053) .095 (.078-.111) .130 (.110-.158) 941

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 624

01-02 * < LOD < LOD < LOD .100 (.070-.120) 562

03-04 .014 (.012-.016) .013 (.011-.016) .022 (.019-.026) .036 (.030-.040) .046 (.036-.058) 426

Non-Hispanic blacks 99-00 * < LOD < LOD .140 (.110-.180) .210 (.150-.400) 400

01-02 * < LOD .070 (.060-.090) .140 (.110-.150) .190 (.140-.230) 510

03-04 .032 (.026-.039) .027 (.023-.033) .060 (.042-.086) .149 (.112-.172) .211 (.150-.306) 447

Non-Hispanic whites 99-00 * < LOD < LOD .090 (<LOD-.100) .110 (.090-.150) 715

01-02 * < LOD < LOD .120 (.100-.160) .190 (.160-.210) 1046 

03-04 .026 (.023-.029) .025 (.022-.027) .043 (.038-.051) .081 (.065-.102) .112 (.098-.127) 883

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 338 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',4,5,5'-Pentachlorobiphenyl (PCB 101) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1929 

01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 1.65 (1.51-1.81) 1.70 (1.50-1.80) 2.70 (2.50-2.94) 4.40 (3.97-4.82) 5.83 (5.29-6.66) 1897 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 669

01-02 * < LOD < LOD < LOD < LOD 758

03-04 1.93 (1.76-2.11) 1.73 (1.51-2.10) 3.20 (3.00-3.60) 5.05 (4.23-5.87) 7.25 (5.10-8.30) 598

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1260 

01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 1.62 (1.46-1.78) 1.67 (1.50-1.80) 2.64 (2.40-2.90) 4.40 (3.88-4.75) 5.51 (5.00-6.60) 1299 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 918

01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 1.71 (1.59-1.84) 1.75 (1.60-1.90) 2.80 (2.60-3.10) 4.50 (3.97-5.06) 6.00 (5.35-6.75) 947

Females 99-00 * < LOD < LOD < LOD < LOD 1011 

01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 1.60 (1.41-1.81) 1.61 (1.41-1.82) 2.57 (2.30-2.98) 4.40 (3.71-4.94) 5.60 (4.88-7.25) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 634

01-02 * < LOD < LOD < LOD < LOD 567

03-04 1.72 (1.55-1.92) 1.70 (1.50-1.96) 3.00 (2.30-3.80) 4.40 (3.56-5.38) 5.38 (4.10-6.60) 427

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 413

01-02 * < LOD < LOD < LOD < LOD 515

03-04 1.69 (1.38-2.07) 1.70 (1.50-2.16) 3.00 (2.57-3.80) 5.88 (3.88-7.39) 7.68 (6.60-11.9) 464

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 724

01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 1.61 (1.46-1.79) 1.61 (1.41-1.80) 2.60 (2.37-2.90) 4.40 (3.75-4.61) 5.50 (5.00-6.15) 885

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 25.7, 10.5, and 0.6, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 339

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',4,5,5'-Pentachlorobiphenyl (PCB 101) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1929 

01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 .010 (.009-.011) .010 (.009-.012) .016 (.015-.018) .027 (.024-.028) .033 (.031-.037) 1897 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 669

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .010 (.009-.011) .009 (.008-.011) .016 (.014-.018) .024 (.021-.028) .030 (.025-.044) 598

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1260 

01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 .010 (.009-.011) .011 (.009-.012) .016 (.015-.018) .027 (.024-.029) .034 (.031-.037) 1299 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 918

01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 .011 (.010-.011) .011 (.010-.012) .017 (.016-.019) .025 (.024-.029) .037 (.031-.041) 947

Females 99-00 * < LOD < LOD < LOD < LOD 1011 

01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 .010 (.009-.011) .010 (.009-.011) .015 (.014-.018) .027 (.022-.029) .032 (.030-.036) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 634

01-02 * < LOD < LOD < LOD < LOD 567

03-04 .011 (.009-.012) .011 (.009-.012) .018 (.014-.021) .024 (.020-.030) .029 (.022-.052) 427

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 413

01-02 * < LOD < LOD < LOD < LOD 515

03-04 .010 (.008-.012) .011 (.008-.013) .016 (.013-.022) .032 (.023-.041) .045 (.032-.059) 464

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 724

01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 .010 (.009-.011) .010 (.009-.011) .016 (.014-.018) .025 (.024-.027) .031 (.029-.037) 885

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 340 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,3,3',4',6-Pentachlorobiphenyl (PCB 110) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 1.22 (1.11-1.33) 1.20 (1.10-1.36) 1.96 (1.80-2.20) 3.40 (3.10-3.57) 4.42 (3.88-4.95) 1882 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 1.44 (1.30-1.59) 1.30 (1.20-1.50) 2.50 (2.19-2.91) 4.13 (3.40-4.90) 5.40 (4.30-7.68) 593

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 1.19 (1.08-1.30) 1.20 (1.09-1.33) 1.88 (1.71-2.11) 3.30 (2.95-3.50) 4.18 (3.66-4.94) 1289 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 1.26 (1.18-1.35) 1.30 (1.19-1.40) 2.05 (1.80-2.30) 3.42 (3.07-3.70) 4.61 (3.80-5.00) 939

Females 01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 1.17 (1.04-1.32) 1.20 (1.00-1.36) 1.82 (1.70-2.20) 3.40 (2.77-3.57) 4.40 (3.57-5.54) 943

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 564

03-04 1.33 (1.18-1.51) 1.29 (1.13-1.50) 2.30 (1.80-2.95) 3.40 (2.70-4.30) 4.10 (3.30-5.50) 420

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 1.36 (1.20-1.53) 1.30 (1.14-1.50) 2.10 (1.72-3.00) 4.19 (2.91-5.10) 5.32 (4.40-6.89) 464

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 1.17 (1.05-1.31) 1.20 (1.00-1.33) 1.86 (1.70-2.16) 3.40 (2.93-3.57) 4.19 (3.69-4.95) 877

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.8. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 341

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,3,3',4',6-Pentachlorobiphenyl (PCB 110) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 .007 (.007-.008) .007 (.007-.008) .012 (.011-.013) .019 (.018-.021) .026 (.023-.028) 1882 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 .007 (.007-.008) .007 (.006-.008) .013 (.010-.015) .020 (.017-.022) .026 (.019-.037) 593

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 .007 (.007-.008) .007 (.007-.008) .012 (.011-.013) .019 (.017-.021) .025 (.023-.028) 1289 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 .008 (.007-.008) .008 (.007-.009) .013 (.011-.014) .019 (.018-.021) .028 (.022-.031) 939

Females 01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 .007 (.006-.008) .007 (.006-.008) .011 (.010-.013) .019 (.016-.022) .024 (.021-.027) 943

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 564

03-04 .008 (.007-.009) .008 (.007-.010) .014 (.011-.016) .019 (.016-.022) .022 (.017-.043) 420

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 .008 (.007-.009) .008 (.006-.009) .012 (.010-.016) .023 (.017-.028) .028 (.023-.032) 464

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 .007 (.006-.008) .007 (.006-.008) .012 (.010-.013) .019 (.017-.021) .026 (.022-.029) 877

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 342 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4'-Hexachlorobiphenyl (PCB 128) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1927 

01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 * < LOD < LOD < LOD .600 (.500-.700) 1877 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 668

01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD < LOD < LOD .510 (<LOD-.700) 589

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1259 

01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 * < LOD < LOD < LOD .620 (.490-.800) 1288 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 917

01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 * < LOD < LOD < LOD .600 (.420-.770) 937

Females 99-00 * < LOD < LOD < LOD < LOD 1010 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 * < LOD < LOD < LOD .630 (.500-.800) 940

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD < LOD < LOD < LOD 564

03-04 * < LOD < LOD < LOD < LOD 424

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 515

03-04 * < LOD < LOD .670 (.500-.800) 1.00 (.770-2.10) 455

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 725

01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 * < LOD < LOD < LOD .500 (.420-.600) 878

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 343

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4'-Hexachlorobiphenyl (PCB 128) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1927 

01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 * < LOD < LOD < LOD .004 (.003-.004) 1877 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 668

01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD < LOD < LOD .003 (<LOD-.004) 589

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1259 

01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 * < LOD < LOD < LOD .004 (.004-.005) 1288 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 917

01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 * < LOD < LOD < LOD .004 (.003-.005) 937

Females 99-00 * < LOD < LOD < LOD < LOD 1010 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 * < LOD < LOD < LOD .004 (.003-.005) 940

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD < LOD < LOD < LOD 564

03-04 * < LOD < LOD < LOD < LOD 424

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 515

03-04 * < LOD < LOD .004 (.003-.005) .006 (.005-.013) 455

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 725

01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 * < LOD < LOD < LOD .003 (.002-.004) 878

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 344 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,4',5' and 2,3,3',4,4',6-Hexachlorobiphenyl (PCB 138 & 158) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 49.3 (42.9-55.8) 71.2 (59.8-82.7) 1930 

01-02 19.9 (18.0-22.0) 20.2 (18.2-23.1) 40.4 (35.3-45.1) 70.1 (61.8-78.8) 94.6 (82.5-107) 2293 

03-04 15.1 (14.1-16.1) 15.1 (13.6-16.6) 30.5 (28.1-34.0) 55.4 (47.3-63.3) 75.3 (69.0-81.8) 1896 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 669

01-02 * < LOD < LOD 17.0 (13.7-20.2) 23.1 (17.7-41.2) 748

03-04 4.97 (4.45-5.55) 4.57 (4.10-5.02) 7.39 (6.35-8.63) 12.7 (10.4-14.5) 15.2 (13.1-21.3) 598

20 years and older 99-00 * < LOD < LOD 54.7 (47.4-60.8) 72.8 (66.0-88.9) 1261 

01-02 23.3 (21.1-25.8) 24.0 (21.4-26.8) 44.6 (40.4-49.2) 73.9 (66.2-83.0) 100 (88.8-109) 1545 

03-04 17.7 (16.5-19.0) 17.6 (15.5-20.4) 34.3 (30.0-38.8) 59.6 (50.6-66.9) 77.4 (72.3-87.7) 1298 

Gender 

Males 99-00 * < LOD < LOD 47.2 (<LOD-55.7) 68.2 (55.7-83.8) 918

01-02 20.1 (17.9-22.6) 20.5 (17.6-23.5) 39.2 (32.2-46.0) 69.2 (58.1-82.5) 94.6 (77.8-109) 1066 

03-04 14.9 (13.8-15.9) 14.4 (12.9-15.8) 29.6 (26.6-33.8) 56.3 (45.3-62.3) 75.8 (63.3-87.7) 947

Females 99-00 * < LOD < LOD 53.7 (44.7-61.2) 72.1 (61.2-88.9) 1012 

01-02 19.7 (17.8-21.7) 20.2 (18.2-23.1) 41.8 (37.5-45.9) 70.1 (63.4-78.5) 93.9 (80.2-109) 1227 

03-04 15.3 (14.0-16.8) 15.8 (14.2-17.8) 31.8 (28.3-36.6) 54.6 (47.3-64.4) 72.5 (68.4-80.9) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD 18.6 (13.6-23.4) 33.3 (26.5-44.2) 51.8 (42.3-57.6) 559

03-04 7.06 (6.02-8.28) 6.52 (5.20-7.60) 12.3 (8.91-16.0) 23.6 (18.9-28.3) 29.2 (24.7-36.1) 427

Non-Hispanic blacks 99-00 * < LOD < LOD 72.6 (61.7-89.4) 122 (86.5-185) 412

01-02 22.3 (19.3-25.6) 22.0 (18.4-27.1) 46.5 (38.0-55.6) 91.5 (70.1-112) 122 (91.5-169) 513

03-04 17.8 (14.9-21.3) 15.9 (12.5-21.0) 41.2 (30.6-57.3) 86.5 (69.4-110) 153 (94.6-191) 464

Non-Hispanic whites 99-00 * < LOD < LOD 49.3 (41.4-55.8) 70.1 (55.7-85.2) 727

01-02 21.5 (19.2-24.0) 22.1 (19.6-24.9) 43.0 (37.7-48.0) 70.7 (62.3-79.7) 96.1 (79.1-110) 1057 

03-04 16.0 (14.5-17.7) 15.8 (14.6-18.4) 31.4 (28.2-36.6) 55.1 (47.2-62.3) 71.6 (64.0-75.8) 883

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 41.1, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 345

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,4',5' and 2,3,3',4,4',6-Hexachlorobiphenyl (PCB 138 & 158) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .340 (.300-.370) .460 (.390-.530) 1930 

01-02 .122 (.110-.135) .120 (.110-.140) .270 (.230-.290) .460 (.410-.510) .650 (.560-.700) 2293 

03-04 .092 (.086-.099) .095 (.082-.105) .206 (.180-.231) .359 (.326-.392) .477 (.450-.528) 1896 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 669

01-02 * < LOD < LOD .090 (.060-.110) .110 (.090-.210) 748

03-04 .025 (.023-.028) .023 (.020-.027) .037 (.030-.047) .062 (.049-.074) .079 (.067-.103) 598

20 years and older 99-00 * < LOD < LOD .360 (.320-.390) .490 (.400-.560) 1261 

01-02 .148 (.133-.163) .150 (.140-.170) .290 (.270-.320) .510 (.450-.550) .680 (.610-.720) 1545 

03-04 .111 (.103-.120) .114 (.099-.128) .232 (.204-.256) .383 (.354-.416) .506 (.467-.594) 1298 

Gender 

Males 99-00 * < LOD < LOD .320 (<LOD-.370) .420 (.370-.530) 918

01-02 .125 (.112-.140) .130 (.110-.140) .260 (.230-.290) .460 (.370-.540) .630 (.510-.710) 1066 

03-04 .092 (.085-.099) .091 (.079-.103) .198 (.172-.229) .354 (.316-.379) .474 (.389-.562) 947

Females 99-00 * < LOD < LOD .340 (.300-.370) .490 (.390-.540) 1012 

01-02 .119 (.107-.132) .120 (.110-.150) .270 (.230-.300) .460 (.420-.500) .660 (.590-.700) 1227 

03-04 .093 (.084-.102) .098 (.085-.115) .212 (.178-.244) .373 (.325-.417) .482 (.450-.568) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 636

01-02 * < LOD .110 (.090-.150) .240 (.170-.330) .350 (.270-.430) 559

03-04 .043 (.036-.051) .040 (.032-.049) .080 (.068-.100) .148 (.122-.203) .239 (.147-.346) 427

Non-Hispanic blacks 99-00 * < LOD < LOD .470 (.360-.670) .830 (.530-1.22) 412

01-02 .125 (.108-.146) .130 (.090-.160) .290 (.230-.350) .560 (.420-.680) .770 (.560-1.06) 513

03-04 .101 (.084-.122) .087 (.068-.113) .239 (.186-.326) .568 (.424-.811) .965 (.698-1.09) 464

Non-Hispanic whites 99-00 * < LOD < LOD .340 (.300-.370) .440 (.370-.530) 727

01-02 .133 (.119-.149) .140 (.120-.160) .280 (.250-.300) .460 (.420-.530) .650 (.550-.720) 1057 

03-04 .099 (.089-.109) .104 (.091-.121) .216 (.179-.252) .355 (.320-.390) .467 (.410-.520) 883

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 346 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4',5,5'-Hexachlorobiphenyl (PCB 146) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 13.3 (<LOD-16.1) 1923 

01-02 * < LOD < LOD 11.0 (<LOD-12.5) 15.4 (13.6-16.9) 2299 

03-04 2.17 (2.02-2.32) 2.21 (2.03-2.54) 4.80 (4.38-5.21) 8.27 (7.10-9.50) 11.7 (10.2-13.3) 1894 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .620 (.562-.685) .600 (.520-.690) 1.02 (.870-1.20) 1.67 (1.50-1.80) 2.30 (1.79-2.97) 594

20 years and older 99-00 * < LOD < LOD < LOD 14.3 (<LOD-17.1) 1256 

01-02 * < LOD < LOD 11.8 (10.7-13.5) 16.5 (14.6-18.1) 1541 

03-04 2.60 (2.41-2.79) 2.60 (2.40-2.90) 5.27 (4.82-5.88) 8.81 (8.00-9.80) 12.7 (10.7-15.2) 1300 

Gender 

Males 99-00 * < LOD < LOD < LOD 13.1 (<LOD-17.1) 915

01-02 * < LOD < LOD 11.0 (<LOD-13.0) 15.4 (13.0-17.2) 1069 

03-04 2.16 (1.97-2.37) 2.10 (1.90-2.50) 4.80 (4.09-5.30) 8.30 (6.90-10.1) 12.4 (10.0-14.9) 945

Females 99-00 * < LOD < LOD < LOD 13.9 (<LOD-16.3) 1008 

01-02 * < LOD < LOD 11.0 (<LOD-12.2) 15.2 (13.2-17.3) 1230 

03-04 2.17 (2.02-2.34) 2.35 (2.04-2.63) 4.83 (4.47-5.37) 8.00 (7.04-9.10) 11.3 (9.95-13.2) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 633

01-02 * < LOD < LOD < LOD < LOD 567

03-04 .940 (.826-1.07) .820 (.780-1.00) 1.74 (1.21-2.60) 3.31 (2.80-4.00) 4.60 (3.47-6.00) 425

Non-Hispanic blacks 99-00 * < LOD < LOD 17.0 (13.4-22.9) 29.8 (20.2-42.2) 412

01-02 * < LOD < LOD 16.6 (12.8-21.4) 23.8 (16.9-31.6) 515

03-04 2.81 (2.37-3.34) 2.60 (2.05-3.50) 7.10 (4.97-8.90) 16.8 (11.5-23.2) 28.5 (17.8-41.6) 463

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 723

01-02 * < LOD < LOD 10.8 (<LOD-12.0) 15.2 (12.8-16.8) 1054 

03-04 2.25 (2.06-2.45) 2.35 (2.10-2.60) 4.82 (4.37-5.41) 7.76 (6.94-8.70) 10.5 (9.51-11.3) 885

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 347

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4',5,5'-Hexachlorobiphenyl (PCB 146) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD .080 (<LOD-.110) 1923 

01-02 * < LOD < LOD .070 (<LOD-.080) .110 (.090-.120) 2299 

03-04 .013 (.012-.014) .014 (.013-.016) .032 (.028-.035) .054 (.047-.062) .077 (.069-.090) 1894 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .003 (.003-.003) .003 (.003-.003) .006 (.004-.007) .008 (.007-.010) .011 (.009-.014) 594

20 years and older 99-00 * < LOD < LOD < LOD .090 (<LOD-.120) 1256 

01-02 * < LOD < LOD .080 (.070-.090) .110 (.100-.120) 1541 

03-04 .016 (.015-.018) .017 (.015-.020) .035 (.032-.038) .058 (.053-.064) .084 (.073-.099) 1300 

Gender 

Males 99-00 * < LOD < LOD < LOD .080 (<LOD-.110) 915

01-02 * < LOD < LOD .070 (<LOD-.090) .100 (.090-.120) 1069 

03-04 .013 (.012-.015) .014 (.012-.016) .032 (.027-.036) .054 (.045-.063) .074 (.064-.096) 945

Females 99-00 * < LOD < LOD < LOD .090 (<LOD-.110) 1008 

01-02 * < LOD < LOD .070 (<LOD-.080) .110 (.090-.120) 1230 

03-04 .013 (.012-.014) .015 (.013-.016) .032 (.028-.036) .054 (.047-.065) .079 (.069-.088) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 633

01-02 * < LOD < LOD < LOD < LOD 567

03-04 .006 (.005-.007) .005 (.004-.007) .012 (.008-.016) .024 (.017-.033) .034 (.024-.046) 425

Non-Hispanic blacks 99-00 * < LOD < LOD .110 (.080-.130) .180 (.120-.270) 412

01-02 * < LOD < LOD .100 (.080-.130) .150 (.110-.200) 515

03-04 .016 (.013-.019) .016 (.012-.019) .041 (.030-.061) .100 (.069-.167) .180 (.126-.224) 463

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 723

01-02 * < LOD < LOD .070 (<LOD-.080) .100 (.090-.120) 1054 

03-04 .014 (.013-.015) .015 (.013-.018) .033 (.028-.036) .053 (.047-.057) .069 (.064-.075) 885

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 348 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4',5',6-Hexachlorobiphenyl (PCB 149) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 .598 (.556-.642) .600 (.550-.680) .900 (.830-1.00) 1.45 (1.28-1.60) 1.90 (1.68-2.20) 1873 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 .650 (.605-.698) .640 (.600-.700) 1.00 (.900-1.10) 1.70 (1.40-2.15) 2.40 (1.80-2.98) 590

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 .590 (.546-.638) .600 (.540-.680) .900 (.800-1.00) 1.40 (1.20-1.60) 1.89 (1.60-2.17) 1283 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 .623 (.578-.671) .650 (.600-.700) .960 (.880-1.06) 1.50 (1.30-1.66) 1.90 (1.60-2.40) 930

Females 01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 .575 (.521-.634) .600 (.500-.620) .890 (.800-.950) 1.40 (1.20-1.67) 1.90 (1.69-2.20) 943

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 567

03-04 .549 (.496-.608) .530 (.500-.600) .900 (.700-1.04) 1.28 (1.03-1.60) 1.60 (1.26-2.30) 408

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 .760 (.678-.853) .800 (.700-.880) 1.20 (1.00-1.58) 1.98 (1.70-2.59) 2.90 (2.20-4.20) 463

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 .574 (.524-.628) .600 (.510-.670) .880 (.800-.950) 1.33 (1.19-1.50) 1.80 (1.50-2.02) 881

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 349

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4',5',6-Hexachlorobiphenyl (PCB 149) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 .004 (.003-.004) .004 (.004-.004) .006 (.005-.006) .009 (.008-.009) .011 (.010-.013) 1873 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 .003 (.003-.004) .003 (.003-.003) .005 (.004-.006) .008 (.007-.009) .012 (.008-.016) 590

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 .004 (.003-.004) .004 (.004-.004) .006 (.005-.006) .009 (.007-.010) .011 (.010-.013) 1283 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 .004 (.004-.004) .004 (.004-.004) .006 (.005-.007) .009 (.008-.010) .011 (.010-.013) 930

Females 01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 .003 (.003-.004) .004 (.003-.004) .005 (.005-.006) .008 (.007-.010) .011 (.009-.013) 943

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 567

03-04 .003 (.003-.004) .003 (.003-.004) .005 (.004-.006) .007 (.006-.008) .009 (.007-.014) 408

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 .004 (.004-.005) .004 (.004-.005) .007 (.006-.008) .012 (.010-.013) .019 (.013-.022) 463

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 .004 (.003-.004) .004 (.003-.004) .005 (.005-.006) .008 (.007-.009) .010 (.009-.012) 881

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 350 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,5,5',6-Hexachlorobiphenyl (PCB 151) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 * < LOD .420 (.400-.500) .700 (.640-.820) 1.00 (.840-1.30) 1870 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD .400 (<LOD-.470) .700 (.510-.820) .880 (.700-1.10) 588

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 * < LOD .440 (.400-.500) .720 (.650-.850) 1.02 (.850-1.40) 1282 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 * < LOD .430 (.400-.500) .720 (.620-.900) 1.10 (.830-1.50) 931

Females 01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 * < LOD .410 (.400-.500) .700 (.600-.820) 1.00 (.830-1.20) 939

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 567

03-04 * < LOD < LOD .500 (.400-.700) .700 (.530-.700) 426

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 * .400 (<LOD-.500) .700 (.500-.900) 1.30 (.900-1.90) 2.20 (1.40-4.55) 461

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 * < LOD .400 (<LOD-.450) .650 (.590-.700) .850 (.750-1.00) 864

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 351

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,5,5',6-Hexachlorobiphenyl (PCB 151) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 * < LOD .003 (.002-.003) .004 (.004-.005) .006 (.005-.008) 1870 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD .002 (<LOD-.002) .003 (.003-.004) .004 (.003-.006) 588

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 * < LOD .003 (.003-.003) .004 (.004-.006) .007 (.005-.010) 1282 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 * < LOD .003 (.003-.003) .005 (.004-.006) .006 (.005-.010) 931

Females 01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 * < LOD .003 (.002-.003) .004 (.004-.005) .006 (.005-.008) 939

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 567

03-04 * < LOD < LOD .003 (.003-.004) .004 (.003-.005) 426

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 515

03-04 * .002 (<LOD-.003) .004 (.003-.006) .008 (.006-.010) .013 (.008-.028) 461

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 * < LOD .003 (<LOD-.003) .004 (.004-.004) .005 (.004-.006) 864

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 352 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 77.8 (70.2-87.3) 114 (93.0-133) 1926 

01-02 27.2 (24.7-30.1) 30.1 (26.1-34.3) 57.8 (52.1-63.2) 94.7 (86.5-104) 126 (109-142) 2306 

03-04 19.8 (18.8-20.9) 20.8 (18.4-22.2) 43.3 (39.1-46.9) 71.8 (64.4-82.8) 97.1 (88.8-111) 1896 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 668

01-02 * < LOD 12.5 (11.1-14.1) 21.2 (17.4-26.7) 31.9 (23.1-64.7) 757

03-04 5.86 (5.25-6.55) 5.40 (4.70-6.21) 8.50 (7.80-9.85) 15.7 (12.9-18.4) 20.7 (16.9-28.3) 596

20 years and older 99-00 * < LOD < LOD 83.2 (75.9-91.8) 122 (100-139) 1258 

01-02 32.6 (29.5-36.1) 35.1 (31.1-39.0) 62.8 (57.6-68.0) 99.5 (90.7-110) 132 (116-146) 1549 

03-04 23.7 (22.3-25.1) 24.2 (21.8-27.4) 47.1 (43.3-50.5) 77.5 (68.0-87.9) 101 (92.9-119) 1300 

Gender 

Males 99-00 * < LOD < LOD 75.0 (66.7-86.2) 111 (87.7-128) 917

01-02 28.5 (25.5-32.0) 31.5 (26.7-35.2) 57.7 (48.3-66.2) 97.5 (82.1-110) 126 (104-150) 1074 

03-04 20.0 (18.7-21.3) 19.7 (17.7-21.2) 42.9 (37.4-47.6) 72.7 (60.4-88.8) 107 (86.8-122) 947

Females 99-00 * < LOD < LOD 79.0 (70.2-92.0) 119 (91.4-142) 1009 

01-02 26.1 (23.6-28.8) 29.0 (25.1-33.4) 57.9 (52.1-62.9) 94.3 (87.8-98.2) 128 (105-145) 1232 

03-04 19.7 (18.4-21.1) 21.9 (19.0-24.1) 43.8 (39.4-47.7) 70.9 (63.0-81.5) 93.3 (83.8-100) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 67.5 (59.5-71.8) 634

01-02 12.5 (10.8-14.4) 11.1 (<LOD-13.3) 24.5 (18.2-33.9) 47.4 (36.2-60.3) 66.7 (55.2-72.3) 567

03-04 8.75 (7.39-10.4) 7.86 (6.17-9.40) 15.6 (11.4-22.2) 30.3 (25.2-34.9) 37.8 (31.1-45.2) 425

Non-Hispanic blacks 99-00 * < LOD 59.4 (<LOD-82.0) 121 (90.3-159) 176 (130-287) 412

01-02 30.0 (26.2-34.4) 31.0 (25.8-36.4) 65.1 (54.2-82.7) 127 (97.1-152) 170 (126-246) 515

03-04 22.8 (19.1-27.2) 20.9 (17.0-28.7) 54.1 (37.3-69.2) 126 (92.9-158) 194 (126-294) 464

Non-Hispanic whites 99-00 * < LOD < LOD 76.4 (69.3-83.9) 102 (87.8-127) 725

01-02 29.9 (26.8-33.4) 33.0 (28.7-37.1) 61.2 (55.8-66.7) 96.3 (86.5-109) 126 (104-142) 1061 

03-04 21.3 (19.7-23.1) 22.2 (20.4-25.9) 44.9 (39.7-49.5) 70.9 (60.4-82.1) 91.3 (82.1-103) 885

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 55.6, 10.5, and 1.1, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 353

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .530 (.490-.560) .750 (.610-.840) 1926 

01-02 .167 (.151-.185) .190 (.170-.210) .380 (.340-.410) .620 (.560-.690) .860 (.760-.950) 2306 

03-04 .121 (.114-.128) .135 (.120-.144) .283 (.258-.310) .477 (.439-.518) .624 (.575-.733) 1896 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 668

01-02 * < LOD .060 (.050-.070) .110 (.080-.140) .150 (.110-.310) 757

03-04 .030 (.027-.033) .027 (.025-.031) .044 (.039-.055) .076 (.062-.098) .101 (.079-.129) 596

20 years and older 99-00 * < LOD < LOD .560 (.510-.610) .790 (.670-.880) 1258 

01-02 .206 (.187-.228) .220 (.200-.250) .410 (.380-.450) .670 (.600-.740) .900 (.820-1.04) 1549 

03-04 .148 (.139-.158) .156 (.141-.179) .313 (.283-.339) .512 (.452-.563) .671 (.603-.756) 1300 

Gender 

Males 99-00 * < LOD < LOD .530 (.470-.560) .690 (.580-.850) 917

01-02 .177 (.159-.198) .200 (.170-.220) .380 (.340-.430) .610 (.510-.730) .850 (.700-1.04) 1074 

03-04 .123 (.115-.133) .127 (.111-.146) .277 (.253-.310) .474 (.413-.522) .608 (.533-.794) 947

Females 99-00 * < LOD < LOD .530 (.480-.590) .770 (.610-.880) 1009 

01-02 .158 (.142-.175) .180 (.150-.210) .380 (.340-.400) .630 (.570-.710) .860 (.760-.950) 1232 

03-04 .119 (.110-.128) .138 (.113-.149) .291 (.253-.319) .492 (.439-.541) .624 (.578-.689) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD .470 (.380-.540) 634

01-02 .075 (.063-.089) .060 (<LOD-.080) .150 (.120-.210) .330 (.270-.420) .470 (.380-.550) 567

03-04 .053 (.044-.064) .047 (.038-.057) .100 (.078-.144) .205 (.164-.241) .323 (.213-.435) 425

Non-Hispanic blacks 99-00 * < LOD .370 (<LOD-.510) .750 (.620-.890) 1.27 (.820-1.64) 412

01-02 .169 (.146-.195) .180 (.140-.200) .390 (.330-.490) .780 (.580-.950) 1.05 (.830-1.43) 515

03-04 .129 (.108-.156) .126 (.098-.149) .330 (.236-.425) .734 (.562-1.06) 1.26 (.892-1.60) 464

Non-Hispanic whites 99-00 * < LOD < LOD .520 (.480-.560) .740 (.580-.850) 725

01-02 .185 (.165-.207) .210 (.180-.230) .390 (.370-.430) .640 (.570-.720) .840 (.740-.990) 1061 

03-04 .131 (.121-.143) .144 (.127-.170) .295 (.268-.329) .474 (.412-.518) .600 (.519-.689) 885

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 354 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4',5-Heptachlorobiphenyl (PCB 170) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 23.6 (22.0-25.4) 30.9 (28.1-35.1) 1798 

01-02 * < LOD 17.5 (15.7-19.3) 26.7 (24.9-29.0) 35.0 (32.4-37.3) 2301 

03-04 5.46 (5.22-5.71) 6.30 (5.96-7.10) 12.9 (12.3-13.9) 21.7 (19.2-23.5) 28.2 (25.8-29.8) 1888 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 645

01-02 * < LOD < LOD < LOD < LOD 756

03-04 1.12 (.974-1.30) 1.12 (1.00-1.30) 1.90 (1.70-2.50) 4.00 (3.53-4.37) 5.60 (4.35-6.69) 592

20 years and older 99-00 * < LOD < LOD 24.9 (23.3-26.4) 33.9 (29.6-37.5) 1153 

01-02 10.5 (<LOD-11.3) 11.1 (<LOD-12.2) 19.1 (17.3-20.9) 28.4 (26.2-30.9) 36.8 (33.4-39.4) 1545 

03-04 6.86 (6.48-7.26) 7.83 (6.87-8.70) 14.2 (13.1-14.9) 22.7 (20.7-24.9) 29.5 (26.7-32.2) 1296 

Gender 

Males 99-00 * < LOD < LOD 24.1 (22.0-27.0) 32.6 (28.1-37.0) 863

01-02 * 10.9 (<LOD-11.9) 18.4 (16.3-20.9) 28.1 (24.7-31.9) 36.1 (32.1-38.3) 1073 

03-04 5.81 (5.43-6.22) 6.40 (5.61-7.68) 13.8 (12.4-14.4) 23.4 (20.4-25.6) 29.4 (26.0-32.7) 942

Females 99-00 * < LOD < LOD 22.4 (20.7-25.4) 29.7 (25.8-36.3) 935

01-02 * < LOD 16.4 (15.0-18.0) 25.9 (24.0-28.4) 34.0 (30.6-38.4) 1228 

03-04 5.14 (4.82-5.48) 6.28 (5.81-7.18) 12.5 (11.5-13.8) 19.2 (17.9-21.7) 26.1 (24.0-29.8) 946

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 23.2 (20.3-26.5) 606

01-02 * < LOD < LOD 15.4 (11.4-18.7) 21.1 (17.1-25.1) 565

03-04 2.34 (1.91-2.86) 2.20 (1.54-3.20) 4.91 (3.40-8.17) 10.4 (8.40-13.5) 13.9 (10.8-20.1) 423

Non-Hispanic blacks 99-00 * < LOD < LOD 30.9 (23.1-36.3) 41.9 (33.7-59.1) 382

01-02 * < LOD 19.0 (14.9-23.2) 32.5 (25.5-43.9) 44.4 (32.5-61.7) 514

03-04 5.42 (4.63-6.35) 6.28 (5.11-7.75) 14.3 (10.7-18.3) 31.7 (23.1-40.7) 48.5 (32.1-66.1) 461

Non-Hispanic whites 99-00 * < LOD < LOD 24.1 (22.1-25.9) 31.0 (26.8-37.3) 658

01-02 * 10.9 (<LOD-12.0) 18.4 (16.8-20.4) 27.7 (25.4-30.2) 35.0 (32.3-38.1) 1059 

03-04 6.13 (5.74-6.56) 7.40 (6.40-8.18) 13.8 (12.6-14.6) 21.7 (19.2-24.2) 27.0 (24.9-29.5) 882

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 17.2, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 355

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4',5-Heptachlorobiphenyl (PCB 170) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .160 (.140-.180) .210 (.200-.230) 1798 

01-02 * < LOD .110 (.110-.120) .180 (.170-.200) .250 (.210-.270) 2301 

03-04 .033 (.032-.035) .041 (.037-.045) .087 (.080-.092) .144 (.134-.149) .188 (.173-.202) 1888 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 645

01-02 * < LOD < LOD < LOD < LOD 756

03-04 .006 (.005-.006) .006 (.005-.007) .010 (.009-.012) .020 (.017-.022) .029 (.022-.033) 592

20 years and older 99-00 * < LOD < LOD .170 (.150-.190) .220 (.200-.250) 1153 

01-02 .067 (<LOD-.072) .070 (<LOD-.080) .120 (.110-.130) .200 (.180-.210) .250 (.230-.290) 1545 

03-04 .043 (.040-.046) .051 (.045-.054) .093 (.089-.099) .149 (.141-.160) .199 (.180-.223) 1296 

Gender 

Males 99-00 * < LOD < LOD .170 (.140-.200) .220 (.200-.250) 863

01-02 * .070 (<LOD-.080) .120 (.110-.130) .190 (.170-.210) .250 (.210-.280) 1073 

03-04 .036 (.033-.039) .043 (.036-.051) .089 (.080-.093) .148 (.132-.164) .200 (.173-.225) 942

Females 99-00 * < LOD < LOD .150 (.130-.170) .210 (.190-.230) 935

01-02 * < LOD .110 (.100-.120) .180 (.160-.200) .250 (.210-.280) 1228 

03-04 .031 (.029-.033) .040 (.034-.044) .083 (.075-.092) .140 (.121-.149) .176 (.160-.194) 946

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD .170 (.130-.190) 606

01-02 * < LOD < LOD .110 (.080-.130) .150 (.120-.190) 565

03-04 .014 (.012-.018) .015 (.010-.018) .032 (.025-.047) .073 (.054-.113) .119 (.078-.134) 423

Non-Hispanic blacks 99-00 * < LOD < LOD .190 (.150-.210) .260 (.190-.370) 382

01-02 * < LOD .110 (.090-.140) .210 (.150-.270) .290 (.210-.390) 514

03-04 .031 (.026-.037) .038 (.027-.044) .087 (.069-.117) .210 (.136-.280) .338 (.221-.380) 461

Non-Hispanic whites 99-00 * < LOD < LOD .160 (.140-.200) .210 (.200-.240) 658

01-02 * .070 (<LOD-.080) .120 (.110-.130) .190 (.170-.210) .250 (.210-.280) 1059 

03-04 .038 (.035-.041) .046 (.042-.052) .091 (.083-.096) .145 (.132-.151) .180 (.164-.207) 882

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 356 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,5,5'-Heptachlorobiphenyl (PCB 172) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1901 

01-02 * < LOD < LOD < LOD < LOD 2199 

03-04 .647 (.606-.691) .900 (.800-1.00) 1.80 (1.69-1.90) 2.98 (2.70-3.30) 4.16 (3.65-4.55) 1878 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660

01-02 * < LOD < LOD < LOD < LOD 679

03-04 * < LOD < LOD .610 (.460-.840) 1.10 (.700-1.43) 585

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1241 

01-02 * < LOD < LOD < LOD < LOD 1520 

03-04 .805 (.746-.869) 1.08 (1.00-1.16) 1.95 (1.80-2.10) 3.20 (2.87-3.60) 4.38 (3.79-5.00) 1293 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 911

01-02 * < LOD < LOD < LOD < LOD 1027 

03-04 .668 (.612-.730) .900 (.800-1.01) 1.82 (1.70-2.00) 3.30 (2.80-3.80) 4.43 (3.76-5.50) 937

Females 99-00 * < LOD < LOD < LOD < LOD 990

01-02 * < LOD < LOD < LOD < LOD 1172 

03-04 .627 (.581-.678) .900 (.800-1.03) 1.72 (1.51-1.90) 2.80 (2.50-3.11) 3.70 (3.37-4.26) 941

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 630

01-02 * < LOD < LOD < LOD < LOD 519

03-04 * < LOD .700 (.470-1.20) 1.40 (1.20-1.95) 2.00 (1.40-2.91) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 494

03-04 .688 (.579-.818) .900 (.700-1.10) 2.20 (1.70-2.60) 5.00 (3.38-6.53) 7.60 (5.00-11.3) 458

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 706

01-02 * < LOD < LOD < LOD < LOD 1027 

03-04 .720 (.665-.781) 1.00 (.870-1.10) 1.80 (1.69-2.00) 2.94 (2.70-3.20) 3.90 (3.53-4.20) 877

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.5, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 357

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,5,5'-Heptachlorobiphenyl (PCB 172) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1901 

01-02 * < LOD < LOD < LOD < LOD 2199 

03-04 .004 (.004-.004) .006 (.005-.006) .012 (.011-.012) .021 (.019-.022) .027 (.024-.031) 1878 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660

01-02 * < LOD < LOD < LOD < LOD 679

03-04 * < LOD < LOD .003 (.002-.004) .005 (.004-.009) 585

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1241 

01-02 * < LOD < LOD < LOD < LOD 1520 

03-04 .005 (.005-.005) .007 (.006-.007) .013 (.012-.014) .022 (.020-.024) .028 (.025-.033) 1293 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 911

01-02 * < LOD < LOD < LOD < LOD 1027 

03-04 .004 (.004-.005) .006 (.005-.007) .012 (.011-.013) .021 (.018-.024) .029 (.024-.036) 937

Females 99-00 * < LOD < LOD < LOD < LOD 990

01-02 * < LOD < LOD < LOD < LOD 1172 

03-04 .004 (.003-.004) .006 (.005-.006) .012 (.010-.012) .019 (.017-.021) .026 (.023-.028) 941

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 630

01-02 * < LOD < LOD < LOD < LOD 519

03-04 * < LOD .005 (.003-.007) .010 (.007-.015) .017 (.011-.022) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 494

03-04 .004 (.003-.005) .006 (.004-.006) .013 (.010-.017) .030 (.020-.048) .052 (.028-.067) 458

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 706

01-02 * < LOD < LOD < LOD < LOD 1027 

03-04 .004 (.004-.005) .006 (.005-.007) .012 (.011-.013) .020 (.018-.022) .026 (.023-.029) 877

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 358 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,5',6'-Heptachlorobiphenyl (PCB 177) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1873 

01-02 * < LOD < LOD < LOD < LOD 2287 

03-04 1.13 (1.07-1.20) 1.30 (1.20-1.40) 2.77 (2.50-3.09) 5.30 (4.70-5.90) 7.20 (6.38-8.50) 1882 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 653

01-02 * < LOD < LOD < LOD < LOD 756

03-04 * < LOD .600 (.500-.720) 1.04 (.800-1.40) 1.70 (1.20-1.95) 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1220 

01-02 * < LOD < LOD < LOD < LOD 1531 

03-04 1.40 (1.30-1.50) 1.50 (1.40-1.71) 3.10 (2.80-3.44) 5.70 (4.99-6.22) 7.80 (6.50-9.50) 1294 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 887

01-02 * < LOD < LOD < LOD < LOD 1065 

03-04 1.12 (1.03-1.21) 1.30 (1.17-1.41) 2.70 (2.40-3.00) 5.30 (4.72-5.80) 7.82 (6.22-9.50) 940

Females 99-00 * < LOD < LOD < LOD < LOD 986

01-02 * < LOD < LOD < LOD < LOD 1222 

03-04 1.15 (1.06-1.23) 1.30 (1.18-1.49) 2.80 (2.57-3.19) 5.30 (4.50-6.06) 6.97 (6.15-7.92) 942

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 622

01-02 * < LOD < LOD < LOD < LOD 562

03-04 .500 (<LOD-.649) .550 (.400-.700) 1.36 (1.00-1.63) 2.40 (1.86-3.30) 3.40 (2.33-4.63) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 399

01-02 * < LOD < LOD < LOD 10.6 (<LOD-12.4) 515

03-04 1.52 (1.25-1.84) 1.56 (1.29-2.05) 4.40 (3.20-5.70) 9.80 (6.30-13.3) 15.8 (10.0-25.7) 458

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 698

01-02 * < LOD < LOD < LOD < LOD 1048 

03-04 1.16 (1.08-1.25) 1.34 (1.20-1.50) 2.74 (2.41-3.09) 5.00 (4.57-5.56) 6.50 (5.98-7.40) 880

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.5, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 359

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,5',6'-Heptachlorobiphenyl (PCB 177) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1873 

01-02 * < LOD < LOD < LOD < LOD 2287 

03-04 .007 (.007-.007) .008 (.008-.009) .018 (.016-.021) .034 (.031-.037) .047 (.043-.056) 1882 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 653

01-02 * < LOD < LOD < LOD < LOD 756

03-04 * < LOD .003 (.003-.004) .006 (.005-.007) .007 (.006-.011) 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1220 

01-02 * < LOD < LOD < LOD < LOD 1531 

03-04 .009 (.008-.009) .010 (.009-.011) .021 (.018-.023) .036 (.033-.041) .053 (.045-.058) 1294 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 887

01-02 * < LOD < LOD < LOD < LOD 1065 

03-04 .007 (.006-.007) .009 (.008-.009) .018 (.016-.021) .032 (.030-.036) .045 (.039-.062) 940

Females 99-00 * < LOD < LOD < LOD < LOD 986

01-02 * < LOD < LOD < LOD < LOD 1222 

03-04 .007 (.006-.008) .008 (.007-.009) .018 (.017-.021) .035 (.032-.042) .051 (.043-.056) 942

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 622

01-02 * < LOD < LOD < LOD < LOD 562

03-04 .003 (<LOD-.004) .003 (.002-.005) .008 (.006-.011) .018 (.012-.025) .025 (.018-.032) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 399

01-02 * < LOD < LOD < LOD .070 (<LOD-.100) 515

03-04 .009 (.007-.011) .009 (.007-.012) .026 (.018-.036) .057 (.044-.090) .105 (.058-.143) 458

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 698

01-02 * < LOD < LOD < LOD < LOD 1048 

03-04 .007 (.007-.008) .009 (.008-.010) .018 (.016-.021) .032 (.029-.036) .044 (.040-.052) 880

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 360 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',5,5',6-Heptachlorobiphenyl (PCB 178) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1932 

01-02 * < LOD < LOD < LOD < LOD 2299 

03-04 .933 (.894-.974) 1.20 (1.10-1.30) 2.50 (2.30-2.67) 4.24 (3.90-4.47) 6.10 (5.13-7.10) 1887 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 669

01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD .400 (<LOD-.480) .850 (.620-1.04) 1.12 (1.00-1.32) 590

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1263 

01-02 * < LOD < LOD < LOD < LOD 1541 

03-04 1.18 (1.11-1.25) 1.46 (1.30-1.60) 2.74 (2.60-2.90) 4.41 (4.10-4.80) 6.50 (5.69-7.58) 1297 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 .991 (.918-1.07) 1.20 (1.10-1.37) 2.66 (2.45-2.80) 4.50 (3.80-5.10) 6.40 (5.30-7.70) 940

Females 99-00 * < LOD < LOD < LOD < LOD 1013 

01-02 * < LOD < LOD < LOD < LOD 1230 

03-04 .881 (.835-.930) 1.20 (1.10-1.30) 2.30 (2.20-2.59) 4.01 (3.71-4.34) 5.40 (4.47-6.70) 947

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 635

01-02 * < LOD < LOD < LOD < LOD 567

03-04 * < LOD .900 (.600-1.34) 1.99 (1.37-2.60) 3.10 (2.00-3.60) 424

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 415

01-02 * < LOD < LOD < LOD < LOD 515

03-04 1.09 (.911-1.30) 1.30 (.910-1.65) 3.10 (2.30-4.21) 7.10 (5.13-10.1) 11.4 (6.80-16.5) 460

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 724

01-02 * < LOD < LOD < LOD < LOD 1054 

03-04 1.03 (.963-1.10) 1.30 (1.19-1.50) 2.61 (2.40-2.80) 4.20 (3.80-4.40) 5.33 (4.58-6.30) 882

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 361

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',5,5',6-Heptachlorobiphenyl (PCB 178) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1932 

01-02 * < LOD < LOD < LOD < LOD 2299 

03-04 .006 (.005-.006) .008 (.007-.008) .016 (.015-.018) .029 (.026-.032) .041 (.035-.045) 1887 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 669

01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD .002 (<LOD-.002) .004 (.003-.005) .006 (.004-.007) 590

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1263 

01-02 * < LOD < LOD < LOD < LOD 1541 

03-04 .007 (.007-.008) .009 (.008-.010) .018 (.017-.019) .031 (.028-.034) .043 (.038-.048) 1297 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 .006 (.006-.007) .008 (.007-.009) .017 (.016-.018) .030 (.025-.034) .042 (.034-.050) 940

Females 99-00 * < LOD < LOD < LOD < LOD 1013 

01-02 * < LOD < LOD < LOD < LOD 1230 

03-04 .005 (.005-.006) .008 (.006-.008) .016 (.014-.017) .028 (.025-.031) .040 (.034-.045) 947

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 635

01-02 * < LOD < LOD < LOD < LOD 567

03-04 * < LOD .005 (.004-.008) .013 (.009-.020) .022 (.014-.028) 424

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 415

01-02 * < LOD < LOD < LOD < LOD 515

03-04 .006 (.005-.008) .008 (.006-.008) .019 (.016-.027) .044 (.032-.061) .077 (.045-.089) 460

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 724

01-02 * < LOD < LOD < LOD < LOD 1054 

03-04 .006 (.006-.007) .008 (.007-.010) .017 (.015-.018) .028 (.025-.031) .037 (.033-.045) 882

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 362 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,4',5,5'-Heptachlorobiphenyl (PCB 180) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 37.5 (32.7-41.8) 62.0 (56.6-66.6) 79.3 (72.1-89.2) 1924 

01-02 19.2 (17.4-21.1) 21.8 (19.0-24.6) 42.2 (38.3-47.5) 69.7 (63.7-75.9) 87.3 (83.3-93.0) 2302 

03-04 15.1 (14.5-15.7) 18.0 (16.4-18.9) 37.1 (34.9-39.5) 63.7 (56.2-68.2) 81.5 (75.8-89.9) 1896 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD 12.2 (<LOD-14.8) 21.3 (14.2-26.0) 755

03-04 3.06 (2.65-3.54) 2.97 (2.57-3.41) 5.00 (4.20-5.80) 11.1 (8.70-13.0) 14.7 (13.0-18.8) 598

20 years and older 99-00 * < LOD 41.1 (37.6-45.2) 65.6 (60.6-69.4) 84.8 (75.6-96.1) 1257 

01-02 23.0 (20.8-25.5) 26.5 (22.7-28.6) 46.7 (41.4-51.3) 74.5 (66.7-79.8) 91.4 (85.0-99.5) 1547 

03-04 19.0 (17.9-20.1) 21.5 (18.9-24.3) 40.4 (37.9-42.8) 66.7 (61.0-70.1) 88.0 (77.8-96.7) 1298 

Gender 

Males 99-00 * < LOD 40.6 (34.5-45.0) 65.1 (58.6-71.4) 83.8 (75.8-96.3) 919

01-02 21.1 (18.8-23.7) 25.1 (21.2-30.0) 46.7 (39.8-51.8) 73.8 (63.2-79.8) 86.9 (78.0-99.4) 1073 

03-04 16.1 (14.8-17.4) 18.5 (15.8-21.3) 39.6 (35.8-41.7) 68.6 (63.7-75.0) 88.3 (76.8-96.7) 947

Females 99-00 * < LOD 34.4 (29.8-39.3) 56.7 (52.2-62.6) 74.6 (66.6-90.5) 1005 

01-02 17.5 (15.9-19.3) 18.5 (16.0-21.6) 39.7 (34.8-43.9) 64.3 (58.0-74.8) 87.9 (79.1-98.1) 1229 

03-04 14.2 (13.4-15.0) 17.8 (15.8-19.2) 35.4 (31.8-38.5) 55.7 (51.2-59.9) 74.3 (64.8-87.6) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD 41.7 (33.2-50.5) 57.8 (49.7-63.8) 633

01-02 * < LOD 18.0 (11.5-22.7) 36.9 (28.2-45.7) 54.2 (42.2-60.0) 566

03-04 6.14 (4.91-7.67) 5.80 (3.80-7.50) 12.6 (8.97-21.5) 27.2 (22.3-35.4) 38.8 (27.2-60.7) 427

Non-Hispanic blacks 99-00 * < LOD 39.3 (32.2-48.4) 78.4 (64.3-93.7) 117 (89.6-144) 414

01-02 19.5 (16.5-23.1) 21.0 (16.9-23.8) 48.4 (36.7-57.9) 90.5 (73.7-101) 116 (96.1-167) 514

03-04 15.1 (12.8-17.7) 18.1 (12.6-20.8) 39.0 (29.7-51.1) 89.9 (64.4-122) 137 (91.4-206) 464

Non-Hispanic whites 99-00 * < LOD 39.9 (34.5-45.3) 62.3 (56.5-68.6) 79.0 (71.3-91.4) 719

01-02 21.4 (19.1-23.9) 24.8 (21.5-28.1) 45.6 (40.2-51.0) 72.4 (63.8-78.0) 87.9 (83.8-94.3) 1059 

03-04 16.9 (15.9-18.0) 19.8 (18.4-23.1) 39.3 (35.8-42.0) 63.7 (55.0-69.1) 79.8 (70.1-89.3) 883

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 28.2, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 363

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,4',5,5'-Heptachlorobiphenyl (PCB 180) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD .250 (.220-.270) .410 (.370-.450) .540 (.490-.600) 1924 

01-02 .118 (.106-.130) .140 (.120-.160) .280 (.250-.300) .460 (.400-.510) .610 (.540-.690) 2302 

03-04 .092 (.088-.096) .114 (.102-.127) .246 (.230-.253) .409 (.386-.438) .534 (.495-.598) 1896 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD .060 (<LOD-.080) .090 (.070-.140) 755

03-04 .016 (.014-.018) .015 (.013-.017) .025 (.022-.030) .050 (.046-.056) .076 (.056-.096) 598

20 years and older 99-00 * < LOD .270 (.240-.300) .440 (.410-.480) .560 (.500-.620) 1257 

01-02 .146 (.131-.162) .170 (.150-.190) .300 (.280-.340) .490 (.430-.560) .640 (.570-.740) 1547 

03-04 .119 (.112-.126) .138 (.125-.151) .270 (.249-.284) .433 (.402-.474) .572 (.511-.635) 1298 

Gender 

Males 99-00 * < LOD .260 (.220-.300) .460 (.370-.510) .570 (.500-.650) 919

01-02 .131 (.117-.147) .170 (.140-.200) .300 (.260-.340) .480 (.410-.550) .620 (.530-.720) 1073 

03-04 .099 (.091-.108) .117 (.098-.148) .250 (.231-.274) .422 (.388-.495) .596 (.499-.654) 947

Females 99-00 * < LOD .230 (.200-.270) .380 (.340-.410) .510 (.430-.560) 1005 

01-02 .106 (.096-.117) .120 (.100-.140) .260 (.230-.280) .420 (.380-.470) .610 (.520-.700) 1229 

03-04 .085 (.080-.092) .110 (.094-.123) .230 (.209-.252) .386 (.349-.421) .494 (.459-.541) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD .280 (.200-.320) .390 (.320-.450) 633

01-02 * < LOD .110 (.080-.160) .260 (.200-.310) .360 (.280-.420) 566

03-04 .037 (.030-.047) .035 (.024-.051) .086 (.059-.118) .191 (.138-.313) .343 (.191-.405) 427

Non-Hispanic blacks 99-00 * < LOD .250 (.190-.300) .500 (.350-.660) .730 (.530-1.04) 414

01-02 .110 (.092-.131) .120 (.090-.140) .290 (.220-.350) .580 (.440-.650) .720 (.520-1.01) 514

03-04 .086 (.072-.102) .098 (.070-.126) .248 (.194-.327) .580 (.373-.824) .919 (.592-1.12) 464

Non-Hispanic whites 99-00 * < LOD .260 (.240-.300) .430 (.380-.470) .540 (.480-.600) 719

01-02 .132 (.118-.148) .160 (.140-.180) .290 (.260-.330) .470 (.410-.530) .620 (.530-.730) 1059 

03-04 .104 (.097-.112) .132 (.115-.151) .253 (.235-.280) .409 (.382-.449) .512 (.478-.572) 883

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 364 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,4',5',6-Heptachlorobiphenyl (PCB 183) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1928 

01-02 * < LOD < LOD < LOD < LOD 2306 

03-04 1.45 (1.38-1.54) 1.60 (1.50-1.77) 3.29 (3.15-3.54) 5.86 (5.50-6.29) 7.90 (7.50-8.74) 1886 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 668

01-02 * < LOD < LOD < LOD < LOD 757

03-04 * .440 (<LOD-.500) .730 (.660-.840) 1.30 (.990-1.62) 1.91 (1.50-2.24) 590

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1260 

01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 1.77 (1.67-1.88) 1.88 (1.73-2.09) 3.70 (3.34-4.00) 6.25 (5.71-6.83) 8.40 (7.70-9.55) 1296 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1074 

03-04 1.47 (1.34-1.61) 1.54 (1.40-1.77) 3.29 (3.10-3.54) 5.80 (5.30-6.50) 7.90 (7.20-9.20) 940

Females 99-00 * < LOD < LOD < LOD < LOD 1009 

01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 1.44 (1.34-1.55) 1.69 (1.50-1.82) 3.30 (3.05-3.80) 5.88 (5.21-6.30) 7.90 (7.31-9.24) 946

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 635

01-02 * < LOD < LOD < LOD < LOD 567

03-04 .703 (.579-.854) .700 (.600-.890) 1.40 (1.19-1.90) 2.62 (2.20-3.47) 3.73 (2.60-5.60) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 12.7 (<LOD-23.1) 413

01-02 * < LOD < LOD < LOD 13.0 (<LOD-14.9) 514

03-04 1.64 (1.41-1.90) 1.60 (1.20-2.00) 4.31 (3.25-5.63) 11.0 (6.69-13.7) 14.8 (11.3-17.4) 459

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 722

01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 1.56 (1.43-1.69) 1.74 (1.55-1.90) 3.30 (3.14-3.73) 5.71 (5.20-6.29) 7.59 (6.70-8.04) 883

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 365

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4,4',5',6-Heptachlorobiphenyl (PCB 183) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1928 

01-02 * < LOD < LOD < LOD < LOD 2306 

03-04 .009 (.008-.009) .010 (.009-.011) .021 (.019-.024) .039 (.036-.042) .054 (.048-.059) 1886 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 668

01-02 * < LOD < LOD < LOD < LOD 757

03-04 * .002 (<LOD-.003) .004 (.004-.004) .007 (.005-.009) .009 (.007-.010) 590

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1260 

01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 .011 (.010-.012) .012 (.011-.014) .024 (.022-.027) .042 (.038-.045) .057 (.052-.064) 1296 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 919

01-02 * < LOD < LOD < LOD < LOD 1074 

03-04 .009 (.008-.010) .010 (.009-.011) .022 (.019-.025) .038 (.035-.042) .052 (.043-.064) 940

Females 99-00 * < LOD < LOD < LOD < LOD 1009 

01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 .009 (.008-.009) .010 (.009-.012) .021 (.019-.023) .042 (.036-.044) .055 (.049-.061) 946

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 635

01-02 * < LOD < LOD < LOD < LOD 567

03-04 .004 (.003-.005) .005 (.004-.006) .009 (.007-.013) .019 (.013-.029) .029 (.017-.044) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD .070 (<LOD-.150) 413

01-02 * < LOD < LOD < LOD .080 (<LOD-.110) 514

03-04 .009 (.008-.011) .009 (.008-.012) .027 (.019-.037) .065 (.043-.084) .090 (.058-.120) 459

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 722

01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 .010 (.009-.010) .011 (.010-.012) .022 (.019-.025) .038 (.035-.042) .049 (.046-.055) 883

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 366 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4',5,5',6-Heptachlorobiphenyl (PCB 187) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 17.7 (15.6-20.4) 24.8 (22.0-27.7) 1930 

01-02 * < LOD 12.2 (10.6-13.8) 21.7 (19.6-23.7) 28.1 (26.8-29.7) 2307 

03-04 4.23 (3.96-4.50) 4.60 (4.20-5.23) 10.1 (9.42-10.5) 17.2 (16.1-18.1) 24.3 (20.5-27.8) 1889 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 758

03-04 1.00 (.859-1.17) 1.00 (.880-1.10) 1.66 (1.50-1.99) 3.20 (2.50-4.34) 5.00 (3.70-6.07) 594

20 years and older 99-00 * < LOD < LOD 19.3 (16.8-21.8) 26.0 (24.1-29.0) 1263 

01-02 * < LOD 13.3 (12.0-15.2) 23.0 (20.9-24.7) 29.2 (27.3-32.0) 1549 

03-04 5.20 (4.83-5.60) 5.71 (5.01-6.19) 10.9 (10.3-11.7) 18.1 (16.9-19.5) 25.9 (22.1-32.1) 1295 

Gender 

Males 99-00 * < LOD < LOD 17.8 (15.8-19.6) 25.9 (21.6-29.8) 917

01-02 * < LOD 12.7 (<LOD-15.8) 22.5 (19.4-24.1) 27.7 (25.2-30.3) 1075 

03-04 4.34 (3.97-4.75) 4.50 (4.00-5.40) 10.4 (9.21-10.9) 17.9 (16.1-19.5) 25.1 (20.4-30.9) 939

Females 99-00 * < LOD < LOD 17.7 (15.1-21.7) 24.2 (21.6-27.0) 1013 

01-02 * < LOD 11.9 (<LOD-13.0) 21.3 (18.5-23.5) 28.5 (26.2-31.3) 1232 

03-04 4.12 (3.84-4.41) 4.67 (4.10-5.30) 9.85 (8.83-10.5) 16.4 (15.3-17.9) 24.2 (19.1-27.8) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 17.6 (15.1-19.1) 636

01-02 * < LOD < LOD 10.8 (<LOD-13.4) 15.7 (12.7-18.2) 567

03-04 1.79 (1.47-2.20) 1.58 (1.26-2.00) 3.96 (2.70-5.90) 7.86 (5.96-10.3) 11.6 (9.41-14.9) 426

Non-Hispanic blacks 99-00 * < LOD 15.5 (<LOD-21.1) 31.6 (26.0-39.0) 47.1 (36.6-72.1) 412

01-02 * < LOD 16.5 (12.3-21.0) 30.3 (22.9-40.6) 44.8 (30.3-61.9) 515

03-04 5.09 (4.39-5.90) 5.40 (4.20-6.21) 13.9 (10.6-17.7) 31.7 (22.7-46.4) 51.5 (31.7-76.5) 458

Non-Hispanic whites 99-00 * < LOD < LOD 16.8 (14.9-18.6) 22.0 (19.1-25.2) 727

01-02 * < LOD 12.5 (10.8-14.6) 21.7 (18.9-23.7) 27.4 (25.2-29.5) 1061 

03-04 4.47 (4.17-4.79) 5.00 (4.40-5.70) 10.1 (9.26-10.8) 16.5 (15.3-17.9) 21.1 (19.1-24.2) 884

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 367

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,4',5,5',6-Heptachlorobiphenyl (PCB 187) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .120 (.110-.130) .170 (.140-.180) 1930 

01-02 * < LOD .080 (.070-.090) .140 (.130-.160) .200 (.180-.220) 2307 

03-04 .026 (.024-.028) .029 (.027-.032) .065 (.061-.069) .115 (.106-.125) .167 (.139-.197) 1889 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .005 (.004-.006) .005 (.004-.006) .009 (.007-.010) .016 (.013-.019) .023 (.016-.029) 594

20 years and older 99-00 * < LOD < LOD .130 (.110-.140) .180 (.160-.190) 1263 

01-02 * < LOD .090 (.080-.100) .150 (.130-.180) .210 (.190-.230) 1549 

03-04 .033 (.030-.035) .036 (.032-.040) .071 (.067-.075) .124 (.112-.139) .172 (.143-.215) 1295 

Gender 

Males 99-00 * < LOD < LOD .120 (.100-.140) .180 (.140-.200) 917

01-02 * < LOD .080 (<LOD-.100) .150 (.130-.160) .190 (.170-.230) 1075 

03-04 .027 (.024-.030) .030 (.026-.035) .067 (.061-.072) .116 (.102-.137) .160 (.137-.215) 939

Females 99-00 * < LOD < LOD .120 (.110-.130) .160 (.140-.180) 1013 

01-02 * < LOD .080 (<LOD-.090) .140 (.120-.150) .200 (.180-.220) 1232 

03-04 .025 (.023-.027) .029 (.026-.033) .063 (.056-.070) .115 (.104-.125) .168 (.141-.191) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD .120 (.100-.130) 636

01-02 * < LOD < LOD .080 (<LOD-.100) .100 (.090-.120) 567

03-04 .011 (.009-.013) .010 (.007-.015) .025 (.018-.038) .057 (.042-.079) .094 (.059-.110) 426

Non-Hispanic blacks 99-00 * < LOD .090 (<LOD-.130) .200 (.160-.230) .290 (.210-.530) 412

01-02 * < LOD .100 (.070-.120) .190 (.150-.260) .290 (.190-.380) 515

03-04 .029 (.025-.034) .032 (.024-.037) .083 (.070-.109) .191 (.140-.273) .330 (.228-.468) 458

Non-Hispanic whites 99-00 * < LOD < LOD .110 (.100-.130) .150 (.130-.170) 727

01-02 * < LOD .080 (.070-.090) .140 (.120-.160) .190 (.170-.220) 1061 

03-04 .028 (.026-.030) .032 (.029-.036) .065 (.061-.071) .111 (.101-.124) .153 (.132-.172) 884

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 368 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4',5,5'-Octachlorobiphenyl (PCB 194) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD 11.1 (<LOD-11.9) 18.2 (16.5-19.5) 23.7 (21.0-27.0) 2279 

03-04 2.69 (2.53-2.85) 4.19 (3.55-4.70) 8.47 (7.79-9.06) 14.3 (13.3-16.0) 19.1 (17.6-20.8) 1835 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 746

03-04 * < LOD 1.11 (.700-1.57) 2.40 (1.70-3.57) 5.18 (2.80-6.81) 572

20 years and older 01-02 * < LOD 12.0 (11.0-13.3) 19.1 (17.7-20.5) 25.3 (22.7-28.0) 1533 

03-04 3.64 (3.40-3.89) 4.95 (4.56-5.42) 9.30 (8.62-9.90) 15.3 (13.9-17.1) 20.1 (18.1-21.9) 1263 

Gender 

Males 01-02 * < LOD 12.3 (10.6-14.1) 19.2 (17.2-21.2) 25.2 (21.7-29.0) 1059 

03-04 2.95 (2.61-3.35) 4.47 (3.55-5.20) 9.60 (8.30-10.9) 17.1 (14.2-18.8) 21.8 (19.8-25.6) 913

Females 01-02 * < LOD < LOD 17.0 (14.7-18.8) 21.9 (19.3-26.2) 1220 

03-04 2.45 (2.28-2.64) 4.00 (3.39-4.49) 7.50 (7.01-8.39) 12.7 (11.2-13.6) 16.6 (13.7-18.6) 922

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD 14.3 (10.5-17.6) 561

03-04 .845 (.582-1.23) .900 (.640-1.49) 2.90 (1.79-4.76) 7.21 (4.80-8.90) 9.50 (7.40-15.0) 410

Non-Hispanic blacks 01-02 * < LOD 12.3 (<LOD-15.3) 22.6 (18.0-27.5) 29.8 (23.7-41.1) 508

03-04 2.45 (1.94-3.08) 3.62 (2.70-4.49) 8.83 (6.80-11.2) 18.1 (13.0-23.2) 28.3 (18.9-35.6) 450

Non-Hispanic whites 01-02 * < LOD 11.9 (10.9-13.1) 18.8 (17.1-20.2) 24.1 (20.9-28.0) 1048 

03-04 3.25 (2.97-3.56) 4.90 (4.19-5.42) 9.08 (8.36-9.80) 14.7 (13.5-16.6) 19.1 (17.4-21.2) 861

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2',3,3',4,4',5,5'-Octachlorobiphenyl (PCB 194) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD .070 (<LOD-.080) .120 (.110-.140) .160 (.150-.190) 2279 

03-04 .016 (.015-.017) .026 (.022-.028) .056 (.052-.060) .096 (.091-.103) .129 (.116-.139) 1835 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 746

03-04 * < LOD .006 (.004-.008) .013 (.009-.020) .023 (.013-.035) 572

20 years and older 01-02 * < LOD .080 (.070-.090) .130 (.110-.150) .170 (.150-.200) 1533 

03-04 .023 (.021-.024) .031 (.027-.035) .061 (.057-.065) .103 (.094-.113) .133 (.122-.145) 1263 

Gender 

Males 01-02 * < LOD .080 (.070-.090) .140 (.110-.160) .170 (.150-.210) 1059 

03-04 .018 (.016-.021) .027 (.023-.034) .061 (.054-.069) .106 (.095-.121) .142 (.129-.166) 913

Females 01-02 * < LOD < LOD .110 (.090-.130) .150 (.130-.180) 1220 

03-04 .015 (.014-.016) .024 (.020-.027) .051 (.047-.056) .088 (.080-.096) .112 (.103-.117) 922

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD .100 (.080-.110) 561

03-04 .005 (.004-.008) .006 (.004-.010) .019 (.012-.031) .049 (.033-.064) .081 (.051-.118) 410

Non-Hispanic blacks 01-02 * < LOD .080 (<LOD-.090) .150 (.100-.180) .200 (.140-.250) 508

03-04 .014 (.011-.018) .020 (.014-.026) .054 (.045-.063) .120 (.081-.155) .172 (.123-.202) 450

Non-Hispanic whites 01-02 * < LOD .080 (.070-.090) .130 (.110-.150) .170 (.150-.190) 1048 

03-04 .020 (.018-.022) .029 (.026-.034) .061 (.056-.066) .099 (.090-.106) .132 (.116-.143) 861

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 369

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4',5,6-Octachlorobiphenyl (PCB 195) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2230 

03-04 * .900 (<LOD-1.01) 1.98 (1.80-2.10) 3.40 (3.10-3.60) 4.51 (3.90-5.18) 1820 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 716

03-04 * < LOD < LOD < LOD 1.74 (.720-3.82) 567

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1514 

03-04 .800 (.721-.888) 1.10 (.980-1.20) 2.10 (2.00-2.30) 3.53 (3.20-3.74) 4.68 (4.12-5.19) 1253 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1035 

03-04 * .800 (<LOD-1.00) 2.08 (1.82-2.20) 3.50 (3.12-3.70) 4.60 (3.82-5.40) 904

Females 01-02 * < LOD < LOD < LOD < LOD 1195 

03-04 * .970 (<LOD-1.10) 1.85 (1.64-2.09) 3.30 (2.86-3.60) 4.50 (3.57-5.25) 916

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 544

03-04 * < LOD < LOD 1.80 (1.11-2.40) 2.40 (1.80-3.50) 407

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 490

03-04 .709 (<LOD-.870) .820 (<LOD-1.14) 2.00 (1.65-2.57) 4.18 (3.16-5.30) 6.90 (4.18-8.10) 444

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1037 

03-04 .749 (<LOD-.850) 1.00 (.800-1.18) 2.10 (1.90-2.30) 3.40 (3.10-3.61) 4.44 (3.80-5.19) 856

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 28.1 and 0.7. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2',3,3',4,4',5,6-Octachlorobiphenyl (PCB 195) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2230 

03-04 * .005 (<LOD-.006) .012 (.012-.013) .022 (.020-.025) .031 (.027-.034) 1820 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 716

03-04 * < LOD < LOD < LOD .007 (.004-.017) 567

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1514 

03-04 .005 (.004-.006) .007 (.006-.007) .014 (.012-.015) .023 (.021-.026) .032 (.028-.035) 1253 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1035 

03-04 * .005 (<LOD-.006) .013 (.012-.014) .022 (.020-.025) .031 (.025-.035) 904

Females 01-02 * < LOD < LOD < LOD < LOD 1195 

03-04 * .006 (<LOD-.007) .012 (.011-.013) .021 (.019-.025) .031 (.026-.035) 916

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 544

03-04 * < LOD < LOD .012 (.008-.018) .018 (.013-.025) 407

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 490

03-04 .004 (<LOD-.005) .004 (<LOD-.006) .012 (.010-.016) .027 (.019-.034) .041 (.029-.048) 444

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1037 

03-04 .005 (<LOD-.005) .006 (.005-.007) .013 (.012-.014) .022 (.020-.025) .030 (.027-.033) 856

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 370 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4',5,6' and 2,2',3,4,4',5,5',6-Octachlorobiphenyl (PCB 196 & 203) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD 14.2 (13.0-15.7) 19.2 (17.4-20.9) 2299 

03-04 2.61 (2.44-2.79) 3.40 (3.01-3.80) 6.70 (6.16-7.23) 11.8 (10.8-12.7) 15.0 (13.2-17.4) 1878 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 755

03-04 .437 (<LOD-.546) .520 (.400-.700) 1.10 (.900-1.42) 2.41 (1.86-3.19) 3.59 (2.93-4.20) 587

20 years and older 01-02 * < LOD < LOD 15.0 (13.7-17.0) 19.9 (18.2-21.4) 1544 

03-04 3.37 (3.15-3.61) 4.07 (3.74-4.46) 7.30 (6.79-8.20) 12.4 (11.5-13.2) 15.9 (13.4-19.5) 1291 

Gender 

Males 01-02 * < LOD < LOD 14.6 (13.3-16.5) 19.4 (16.3-21.2) 1071 

03-04 2.77 (2.49-3.08) 3.45 (3.07-3.98) 6.92 (6.12-7.71) 12.5 (11.2-13.7) 16.3 (13.7-23.1) 935

Females 01-02 * < LOD < LOD 13.8 (11.9-15.9) 19.1 (17.0-21.3) 1228 

03-04 2.46 (2.27-2.66) 3.32 (2.83-3.80) 6.68 (6.12-7.20) 11.1 (9.74-12.3) 13.4 (12.8-14.9) 943

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD 11.1 (<LOD-12.5) 565

03-04 .947 (.689-1.30) 1.00 (.700-1.50) 2.80 (1.60-4.30) 5.90 (4.30-7.40) 8.35 (6.00-12.3) 424

Non-Hispanic blacks 01-02 * < LOD < LOD 17.6 (14.2-21.0) 23.1 (19.6-30.2) 513

03-04 2.45 (2.06-2.90) 2.90 (2.33-3.80) 7.18 (5.80-9.00) 13.8 (11.5-16.8) 21.6 (14.0-32.3) 453

Non-Hispanic whites 01-02 * < LOD < LOD 14.7 (13.6-16.5) 19.6 (18.1-21.3) 1058 

03-04 3.01 (2.76-3.27) 3.88 (3.44-4.20) 7.10 (6.32-8.20) 11.8 (10.8-13.1) 15.4 (12.9-19.0) 882

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2',3,3',4,4',5,6' and 2,2',3,4,4',5,5',6-Octachlorobiphenyl (PCB 196 & 203) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD .100 (.090-.110) .130 (.110-.140) 2299 

03-04 .016 (.015-.017) .022 (.019-.025) .044 (.042-.048) .082 (.071-.087) .101 (.091-.112) 1878 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 755

03-04 .002 (<LOD-.003) .003 (.002-.004) .006 (.005-.007) .013 (.009-.016) .016 (.014-.025) 587

20 years and older 01-02 * < LOD < LOD .100 (.090-.110) .130 (.120-.150) 1544 

03-04 .021 (.020-.023) .026 (.024-.028) .049 (.045-.052) .084 (.077-.090) .104 (.092-.123) 1291 

Gender 

Males 01-02 * < LOD < LOD .100 (.090-.120) .130 (.110-.150) 1071 

03-04 .017 (.015-.019) .023 (.020-.026) .045 (.042-.050) .084 (.077-.091) .106 (.093-.127) 935

Females 01-02 * < LOD < LOD .090 (.080-.100) .130 (.110-.140) 1228 

03-04 .015 (.014-.016) .020 (.017-.023) .043 (.038-.047) .076 (.066-.084) .093 (.085-.111) 943

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD .070 (<LOD-.090) 565

03-04 .006 (.004-.008) .007 (.004-.010) .017 (.011-.026) .038 (.028-.054) .058 (.035-.087) 424

Non-Hispanic blacks 01-02 * < LOD < LOD .110 (.090-.140) .150 (.110-.210) 513

03-04 .014 (.012-.017) .017 (.012-.022) .046 (.038-.054) .090 (.065-.111) .141 (.094-.209) 453

Non-Hispanic whites 01-02 * < LOD < LOD .100 (.090-.110) .130 (.110-.140) 1058 

03-04 .019 (.017-.020) .025 (.022-.028) .048 (.043-.052) .084 (.070-.090) .100 (.090-.120) 882

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 371

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,5,5',6-Octachlorobiphenyl (PCB 199) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD 17.0 (15.4-18.1) 22.4 (19.9-25.9) 2292 

03-04 2.81 (2.64-3.00) 3.80 (3.26-4.26) 8.30 (7.70-9.08) 14.9 (13.8-15.7) 18.9 (17.9-21.3) 1861 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 756

03-04 .416 (<LOD-.522) .500 (<LOD-.700) 1.17 (.890-1.59) 2.43 (2.02-2.73) 3.92 (2.90-4.10) 579

20 years and older 01-02 * < LOD 10.6 (<LOD-11.8) 17.9 (16.2-19.2) 24.4 (20.7-27.4) 1536 

03-04 3.71 (3.41-4.02) 4.60 (4.10-5.08) 9.40 (8.73-10.0) 15.7 (14.7-16.9) 20.6 (18.3-23.6) 1282 

Gender 

Males 01-02 * < LOD < LOD 17.3 (15.4-18.7) 21.3 (19.3-24.6) 1066 

03-04 3.01 (2.68-3.39) 3.95 (3.30-4.67) 9.10 (7.60-9.94) 16.6 (14.0-17.3) 22.1 (18.1-27.4) 925

Females 01-02 * < LOD < LOD 16.2 (14.5-17.9) 22.9 (19.4-27.3) 1226 

03-04 2.63 (2.49-2.79) 3.70 (3.20-4.00) 7.70 (6.92-8.81) 14.0 (11.6-15.3) 17.0 (15.7-18.9) 936

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD 12.3 (<LOD-14.2) 565

03-04 .943 (.664-1.34) 1.00 (.600-1.50) 3.35 (1.50-5.33) 7.37 (5.10-10.2) 10.2 (7.40-13.5) 418

Non-Hispanic blacks 01-02 * < LOD 12.5 (<LOD-15.3) 21.9 (17.0-28.1) 30.7 (22.4-37.4) 513

03-04 3.03 (2.46-3.74) 3.60 (2.70-4.70) 10.0 (7.70-13.7) 21.3 (15.9-30.4) 35.1 (21.3-43.3) 452

Non-Hispanic whites 01-02 * < LOD < LOD 17.3 (15.9-18.9) 22.7 (19.8-26.3) 1051 

03-04 3.24 (3.03-3.47) 4.19 (3.78-4.69) 9.08 (7.88-9.86) 14.8 (13.5-16.3) 18.6 (16.9-21.7) 871

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2',3,3',4,5,5',6-Octachlorobiphenyl (PCB 199) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD .110 (.100-.130) .150 (.140-.170) 2292 

03-04 .017 (.016-.018) .023 (.020-.027) .056 (.053-.060) .100 (.091-.106) .127 (.119-.144) 1861 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 756

03-04 .002 (<LOD-.003) .002 (<LOD-.003) .006 (.005-.008) .012 (.009-.015) .016 (.015-.019) 579

20 years and older 01-02 * < LOD .070 (<LOD-.080) .120 (.110-.140) .160 (.140-.180) 1536 

03-04 .023 (.021-.025) .029 (.026-.033) .062 (.058-.067) .106 (.097-.113) .135 (.120-.158) 1282 

Gender 

Males 01-02 * < LOD < LOD .110 (.100-.130) .150 (.130-.180) 1066 

03-04 .019 (.016-.021) .025 (.020-.030) .059 (.053-.068) .105 (.090-.113) .138 (.120-.162) 925

Females 01-02 * < LOD < LOD .110 (.100-.130) .150 (.130-.170) 1226 

03-04 .016 (.015-.017) .022 (.019-.025) .054 (.047-.058) .094 (.085-.105) .120 (.108-.133) 936

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD .090 (<LOD-.110) 565

03-04 .006 (.004-.008) .007 (.004-.010) .019 (.011-.031) .051 (.029-.079) .079 (.051-.093) 418

Non-Hispanic blacks 01-02 * < LOD .070 (<LOD-.090) .140 (.100-.180) .190 (.130-.300) 513

03-04 .017 (.014-.021) .021 (.015-.026) .064 (.054-.073) .135 (.102-.173) .207 (.147-.297) 452

Non-Hispanic whites 01-02 * < LOD < LOD .120 (.100-.130) .150 (.130-.180) 1051 

03-04 .020 (.019-.022) .027 (.023-.030) .059 (.054-.065) .101 (.087-.108) .125 (.108-.144) 871

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 372 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4',5,5',6-Nonachlorobiphenyl (PCB 206) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2208 

03-04 2.13 (1.97-2.31) 2.34 (2.00-2.60) 5.00 (4.69-5.50) 9.20 (8.55-9.79) 13.7 (11.5-15.6) 1867 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 723

03-04 * < LOD .900 (.750-1.20) 1.75 (1.23-2.92) 3.12 (1.60-6.91) 585

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1485 

03-04 2.59 (2.37-2.83) 2.80 (2.42-3.06) 5.53 (5.10-6.10) 9.61 (9.03-11.0) 14.2 (12.2-17.1) 1282 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1033 

03-04 2.23 (2.03-2.45) 2.30 (1.90-2.70) 5.10 (4.78-5.53) 9.31 (8.18-10.8) 13.8 (10.8-15.7) 933

Females 01-02 * < LOD < LOD < LOD < LOD 1175 

03-04 2.05 (1.86-2.25) 2.34 (1.95-2.78) 5.00 (4.30-5.70) 9.00 (8.00-9.79) 13.6 (11.2-16.5) 934

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 533

03-04 .861 (<LOD-1.15) .730 (<LOD-1.10) 1.70 (1.00-3.14) 4.40 (2.61-6.20) 6.20 (4.40-8.40) 421

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 483

03-04 2.27 (1.98-2.60) 2.26 (1.85-2.51) 5.60 (4.30-7.40) 11.5 (9.49-16.5) 20.9 (12.1-31.7) 456

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1034 

03-04 2.40 (2.19-2.63) 2.70 (2.37-3.01) 5.37 (4.88-6.06) 9.20 (8.65-10.1) 13.8 (11.2-16.6) 872

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 28.1 and 0.7. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2',3,3',4,4',5,5',6-Nonachlorobiphenyl (PCB 206) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2208 

03-04 .013 (.012-.014) .015 (.012-.017) .034 (.031-.037) .060 (.054-.068) .086 (.077-.104) 1867 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 723

03-04 * < LOD .005 (.004-.006) .010 (.006-.013) .014 (.008-.035) 585

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1485 

03-04 .016 (.015-.018) .017 (.016-.020) .038 (.034-.042) .066 (.059-.074) .090 (.081-.112) 1282 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1033 

03-04 .014 (.012-.015) .015 (.012-.018) .034 (.032-.038) .060 (.051-.070) .082 (.070-.097) 933

Females 01-02 * < LOD < LOD < LOD < LOD 1175 

03-04 .012 (.011-.014) .014 (.012-.016) .035 (.029-.038) .061 (.054-.069) .088 (.078-.118) 934

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 533

03-04 .005 (<LOD-.007) .005 (<LOD-.007) .011 (.008-.018) .031 (.019-.044) .044 (.030-.062) 421

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 483

03-04 .013 (.011-.015) .012 (.010-.014) .035 (.028-.045) .078 (.052-.107) .128 (.080-.213) 456

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1034 

03-04 .015 (.013-.016) .017 (.015-.020) .036 (.033-.040) .063 (.058-.069) .088 (.077-.107) 872

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 373

 Non-Dioxin-Like Polychlorinated Biphenyls

Serum 2,2',3,3',4,4',5,5',6,6'-Decachlorobiphenyl (PCB 209) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 1.40 (1.21-1.61) 1.18 (1.00-1.48) 3.20 (2.67-4.01) 7.58 (6.20-8.81) 11.1 (9.00-15.7) 1854

Age group 

12-19 years 03-04 * < LOD < LOD 1.12 (.800-4.60) 3.49 (1.12-6.64) 578

20 years and older 03-04 1.63 (1.42-1.88) 1.40 (1.18-1.70) 3.80 (3.04-4.44) 8.09 (6.60-9.30) 12.3 (9.05-18.0) 1276

Gender 

Males 03-04 1.37 (1.18-1.60) 1.15 (1.00-1.50) 3.00 (2.70-3.58) 6.22 (4.97-8.20) 9.10 (7.09-13.0) 925

Females 03-04 1.42 (1.22-1.66) 1.20 (1.00-1.50) 3.46 (2.45-4.61) 8.78 (7.45-9.47) 13.9 (10.0-18.7) 929

Race/ethnicity 

Mexican Americans 03-04 * < LOD 1.10 (.770-1.60) 2.40 (1.60-3.60) 3.71 (2.40-4.97) 416

Non-Hispanic blacks 03-04 1.56 (1.37-1.78) 1.35 (1.10-1.52) 3.40 (2.62-4.82) 9.83 (6.70-13.6) 18.0 (11.8-27.7) 455

Non-Hispanic whites 03-04 1.53 (1.31-1.79) 1.30 (1.09-1.70) 3.89 (3.04-4.50) 7.95 (6.49-9.09) 11.3 (9.07-16.3) 864

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.7. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Serum 2,2',3,3',4,4',5,5',6,6'-Decachlorobiphenyl (PCB 209) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 .009 (.007-.010) .008 (.006-.009) .021 (.017-.026) .049 (.040-.058) .073 (.059-.097) 1854

Age group 

12-19 years 03-04 * < LOD < LOD .006 (.004-.018) .017 (.005-.033) 578

20 years and older 03-04 .010 (.009-.012) .009 (.008-.011) .024 (.020-.028) .053 (.044-.063) .077 (.065-.105) 1276

Gender 

Males 03-04 .008 (.007-.010) .008 (.006-.010) .019 (.017-.023) .039 (.032-.051) .063 (.042-.077) 925

Females 03-04 .009 (.007-.010) .008 (.006-.009) .024 (.016-.032) .057 (.049-.064) .092 (.068-.134) 929

Race/ethnicity 

Mexican Americans 03-04 * < LOD .007 (.005-.010) .018 (.010-.023) .024 (.018-.035) 416

Non-Hispanic blacks 03-04 .009 (.008-.010) .008 (.006-.009) .022 (.018-.027) .065 (.039-.077) .097 (.065-.144) 455

Non-Hispanic whites 03-04 .009 (.008-.011) .009 (.007-.011) .024 (.020-.029) .053 (.044-.061) .076 (.063-.099) 864

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 374 Fourth National Report on Human Exposure to Environmental Chemicals 

Non-Dioxin-Like Polychlorinated Biphenyls

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Roegge CS, Morris JR, Villareal S, Wang VC, Powers BE, 

Klintsova AY, et al. Purkinje cell and cerebellar effects following 

developmental exposure to PCBs and/or MeHg. Neurotoxicol 

Teratol 2006;28(1):74-85.

Ross G. The public health implications of polychlorinated 

biphenyls (PCBs) in the environment. Ecotoxicol Environ Saf 

2004;59(3):275-291.

Sagiv SK, Tolbert PE, Altshul LM, Korrick SA. Organochlorine 

exposures during pregnancy and infant size at birth. Epidemiology 

2007;18(1):120-129.

Sala M, Ribas-Fito N, Cardo E, de Muga ME, Marco E, Mazon 

C, et al. Levels of hexachlorobenzene and other organochlorine 

compounds in cord blood: exposure across placenta. Chemosphere 

2001;43:895-901.

Toft G, Rignell-Hydbom A, Tyrkiel E, Shvets M, Giwercman 

A, Lindh CH, et al. Semen quality and exposure to persistent 

organochlorine pollutants. Epidemiology 2006;17(4):450-548.

Turci R, Finozzi E, Catenacci G, Marinaccio A, Balducci C, 

Minoia C. Reference values of coplanar and non-coplanar PCBs 

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183.

United States Environmental Protection Agency (U.S.EPA). 

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Fourth National Report on Human Exposure to Environmental Chemicals 377

 Dioxin-Like Chemicals

Dioxin-Like Chemicals: Polychlorinated 

Dibenzo-p-dioxins, Polychlorinated 

Dibenzofurans, and Coplanar and 

Mono-ortho-substituted Polychlorinated 

Biphenyls

General Information

Polychlorinated dibenzo-p-dioxins and dibenzofurans are 

two similar classes of chlorinated aromatic chemicals that 

are produced as contaminants or by-products. They have 

no known commercial or natural use. Dioxins are produced 

primarily during the incineration or burning of waste; the 

bleaching processes used in pulp and paper mills; and 

the chemical syntheses of trichlorophenoxyacetic acid, 

hexachlorophene, vinyl chloride, trichlorophenol, and 

pentachlorophenol. Both the synthesis and heat-related 

degradation of polychlorinated biphenyls (PCBs) will 

produce dibenzofuran byproducts. Releases from industrial 

sources have decreased approximately 80% since the 

1980s (U.S. EPA, 2004). Today, the largest release of these 

chemicals occurs as a result of the open burning of household and municipal trash, landfill fires, and agricultural and 

forest fires. When advanced analytical techniques are used, 

most soil and water samples will reveal trace amounts of 

polychlorinated dibenzo-p-dioxins and dibenzofurans.

The coplanar and mono-ortho-substituted PCBs are 

chlorinated aromatic hydrocarbon chemicals that belong to 

the general class PCBs which were once synthesized for use 

as heat-exchanger, transformer, and hydraulic fluids, and 

also used as additives to paints, oils, window caulking, and 

floor tiles. Production of PCBs peaked in the early 1970s 

and was banned in the United States after 1979. Together 

Dioxin-like Chemicals in this Report

Polychlorinated dibenzo-p-dioxins CAS 

number 

1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) 35822-46-9 

1,2,3,4,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) 39227-28-6 

1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) 57653-85-7 

1,2,3,7,8,9-Hexachlorodibenzo-p-dioxin (HxCDD) 19408-74-3 

1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin (OCDD) 3268-87-9 

1,2,3,7,8-Pentachlorodibenzo-p-dioxin (PeCDD) 40321-76-4 

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) 1746-01-6 

Polychlorinated dibenzofurans CAS 

number 

1,2,3,4,6,7,8-Heptachlorodibenzofuran (HpCDF) 67562-39-4 

1,2,3,4,7,8,9-Heptachlorodibenzofuran (HpCDF) 55673-89-7 

1,2,3,4,7,8-Hexachlorodibenzofuran (HxCDF) 70648-26-9 

1,2,3,6,7,8-Hexachlorodibenzofuran (HxCDF) 57117-44-9 

1,2,3,7,8,9-Hexachlorodibenzofuran (HxCDF) 72918-21-9 

2,3,4,6,7,8-Hexchlorodibenzofuran (HxCDF) 60851-34-5 

1,2,3,4,6,7,8,9-Octachlorodibenzofuran (OCDF) 39001-02-0 

1,2,3,7,8-Pentachlorodibenzofuran (PeCDF) 57117-41-6 

2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) 57117-31-4 

2,3,7,8-Tetrachlorodibenzofuran (TCDF) 51207-31-9 

Coplanar polychlorinated biphenyls (IUPAC number) CAS 

number 

3,4,4',5-Tetrachlorobiphenyl (PCB 81) 70362-50-4 

3,3',4,4',5-Pentachlorobiphenyl (PCB 126) 57465-28-8 

3,3',4,4',5,5'-Hexachlorobiphenyl (PCB 169) 32774-16-6 

Mono-ortho-substituted polychlorinated biphenyls (IUPAC number) CAS 

number 

2,3,3',4,4'-Pentachlorobiphenyl (PCB 105) 32598-14-4 

2,3',4,4',5-Pentachlorobiphenyl (PCB 118) 31508-00-6 

2,3,3',4,4',5-Hexachlorobiphenyl (PCB 156) 38380-08-4 

2,3,3',4,4',5'-Hexachlorobiphenyl (PCB 157) 69782-90-7 

2,3',4,4',5,5'-Hexachlorobiphenyl (PCB 167) 52663-72-6 

2,3,3',4,4',5,5'-Heptachlorobiphenyl (PCB 189) 39635-31-9 
 378 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

with the polychlorinated dioxins and furans, these two 

special classes of PCBs are often referred to as “dioxin-like” 

chemicals because they act in the body through a similar 

mechanism. Structural nomenclature is available at: http://

www.epa.gov/oswer/riskassessment/pdf/1340-erasc-003.

pdf. Commonly measured polychlorinated dibenzo-pdioxins, polychlorinated dibenzofurans, and coplanar and 

mono-ortho-substituted PCBs are listed in the table.

In the environment, these dioxin-like chemicals are persistent 

and usually occur as a mixture of congeners (i.e., compounds 

that differ by the numbers and positions of chlorine atoms 

attached to the dibenzo-p-dioxin, dibenzofuran, or biphenyl 

structures). The general population is exposed to low levels 

of polychlorinated dibenzo-p-dioxins and dibenzofurans 

primarily through ingestion of high-fat foods such as 

dairy products, eggs, and animal fats, and some fish and 

wildlife. Dioxin-like chemicals are measurable in U.S. 

meats and poultry (Hoffman et al., 2006) as a result of the 

accumulation of these substances in the food chain. Breast 

milk is a substantial source of exposure for infants (Beck 

et al., 1994; Lundqvist et al., 2006), though breast milk 

levels have been decreasing in recent years (Arisawa et 

al., 2005). The lesser chlorinated PCBs, including some 

dioxin-like PCBs, are more volatile. These PCBs can enter 

air of buildings containing joint sealants made with PCBs 

prior to 1980 and can increase background serum levels 

via inhalational exposure (Johansson et al., 2003; Kohler 

et al., 2005). Volatilization of PCBs from nearby hazardous 

waste sites may also contribute to human inhalational 

exposure. Exposure to high levels of these chemicals has 

occurred in the past as a result of industrial accidents (e.g., 

after an explosion in a factory in Seveso, Italy); the use of 

accidentally contaminated cooking oils (e.g., as occurred 

in Yusho in Japan and Yucheng in Taiwan); the spraying of 

herbicides contaminated with 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) (e.g., as Agent Orange in Vietnam); and the 

burning of PCBs producing polychlorinated dibenzofurans 

Serum 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 58.2 (<LOD-63.6) 86.0 (75.5-96.7) 112 (101-131) 1894 

01-02 39.0 (33.7-45.0) 40.2 (34.9-46.9) 68.7 (56.7-82.2) 115 (88.2-138) 147 (126-181) 1220 

03-04 25.3 (23.4-27.3) 24.9 (22.8-26.9) 42.5 (38.8-48.1) 70.4 (62.7-80.1) 91.3 (73.5-117) 1874 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD 63.6 (<LOD-75.6) 657

01-02 † † † † † †

03-04 16.7 (15.1-18.4) 16.4 (15.1-18.3) 23.6 (21.5-25.8) 33.4 (28.6-36.8) 46.7 (34.5-78.1) 586

20 years and older 99-00 * < LOD 62.0 (57.1-66.7) 92.9 (81.2-101) 120 (102-139) 1237 

01-02 39.0 (33.7-45.0) 40.2 (34.9-46.9) 68.7 (56.7-82.2) 115 (88.2-138) 147 (126-181) 1220 

03-04 26.8 (24.6-29.2) 27.3 (24.6-29.0) 45.6 (41.3-53.2) 73.7 (64.1-88.6) 95.0 (76.1-126) 1288 

Gender 

Males 99-00 * < LOD < LOD 73.6 (69.0-80.8) 94.7 (83.1-103) 910

01-02 36.6 (31.7-42.3) 39.0 (33.3-42.6) 62.1 (49.7-75.0) 102 (75.8-132) 138 (103-169) 553

03-04 24.2 (21.7-27.0) 23.2 (21.1-25.6) 40.6 (35.3-46.9) 64.2 (58.8-73.7) 85.0 (65.8-113) 920

Females 99-00 * < LOD 62.7 (<LOD-69.1) 102 (86.0-118) 131 (111-164) 984

01-02 41.2 (34.9-48.7) 43.6 (35.3-52.4) 76.0 (59.5-90.1) 125 (93.4-150) 158 (130-191) 667

03-04 26.3 (24.4-28.3) 26.8 (24.3-28.3) 44.4 (41.1-50.2) 76.1 (65.3-89.1) 95.7 (80.7-128) 954

Race/ethnicity 

Mexican Americans 99-00 * < LOD 61.4 (<LOD-69.0) 97.7 (82.8-111) 132 (108-159) 621

01-02 39.6 (35.7-43.9) 39.7 (33.6-47.4) 64.0 (55.8-74.7) 107 (82.4-128) 149 (111-171) 262

03-04 25.8 (22.6-29.4) 26.1 (20.9-30.9) 41.9 (36.7-44.7) 61.0 (49.7-71.9) 80.1 (65.0-89.1) 424

Non-Hispanic blacks 99-00 * < LOD 58.1 (<LOD-71.1) 95.0 (75.1-110) 125 (102-183) 408

01-02 43.7 (35.4-54.0) 42.8 (32.2-59.8) 80.6 (60.9-106) 134 (101-166) 167 (130-230) 218

03-04 25.8 (22.6-29.4) 23.7 (20.7-27.1) 41.2 (32.6-56.4) 69.2 (54.6-115) 115 (67.1-164) 454

Non-Hispanic whites 99-00 * < LOD 59.0 (<LOD-64.8) 84.9 (72.0-97.0) 106 (96.7-122) 709

01-02 39.3 (33.0-46.8) 40.5 (34.0-50.1) 71.0 (56.3-87.5) 117 (87.1-147) 147 (125-186) 657

03-04 25.0 (22.6-27.7) 24.6 (22.3-27.4) 42.6 (39.4-48.5) 73.5 (60.4-86.7) 93.7 (71.6-127) 875

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 55.9, 10.3, and 13.0, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 379

 Dioxin-Like Chemicals

(e.g., such as from electrical transformer fires). Workplace 

exposures are infrequent today, but incineration plant 

workers and chemical synthesis workers can be exposed via 

inhalation and dust exposures. The dioxin-like chemicals 

are easily absorbed, tend to distribute into body fat, have 

limited metabolism, and slow elimination from the body. 

Serum levels may be influenced by both past (stored in 

body fat) and recent exposures, though the current intakes 

for most people are now low. Half-lives of the dioxins and 

furans in the body vary from three to 19 years, with the 

half-life of TCDD estimated at around seven years (Geyer 

et al., 2002).

Because exposure to these chemicals includes a mixture of 

varying congeners, congener-specific effects are difficult to 

determine (Masuda, 2001; Masuda et al., 1998). However, 

these four groups of chemicals (polychlorinated dibenzop-dioxins, polychlorinated dibenzofurans, and the coplanar 

and mono-ortho- substituted PCBs) are considered to act 

through a similar mechanism to produce toxic effects. These 

dioxin-like effects are thought to result from interaction 

with the aryl hydrocarbon receptor (AhR), particularly in 

the induction of gene expression for cytochromes P450, 

CYP1A1 and CYP1A2. Dioxins and furans have a planar 

configuration and require four lateral chlorine atoms 

(2,3,7,8 positions) on the dibenzo-p-dioxin or dibenzofuran 

backbone to bind this receptor. The rank order of interaction 

with the AhR receptor by degree and position of chlorination 

is roughly similar for both the dioxin and furan series. The 

coplanar polychlorinated biphenyls (unsubstituted at ortho

positions) and the mono-ortho-substituted polychlorinated 

biphenyls (which contain a chlorine atom at one of the 

ortho positions) can achieve a planar configuration and also 

interact with the AhR receptor. The variation in the effect 

on AhR among the dioxin-like chemicals is 10,000-fold, 

with TCDD and 1,2,3,7,8-pentachlorodibenzo-p-dioxin 

being the most potent. To compare potency, each of these 

congeners has been assigned a potency value relative to 

Serum 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 354 (<LOD384) 564 (501-617) 749 (646-869) 1894 

01-02 252 (219-289) 267 (232-305) 440 (376-529) 779 (591-989) 1030 (840-1290) 1220 

03-04 155 (143-167) 150 (134-163) 288 (242-319) 465 (399-550) 618 (516-787) 1874 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD 289 (<LOD340) 657

01-02 † † † † † †

03-04 84.6 (77.4-92.5) 83.9 (76.1-92.0) 118 (106-131) 165 (139-185) 210 (176-319) 586

20 years and older 99-00 * < LOD 385 (354-418) 610 (534-677) 802 (681-936) 1237 

01-02 252 (219-289) 267 (232-305) 440 (376-529) 779 (591-989) 1030 (840-1290) 1220 

03-04 169 (155-184) 170 (150-186) 314 (267-348) 506 (419-576) 628 (546-810) 1288 

Gender 

Males 99-00 * < LOD < LOD 489 (436-543) 613 (535-681) 910

01-02 243 (211-279) 245 (213-291) 422 (349-527) 766 (536-976) 983 (766-1260) 553

03-04 150 (135-167) 144 (129-161) 273 (236-305) 424 (365-516) 554 (440-667) 920

Females 99-00 * < LOD 373 (<LOD428) 637 (562-802) 907 (806-1040) 984

01-02 260 (221-306) 281 (236-324) 466 (386-551) 795 (621-997) 1140 (849-1330) 667

03-04 159 (147-172) 158 (138-170) 303 (249-345) 520 (429-591) 623 (545-848) 954

Race/ethnicity 

Mexican Americans 99-00 * < LOD 372 (<LOD404) 598 (546-657) 849 (657-1020) 621

01-02 254 (232-278) 249 (229-286) 403 (360-521) 791 (643-929) 988 (817-1240) 262

03-04 158 (139-180) 159 (138-193) 274 (241-299) 414 (349-469) 556 (451-592) 424

Non-Hispanic blacks 99-00 * < LOD 323 (<LOD391) 567 (422-716) 778 (574-1130) 408

01-02 258 (208-319) 262 (180-339) 478 (343-600) 852 (578-1170) 1170 (821-1660) 218

03-04 148 (128-170) 137 (117-156) 247 (188-344) 434 (345-599) 715 (405-1090) 454

Non-Hispanic whites 99-00 * < LOD 370 (<LOD401) 565 (491-634) 733 (637-816) 709

01-02 255 (216-302) 277 (228-328) 442 (374-547) 782 (551-1020) 1020 (803-1290) 657

03-04 155 (140-170) 152 (131-171) 292 (248-325) 492 (390-571) 621 (506-810) 875

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 380 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

TCDD (toxic equivalency factor [TEF]). When each TEF 

is multiplied by the concentration of the congener, a toxic 

equivalency (TEQ) value is obtained. Thus, the dioxinlike toxicity contributed by each of the polychlorinated 

dibenzo-p-dioxins, dibenzofurans, and PCBs can then be 

compared. The sum of all congener TEQs in a specimen 

(total TEQ) can be used to compare dioxin-like activity 

among specimens. Many of the dioxin-like PCBs have 

lower potency but are found at higher concentrations than 

TCDD (Kang et al., 1997; Patterson et al., 1994, Van den 

Berg et al., 2006), so these less potent chemicals may still 

contribute substantially to the total TEQ.

In animal studies, TCDD and dioxin-like chemicals have 

demonstrated many effects including: altered transcription 

of genes; induction of various enzymes; wasting syndrome; 

hepatotoxicity; altered immune function; testicular 

atrophy; altered thyroid function; chloracne; porphyria; 

neurotoxicity; teratogenicity; and carcinogenicity (EPA, 

2004). Since animal species differ dramatically in sensitivity 

to these chemicals, it is difficult to predict human health 

effects though animal studies have provided support to 

observations of effects in human populations. Health effects 

of exposure to dioxin-like chemicals in people have been 

observed as a result of industrial or accidental exposures 

involving large doses of these chemicals. Chloracne, 

biochemical liver test abnormalities, elevated blood lipids, 

fetal injury, and porphyria cutanea tarda have been reported 

in episodes of high exposure. Developmental effects in 

humans are of concern since congenital anomalies and 

intrauterine growth retardation were observed in offspring 

of Yucheng mothers exposed to cooking oil contaminated 

with electrical oil containing very high levels of PCB and 

polychlorinated dibenzofurans. Environmental serum levels 

of primarily non-dioxin-like PCBs, and some dioxin-like 

chemicals, have been associated with altered psychomotor 

development in newborns and children (Arisawa et al., 

2005; Jacobsen and Jacobsen, 1996; Koopman-Esseboom 

et al., 1996; Longnecker et al., 2003; Lundqvist et al., 2006; 

U.S. EPA, 2004; also see section on Non-Dioxin-Like 

Polychlorinated Biphenyls).

Cross-sectional associations of type II diabetes or markers of 

insulin resistance with serum levels of TCDD, other dioxinlike chemicals, non-dioxin-like PCBs and organochlorine 

pesticides have been reported in both highly exposed and 

environmentally exposed human populations, though some 

studies have not found an association (Calvert et al., 1999; 

Everett et al., 2007; Fierens et al., 2003; Fujiyoshi et al., 

2006; Henriksen et al., 1997; Kang et al., 2006; Kern et al., 

Serum 1,2,3,4,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD 10.7 (<LOD-13.9) 14.9 (11.7-20.0) 1239 

03-04 * < LOD < LOD < LOD < LOD 1861 

Age group 

12-19 years 01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 582

20 years and older 01-02 * < LOD < LOD 10.7 (<LOD-13.9) 14.9 (11.7-20.0) 1239 

03-04 * < LOD < LOD < LOD < LOD 1279 

Gender 

Males 01-02 * < LOD < LOD 10.9 (<LOD-14.3) 14.7 (11.5-17.6) 566

03-04 * < LOD < LOD < LOD < LOD 914

Females 01-02 * < LOD < LOD 10.7 (<LOD-14.1) 15.6 (11.1-23.0) 673

03-04 * < LOD < LOD < LOD < LOD 947

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD 9.20 (<LOD-11.8) 263

03-04 * < LOD < LOD < LOD < LOD 421

Non-Hispanic blacks 01-02 * < LOD < LOD 13.9 (<LOD-17.6) 18.3 (13.9-23.0) 220

03-04 * < LOD < LOD < LOD < LOD 450

Non-Hispanic whites 01-02 * < LOD < LOD 11.3 (<LOD-14.4) 15.1 (12.0-20.5) 672

03-04 * < LOD < LOD < LOD < LOD 870

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 9.0 and 11.9. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 381

 Dioxin-Like Chemicals

2004; Lee et al., 2006; Michalek et al., 1999, and 2003; ) and 

in vitro and in vivo animal studies have provided possible 

mechanistic plausibility. Immune effects of dioxin-like 

chemicals and non-dioxin-like PCBs have been reported 

in animal studies (Carpenter, 2006; U.S.EPA, 2004), but 

few or consistent effects in humans have been observed 

(Baccarelli et al., 2002; Halperin et al., 1998; Jung et al., 

1998; IARC, 1997).

Similar to some other organochlorine-type chemicals, the 

dioxin-like chemicals weakly mimic or interfere with the 

action of estrogen; for instance, dioxin-like chemicals 

may decrease the effect of estrogen through induction of 

its metabolism. This action contrasts with the non-dioxinlike PCBs and their metabolites, which may have direct 

estrogenic action (Carpenter, 2006; Wang et al., 2006; 

Yoshida et al., 2005). Dioxin and other organochlorine 

chemicals have been shown to interfere with male and 

female reproductive development in experimental and wild 

animals, particularly during gestational exposure (Gao et 

al., 1999; Grey and Ostby, 1995; Roman et al., 1998; Sonne 

et al., 2006; Theobald et al., 1997). In studies of women 

with environmental or accidental exposures, associations 

between dioxin-like chemical exposures and various 

reproductive endpoints (Eskenazi et al., 2003; Lawson 

et al., 2004; Schnorr et al., 2001; Warner et al., 2004 and 

2007) and endometriosis (Eskenazi et al., 2002; Fierens et 

al., 2003; Heilier et al., 2005; Hoffman et al., 2007) have 

been either absent or of unknown significance, though 

animal studies have demonstrated reproductive effects at 

high doses (Arisawa et al., 2005; U.S. EPA, 2004). In men, 

lowered levels of testosterone have been associated with 

environmental and occupational exposures to dioxin-like 

chemicals (Dhooge et al., 2006; Egeland et al., 1994; Gupta 

et al., 2006; Henriksen et al., 1996; Johnson et al., 2001; 

Sweeney et al., 1998) and gonadal atrophy and lowered 

testosterone levels have been observed in animal studies.

TCDD is classified separately by the IARC and NTP as a 

known human carcinogen. The U.S. EPA (2004) and IARC 

(1997) concluded that the aggregate evidence supports 

an association between high-dose TCDD exposure (e.g., 

encountered in contaminated occupational settings or 

massive unintentional releases) and increases in the allcancer category (Steenland et al., 2004). The Institute of 

Medicine (2005) concluded that human epidemiologic 

evidence is sufficient for a positive association of 

herbicides contaminated with TCDD and an increased 

risk for non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, 

chronic lymphocytic leukemia, and soft tissue sarcoma. 

Other individual polychlorinated dibenzo-p-dioxins and 

dibenzofurans have not been studied sufficiently for IARC 

Serum 1,2,3,4,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD 74.7 (<LOD-90.7) 105 (81.2-139) 1239 

03-04 * < LOD < LOD < LOD < LOD 1861 

Age group 

12-19 years 01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 582

20 years and older 01-02 * < LOD < LOD 74.7 (<LOD-90.7) 105 (81.2-139) 1239 

03-04 * < LOD < LOD < LOD < LOD 1279 

Gender 

Males 01-02 * < LOD < LOD 73.6 (<LOD-90.7) 105 (77.9-134) 566

03-04 * < LOD < LOD < LOD < LOD 914

Females 01-02 * < LOD < LOD 74.7 (<LOD-90.7) 102 (78.0-152) 673

03-04 * < LOD < LOD < LOD < LOD 947

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD 71.2 (<LOD-118) 263

03-04 * < LOD < LOD < LOD < LOD 421

Non-Hispanic blacks 01-02 * < LOD < LOD 82.1 (<LOD-130) 130 (75.7-184) 220

03-04 * < LOD < LOD < LOD < LOD 450

Non-Hispanic whites 01-02 * < LOD < LOD 77.5 (<LOD-97.1) 105 (78.8-143) 672

03-04 * < LOD < LOD < LOD < LOD 870

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 382 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

to classify their human potential for carcinogenicity, 

although EPA considers these other chemicals as likely 

human carcinogens (U.S.EPA, 2004). Both IARC and NTP 

consider polychlorinated biphenyls as likely and probable 

human carcinogens. Additional information about external 

exposure (i.e., environmental levels) and health effects 

is available from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html and from U.S. EPA at: http://www.epa.gov/

ncea/pdfs/dioxin/nas-review/.

Biomonitoring Information

Serum levels of the dioxin-like chemicals reflect 

accumulated exposure due to their storage in body fat and 

slow elimination. Observed differences between people in 

the levels of these chemicals are due in part to differences 

in environmental exposure. For instance, eating fish 

from the Great Lakes region can contain higher levels of 

certain dioxin-like chemicals, particularly coplanar PCBs 

and therefore can result in mean lipid adjusted serum 

concentrations that are several times background values 

in the U.S. population (Anderson et al., 1998; Falk et al., 

1999; Hanrahan et al., 1999; Turyk et al., 2006). Observed 

differences between people may also be due to longer 

periods of accumulation of these persistent chemicals. 

Several studies have shown that levels of the more highly 

chlorinated dioxins, furans, and PCBs in serum or fat will 

increase with the age of the population studied (Falk et al., 

1999; Geyer et al., 2002; Kang et al., 1997; Luotamo et al., 

1991; Patterson et al., 1986). Many of the dioxins, furans 

and PCBs measured in a representative New Zealand 

population pooled sampling showed an increasing trend 

with age (Bates et al., 2004). Also, in a U.S. representative 

sample from NHANES 1999-2000, participants aged 20 

years and older had higher levels than participants aged 12-

19 years when levels at the higher percentiles of the more 

Serum 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 32.6 (28.3-38.2) 56.9 (47.4-67.3) 74.0 (68.3-82.4) 1885 

01-02 34.6 (29.6-40.6) 39.2 (32.7-44.7) 60.8 (50.3-74.2) 95.2 (76.2-120) 128 (99.4-153) 1234 

03-04 17.2 (15.7-18.9) 20.0 (17.8-22.9) 36.5 (32.2-40.0) 53.0 (48.1-59.6) 68.5 (59.6-74.9) 1871 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD 26.7 (20.2-29.6) 648

01-02 † † † † † †

03-04 * < LOD < LOD 16.1 (14.3-18.1) 19.4 (16.4-27.7) 584

20 years and older 99-00 * < LOD 36.2 (31.5-40.7) 62.8 (53.6-69.1) 75.6 (70.5-84.2) 1237 

01-02 34.6 (29.6-40.6) 39.2 (32.7-44.7) 60.8 (50.3-74.2) 95.2 (76.2-120) 128 (99.4-153) 1234 

03-04 19.7 (17.8-21.8) 23.8 (20.7-26.4) 39.3 (35.4-42.2) 56.6 (49.7-63.8) 70.8 (60.7-82.2) 1287 

Gender 

Males 99-00 * < LOD 31.5 (23.7-38.2) 55.0 (45.7-64.2) 71.3 (59.4-79.4) 908

01-02 34.1 (28.3-41.1) 38.9 (32.1-44.7) 61.9 (50.0-79.5) 94.9 (70.8-131) 130 (88.5-181) 564

03-04 17.5 (15.5-19.8) 19.8 (17.8-21.6) 35.5 (29.8-40.3) 52.9 (45.4-63.2) 70.2 (57.5-88.7) 920

Females 99-00 * < LOD 34.9 (29.1-39.7) 61.2 (51.0-69.2) 74.9 (68.4-92.2) 977

01-02 35.1 (29.9-41.2) 40.1 (32.4-46.3) 59.8 (49.8-72.3) 97.6 (77.1-114) 126 (108-142) 670

03-04 16.9 (15.3-18.6) 20.5 (17.8-24.6) 36.9 (33.2-41.0) 53.6 (48.3-59.6) 65.6 (60.0-73.4) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD 21.3 (<LOD-27.6) 43.3 (34.1-52.3) 58.0 (49.5-64.8) 624

01-02 18.3 (15.6-21.4) 21.2 (19.4-25.0) 31.9 (27.5-40.3) 51.5 (40.3-69.9) 68.3 (48.0-111) 260

03-04 * < LOD 21.1 (16.3-26.5) 32.2 (24.5-47.4) 43.0 (31.5-65.3) 424

Non-Hispanic blacks 99-00 * < LOD 31.9 (26.6-41.2) 56.7 (44.9-74.6) 81.6 (72.2-91.7) 402

01-02 38.9 (33.6-45.0) 40.3 (33.5-47.3) 63.5 (54.6-76.9) 93.9 (78.7-133) 136 (92.6-185) 219

03-04 16.2 (12.9-20.4) 18.1 (14.4-21.6) 34.9 (28.4-42.9) 54.5 (44.4-69.4) 74.0 (54.3-122) 454

Non-Hispanic whites 99-00 * < LOD 35.5 (29.7-40.0) 60.9 (51.4-68.3) 74.3 (68.3-83.0) 703

01-02 37.8 (31.5-45.4) 42.8 (33.9-51.2) 65.0 (52.3-82.9) 99.6 (78.4-130) 131 (103-165) 671

03-04 18.7 (17.0-20.6) 22.9 (19.9-26.2) 38.0 (35.2-41.5) 56.6 (48.7-63.8) 69.0 (60.6-74.9) 872

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 20.1, 9.1, and 12.3, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 383

 Dioxin-Like Chemicals

highly chlorinated congeners were compared (CDC, 2005). 

Similarly, the TEQ increased with age in an analysis of the 

NHANES 2003-2004 subsample (Patterson et al., 2009). 

Other factors also explain differences in levels observed 

between people. In a TEQ analysis of the NHANES 2001-

2002 subsample, the total TEQ increased with age, was 

lower for Mexican Americans than non-Hispanic whites or 

blacks, and was higher in smokers than nonsmokers older 

than 60 years of age (Ferriby et al., 2007). Body mass is 

also a factor associated with increasing levels of some 

polychlorinated dibenzo-p-dioxins (Collins et al., 2007; 

Michalek et al., 1999). Gender is another predictor of levels 

of some dioxin-like chemicals. Compared with Japanese 

men, women had higher levels of octachlorodibenzop-dioxin, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 

and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin, but men 

had higher levels of PCBs 169, 156, and 189 (Arisawa 

et al., 2003). In the NHANES 2001-2002 subsample, 

females had higher adjusted geometric mean levels 

than males for 1,2,3,4,6,7,8-heptachlorodibenzo-pdioxin, and 3,3’,4,4’,5-pentachlorobiphenyl (PCB 126). 

However, males had higher levels than females for 

3,3’,4,4’,5,5’-hexachlorobiphenyl (PCB 169) (CDC, 2005).

The generally low lipid-adjusted levels observed in the 

U.S. representative NHANES subsamples of 1999-2000, 

2001-2002, and 2003-2004 support the observation that 

human serum levels of polychlorinated dibenzo-p-dioxins, 

dibenzofurans, and PCBs have decreased by more than 

80% since the 1980s (Aylward and Hays, 2002; Lorber, 

2002; Patterson et al., 2009). Levels of some dioxin-like 

chemicals, such as the hexachlordibenzo-p-dioxins, were

shown to decrease gradually from 1993 to 2003 in pooled 

samples from children in selected regions of Germany, 

whereas the hexachlordibenzofuran levels showed little 

change (Link et al., 2005). The levels of polychlorinated 

dibenzo-p-dioxins, dibenzofurans, and coplanar and monoortho-substituted biphenyls seen in the U.S. population

Serum 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin (HxCDD) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 202 (168-239) 374 (314-426) 496 (429-571) 1885 

01-02 224 (192-261) 247 (219-287) 412 (347-498) 663 (549-785) 870 (696-1100) 1234 

03-04 105 (95.7-116) 123 (111-136) 240 (219-263) 357 (325-395) 443 (395-487) 1871 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD 126 (93.2-155) 648

01-02 † † † † † †

03-04 * < LOD < LOD 77.6 (67.4-84.8) 94.5 (77.6-122) 584

20 years and older 99-00 * < LOD 232 (196-268) 403 (349-458) 521 (458-607) 1237 

01-02 224 (192-261) 247 (219-287) 412 (347-498) 663 (549-785) 870 (696-1100) 1234 

03-04 124 (112-138) 146 (125-172) 259 (235-285) 376 (334-422) 466 (403-528) 1287 

Gender 

Males 99-00 * < LOD 189 (134-239) 353 (278-417) 449 (378-526) 908

01-02 226 (190-270) 263 (223-301) 425 (347-540) 678 (547-794) 883 (666-1180) 564

03-04 108 (95.4-123) 123 (108-141) 231 (206-261) 351 (286-424) 450 (374-538) 920

Females 99-00 * < LOD 213 (174-263) 400 (344-467) 553 (467-651) 977

01-02 222 (190-260) 239 (207-281) 397 (338-474) 644 (526-771) 864 (720-1060) 670

03-04 103 (92.8-113) 121 (101-142) 249 (225-277) 363 (336-395) 429 (395-512) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD 128 (<LOD-167) 284 (242-334) 380 (328-419) 624

01-02 117 (99.4-139) 130 (107-157) 233 (198-270) 409 (278-524) 524 (384-731) 260

03-04 * < LOD 141 (106-188) 221 (188-337) 327 (210-426) 424

Non-Hispanic blacks 99-00 * < LOD 191 (150-234) 374 (267-424) 477 (389-568) 402

01-02 229 (199-264) 229 (190-284) 371 (333-477) 643 (480-799) 821 (596-1260) 219

03-04 92.9 (73.3-118) 106 (77.0-125) 219 (165-260) 362 (279-460) 461 (372-689) 454

Non-Hispanic whites 99-00 * < LOD 222 (183-270) 403 (346-460) 520 (450-615) 703

01-02 246 (206-293) 275 (233-325) 443 (365-553) 684 (549-870) 897 (718-1150) 671

03-04 116 (105-127) 136 (120-165) 258 (231-286) 375 (333-418) 466 (402-519) 872

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 384 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

are generally well below the levels associated with 

occupational or unintentional exposures that have produced 

health effects. There are no firmly established relationships 

between concentrations (mainly considering TCDD) and 

health effects in people. Observations following industrial 

and accidental exposures have suggested that acute 

exposures resulting in serum concentrations of about 800 

pg/g of lipid might be necessary to induce clinical effects 

such as chloracne, although levels in the thousands of pg/g 

of lipid do not always produce this effect (Mocarelli et al., 

1991). Such studies of clinical effects in people after large 

unintentional exposures have measured concentrations 

ranging from several hundred to the tens of thousands of 

pg/g of lipid of TCDD or equivalent (Eskenazi et al., 2004; 

Masuda, 2001; Masuda et al., 1998; Mocarelli et al., 1991). 

However, it has been suggested that background total 

TEQ for the general population are about 10-100 times 

the TEQ levels associated with a possible risk for adaptive 

or subclinical adverse effects (e.g., endocrine changes) 

(U.S.EPA, 2004).

In general, observations of the levels of dioxin-like 

chemicals across percentiles in the NHANES 2003-2004 

subsample appear roughly similar to previous NHANES 

surveys. Note that for some chemicals, detection rates and 

percentile values will change over survey periods due to 

improvements in analytical methods and limitations of 

sample volume. In keeping with results from reports from 

Germany (Papke et al., 1998), New Zealand (Bates et al., 

2004) and elsewhere, U.S. NHANES subsamples have 

shown that the highly chlorinated and laterally substituted 

congeners are detected most often (CDC, 2005, Patterson et 

al., 2009). The following listed dioxin-like chemicals were 

detectable in greater than 10% of the NHANES 2003-2004 

subsample (those in bold letters were detectable in greater 

than 60% of the subsample). Many of these contribute to a 

Serum 1,2,3,7,8,9-Hexachlorodibenzo-p-dioxin (HxCDD) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1870 

01-02 * < LOD < LOD 12.5 (10.5-15.3) 17.0 (14.3-20.0) 1238 

03-04 * < LOD < LOD < LOD < LOD 1869 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 642

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 585

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1228 

01-02 * < LOD < LOD 12.5 (10.5-15.3) 17.0 (14.3-20.0) 1238 

03-04 * < LOD < LOD < LOD < LOD 1284 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 895

01-02 * < LOD < LOD 12.1 (<LOD-14.8) 15.1 (12.9-18.5) 567

03-04 * < LOD < LOD < LOD < LOD 918

Females 99-00 * < LOD < LOD < LOD < LOD 975

01-02 * < LOD < LOD 13.0 (10.7-16.8) 18.3 (15.7-21.1) 671

03-04 * < LOD < LOD < LOD < LOD 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 618

01-02 * < LOD < LOD 9.60 (<LOD-11.6) 12.2 (<LOD-20.6) 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 396

01-02 * < LOD < LOD 14.6 (11.2-20.0) 19.9 (14.6-23.9) 220

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 701

01-02 * < LOD < LOD 12.9 (9.90-15.9) 17.3 (14.7-20.6) 672

03-04 * < LOD < LOD < LOD < LOD 871

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 20.3, 9.3, and 12.3, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 385

 Dioxin-Like Chemicals

significant portion of the total TEQ. The total TEQ at the 

90th percentile of the U.S. population in NHANES 2003-

2004 was 30.0 pg/g of lipid (Patterson et al. 2009).

	1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin

	1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin

	1,2,3,6,7,8-hexachlorodibenzo-p-dioxin

	1,2,3,7,8-pentachlorodibenzo-p-dioxin

	2,3,7,8-tetachlordibenzo-p-dioxin

	1,2,3,4,6,7,8-heptachlorodibenzofuran

	1,2,3,4,7,8-hexachlorodibenzofuran

	2,3,4,7,8-pentachlorodibenzofuran

	coplanar PCBs 126 and 169

	mono-ortho substituted PCBs 105, 118, 156, 157, 167, 

189

Octachlorodibenzo-p-dioxin

Of the dioxins and furans measured in the U.S. representative 

subsamples of NHANES 1999-2000, 2001-2002, and 

2003-2004, octachlorodibenzo-p-dioxin typically is 

present in the highest concentration, but contributes little 

to the TEQ, with the other commonly detected dioxin 

and furan congeners being more than eight-fold lower in 

concentration. Levels of octachlorodibenzo-p-dioxin that 

were similar to slightly higher than those in these NHANES 

subsamples were seen in a representative pooled sampling 

New Zealander residents aged 15 years and older obtained 

during 1997-1998 and also in a small convenience sample 

of German residents aged 18-71 years in 1996 (Bates et al., 

2004; Papke et al., 1998; CDC, 2005). Similar levels were 

also found in 232 Belgian blood donors in 2000 (Debacker 

et al., 2007).

Hexachlorodibenzo-p-dioxins

The three major hexachlorodibenzo-p-dioxins are assigned 

equal TEF values, but the 1,2,3,6,7,8-hexachlorodibenzop-dioxin often demonstrates multifold higher 

concentrations than the other two hexachlorodibenzoSerum 1,2,3,7,8,9-Hexachlorodibenzo-p-dioxin (HxCDD) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1870 

01-02 * < LOD < LOD 86.5 (68.8-108) 121 (99.5-146) 1238 

03-04 * < LOD < LOD < LOD < LOD 1869 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 642

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 585

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1228 

01-02 * < LOD < LOD 86.5 (68.8-108) 121 (99.5-146) 1238 

03-04 * < LOD < LOD < LOD < LOD 1284 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 895

01-02 * < LOD < LOD 84.1 (<LOD-104) 108 (90.6-142) 567

03-04 * < LOD < LOD < LOD < LOD 918

Females 99-00 * < LOD < LOD < LOD < LOD 975

01-02 * < LOD < LOD 89.8 (67.9-121) 123 (102-157) 671

03-04 * < LOD < LOD < LOD < LOD 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 618

01-02 * < LOD < LOD 74.7 (<LOD-104) 107 (<LOD-167) 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 396

01-02 * < LOD < LOD 92.6 (62.8-126) 123 (82.6-169) 220

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 701

01-02 * < LOD < LOD 88.1 (67.9-119) 124 (96.6-152) 672

03-04 * < LOD < LOD < LOD < LOD 871

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 386 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

p-dioxins; about six-fold higher in the NHANES 2001-

2002 subsample (CDC, 2005). The unadjusted geometric 

mean levels of 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin 

in 2003-2004 and in 2001-2002 were 34.6 vs. 17.2 pg/g 

of lipid, respectively. The geometric mean levels of 

1,2,3,6,7,8-hexachlorodibenzo-p-dioxin in the 2001-2002 

subsample were slightly higher than levels in either the 

German or New Zealand study mentioned above (Bates 

et al., 2004; Papke et al., 1998). A convenience sample of 

Japanese men and women aged 20-76 years studied during 

1996-1997 also showed lower median levels than levels in 

the NHANES 2001-2002 subsample (Arisawa et al., 2003; 

CDC, 2005)

1,2,3,7,8-Pentachlorodibenzo-p-dioxin

In prior NHANES surveys, 1,2,3,7,8-pentachlorodibenzop-dioxin concentrations were nearly 60-fold lower than 

octachlorodibenzo-p-dioxin levels (at the comparable 

percentiles) (CDC, 2005), but because of a 10,000-fold 

greater TEF (equal to that of TCDD), the contribution of 

1,2,3,7,8-pentachlorodibenzo-p-dioxin to the total TEQ 

would be about 160 times greater than the octachlorodibenzop-dioxin. Levels of 1,2,3,7,8-pentachlorodibenzo-p-dioxin 

for the total population at the 95th percentile in the NHANES 

2001-2002 and 2003-2004 subsamples were 15.8 pg/g and 

11.0 pg/g lipid, respectively. In 1996, a convenience sample 

of German residents aged 18-71 years showed that levels of 

1,2,3,7,8-pentachlorodibenzo-p-dioxin at the 95th percentile 

were 9.9 pg/g lipid (Papke et al., 1998). The 95th percentile 

of a group of workers with distant past trichlorophenol 

exposure was about twice as high as the 95th percentile for 

adults in NHANES 2001-2002 (CDC, 2005; Collins et al., 

2006)

2,3,7,8-Tetrachlorodibenzo-p-dioxin

TCDD is considered the most potent of the dioxin-like 

Serum 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin (OCDD) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 406 (359-453) 674 (597-767) 913 (787-1010) 1921 

01-02 346 (<LOD-394) 333 (<LOD-402) 573 (498-668) 944 (780-1090) 1260 (998-1610) 1171 

03-04 * < LOD 336 (283-389) 582 (490-658) 767 (645-913) 1851 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD 421 (363-517) 667

01-02 † † † † † †

03-04 * < LOD < LOD 244 (<LOD-330) 352 (264-458) 581

20 years and older 99-00 * < LOD 445 (389-496) 710 (624-802) 948 (822-1080) 1254 

01-02 346 (<LOD-394) 333 (<LOD-402) 573 (498-668) 944 (780-1090) 1260 (998-1610) 1171 

03-04 220 (<LOD-244) 223 (<LOD-243) 358 (297-421) 597 (502-719) 794 (665-978) 1270 

Gender 

Males 99-00 * < LOD < LOD 517 (447-580) 704 (563-838) 919

01-02 * < LOD 442 (346-579) 767 (593-968) 1030 (837-1240) 517

03-04 * < LOD 270 (244-320) 457 (377-559) 668 (501-856) 910

Females 99-00 * < LOD 504 (422-579) 802 (674-928) 1010 (928-1180) 1002 

01-02 410 (356-472) 405 (335-502) 647 (574-751) 1020 (858-1360) 1450 (1060-1780) 654

03-04 235 (<LOD-256) 238 (225-248) 402 (321-486) 640 (551-749) 829 (675-1020) 941

Race/ethnicity 

Mexican Americans 99-00 * < LOD 418 (365-502) 703 (610-873) 940 (737-1230) 632

01-02 * < LOD 432 (394-545) 755 (578-1220) 1150 (696-1640) 250

03-04 * < LOD 296 (225-356) 452 (363-540) 588 (417-861) 419

Non-Hispanic blacks 99-00 * < LOD 444 (371-519) 741 (566-983) 1120 (799-1560) 411

01-02 421 (352-503) 420 (339-509) 682 (537-907) 1110 (956-1520) 1640 (1130-1900) 210

03-04 * < LOD 345 (276-455) 642 (513-883) 926 (636-1310) 448

Non-Hispanic whites 99-00 * < LOD 391 (333-452) 625 (562-754) 861 (676-1010) 721

01-02 349 (<LOD-409) 335 (<LOD-421) 574 (496-679) 945 (764-1170) 1290 (972-1660) 632

03-04 * < LOD 343 (282-403) 585 (464-674) 758 (635-922) 865

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 329.0, 319.0, and 218.0, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 387

 Dioxin-Like Chemicals

chemicals and environmental exposure usually results in 

very low serum concentrations. In the NHANES 2003-

2004 subsample, the 95th percentile for the total population 

(12 years and older) was 5.2 picograms/gram (pg/g) of 

lipid. In 1996, the 95th percentile for lipid adjusted serum 

TCDD levels in 139 Germans aged 18-71 years was 4.3 

pg/g of lipid, with that percentile comprising mainly older 

individuals (Papke, 1998). In contrast, the most highly 

exposed females following the Seveso, Italy, factory 

explosion in 1976 had median lipid adjusted levels of 272 

pg/g lipid (Eskenazi et al., 2004). TCDD levels in chemical 

plant workers with higher exposures have ranged as high as 

2,000 pg/g lipid (IARC, 1997). Median serum TCDD levels 

measured in chemical production workers 15 years after 

workplace exposure ended were 68 pg/g of lipid (Calvert 

et al., 1996; Calvert et al., 1999). TCDD levels in the U.S. 

general population were also lower than workers with past 

trichlorophenol exposure (Collins et al., 2006) and lower 

than Vietnam veterans 20 years after duty-related exposure 

to Agent Orange (median serum TCDD concentration was 

12.2 pg/g of lipid) (Henriksen et al., 1997).

Polychlorinated dibenzofurans

Of the polychlorinated dibenzofurans, the following 

could be characterized at the 95th percentiles (or lower) 

in the NHANES 1999-2000, 2001-2002 and 2003-2004 

subsamples: 1,2,3,4,6,7,8-heptachlorodibenzofuran, 

1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,6,7,8-hexachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran. 

Generally, these levels are similar to other large population 

studies. In 237 workers with past exposure to trichlorophenol, where little polychlorinated dibenzofuran exposure 

would be expected, higher percentiles values were similar 

to a referent population and to the NHANES 1999-2000 

and 2001-2002 subsamples (Collins et al., 2007; CDC, 

2005). In 232 Belgian blood donors from the year 2000, the 

geometric mean level of 1,2,3,4,6,7,8-heptachlorodibenzofuran was several times lower than the geometric mean 

Serum 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin (OCDD) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 2530 (2230-2880) 4260 (3770-4760) 5950 (5090-6790) 1921 

01-02 2230 (<LOD-2540) 2170 (<LOD-2550) 3860 (3180-4520) 6460 (5140-8290) 9110 (6940-11400) 1171 

03-04 * < LOD 2180 (1830-2540) 3760 (3100-4540) 5020 (4190-6070) 1851 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD 1910 (1600-2340) 667

01-02 † † † † † †

03-04 * < LOD < LOD 1160 (<LOD1590) 1780 (1160-2850) 581

20 years and older 99-00 * < LOD 2810 (2480-3110) 4570 (4100-5020) 6200 (5340-7300) 1254 

01-02 2230 (<LOD-2540) 2170 (<LOD-2550) 3860 (3180-4520) 6460 (5140-8290) 9110 (6940-11400) 1171 

03-04 1380 (<LOD-1540) 1360 (<LOD-1470) 2350 (1970-2900) 4030 (3370-4700) 5340 (4490-6370) 1270 

Gender 

Males 99-00 * < LOD < LOD 3160 (2760-3760) 4160 (3320-5570) 919

01-02 * < LOD 3160 (2410-4070) 5270 (4070-7140) 7620 (6020-9760) 517

03-04 * < LOD 1780 (1540-2070) 3090 (2410-4020) 4190 (3410-5350) 910

Females 99-00 * < LOD 3110 (2680-3560) 5090 (4610-5740) 6760 (5870-8710) 1002 

01-02 2590 (2250-2980) 2620 (2160-3000) 4340 (3880-4860) 6990 (5870-9040) 10000 (7070-12300) 654

03-04 1420 (<LOD-1560) 1410 (1300-1510) 2700 (2210-3030) 4340 (3750-4830) 5770 (4590-6740) 941

Race/ethnicity 

Mexican Americans 99-00 * < LOD 2470 (2240-2990) 4350 (3660-5570) 6560 (5340-7590) 632

01-02 * < LOD 3410 (2760-3860) 5810 (4250-7670) 8050 (5760-11800) 250

03-04 * < LOD 1880 (1560-2220) 3240 (2450-3880) 3910 (3240-4630) 419

Non-Hispanic blacks 99-00 * < LOD 2520 (2090-2950) 4770 (4040-5740) 7140 (4740-10700) 411

01-02 2480 (2050-3000) 2460 (2060-2970) 4170 (3160-5560) 7250 (5470-9920) 9920 (7990-12000) 210

03-04 * < LOD 2150 (1780-2880) 3860 (3080-5640) 5720 (3750-7830) 448

Non-Hispanic whites 99-00 * < LOD 2560 (2160-2910) 4120 (3580-4780) 5800 (4740-6790) 721

01-02 2270 (<LOD-2660) 2200 (<LOD-2770) 3860 (3090-4720) 6530 (4890-8860) 9150 (6630-12300) 632

03-04 * < LOD 2220 (1830-2700) 3770 (3040-4680) 5050 (4190-6350) 865

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 388 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

value in the NHANES 2001-2002 subsample of adults and 

the other dibenzofurans examined in the Belgian donors 

were lower than the limits of detection in NHANES 2000-

2001 (CDC, 2005; Debacker et al., 2007). In Yucheng rice 

oil contamination victims when examined 15 years after 

their exposure, levels of the polychlorinated dibenzofurans 

were still hundreds of times higher than in levels for the 

U.S. population observed in the NHANES subsamples in 

this Report (Hsu et al., 2005).

Coplanar PCBs

The coplanar PCBs typically contribute less than about 

15% to the total TEQ in the U.S. population (Ferriby et 

al., 2007). In the NHANES 2001-2002 subsample, the 

geometric mean levels of PCBs 126 and 169 for adults 

aged 20 years and older were similar or slightly lower 

than those reported from a representative pooled sample of 

New Zealanders in 1996-1997 (Bates et al., 2004; CDC, 

2005) and from a smaller sample of non-occupationally 

exposed men and women aged 20-76 years in Japan in 1999 

(Arisawa et al., 2003). Higher levels of these PCBs have 

been reported for persons consuming sport fish caught in the 

Great Lakes region (Turyk et al., 2006). In 311 residents of 

northern Italy, serum PCB 126 and 169 were not detectable, 

though other PCBs tended to be higher than in the recent 

NHANES subsamples (Apostoli et al., 2005; CDC, 2005).

Mono-ortho-substituted PCBs

Of the mono-ortho-substituted PCB congeners, the most 

frequently detected in general population studies are PCBs 

118 and 156. Of these, PCB 118 levels were higher than 

levels of PCB 156 in the NHANES 1999-2000, 2001-

2002, and 2003-2004 subsamples, although PCB 156 

contributes more to the TEQ because its TEF is five-fold 

greater than the TEF of PCB 118. Although these PCBs are 

relatively less potent (i.e., lower TEFs), their contribution 

Serum 1,2,3,7,8-Pentachlorodibenzo-p-dioxin (PeCDD) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1915 

01-02 * < LOD < LOD 11.3 (9.30-13.6) 15.8 (13.3-19.8) 1236 

03-04 * < LOD 6.10 (5.50-6.80) 9.00 (8.30-9.70) 11.0 (9.90-12.2) 1878 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 659

01-02 † † † † † †

03-04 * < LOD < LOD < LOD 4.80 (<LOD-5.90) 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1256 

01-02 * < LOD < LOD 11.3 (9.30-13.6) 15.8 (13.3-19.8) 1236 

03-04 * < LOD 6.60 (5.90-7.20) 9.30 (8.60-10.1) 11.3 (10.1-12.7) 1290 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 920

01-02 * < LOD < LOD 10.8 (9.10-13.3) 14.5 (11.7-19.4) 564

03-04 * < LOD 5.90 (5.30-6.40) 8.90 (7.90-9.60) 11.0 (9.60-12.7) 923

Females 99-00 * < LOD < LOD < LOD < LOD 995

01-02 * < LOD 6.10 (<LOD-7.80) 11.8 (9.40-14.3) 16.6 (13.7-20.8) 672

03-04 * < LOD 6.50 (5.70-7.20) 9.10 (8.30-10.1) 11.0 (10.0-12.2) 955

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 632

01-02 * < LOD < LOD < LOD 8.70 (<LOD-12.7) 262

03-04 * < LOD < LOD 6.50 (5.20-7.90) 7.80 (6.70-9.20) 425

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD 7.70 (<LOD-9.30) 13.9 (9.60-18.4) 18.4 (14.2-24.0) 218

03-04 * < LOD 6.40 (5.30-8.20) 9.90 (8.50-13.4) 14.4 (9.60-20.1) 455

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 717

01-02 * < LOD < LOD 11.7 (9.50-14.3) 16.7 (13.6-20.2) 672

03-04 * < LOD 6.50 (5.80-7.10) 9.30 (8.60-10.0) 11.1 (10.1-12.2) 877

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 14.2, 6.0, and 4.5, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 389

 Dioxin-Like Chemicals

to the total TEQ in the U.S. population is about 25% 

(Ferriby et al., 2007) since they are present in much higher 

concentrations than are the coplanar PCBs, dioxins, and 

furans. In a convenience sample of the U.S. population in 

1988 (Patterson et al., 1994), levels of PCB 118 were fivefold higher than in the NHANES 1999-2002 subsamples 

(CDC, 2005). Comparable levels of PCB 156 levels in 

NHANES 1999-2000 are slightly lower than those reported 

for a Canadian population study in 1994 (Longnecker 

et al., 2000). In a referent population of 311 residents in 

northern Italy during 2001-2003, the 95th percentile levels 

of PCB 156 and PCB 118 were two to threefold higher than 

for the NHANES 1999-2002 subsamples (Apostoli et al., 

2005; CDC, 2005). Levels of PCB 156 and PCB 118 were 

slightly higher in a Swedish study of 150 men than in the 

NHANES 1999-2000 subsample, possibly due to higher 

fish intake in the Swedish population (Glynn et al., 2000; 

CDC, 2005). However, in fish-consuming Japanese men 

and women studied during 1996-1997, PCB 118 levels at 

the 75th percentile were similar to levels in the NHANES 

2001-2002 subsample (Arisawa et al., 2003).

Finding a measurable amount of one or more of the 

polychlorinated dibenzo-p-dioxins, dibenzofurans, 

coplanar or mono-ortho-substituted biphenyls in serum does 

not mean that the level of one or more of these chemicals 

causes an adverse health effect. Biomonitoring studies of 

serum polychlorinated dibenzo-p-dioxins, dibenzofurans, 

coplanar or mono-ortho-substituted biphenyls provide 

physicians and public health officials with reference values 

so that they can determine whether or not people have 

been exposed to higher levels of polychlorinated dibenzop-dioxins, dibenzofurans, coplanar or mono-orthosubstituted biphenyls than levels found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Serum 1,2,3,7,8-Pentachlorodibenzo-p-dioxin (PeCDD) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1915 

01-02 * < LOD < LOD 77.8 (62.8-96.3) 117 (90.3-133) 1236 

03-04 * < LOD 40.7 (37.4-43.0) 60.3 (53.2-67.4) 76.1 (66.9-87.4) 1878 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 659

01-02 † † † † † †

03-04 * < LOD < LOD < LOD 23.8 (<LOD-27.2) 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1256 

01-02 * < LOD < LOD 77.8 (62.8-96.3) 117 (90.3-133) 1236 

03-04 * < LOD 43.0 (39.2-47.8) 63.5 (55.6-71.5) 80.7 (67.9-89.9) 1290 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 920

01-02 * < LOD < LOD 76.1 (54.7-93.7) 107 (83.5-133) 564

03-04 * < LOD 39.3 (35.1-43.4) 57.3 (49.3-66.1) 67.8 (58.7-90.4) 923

Females 99-00 * < LOD < LOD < LOD < LOD 995

01-02 * < LOD 37.8 (<LOD-50.2) 80.4 (62.9-107) 121 (85.7-167) 672

03-04 * < LOD 41.8 (37.7-45.2) 63.6 (55.9-72.9) 80.7 (70.5-88.3) 955

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 632

01-02 * < LOD < LOD < LOD 66.0 (<LOD-111) 262

03-04 * < LOD < LOD 44.5 (34.2-52.0) 52.8 (44.5-76.6) 425

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD 43.8 (<LOD-53.8) 81.9 (58.2-117) 123 (81.9-169) 218

03-04 * < LOD 39.7 (30.6-48.0) 67.3 (48.0-93.0) 93.0 (66.7-137) 455

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 717

01-02 * < LOD < LOD 80.8 (61.6-107) 121 (88.6-142) 672

03-04 * < LOD 42.6 (38.6-45.1) 63.4 (55.4-67.9) 78.8 (67.9-84.7) 877

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 390 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1898 

01-02 * < LOD < LOD < LOD < LOD 1228 

03-04 * < LOD < LOD 4.10 (<LOD-4.40) 5.20 (4.30-5.80) 1876 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 658

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1240 

01-02 * < LOD < LOD < LOD < LOD 1228 

03-04 * < LOD < LOD 4.30 (3.90-4.60) 5.30 (4.50-6.10) 1288 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 912

01-02 * < LOD < LOD < LOD < LOD 559

03-04 * < LOD < LOD < LOD 4.60 (3.80-5.30) 921

Females 99-00 * < LOD < LOD < LOD < LOD 986

01-02 * < LOD < LOD < LOD 6.40 (<LOD-9.20) 669

03-04 * < LOD < LOD 4.40 (4.00-4.90) 5.50 (4.50-6.60) 955

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 630

01-02 * < LOD < LOD < LOD < LOD 262

03-04 * < LOD < LOD < LOD 3.80 (<LOD-5.50) 424

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 404

01-02 * < LOD < LOD < LOD 7.50 (<LOD-10.0) 217

03-04 * < LOD < LOD 4.50 (<LOD-6.10) 6.20 (4.40-10.3) 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 709

01-02 * < LOD < LOD < LOD < LOD 665

03-04 * < LOD < LOD 4.10 (<LOD-4.50) 5.20 (4.30-5.90) 877

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.1, 5.8, and 3.8, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 391

 Dioxin-Like Chemicals

Serum 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1898 

01-02 * < LOD < LOD < LOD < LOD 1228 

03-04 * < LOD < LOD 27.5 (<LOD-30.1) 34.1 (30.2-39.6) 1876 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 658

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 588

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1240 

01-02 * < LOD < LOD < LOD < LOD 1228 

03-04 * < LOD < LOD 28.6 (26.4-31.2) 36.4 (31.5-42.7) 1288 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 912

01-02 * < LOD < LOD < LOD < LOD 559

03-04 * < LOD < LOD < LOD 28.8 (25.4-34.5) 921

Females 99-00 * < LOD < LOD < LOD < LOD 986

01-02 * < LOD < LOD < LOD 50.7 (<LOD-74.3) 669

03-04 * < LOD < LOD 30.2 (27.4-33.1) 38.7 (32.3-44.5) 955

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 630

01-02 * < LOD < LOD < LOD < LOD 262

03-04 * < LOD < LOD < LOD 23.6 (<LOD-32.5) 424

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 404

01-02 * < LOD < LOD < LOD 55.6 (<LOD-72.0) 217

03-04 * < LOD < LOD 31.1 (<LOD-42.0) 42.4 (29.5-67.8) 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 709

01-02 * < LOD < LOD < LOD < LOD 665

03-04 * < LOD < LOD 28.0 (<LOD-30.0) 33.6 (31.1-38.8) 877

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 392 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 1,2,3,4,6,7,8-Heptachlorodibenzofuran (HpCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 14.7 (<LOD-18.0) 19.5 (17.4-23.0) 1709 

01-02 9.64 (8.53-10.9) 10.3 (8.80-11.7) 14.6 (12.7-16.7) 21.3 (18.0-25.5) 27.1 (22.5-32.0) 1219 

03-04 * < LOD 10.6 (9.90-11.4) 14.6 (13.1-16.5) 18.7 (16.5-24.2) 1858 

Age group 

12-19 years 99-00 * < LOD < LOD 18.4 (16.2-20.9) 24.7 (20.9-28.1) 600

01-02 † † † † † †

03-04 9.36 (8.60-10.2) 8.80 (<LOD-9.80) 13.4 (12.3-14.6) 19.3 (16.2-29.6) 33.2 (21.2-54.2) 583

20 years and older 99-00 * < LOD < LOD 14.2 (<LOD-17.5) 18.4 (15.0-23.8) 1109 

01-02 9.64 (8.53-10.9) 10.3 (8.80-11.7) 14.6 (12.7-16.7) 21.3 (18.0-25.5) 27.1 (22.5-32.0) 1219 

03-04 * < LOD 10.3 (9.60-11.1) 13.8 (12.5-16.0) 18.0 (16.0-20.9) 1275 

Gender 

Males 99-00 * < LOD < LOD 16.4 (<LOD-20.0) 21.0 (18.1-26.8) 815

01-02 10.1 (8.74-11.6) 11.0 (9.30-12.6) 15.2 (12.9-17.2) 20.8 (17.2-27.8) 28.9 (22.0-34.8) 557

03-04 * < LOD 11.3 (10.1-12.9) 17.1 (14.3-19.1) 23.9 (18.3-30.9) 913

Females 99-00 * < LOD < LOD < LOD 17.5 (14.3-20.3) 894

01-02 9.28 (8.20-10.5) 9.40 (8.20-11.2) 14.1 (12.4-16.6) 21.3 (17.4-25.5) 26.5 (22.3-31.9) 662

03-04 * < LOD 9.90 (9.30-10.5) 13.0 (12.2-14.3) 16.0 (14.3-18.4) 945

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 19.7 (<LOD-25.4) 570

01-02 7.73 (7.19-8.31) 8.20 (7.80-8.70) 11.2 (10.6-12.5) 16.5 (14.5-19.6) 20.8 (17.2-26.8) 260

03-04 * < LOD 9.10 (<LOD-10.6) 12.0 (10.1-16.8) 15.1 (11.6-20.0) 420

Non-Hispanic blacks 99-00 * < LOD < LOD 22.4 (15.2-28.2) 28.2 (26.5-29.6) 359

01-02 12.3 (10.6-14.4) 12.8 (10.9-15.2) 17.4 (15.4-21.0) 25.5 (22.4-31.2) 32.1 (25.7-37.6) 214

03-04 * < LOD 11.3 (10.7-12.2) 16.1 (13.4-19.0) 20.4 (16.7-26.8) 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 17.5 (14.9-18.9) 636

01-02 9.50 (8.30-10.9) 10.1 (8.40-12.0) 14.4 (12.6-16.6) 20.5 (16.9-25.5) 25.8 (20.5-31.7) 665

03-04 * < LOD 10.5 (9.60-11.5) 14.6 (12.9-17.4) 19.0 (16.3-26.2) 864

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 13.5, 7.0, and 8.6, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 393

 Dioxin-Like Chemicals

Serum 1,2,3,4,6,7,8-Heptachlorodibenzofuran (HpCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 85.3 (<LOD-95.8) 108 (95.8-120) 1709 

01-02 62.2 (55.4-69.9) 64.5 (58.0-71.6) 94.1 (82.3-110) 134 (119-165) 181 (147-206) 1219 

03-04 * < LOD 63.6 (59.9-67.7) 88.3 (81.0-100) 116 (101-137) 1858 

Age group 

12-19 years 99-00 * < LOD < LOD 79.3 (69.5-84.2) 102 (83.4-120) 600

01-02 † † † † † †

03-04 47.5 (44.0-51.3) 43.7 (<LOD-49.3) 63.7 (59.1-72.3) 102 (85.3-114) 175 (113-222) 583

20 years and older 99-00 * < LOD < LOD 85.7 (<LOD-97.7) 108 (93.6-127) 1109 

01-02 62.2 (55.4-69.9) 64.5 (58.0-71.6) 94.1 (82.3-110) 134 (119-165) 181 (147-206) 1219 

03-04 * < LOD 63.5 (59.6-67.6) 86.5 (78.8-100) 112 (94.9-135) 1275 

Gender 

Males 99-00 * < LOD < LOD 91.4 (<LOD-108) 112 (99.3-133) 815

01-02 66.3 (58.2-75.6) 70.4 (59.8-81.8) 99.3 (85.5-120) 143 (120-181) 182 (146-237) 557

03-04 * < LOD 69.7 (62.9-76.0) 100 (85.9-116) 135 (113-193) 913

Females 99-00 * < LOD < LOD < LOD 97.8 (86.2-130) 894

01-02 58.8 (52.0-66.4) 60.2 (53.5-67.6) 89.5 (74.7-107) 131 (108-165) 169 (131-225) 662

03-04 * < LOD 58.5 (54.5-62.4) 83.5 (74.7-87.7) 102 (87.7-116) 945

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 113 (<LOD-133) 570

01-02 49.5 (46.0-53.4) 50.4 (45.7-57.2) 76.9 (67.1-82.1) 99.7 (90.9-124) 133 (94.8-202) 260

03-04 * < LOD 56.0 (<LOD-64.6) 74.2 (62.6-91.4) 90.5 (76.4-107) 420

Non-Hispanic blacks 99-00 * < LOD < LOD 117 (89.0-143) 153 (109-197) 359

01-02 72.6 (61.9-85.2) 70.9 (62.4-85.2) 107 (91.5-128) 147 (131-177) 193 (154-259) 214

03-04 * < LOD 66.2 (60.2-75.5) 91.3 (80.3-112) 119 (102-151) 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 97.7 (89.3-104) 636

01-02 61.8 (54.3-70.4) 65.4 (57.4-72.2) 94.3 (78.1-112) 133 (114-166) 180 (137-222) 665

03-04 * < LOD 63.9 (59.6-69.2) 87.8 (79.8-100) 116 (102-139) 864

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 394 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 1,2,3,4,7,8,9-Heptachlorodibenzofuran (HpCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 1224 

03-04 * < LOD < LOD < LOD < LOD 1852 

Age group 

12-19 years 01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 583

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1224 

03-04 * < LOD < LOD < LOD < LOD 1269 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 558

03-04 * < LOD < LOD < LOD < LOD 908

Females 01-02 * < LOD < LOD < LOD < LOD 666

03-04 * < LOD < LOD < LOD < LOD 944

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 217

03-04 * < LOD < LOD < LOD < LOD 452

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 661

03-04 * < LOD < LOD < LOD < LOD 856

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 7.0 and 8.6. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 395

 Dioxin-Like Chemicals

Serum 1,2,3,4,7,8,9-Heptachlorodibenzofuran (HpCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 1224 

03-04 * < LOD < LOD < LOD < LOD 1852 

Age group 

12-19 years 01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 583

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1224 

03-04 * < LOD < LOD < LOD < LOD 1269 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 558

03-04 * < LOD < LOD < LOD < LOD 908

Females 01-02 * < LOD < LOD < LOD < LOD 666

03-04 * < LOD < LOD < LOD < LOD 944

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 217

03-04 * < LOD < LOD < LOD < LOD 452

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 661

03-04 * < LOD < LOD < LOD < LOD 856

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 396 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 1,2,3,4,7,8-Hexachlorodibenzofuran (HxCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1890 

01-02 * < LOD 8.00 (6.90-9.60) 12.1 (9.40-14.9) 15.4 (12.9-18.6) 1223 

03-04 * < LOD < LOD 7.50 (<LOD-7.90) 8.90 (7.90-10.2) 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 657

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 583

20 years and older 99-00 * < LOD < LOD < LOD 12.8 (<LOD-14.5) 1233 

01-02 * < LOD 8.00 (6.90-9.60) 12.1 (9.40-14.9) 15.4 (12.9-18.6) 1223 

03-04 * < LOD < LOD 7.60 (<LOD-8.20) 9.50 (8.00-10.5) 1283 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 908

01-02 * < LOD 8.20 (7.10-10.0) 12.8 (9.50-15.9) 15.9 (12.2-20.9) 562

03-04 * < LOD < LOD 7.40 (<LOD-8.00) 8.50 (7.80-10.0) 916

Females 99-00 * < LOD < LOD < LOD 12.9 (<LOD-16.4) 982

01-02 * < LOD 7.90 (6.70-9.00) 11.7 (9.40-13.8) 14.5 (12.2-18.6) 661

03-04 * < LOD < LOD 7.50 (<LOD-8.40) 9.30 (7.80-10.4) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631

01-02 * < LOD < LOD 7.30 (<LOD-8.00) 8.00 (7.00-10.9) 261

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 14.3 (<LOD-15.1) 399

01-02 * < LOD 8.90 (7.70-10.1) 13.6 (11.1-17.1) 18.6 (14.6-22.6) 214

03-04 * < LOD < LOD 7.80 (<LOD-10.9) 10.9 (7.50-19.4) 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 703

01-02 * < LOD 8.30 (7.10-10.2) 12.5 (10.0-15.9) 15.9 (13.1-19.0) 664

03-04 * < LOD < LOD 7.60 (<LOD-8.10) 9.40 (8.00-10.2) 869

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.7, 6.5, and 7.4, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 397

 Dioxin-Like Chemicals

Serum 1,2,3,4,7,8-Hexachlorodibenzofuran (HxCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1890 

01-02 * < LOD 54.0 (46.5-63.6) 82.3 (65.5-104) 108 (88.0-138) 1223 

03-04 * < LOD < LOD 49.1 (<LOD-54.5) 60.1 (53.4-68.8) 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 657

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 583

20 years and older 99-00 * < LOD < LOD < LOD 84.2 (<LOD-97.2) 1233 

01-02 * < LOD 54.0 (46.5-63.6) 82.3 (65.5-104) 108 (88.0-138) 1223 

03-04 * < LOD < LOD 51.0 (<LOD-57.2) 62.2 (56.2-72.7) 1283 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 908

01-02 * < LOD 56.9 (48.6-71.4) 90.1 (71.1-108) 108 (87.4-144) 562

03-04 * < LOD < LOD 49.3 (<LOD-54.9) 59.3 (52.9-68.8) 916

Females 99-00 * < LOD < LOD < LOD 82.8 (<LOD-102) 982

01-02 * < LOD 51.6 (43.7-59.6) 76.1 (62.6-97.0) 105 (81.6-140) 661

03-04 * < LOD < LOD 48.9 (<LOD-57.2) 61.9 (53.3-72.7) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631

01-02 * < LOD < LOD 48.4 (<LOD-56.3) 65.3 (48.6-79.4) 261

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 90.8 (<LOD-105) 399

01-02 * < LOD 52.7 (45.0-62.7) 87.1 (63.7-108) 122 (85.2-147) 214

03-04 * < LOD < LOD 56.9 (<LOD-71.7) 71.7 (53.8-112) 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 703

01-02 * < LOD 56.0 (48.6-66.1) 84.2 (64.5-115) 112 (88.6-142) 664

03-04 * < LOD < LOD 50.6 (<LOD-56.3) 61.4 (54.0-71.8) 869

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 398 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 1,2,3,6,7,8-Hexachlorodibenzofuran (HxCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1898 

01-02 * < LOD 7.10 (<LOD-8.20) 10.4 (9.00-13.1) 14.0 (11.0-17.1) 1236 

03-04 * < LOD < LOD < LOD 8.80 (<LOD-9.80) 1868 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 656

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 585

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1242 

01-02 * < LOD 7.10 (<LOD-8.20) 10.4 (9.00-13.1) 14.0 (11.0-17.1) 1236 

03-04 * < LOD < LOD < LOD 9.00 (8.00-10.1) 1283 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 913

01-02 * < LOD 7.10 (<LOD-8.60) 11.3 (8.50-13.8) 15.1 (11.3-18.7) 566

03-04 * < LOD < LOD < LOD 9.10 (7.90-10.8) 918

Females 99-00 * < LOD < LOD < LOD < LOD 985

01-02 * < LOD 7.00 (6.20-8.00) 10.0 (9.20-11.4) 13.1 (10.5-15.6) 670

03-04 * < LOD < LOD < LOD 8.50 (<LOD-9.20) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 625

01-02 * < LOD < LOD < LOD 6.90 (<LOD-11.1) 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD 7.60 (6.10-9.10) 12.1 (10.0-14.1) 16.0 (12.3-21.0) 219

03-04 * < LOD < LOD < LOD 8.50 (<LOD-12.1) 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 708

01-02 * < LOD 7.40 (6.20-9.00) 10.7 (9.20-14.3) 14.8 (11.6-17.2) 670

03-04 * < LOD < LOD < LOD 9.10 (8.00-10.6) 871

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.6, 6.1, and 7.9, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 399

 Dioxin-Like Chemicals

Serum 1,2,3,6,7,8-Hexachlorodibenzofuran (HxCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1898 

01-02 * < LOD 46.2 (<LOD-56.5) 70.3 (58.4-90.7) 101 (77.6-120) 1236 

03-04 * < LOD < LOD < LOD 59.8 (<LOD-65.4) 1868 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 656

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 585

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1242 

01-02 * < LOD 46.2 (<LOD-56.5) 70.3 (58.4-90.7) 101 (77.6-120) 1236 

03-04 * < LOD < LOD < LOD 61.0 (57.6-65.7) 1283 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 913

01-02 * < LOD 47.9 (<LOD-60.5) 72.3 (57.5-105) 104 (73.5-133) 566

03-04 * < LOD < LOD < LOD 61.0 (54.0-67.7) 918

Females 99-00 * < LOD < LOD < LOD < LOD 985

01-02 * < LOD 45.0 (37.0-54.3) 66.2 (58.3-79.1) 90.7 (71.9-115) 670

03-04 * < LOD < LOD < LOD 58.1 (<LOD-65.0) 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 625

01-02 * < LOD < LOD < LOD 52.7 (<LOD-65.9) 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD 44.4 (37.2-57.3) 71.5 (59.8-90.9) 107 (70.7-142) 219

03-04 * < LOD < LOD < LOD 58.4 (<LOD-73.0) 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 708

01-02 * < LOD 49.6 (41.9-57.9) 72.8 (58.4-102) 103 (82.6-121) 670

03-04 * < LOD < LOD < LOD 63.4 (57.3-67.7) 871

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 400 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 1,2,3,7,8,9-Hexachlorodibenzofuran (HxCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1875 

01-02 * < LOD < LOD < LOD < LOD 1223 

03-04 * < LOD < LOD < LOD < LOD 1864 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 645

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 583

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1230 

01-02 * < LOD < LOD < LOD < LOD 1223 

03-04 * < LOD < LOD < LOD < LOD 1281 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 894

01-02 * < LOD < LOD < LOD < LOD 559

03-04 * < LOD < LOD < LOD < LOD 914

Females 99-00 * < LOD < LOD < LOD < LOD 981

01-02 * < LOD < LOD < LOD < LOD 664

03-04 * < LOD < LOD < LOD < LOD 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 620

01-02 * < LOD < LOD < LOD < LOD 261

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 400

01-02 * < LOD < LOD < LOD < LOD 216

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 699

01-02 * < LOD < LOD < LOD < LOD 665

03-04 * < LOD < LOD < LOD < LOD 866

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.7, 6.0, and 8.3, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 401

 Dioxin-Like Chemicals

Serum 1,2,3,7,8,9-Hexachlorodibenzofuran (HxCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1875 

01-02 * < LOD < LOD < LOD < LOD 1223 

03-04 * < LOD < LOD < LOD < LOD 1864 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 645

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 583

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1230 

01-02 * < LOD < LOD < LOD < LOD 1223 

03-04 * < LOD < LOD < LOD < LOD 1281 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 894

01-02 * < LOD < LOD < LOD < LOD 559

03-04 * < LOD < LOD < LOD < LOD 914

Females 99-00 * < LOD < LOD < LOD < LOD 981

01-02 * < LOD < LOD < LOD < LOD 664

03-04 * < LOD < LOD < LOD < LOD 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 620

01-02 * < LOD < LOD < LOD < LOD 261

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 400

01-02 * < LOD < LOD < LOD < LOD 216

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 699

01-02 * < LOD < LOD < LOD < LOD 665

03-04 * < LOD < LOD < LOD < LOD 866

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 402 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,4,6,7,8-Hexachlorodibenzofuran (HxCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1884 

01-02 * < LOD < LOD < LOD < LOD 1230 

03-04 * < LOD < LOD < LOD < LOD 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 652

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 584

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1232 

01-02 * < LOD < LOD < LOD < LOD 1230 

03-04 * < LOD < LOD < LOD < LOD 1282 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 900

01-02 * < LOD < LOD < LOD < LOD 565

03-04 * < LOD < LOD < LOD < LOD 916

Females 99-00 * < LOD < LOD < LOD < LOD 984

01-02 * < LOD < LOD < LOD < LOD 665

03-04 * < LOD < LOD < LOD < LOD 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 614

01-02 * < LOD < LOD < LOD < LOD 260

03-04 * < LOD < LOD < LOD < LOD 422

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD < LOD < LOD < LOD 218

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 704

01-02 * < LOD < LOD < LOD < LOD 671

03-04 * < LOD < LOD < LOD < LOD 869

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.9, 5.8, and 8.2, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 403

 Dioxin-Like Chemicals

Serum 2,3,4,6,7,8-Hexachlorodibenzofuran (HxCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1884 

01-02 * < LOD < LOD < LOD < LOD 1230 

03-04 * < LOD < LOD < LOD < LOD 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 652

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 584

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1232 

01-02 * < LOD < LOD < LOD < LOD 1230 

03-04 * < LOD < LOD < LOD < LOD 1282 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 900

01-02 * < LOD < LOD < LOD < LOD 565

03-04 * < LOD < LOD < LOD < LOD 916

Females 99-00 * < LOD < LOD < LOD < LOD 984

01-02 * < LOD < LOD < LOD < LOD 665

03-04 * < LOD < LOD < LOD < LOD 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 614

01-02 * < LOD < LOD < LOD < LOD 260

03-04 * < LOD < LOD < LOD < LOD 422

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 408

01-02 * < LOD < LOD < LOD < LOD 218

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 704

01-02 * < LOD < LOD < LOD < LOD 671

03-04 * < LOD < LOD < LOD < LOD 869

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 404 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 1,2,3,4,6,7,8,9-Octachlorodibenzofuran (OCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1884 

01-02 * < LOD < LOD < LOD < LOD 1202 

03-04 * < LOD < LOD < LOD < LOD 1849 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 652

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 581

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1232 

01-02 * < LOD < LOD < LOD < LOD 1202 

03-04 * < LOD < LOD < LOD < LOD 1268 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 904

01-02 * < LOD < LOD < LOD < LOD 541

03-04 * < LOD < LOD < LOD < LOD 905

Females 99-00 * < LOD < LOD < LOD < LOD 980

01-02 * < LOD < LOD < LOD < LOD 661

03-04 * < LOD < LOD < LOD < LOD 944

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 623

01-02 * < LOD < LOD < LOD < LOD 257

03-04 * < LOD < LOD < LOD < LOD 420

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 404

01-02 * < LOD < LOD < LOD < LOD 212

03-04 * < LOD < LOD < LOD < LOD 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 705

01-02 * < LOD < LOD < LOD < LOD 653

03-04 * < LOD < LOD < LOD < LOD 857

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 35.6, 21.0, and 12.0, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 405

 Dioxin-Like Chemicals

Serum 1,2,3,4,6,7,8,9-Octachlorodibenzofuran (OCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1884 

01-02 * < LOD < LOD < LOD < LOD 1202 

03-04 * < LOD < LOD < LOD < LOD 1849 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 652

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 581

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1232 

01-02 * < LOD < LOD < LOD < LOD 1202 

03-04 * < LOD < LOD < LOD < LOD 1268 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 904

01-02 * < LOD < LOD < LOD < LOD 541

03-04 * < LOD < LOD < LOD < LOD 905

Females 99-00 * < LOD < LOD < LOD < LOD 980

01-02 * < LOD < LOD < LOD < LOD 661

03-04 * < LOD < LOD < LOD < LOD 944

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 623

01-02 * < LOD < LOD < LOD < LOD 257

03-04 * < LOD < LOD < LOD < LOD 420

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 404

01-02 * < LOD < LOD < LOD < LOD 212

03-04 * < LOD < LOD < LOD < LOD 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 705

01-02 * < LOD < LOD < LOD < LOD 653

03-04 * < LOD < LOD < LOD < LOD 857

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 406 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 1,2,3,7,8-Pentachlorodibenzofuran (PeCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1922 

01-02 * < LOD < LOD < LOD < LOD 1235 

03-04 * < LOD < LOD < LOD < LOD 1867 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 663

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 586

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1259 

01-02 * < LOD < LOD < LOD < LOD 1235 

03-04 * < LOD < LOD < LOD < LOD 1281 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 920

01-02 * < LOD < LOD < LOD < LOD 565

03-04 * < LOD < LOD < LOD < LOD 917

Females 99-00 * < LOD < LOD < LOD < LOD 1002 

01-02 * < LOD < LOD < LOD < LOD 670

03-04 * < LOD < LOD < LOD < LOD 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 637

01-02 * < LOD < LOD < LOD < LOD 263

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 217

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 717

01-02 * < LOD < LOD < LOD < LOD 670

03-04 * < LOD < LOD < LOD < LOD 869

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 13.2, 5.8, and 7.1, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 407

 Dioxin-Like Chemicals

Serum 1,2,3,7,8-Pentachlorodibenzofuran (PeCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1922 

01-02 * < LOD < LOD < LOD < LOD 1235 

03-04 * < LOD < LOD < LOD < LOD 1867 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 663

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 586

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1259 

01-02 * < LOD < LOD < LOD < LOD 1235 

03-04 * < LOD < LOD < LOD < LOD 1281 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 920

01-02 * < LOD < LOD < LOD < LOD 565

03-04 * < LOD < LOD < LOD < LOD 917

Females 99-00 * < LOD < LOD < LOD < LOD 1002 

01-02 * < LOD < LOD < LOD < LOD 670

03-04 * < LOD < LOD < LOD < LOD 950

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 637

01-02 * < LOD < LOD < LOD < LOD 263

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 217

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 717

01-02 * < LOD < LOD < LOD < LOD 670

03-04 * < LOD < LOD < LOD < LOD 869

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 408 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 15.9 (13.7-17.1) 1895 

01-02 * < LOD 9.20 (7.50-11.1) 14.3 (12.3-16.2) 18.1 (16.1-21.1) 1230 

03-04 * < LOD 6.80 (<LOD-7.20) 9.90 (8.90-10.7) 12.3 (11.0-13.3) 1871 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 656

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 586

20 years and older 99-00 * < LOD < LOD 12.7 (<LOD-13.9) 16.1 (14.1-17.6) 1239 

01-02 * < LOD 9.20 (7.50-11.1) 14.3 (12.3-16.2) 18.1 (16.1-21.1) 1230 

03-04 * < LOD 7.20 (<LOD-7.70) 10.3 (9.40-11.2) 13.0 (11.4-14.7) 1285 

Gender 

Males 99-00 * < LOD < LOD < LOD 13.9 (12.8-15.4) 906

01-02 * < LOD 9.40 (7.30-11.6) 14.1 (11.6-16.7) 16.7 (14.0-22.8) 560

03-04 * < LOD 7.00 (<LOD-7.30) 9.80 (8.70-10.6) 12.2 (10.4-14.8) 920

Females 99-00 * < LOD < LOD 13.1 (<LOD-16.1) 16.7 (14.3-19.2) 989

01-02 * < LOD 9.10 (7.50-10.7) 14.5 (13.0-16.1) 18.5 (16.4-21.2) 670

03-04 * < LOD < LOD 10.3 (8.90-11.0) 12.6 (11.0-13.7) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 632

01-02 * < LOD < LOD 7.80 (6.10-9.80) 9.80 (7.80-12.5) 264

03-04 * < LOD < LOD < LOD 7.90 (<LOD-10.5) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 16.3 (13.4-19.0) 400

01-02 * < LOD 8.40 (6.80-9.30) 14.1 (11.7-16.4) 19.1 (15.1-23.0) 216

03-04 * < LOD < LOD 9.80 (8.00-13.9) 15.9 (9.70-23.9) 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 15.6 (13.8-17.1) 706

01-02 * 5.90 (<LOD-6.90) 10.3 (8.10-12.0) 15.5 (13.0-17.6) 18.5 (16.5-22.2) 665

03-04 * < LOD 7.10 (<LOD-7.70) 10.3 (9.10-11.2) 12.4 (11.0-13.7) 873

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.7, 5.5, and 6.8, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 409

 Dioxin-Like Chemicals

Serum 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD 103 (96.0-113) 1895 

01-02 * < LOD 60.8 (51.3-70.6) 99.4 (83.4-114) 134 (113-152) 1230 

03-04 * < LOD 44.2 (<LOD-46.9) 65.7 (60.5-71.1) 83.9 (74.9-92.9) 1871 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 656

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 586

20 years and older 99-00 * < LOD < LOD 85.2 (<LOD-96.0) 107 (98.3-125) 1239 

01-02 * < LOD 60.8 (51.3-70.6) 99.4 (83.4-114) 134 (113-152) 1230 

03-04 * < LOD 46.5 (<LOD-50.6) 69.3 (62.2-74.6) 86.8 (78.3-99.8) 1285 

Gender 

Males 99-00 * < LOD < LOD < LOD 95.7 (80.1-101) 906

01-02 * < LOD 62.7 (49.3-76.6) 98.5 (76.6-134) 135 (105-160) 560

03-04 * < LOD 43.4 (<LOD-46.3) 62.0 (56.8-71.9) 83.2 (72.4-95.0) 920

Females 99-00 * < LOD < LOD 90.0 (<LOD-101) 111 (97.2-129) 989

01-02 * < LOD 59.8 (52.0-67.6) 100 (90.5-105) 126 (107-146) 670

03-04 * < LOD < LOD 66.9 (59.7-74.3) 84.4 (74.7-95.7) 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 632

01-02 * < LOD < LOD 55.8 (48.7-69.7) 76.3 (61.9-92.4) 264

03-04 * < LOD < LOD < LOD 57.1 (<LOD-70.2) 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 105 (82.7-116) 400

01-02 * < LOD 50.0 (41.3-60.4) 89.5 (72.3-107) 121 (92.0-154) 216

03-04 * < LOD < LOD 66.8 (48.5-93.2) 97.4 (79.1-129) 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD 103 (96.8-122) 706

01-02 * 37.5 (<LOD-44.1) 65.7 (52.9-78.2) 104 (90.7-118) 136 (118-154) 665

03-04 * < LOD 45.9 (<LOD-50.6) 68.3 (61.3-73.6) 85.0 (74.6-102) 873

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 410 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,7,8-Tetrachlorodibenzofuran (TCDF) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1903 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 * < LOD < LOD < LOD < LOD 1868 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 586

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1243 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 * < LOD < LOD < LOD < LOD 1282 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 912

01-02 * < LOD < LOD < LOD < LOD 558

03-04 * < LOD < LOD < LOD < LOD 917

Females 99-00 * < LOD < LOD < LOD < LOD 991

01-02 * < LOD < LOD < LOD < LOD 671

03-04 * < LOD < LOD < LOD < LOD 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 628

01-02 * < LOD < LOD < LOD < LOD 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 217

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 707

01-02 * < LOD < LOD < LOD < LOD 667

03-04 * < LOD < LOD < LOD < LOD 870

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 11.9, 5.2, and 6.0, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 411

 Dioxin-Like Chemicals

Serum 2,3,7,8-Tetrachlorodibenzofuran (TCDF) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1903 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 * < LOD < LOD < LOD < LOD 1868 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 660

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 586

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1243 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 * < LOD < LOD < LOD < LOD 1282 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 912

01-02 * < LOD < LOD < LOD < LOD 558

03-04 * < LOD < LOD < LOD < LOD 917

Females 99-00 * < LOD < LOD < LOD < LOD 991

01-02 * < LOD < LOD < LOD < LOD 671

03-04 * < LOD < LOD < LOD < LOD 951

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 628

01-02 * < LOD < LOD < LOD < LOD 262

03-04 * < LOD < LOD < LOD < LOD 423

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 409

01-02 * < LOD < LOD < LOD < LOD 217

03-04 * < LOD < LOD < LOD < LOD 454

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 707

01-02 * < LOD < LOD < LOD < LOD 667

03-04 * < LOD < LOD < LOD < LOD 870

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 412 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 3,4,4',5-Tetrachlorobiphenyl (PCB 81) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1883 

01-02 * < LOD < LOD < LOD < LOD 1215 

03-04 * < LOD < LOD < LOD 13.4 (<LOD-16.4) 1860 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 651

01-02 † † † † † †

03-04 * < LOD < LOD < LOD 14.7 (<LOD-16.5) 579

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1232 

01-02 * < LOD < LOD < LOD < LOD 1215 

03-04 * < LOD < LOD < LOD 13.1 (<LOD-16.5) 1281 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 900

01-02 * < LOD < LOD < LOD < LOD 554

03-04 * < LOD < LOD < LOD 14.4 (<LOD-17.9) 913

Females 99-00 * < LOD < LOD < LOD < LOD 983

01-02 * < LOD < LOD < LOD < LOD 661

03-04 * < LOD < LOD < LOD < LOD 947

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 621

01-02 * < LOD < LOD < LOD < LOD 259

03-04 * < LOD < LOD < LOD 18.7 (<LOD-25.2) 420

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 405

01-02 * < LOD < LOD < LOD < LOD 218

03-04 * < LOD < LOD < LOD < LOD 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 699

01-02 * < LOD < LOD < LOD < LOD 657

03-04 * < LOD < LOD < LOD 13.1 (<LOD-16.4) 867

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 68.4, 26.8, and 13.1, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 413

 Dioxin-Like Chemicals

Serum 3,4,4',5-Tetrachlorobiphenyl (PCB 81) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1883 

01-02 * < LOD < LOD < LOD < LOD 1215 

03-04 * < LOD < LOD < LOD 80.3 (<LOD-96.2) 1860 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 651

01-02 † † † † † †

03-04 * < LOD < LOD < LOD 71.4 (<LOD-82.8) 579

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1232 

01-02 * < LOD < LOD < LOD < LOD 1215 

03-04 * < LOD < LOD < LOD 80.7 (<LOD-99.3) 1281 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 900

01-02 * < LOD < LOD < LOD < LOD 554

03-04 * < LOD < LOD < LOD 81.1 (<LOD-104) 913

Females 99-00 * < LOD < LOD < LOD < LOD 983

01-02 * < LOD < LOD < LOD < LOD 661

03-04 * < LOD < LOD < LOD < LOD 947

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 621

01-02 * < LOD < LOD < LOD < LOD 259

03-04 * < LOD < LOD < LOD 103 (<LOD-199) 420

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 405

01-02 * < LOD < LOD < LOD < LOD 218

03-04 * < LOD < LOD < LOD < LOD 453

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 699

01-02 * < LOD < LOD < LOD < LOD 657

03-04 * < LOD < LOD < LOD 80.5 (<LOD-106) 867

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 414 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 28.5 (24.9-32.8) 53.2 (45.7-59.9) 80.5 (62.8-100) 1896 

01-02 22.7 (20.9-24.7) 24.5 (22.2-26.8) 40.8 (36.1-47.5) 69.3 (61.6-80.8) 108 (92.7-116) 1226 

03-04 16.3 (14.9-17.9) 14.7 (<LOD-16.5) 24.8 (22.4-27.4) 46.7 (41.6-51.9) 68.7 (58.1-84.4) 1860 

Age group 

12-19 years 99-00 * < LOD < LOD 24.3 (<LOD-27.5) 31.1 (26.4-36.4) 658

01-02 † † † † † †

03-04 * < LOD < LOD 17.0 (15.2-20.2) 21.2 (17.3-25.6) 577

20 years and older 99-00 * < LOD 30.8 (27.2-36.3) 57.1 (50.5-65.8) 89.5 (66.1-110) 1238 

01-02 22.7 (20.9-24.7) 24.5 (22.2-26.8) 40.8 (36.1-47.5) 69.3 (61.6-80.8) 108 (92.7-116) 1226 

03-04 17.6 (16.0-19.3) 16.0 (14.2-18.6) 26.8 (24.2-30.3) 49.8 (43.5-59.1) 74.8 (60.2-94.4) 1283 

Gender 

Males 99-00 * < LOD 25.8 (<LOD-28.9) 41.6 (36.1-45.7) 62.0 (49.7-75.0) 911

01-02 20.3 (18.5-22.3) 23.1 (20.8-25.4) 36.6 (32.8-39.4) 52.7 (46.4-62.3) 81.9 (61.0-101) 561

03-04 14.9 (<LOD-16.4) < LOD 21.8 (20.1-25.4) 38.5 (31.0-46.1) 51.5 (46.5-60.5) 912

Females 99-00 * < LOD 33.6 (27.4-41.4) 59.4 (53.0-78.7) 98.1 (69.9-120) 985

01-02 25.1 (22.9-27.4) 26.1 (23.0-28.8) 48.6 (41.4-54.4) 82.9 (71.1-96.8) 116 (98.6-128) 665

03-04 17.8 (16.0-19.7) 15.7 (<LOD-18.4) 27.6 (24.3-33.4) 57.1 (46.0-67.1) 82.5 (63.0-109) 948

Race/ethnicity 

Mexican Americans 99-00 * < LOD 23.8 (<LOD-30.3) 43.2 (37.0-52.6) 66.1 (52.4-79.2) 631

01-02 17.8 (15.5-20.4) 19.9 (18.3-21.2) 28.5 (26.5-34.2) 47.9 (39.7-54.9) 69.2 (49.3-103) 262

03-04 15.5 (<LOD-17.9) 14.2 (<LOD-17.5) 22.5 (18.9-26.8) 31.2 (27.4-37.8) 42.0 (33.5-48.0) 420

Non-Hispanic blacks 99-00 * < LOD 30.6 (25.2-43.1) 67.4 (45.0-126) 126 (67.4-224) 404

01-02 22.2 (18.2-27.0) 22.1 (19.6-25.4) 44.3 (37.9-51.5) 88.4 (59.0-111) 115 (96.1-153) 217

03-04 16.5 (13.9-19.5) < LOD 23.5 (18.9-34.6) 63.4 (41.5-126) 142 (52.1-292) 452

Non-Hispanic whites 99-00 * < LOD 28.3 (<LOD-34.0) 50.5 (41.6-57.0) 67.8 (57.0-94.1) 704

01-02 23.1 (20.9-25.4) 24.7 (22.0-27.6) 42.0 (35.4-49.6) 72.3 (63.9-82.9) 114 (91.0-128) 663

03-04 16.0 (14.3-17.8) 14.5 (<LOD-16.9) 24.3 (21.4-28.2) 46.5 (41.6-50.9) 64.0 (52.1-76.1) 869

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 23.2, 10.8, and 13.9, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 415

 Dioxin-Like Chemicals

Serum 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 177 (151-212) 336 (294-404) 564 (455-663) 1896 

01-02 147 (135-160) 158 (143-175) 270 (249-298) 482 (436-541) 738 (625-840) 1226 

03-04 100 (91.0-110) 89.8 (<LOD-101) 159 (146-178) 308 (273-349) 475 (378-590) 1860 

Age group 

12-19 years 99-00 * < LOD < LOD 108 (<LOD-126) 144 (116-196) 658

01-02 † † † † † †

03-04 * < LOD < LOD 88.2 (78.8-106) 109 (89.2-135) 577

20 years and older 99-00 * < LOD 204 (173-232) 381 (319-451) 596 (479-709) 1238 

01-02 147 (135-160) 158 (143-175) 270 (249-298) 482 (436-541) 738 (625-840) 1226 

03-04 111 (100-122) 100 (88.7-115) 176 (158-194) 326 (286-394) 534 (394-668) 1283 

Gender 

Males 99-00 * < LOD 154 (<LOD182) 260 (241-274) 382 (308-509) 911

01-02 134 (121-149) 152 (130-169) 249 (233-267) 399 (346-467) 566 (467-693) 561

03-04 92.3 (<LOD-102) < LOD 148 (131-168) 245 (203-296) 360 (296-442) 912

Females 99-00 * < LOD 212 (159-250) 429 (350-531) 648 (534-744) 985

01-02 159 (146-172) 160 (149-186) 301 (270-348) 550 (483-637) 818 (658-958) 665

03-04 108 (96.2-121) 94.5 (<LOD-110) 180 (153-212) 370 (303-455) 559 (438-843) 948

Race/ethnicity 

Mexican Americans 99-00 * < LOD 146 (<LOD213) 285 (229-364) 424 (361-534) 631

01-02 114 (97.8-133) 125 (106-150) 217 (175-257) 335 (272-460) 593 (354-784) 262

03-04 95.3 (<LOD-111) 91.4 (<LOD-99.4) 145 (116-180) 238 (172-288) 298 (238-461) 420

Non-Hispanic blacks 99-00 * < LOD 192 (147-258) 457 (308-691) 786 (457-1520) 404

01-02 131 (106-161) 128 (110-158) 266 (214-304) 532 (361-662) 779 (585-1060) 217

03-04 94.3 (79.0-112) < LOD 143 (106-254) 483 (254-847) 976 (483-1430) 452

Non-Hispanic whites 99-00 * < LOD 175 (<LOD215) 311 (274-356) 508 (394-660) 704

01-02 150 (136-164) 160 (146-179) 276 (249-301) 486 (431-553) 746 (600-937) 663

03-04 98.4 (87.5-111) 89.4 (<LOD-104) 158 (142-182) 297 (260-346) 431 (365-541) 869

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 416 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 3,3',4,4',5,5'-Hexachlorobiphenyl (PCB 169) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in pg/g lipid or parts per trillion on a lipid-weight basis) 

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 34.4 (31.0-38.7) 44.9 (40.6-48.9) 1888 

01-02 17.9 (16.0-19.9) 19.0 (17.0-22.0) 33.1 (27.7-38.6) 50.0 (43.9-55.0) 60.9 (56.1-65.8) 1223 

03-04 * < LOD 19.5 (16.8-22.7) 31.0 (27.9-36.0) 40.6 (36.5-47.3) 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 648

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 581

20 years and older 99-00 * < LOD < LOD 36.4 (33.8-40.3) 47.8 (42.8-51.0) 1240 

01-02 17.9 (16.0-19.9) 19.0 (17.0-22.0) 33.1 (27.7-38.6) 50.0 (43.9-55.0) 60.9 (56.1-65.8) 1223 

03-04 * < LOD 21.9 (19.0-24.2) 32.7 (28.6-37.3) 43.2 (37.3-49.5) 1285 

Gender 

Males 99-00 * < LOD < LOD 36.2 (31.9-40.1) 44.3 (39.0-51.3) 908

01-02 20.2 (17.8-22.8) 22.1 (18.5-25.3) 36.0 (29.5-43.2) 53.7 (46.5-57.3) 60.9 (55.7-69.0) 559

03-04 * < LOD 22.3 (17.7-24.8) 36.3 (29.3-41.1) 46.1 (38.8-52.0) 917

Females 99-00 * < LOD < LOD 34.0 (29.4-38.6) 46.5 (37.9-51.1) 980

01-02 16.0 (14.2-18.1) 17.0 (14.7-19.2) 30.2 (24.5-36.5) 46.4 (40.7-51.9) 60.9 (52.2-70.0) 664

03-04 * < LOD 18.4 (<LOD-20.4) 28.4 (27.2-30.6) 35.8 (31.0-41.1) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 31.9 (28.8-35.2) 622

01-02 * < LOD 15.0 (11.3-18.3) 25.4 (18.3-32.3) 32.5 (26.7-41.9) 260

03-04 * < LOD < LOD < LOD 20.9 (16.5-30.2) 420

Non-Hispanic blacks 99-00 * < LOD < LOD 40.3 (28.7-48.6) 52.2 (44.3-63.6) 403

01-02 17.2 (15.4-19.1) 18.5 (15.7-20.0) 31.7 (25.8-35.4) 47.5 (42.0-54.0) 57.3 (48.3-64.5) 217

03-04 * < LOD 17.3 (<LOD-22.6) 31.5 (26.8-36.9) 58.7 (31.5-97.9) 453

Non-Hispanic whites 99-00 * < LOD < LOD 34.6 (31.7-40.1) 45.3 (40.1-50.9) 709

01-02 19.5 (17.2-22.2) 21.4 (17.4-24.7) 36.0 (29.8-41.1) 53.5 (47.0-58.3) 64.3 (59.2-72.8) 662

03-04 * < LOD 21.2 (17.4-24.5) 32.6 (27.3-38.8) 41.1 (35.9-50.2) 873

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 27.0, 11.0, and 15.9, respectively. 

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 417

 Dioxin-Like Chemicals

Serum 3,3',4,4',5,5'-Hexachlorobiphenyl (PCB 169) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in fg/g of serum or parts per quadrillion) for the U.S. 

population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 230 (219-244) 287 (274-319) 1888 

01-02 115 (103-129) 125 (108-146) 217 (189-253) 344 (300-376) 416 (379-490) 1223 

03-04 * < LOD 133 (114-149) 203 (191-226) 269 (243-305) 1866 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 648

01-02 † † † † † †

03-04 * < LOD < LOD < LOD < LOD 581

20 years and older 99-00 * < LOD < LOD 241 (227-261) 303 (281-339) 1240 

01-02 115 (103-129) 125 (108-146) 217 (189-253) 344 (300-376) 416 (379-490) 1223 

03-04 * < LOD 146 (130-160) 216 (198-242) 287 (245-325) 1285 

Gender 

Males 99-00 * < LOD < LOD 229 (215-258) 286 (256-338) 908

01-02 133 (117-152) 151 (130-168) 244 (198-293) 363 (309-409) 449 (372-529) 559

03-04 * < LOD 143 (122-159) 225 (190-259) 291 (245-334) 917

Females 99-00 * < LOD < LOD 234 (197-257) 293 (261-346) 980

01-02 102 (90.0-115) 107 (91.0-123) 195 (170-234) 319 (282-368) 402 (373-462) 664

03-04 * < LOD 120 (<LOD140) 194 (182-203) 249 (222-284) 949

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD 215 (181-261) 622

01-02 * < LOD 98.1 (79.3-138) 184 (143-250) 266 (179-341) 260

03-04 * < LOD < LOD < LOD 168 (109-237) 420

Non-Hispanic blacks 99-00 * < LOD < LOD 251 (190-299) 320 (262-410) 403

01-02 101 (91.2-113) 104 (88.0-118) 190 (147-234) 299 (267-335) 362 (309-423) 217

03-04 * < LOD 110 (<LOD-144) 216 (162-257) 338 (221-556) 453

Non-Hispanic whites 99-00 * < LOD < LOD 238 (222-257) 286 (267-340) 709

01-02 127 (112-144) 145 (124-157) 229 (195-275) 368 (317-388) 438 (388-515) 662

03-04 * < LOD 141 (116-165) 210 (189-242) 277 (239-324) 873

† Data not collected for this age group for Survey year 01-02. 

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 418 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,3',4,4'-Pentachlorobiphenyl (PCB 105) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1915 

01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 1.20 (1.09-1.31) 1.09 (1.00-1.20) 1.90 (1.75-2.20) 4.04 (3.40-4.89) 6.24 (5.20-7.79) 1879 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 665

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .686 (.603-.781) .700 (.600-.720) 1.00 (.900-1.11) 1.50 (1.20-2.00) 2.26 (1.50-3.50) 593

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1250 

01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 1.30 (1.18-1.43) 1.15 (1.04-1.30) 2.10 (1.86-2.40) 4.44 (3.80-5.20) 6.82 (5.70-8.30) 1286 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 913

01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 1.02 (.923-1.12) .980 (.850-1.08) 1.60 (1.40-1.80) 3.20 (2.76-3.42) 4.70 (3.83-5.50) 937

Females 99-00 * < LOD < LOD < LOD < LOD 1002 

01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 1.40 (1.25-1.57) 1.20 (1.05-1.40) 2.30 (2.00-2.79) 5.17 (4.47-5.90) 7.70 (6.00-9.55) 942

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 635

01-02 * < LOD < LOD < LOD < LOD 567

03-04 .719 (.624-.829) .700 (.600-.800) 1.10 (.900-1.36) 1.90 (1.80-2.20) 2.90 (1.98-3.52) 427

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD 12.8 (<LOD-18.0) 409

01-02 * < LOD < LOD < LOD < LOD 515

03-04 1.41 (1.15-1.74) 1.14 (.980-1.32) 2.47 (1.70-3.90) 6.70 (4.09-10.1) 11.9 (6.40-18.1) 456

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 714

01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 1.21 (1.08-1.36) 1.10 (1.00-1.20) 1.90 (1.74-2.28) 3.91 (3.22-4.85) 5.93 (4.98-7.79) 878

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 419

 Dioxin-Like Chemicals

Serum 2,3,3',4,4'-Pentachlorobiphenyl (PCB 105) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1915 

01-02 * < LOD < LOD < LOD < LOD 2307 

03-04 .007 (.007-.008) .007 (.006-.007) .012 (.011-.014) .027 (.023-.031) .043 (.037-.049) 1879 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 665

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .003 (.003-.004) .003 (.003-.004) .005 (.005-.006) .008 (.006-.010) .011 (.008-.020) 593

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1250 

01-02 * < LOD < LOD < LOD < LOD 1549 

03-04 .008 (.007-.009) .007 (.006-.008) .014 (.012-.015) .030 (.026-.035) .047 (.039-.053) 1286 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 913

01-02 * < LOD < LOD < LOD < LOD 1075 

03-04 .006 (.006-.007) .006 (.005-.007) .010 (.009-.011) .019 (.016-.023) .030 (.027-.039) 937

Females 99-00 * < LOD < LOD < LOD < LOD 1002 

01-02 * < LOD < LOD < LOD < LOD 1232 

03-04 .008 (.007-.010) .007 (.006-.009) .015 (.013-.017) .033 (.029-.040) .049 (.043-.067) 942

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 635

01-02 * < LOD < LOD < LOD < LOD 567

03-04 .004 (.004-.005) .004 (.004-.005) .007 (.006-.009) .014 (.011-.017) .019 (.015-.023) 427

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD .090 (<LOD-.110) 409

01-02 * < LOD < LOD < LOD < LOD 515

03-04 .008 (.007-.010) .007 (.005-.008) .015 (.010-.020) .041 (.027-.067) .082 (.041-.116) 456

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 714

01-02 * < LOD < LOD < LOD < LOD 1061 

03-04 .007 (.007-.008) .007 (.006-.007) .012 (.011-.014) .027 (.022-.031) .043 (.035-.049) 878

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 420 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3',4,4',5-Pentachlorobiphenyl (PCB 118) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD 13.1 (<LOD-15.1) 27.0 (22.1-30.3) 40.8 (32.8-48.6) 1926 

01-02 * < LOD 15.1 (13.0-17.5) 29.0 (26.1-33.7) 44.6 (39.6-48.9) 2307 

03-04 6.00 (5.54-6.50) 5.19 (4.80-5.61) 10.4 (9.70-11.6) 21.8 (19.3-23.8) 31.3 (28.2-36.6) 1887 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 758

03-04 3.06 (2.76-3.39) 2.83 (2.70-3.10) 4.15 (3.60-4.56) 6.80 (4.70-9.60) 9.60 (6.80-13.2) 596

20 years and older 99-00 * < LOD 14.9 (12.9-17.4) 28.1 (24.8-33.8) 43.8 (35.6-52.3) 1259 

01-02 * < LOD 16.9 (15.1-19.0) 32.4 (28.3-37.3) 46.5 (41.1-51.0) 1549 

03-04 6.62 (6.10-7.18) 5.65 (5.21-6.40) 11.5 (10.2-12.6) 22.8 (20.7-25.9) 34.3 (29.6-39.6) 1291 

Gender 

Males 99-00 * < LOD < LOD 19.6 (16.6-24.4) 28.0 (24.4-38.1) 919

01-02 * < LOD 12.0 (<LOD-14.9) 22.0 (17.6-27.1) 32.7 (25.4-47.5) 1075 

03-04 5.11 (4.70-5.57) 4.71 (4.16-5.06) 8.72 (7.30-9.70) 16.4 (14.0-18.9) 23.2 (20.7-25.1) 940

Females 99-00 * < LOD 16.7 (13.6-19.7) 32.0 (27.1-40.3) 46.8 (41.2-57.8) 1007 

01-02 * < LOD 18.7 (16.5-21.0) 36.4 (31.6-40.9) 48.9 (44.5-54.3) 1232 

03-04 6.99 (6.32-7.73) 6.02 (5.31-6.84) 12.3 (11.1-14.4) 27.3 (22.7-30.0) 37.8 (31.3-45.0) 947

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD 17.3 (14.5-19.6) 23.7 (20.9-27.1) 636

01-02 * < LOD < LOD 16.8 (12.5-21.7) 26.4 (19.3-33.2) 567

03-04 3.56 (3.04-4.18) 3.15 (2.60-3.82) 5.02 (4.26-6.66) 9.37 (7.45-11.7) 14.0 (10.0-17.6) 426

Non-Hispanic blacks 99-00 * < LOD 19.0 (13.6-21.7) 38.7 (28.4-54.4) 59.7 (45.7-80.8) 413

01-02 * < LOD 15.6 (12.6-19.9) 37.3 (26.1-46.4) 54.9 (40.0-66.6) 515

03-04 6.70 (5.52-8.14) 5.25 (4.40-6.10) 12.7 (8.80-18.0) 35.1 (21.1-45.0) 57.8 (33.5-110) 462

Non-Hispanic whites 99-00 * < LOD 13.1 (<LOD-15.6) 25.6 (20.8-32.0) 40.3 (30.4-46.8) 720

01-02 * < LOD 15.9 (13.6-18.1) 31.1 (27.1-35.9) 45.3 (38.7-50.1) 1061 

03-04 6.19 (5.57-6.87) 5.46 (4.85-6.20) 10.9 (9.62-12.1) 22.0 (19.3-24.4) 30.7 (26.2-36.6) 878

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.5, 10.5, and 0.6, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 421

 Dioxin-Like Chemicals

Serum 2,3',4,4',5-Pentachlorobiphenyl (PCB 118) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD .090 (<LOD-.100) .180 (.150-.200) .260 (.220-.320) 1926 

01-02 * < LOD .100 (.090-.110) .190 (.160-.220) .300 (.270-.320) 2307 

03-04 .037 (.034-.040) .032 (.029-.036) .066 (.061-.073) .143 (.127-.160) .216 (.192-.233) 1887 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 667

01-02 * < LOD < LOD < LOD < LOD 758

03-04 .015 (.014-.017) .014 (.013-.016) .021 (.018-.023) .036 (.024-.046) .047 (.035-.076) 596

20 years and older 99-00 * < LOD .100 (.090-.110) .190 (.170-.220) .280 (.230-.360) 1259 

01-02 * < LOD .110 (.100-.130) .210 (.180-.250) .310 (.280-.370) 1549 

03-04 .041 (.038-.045) .036 (.032-.041) .072 (.066-.081) .159 (.137-.174) .226 (.202-.249) 1291 

Gender 

Males 99-00 * < LOD < LOD .130 (.110-.140) .190 (.160-.220) 919

01-02 * < LOD .080 (<LOD-.100) .140 (.120-.170) .210 (.160-.300) 1075 

03-04 .032 (.029-.035) .030 (.026-.033) .054 (.046-.062) .110 (.083-.125) .160 (.136-.180) 940

Females 99-00 * < LOD .110 (.090-.130) .210 (.180-.260) .320 (.260-.410) 1007 

01-02 * < LOD .130 (.100-.140) .240 (.210-.260) .360 (.300-.380) 1232 

03-04 .042 (.038-.047) .036 (.030-.043) .081 (.068-.097) .176 (.152-.206) .242 (.217-.290) 947

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD .110 (.090-.130) .140 (.130-.180) 636

01-02 * < LOD < LOD .120 (.080-.160) .180 (.130-.220) 567

03-04 .022 (.018-.026) .019 (.016-.024) .034 (.029-.039) .069 (.046-.086) .094 (.075-.117) 426

Non-Hispanic blacks 99-00 * < LOD .120 (.080-.150) .220 (.180-.320) .400 (.260-.500) 413

01-02 * < LOD .100 (.070-.120) .210 (.170-.270) .320 (.230-.460) 515

03-04 .038 (.031-.046) .030 (.026-.034) .074 (.054-.106) .218 (.133-.277) .370 (.218-.618) 462

Non-Hispanic whites 99-00 * < LOD .090 (<LOD-.100) .180 (.150-.200) .250 (.200-.330) 720

01-02 * < LOD .100 (.090-.120) .210 (.170-.240) .300 (.270-.360) 1061 

03-04 .038 (.034-.043) .034 (.029-.040) .067 (.062-.076) .143 (.127-.165) .209 (.178-.234) 878

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 422 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,3',4,4',5-Hexachlorobiphenyl (PCB 156) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD 12.6 (<LOD-13.8) 17.0 (15.5-18.0) 1907 

01-02 * < LOD < LOD 14.3 (12.1-16.0) 18.3 (15.6-21.1) 2296 

03-04 2.54 (2.36-2.74) 3.29 (2.90-3.80) 7.00 (6.20-8.07) 11.4 (10.4-12.6) 15.3 (13.8-17.5) 1880 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 665

01-02 * < LOD < LOD < LOD < LOD 756

03-04 * .500 (<LOD-.660) 1.20 (1.00-1.43) 2.30 (2.06-2.45) 3.00 (2.37-3.60) 586

20 years and older 99-00 * < LOD < LOD 13.6 (<LOD-14.7) 17.5 (16.0-20.1) 1242 

01-02 * < LOD < LOD 15.0 (13.3-17.0) 19.7 (17.0-22.1) 1540 

03-04 3.31 (3.05-3.60) 4.10 (3.40-4.66) 7.81 (6.80-8.70) 12.0 (10.9-13.5) 16.8 (14.7-18.6) 1294 

Gender 

Males 99-00 * < LOD < LOD 12.6 (<LOD-14.0) 17.0 (14.6-18.0) 912

01-02 * < LOD < LOD 13.7 (11.3-16.4) 18.4 (14.3-22.1) 1069 

03-04 2.57 (2.34-2.82) 3.10 (2.80-3.80) 6.92 (5.82-8.00) 11.8 (9.79-14.2) 17.1 (14.7-19.3) 940

Females 99-00 * < LOD < LOD 12.8 (<LOD-14.7) 16.5 (15.4-20.7) 995

01-02 * < LOD < LOD 14.8 (13.2-15.5) 18.2 (16.2-21.0) 1227 

03-04 2.51 (2.28-2.76) 3.42 (2.80-4.10) 7.09 (6.35-8.10) 11.1 (10.4-12.0) 14.1 (12.7-16.8) 940

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631

01-02 * < LOD < LOD < LOD < LOD 566

03-04 .858 (.640-1.15) 1.00 (.700-1.40) 2.48 (1.50-3.60) 4.78 (4.00-5.68) 6.40 (5.40-7.70) 423

Non-Hispanic blacks 99-00 * < LOD < LOD 14.6 (<LOD-20.5) 23.1 (17.2-32.1) 412

01-02 * < LOD < LOD 15.5 (12.7-21.0) 23.5 (16.4-31.4) 511

03-04 2.32 (1.87-2.89) 3.04 (2.40-3.60) 7.40 (5.48-9.80) 14.7 (11.5-18.6) 24.8 (15.0-33.0) 456

Non-Hispanic whites 99-00 * < LOD < LOD 13.6 (<LOD-15.2) 17.4 (16.0-18.9) 711

01-02 * < LOD < LOD 15.0 (13.2-17.5) 19.4 (16.2-22.1) 1056 

03-04 3.03 (2.70-3.39) 4.03 (3.15-4.66) 7.76 (6.51-8.79) 11.7 (10.5-13.1) 15.7 (13.5-18.5) 880

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.5, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 423

 Dioxin-Like Chemicals

Serum 2,3,3',4,4',5-Hexachlorobiphenyl (PCB 156) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD .090 (<LOD-.090) .110 (.100-.130) 1907 

01-02 * < LOD < LOD .100 (.080-.110) .130 (.110-.140) 2296 

03-04 .016 (.014-.017) .021 (.018-.024) .048 (.041-.052) .075 (.069-.085) .103 (.094-.112) 1880 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 665

01-02 * < LOD < LOD < LOD < LOD 756

03-04 * .003 (<LOD-.003) .006 (.005-.007) .012 (.011-.012) .015 (.012-.018) 586

20 years and older 99-00 * < LOD < LOD .090 (<LOD-.100) .120 (.100-.140) 1242 

01-02 * < LOD < LOD .100 (.090-.120) .130 (.120-.140) 1540 

03-04 .021 (.019-.023) .026 (.021-.030) .051 (.045-.057) .082 (.072-.093) .109 (.098-.121) 1294 

Gender 

Males 99-00 * < LOD < LOD .090 (<LOD-.100) .110 (.090-.130) 912

01-02 * < LOD < LOD .090 (.080-.120) .120 (.110-.150) 1069 

03-04 .016 (.014-.018) .021 (.017-.025) .045 (.037-.054) .076 (.068-.094) .108 (.094-.123) 940

Females 99-00 * < LOD < LOD .090 (<LOD-.090) .110 (.090-.140) 995

01-02 * < LOD < LOD .100 (.090-.100) .130 (.110-.140) 1227 

03-04 .015 (.014-.017) .020 (.017-.025) .049 (.044-.052) .073 (.064-.085) .101 (.089-.112) 940

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 631

01-02 * < LOD < LOD < LOD < LOD 566

03-04 .005 (.004-.007) .007 (.004-.009) .015 (.011-.022) .036 (.025-.041) .046 (.037-.070) 423

Non-Hispanic blacks 99-00 * < LOD < LOD .090 (<LOD-.120) .150 (.110-.190) 412

01-02 * < LOD < LOD .100 (.080-.130) .150 (.100-.180) 511

03-04 .013 (.010-.017) .018 (.014-.022) .044 (.032-.056) .099 (.067-.127) .166 (.108-.198) 456

Non-Hispanic whites 99-00 * < LOD < LOD .090 (<LOD-.100) .110 (.100-.130) 711

01-02 * < LOD < LOD .100 (.090-.120) .130 (.120-.140) 1056 

03-04 .019 (.017-.021) .025 (.020-.031) .051 (.044-.057) .078 (.069-.089) .104 (.094-.119) 880

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 424 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,3',4,4',5'-Hexachlorobiphenyl (PCB 157) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1897 

01-02 * < LOD < LOD < LOD < LOD 2294 

03-04 .605 (.554-.661) .800 (.700-.940) 1.73 (1.47-1.93) 2.80 (2.50-3.10) 3.80 (3.36-4.30) 1858 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 654

01-02 * < LOD < LOD < LOD < LOD 755

03-04 * < LOD < LOD .690 (.540-.760) .980 (.750-1.12) 580

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1243 

01-02 * < LOD < LOD < LOD < LOD 1539 

03-04 .743 (.675-.817) .980 (.800-1.10) 1.88 (1.69-2.05) 2.98 (2.68-3.30) 3.97 (3.51-4.59) 1278 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 901

01-02 * < LOD < LOD < LOD < LOD 1068 

03-04 .594 (.541-.653) .750 (.700-.900) 1.65 (1.38-1.88) 2.90 (2.39-3.50) 4.00 (3.57-4.87) 928

Females 99-00 * < LOD < LOD < LOD < LOD 996

01-02 * < LOD < LOD < LOD < LOD 1226 

03-04 .615 (.552-.685) .890 (.700-1.00) 1.79 (1.60-1.99) 2.70 (2.50-2.91) 3.40 (3.20-3.93) 930

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 622

01-02 * < LOD < LOD < LOD < LOD 566

03-04 * < LOD .600 (<LOD-.820) 1.12 (.960-1.32) 1.59 (1.20-1.80) 422

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 405

01-02 * < LOD < LOD < LOD < LOD 510

03-04 .568 (.488-.662) .720 (.600-.930) 1.80 (1.39-2.26) 3.55 (3.10-4.40) 5.35 (3.60-8.80) 448

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 716

01-02 * < LOD < LOD < LOD < LOD 1055 

03-04 .713 (.635-.801) .980 (.760-1.12) 1.81 (1.58-2.06) 2.86 (2.54-3.27) 3.80 (3.27-4.73) 869

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.5, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 425

 Dioxin-Like Chemicals

Serum 2,3,3',4,4',5'-Hexachlorobiphenyl (PCB 157) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1897 

01-02 * < LOD < LOD < LOD < LOD 2294 

03-04 .004 (.003-.004) .005 (.004-.006) .011 (.010-.013) .018 (.016-.021) .024 (.022-.027) 1858 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 654

01-02 * < LOD < LOD < LOD < LOD 755

03-04 * < LOD < LOD .004 (.003-.004) .005 (.004-.005) 580

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1243 

01-02 * < LOD < LOD < LOD < LOD 1539 

03-04 .005 (.004-.005) .006 (.005-.007) .012 (.011-.014) .019 (.017-.022) .026 (.023-.031) 1278 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 901

01-02 * < LOD < LOD < LOD < LOD 1068 

03-04 .004 (.003-.004) .005 (.004-.006) .011 (.009-.012) .018 (.016-.022) .025 (.022-.027) 928

Females 99-00 * < LOD < LOD < LOD < LOD 996

01-02 * < LOD < LOD < LOD < LOD 1226 

03-04 .004 (.003-.004) .005 (.004-.006) .012 (.010-.013) .017 (.016-.020) .024 (.021-.027) 930

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 622

01-02 * < LOD < LOD < LOD < LOD 566

03-04 * < LOD .004 (<LOD-.006) .008 (.006-.009) .011 (.009-.014) 422

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 405

01-02 * < LOD < LOD < LOD < LOD 510

03-04 .003 (.003-.004) .004 (.003-.006) .011 (.008-.014) .025 (.016-.031) .040 (.026-.050) 448

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 716

01-02 * < LOD < LOD < LOD < LOD 1055 

03-04 .004 (.004-.005) .006 (.005-.008) .012 (.010-.014) .018 (.016-.021) .025 (.022-.027) 869

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 426 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3',4,4',5,5'-Hexachlorobiphenyl (PCB 167) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1908 

01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 .494 (.441-.553) .700 (.560-.800) 1.60 (1.40-1.70) 2.99 (2.74-3.36) 4.10 (3.80-4.47) 1864 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 666

01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD < LOD .640 (.500-.770) .870 (.700-1.10) 584

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1242 

01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 .592 (.521-.673) .860 (.700-1.00) 1.72 (1.55-2.03) 3.30 (2.90-3.60) 4.30 (3.90-4.81) 1280 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 908

01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 .423 (<LOD-.471) .500 (.440-.600) 1.33 (1.16-1.60) 2.70 (2.25-3.50) 3.80 (3.50-4.70) 931

Females 99-00 * < LOD < LOD < LOD < LOD 1000 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 .573 (.492-.669) .880 (.660-1.06) 1.71 (1.51-2.10) 3.21 (2.82-3.62) 4.30 (3.80-4.70) 933

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 627

01-02 * < LOD < LOD < LOD < LOD 564

03-04 * < LOD .600 (.400-.800) 1.20 (.960-1.44) 1.70 (1.30-1.94) 419

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 411

01-02 * < LOD < LOD < LOD < LOD 515

03-04 .521 (.432-.628) .560 (.460-.800) 1.95 (1.25-2.40) 4.30 (3.27-6.79) 7.90 (4.70-11.8) 451

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 715

01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 .538 (.458-.632) .800 (.600-.990) 1.66 (1.42-1.90) 2.98 (2.70-3.45) 3.94 (3.62-4.47) 875

Limit of detection (LOD, see Data Analysis section) for Survey years 99-00, 01-02, and 03-04 are 12.4, 10.5, and 0.4, respectively. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 427

 Dioxin-Like Chemicals

Serum 2,3',4,4',5,5'-Hexachlorobiphenyl (PCB 167) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 99-00 * < LOD < LOD < LOD < LOD 1908 

01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 .003 (.003-.003) .004 (.003-.005) .010 (.009-.012) .020 (.018-.022) .026 (.024-.027) 1864 

Age group 

12-19 years 99-00 * < LOD < LOD < LOD < LOD 666

01-02 * < LOD < LOD < LOD < LOD 758

03-04 * < LOD < LOD .004 (.003-.004) .005 (.004-.005) 584

20 years and older 99-00 * < LOD < LOD < LOD < LOD 1242 

01-02 * < LOD < LOD < LOD < LOD 1540 

03-04 .004 (.003-.004) .005 (.004-.006) .012 (.010-.013) .021 (.019-.023) .027 (.025-.030) 1280 

Gender 

Males 99-00 * < LOD < LOD < LOD < LOD 908

01-02 * < LOD < LOD < LOD < LOD 1069 

03-04 .003 (<LOD-.003) .003 (.003-.004) .009 (.008-.010) .018 (.015-.021) .023 (.021-.026) 931

Females 99-00 * < LOD < LOD < LOD < LOD 1000 

01-02 * < LOD < LOD < LOD < LOD 1229 

03-04 .003 (.003-.004) .005 (.004-.006) .012 (.010-.013) .022 (.019-.024) .027 (.025-.031) 933

Race/ethnicity 

Mexican Americans 99-00 * < LOD < LOD < LOD < LOD 627

01-02 * < LOD < LOD < LOD < LOD 564

03-04 * < LOD .004 (.003-.004) .009 (.007-.011) .013 (.010-.015) 419

Non-Hispanic blacks 99-00 * < LOD < LOD < LOD < LOD 411

01-02 * < LOD < LOD < LOD < LOD 515

03-04 .003 (.002-.004) .003 (.003-.005) .012 (.008-.015) .028 (.019-.042) .051 (.030-.072) 451

Non-Hispanic whites 99-00 * < LOD < LOD < LOD < LOD 715

01-02 * < LOD < LOD < LOD < LOD 1056 

03-04 .003 (.003-.004) .005 (.004-.006) .011 (.009-.013) .020 (.018-.022) .025 (.023-.027) 875

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 428 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

Serum 2,3,3’,4,4’,5,5’-Heptachlorobiphenyl (PCB 189) (lipid adjusted) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of lipid or parts per billion on a lipid-weight basis)

for the U.S. population from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 * < LOD < LOD .900 (.700-1.16) 1.47 (1.10-2.18) 1817 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 752

03-04 * < LOD < LOD < LOD 1.00 (<LOD-3.09) 570

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1546 

03-04 * < LOD < LOD 1.00 (.760-1.20) 1.50 (1.10-2.14) 1247 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1070 

03-04 * < LOD < LOD 1.00 (.800-1.20) 1.54 (1.20-2.23) 903

Females 01-02 * < LOD < LOD < LOD < LOD 1228 

03-04 * < LOD < LOD .830 (.600-1.14) 1.39 (.890-2.18) 914

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 564

03-04 * < LOD < LOD < LOD .700 (<LOD-1.00) 406

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 514

03-04 * < LOD < LOD 1.20 (.840-1.60) 1.85 (1.20-2.83) 444

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1057 

03-04 * < LOD < LOD .900 (.700-1.26) 1.51 (1.04-2.19) 851

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 10.5 and 0.4. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 429

 Dioxin-Like Chemicals

Serum 2,3,3’,4,4’,5,5’-Heptachlorobiphenyl (PCB 189) (whole weight) 

Geometric mean and selected percentiles of serum concentrations (in ng/g of serum or parts per billion) for the U.S. population

from the National Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 * < LOD < LOD < LOD < LOD 2298 

03-04 * < LOD < LOD .006 (.005-.008) .010 (.007-.014) 1817 

Age group 

12-19 years 01-02 * < LOD < LOD < LOD < LOD 752

03-04 * < LOD < LOD < LOD .005 (<LOD-.017) 570

20 years and older 01-02 * < LOD < LOD < LOD < LOD 1546 

03-04 * < LOD < LOD .006 (.005-.008) .010 (.007-.014) 1247 

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 1070 

03-04 * < LOD < LOD .006 (.005-.009) .011 (.008-.014) 903

Females 01-02 * < LOD < LOD < LOD < LOD 1228 

03-04 * < LOD < LOD .005 (.004-.008) .009 (.006-.014) 914

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 564

03-04 * < LOD < LOD < LOD .005 (<LOD-.007) 406

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 514

03-04 * < LOD < LOD .008 (.005-.010) .012 (.007-.016) 444

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 1057 

03-04 * < LOD < LOD .006 (.005-.008) .010 (.007-.014) 851

< LOD means less than the limit of detection for the lipid adjusted serum level, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 430 Fourth National Report on Human Exposure to Environmental Chemicals 

Dioxin-Like Chemicals

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burdens of polychlorinated dibenzo-p-dioxins, dibenzofurans, 

and biphenyls and their relations to estrogen metabolism in 

pregnant women. Environ Health Perspect 2006;114(5):740-745.

Warner M, Eskenazi B, Olive DL, Samuels S, Quick-Miles S, 

Vercellini P, et al. Serum dioxin concentrations and quality of 

ovarian function in women of Seveso. Environ Health Perspect 

2007;115(3):336-340.

Warner M, Samuels S, Mocarelli P, Gerthoux PM, Needham L, 

Patterson DG Jr, et al. Serum dioxin concentrations and age at 

menarche. Environ Health Perspect 2004;112(13):1289-1292.

Yoshida J, Kumagai S, Tabuchi T, Kosaka H, Akasaka S, Oda H. 

Effects of dioxin on metabolism of estrogens in waste incinerator 

workers. Arch Environ Occup Health 2005;60(4):215-222.
 434 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Polycyclic Aromatic Hydrocarbons

General Information

Polycyclic aromatic hydrocarbons (PAHs) are a class of 

more than 100 chemicals generally produced during the 

incomplete burning of organic materials, including coal, 

oil, gas, wood, garbage, and tobacco. PAHs are composed 

of up to six benzene rings fused together such that any two 

adjacent benzene rings share two carbon bonds. Examples 

include phenanthrenes, naphthalene, and pyrene. Important 

PAH sources include motor vehicle exhaust, residential and 

industrial heating sources, coal, crude oil and natural gas 

processing, waste incineration, and tobacco smoke. The 

emitted PAHs can form or bind to particles in the air, and 

particle size depends in part on the source of the PAHs. The 

smaller or fine particulates (e.g., PM2.5 or smaller) have 

higher concentrations of PAHs than the larger or coarse 

particulates (Bostrom et al., 2002; Rehwagen et al., 2005). 

Ambient air PAH concentrations show seasonal variation 

(IPCS, 1998; Rehwagen et al., 2005). Smoking, grilling, 

broiling, or other high temperature processing leads to PAH 

formation in meat and in other foods, as well. Uncooked 

foods and vegetables generally contain low levels of PAHs 

but can be contaminated by airborne particle deposition 

or growth in contaminated soil. With the exception of 

naphthalene, the PAHs described here are not produced 

commercially in the U.S.

Human exposure usually occurs to PAH mixtures rather 

than to individual chemicals, and PAH mixture composition 

varies with the combustion source and temperature (ATSDR, 

1995). For persons without occupational exposure, 

important sources of PAHs include ambient air pollution 

(especially motor vehicle exhaust), smoke from wood or 

fossil fuels, tobacco smoke, and foods. PAH exposure can 

occur in workplaces where petroleum products are burned 

or coked, such as coke production, coal gasification and gas 

refining, iron or steel production, roofing tar and asphalt 

application, waste incineration, and aluminum smelting. 

Coal tar ointments containing PAHs are used to treat several 

inflammatory skin conditions.

PAHs are lipid soluble and can be absorbed through the 

skin, respiratory tract, and gastrointestinal tract. PAH 

metabolism is complex and occurs primarily in the liver, and 

to a lesser extent, in other tissues. PAH elimination occurs 

via urine and feces, and urinary metabolites are eliminated 

within a few days (Ramesh et al., 2004). PAHs and their 

urinary hydroxylated metabolites that are measured in this 

Report are shown in the table. The metabolic pathways and 

enzyme-inducing effects of specific PAHs, such as benz[a]

pyrene, have been actively studied to elucidate cancer 

potential and causal mechanisms (Ramesh et al., 2004). 

Although immunologic, kidney and brain toxicity have 

been seen in animals after high doses were administered, 

it is unclear if similar effects may occur in humans. Lung, 

bladder, and skin cancers have been reported in occupational 

settings following high PAH exposures (Bosetti et al., 

2007; Bostrom et al., 2002; Lloyd, 1971). Exposure to 

fine particulates has been associated with fetal growth 

retardation, respiratory disorders, and cardiovascular 

disease, but it is unknown whether PAHs contained within 

fine particulates are etiologic (ATSDR, 1995; Choi, 2006).

IARC classifies naphthalene as a possible human carcinogen. 

NTP determined that naphthalene is reasonably anticipated 

to be a human carcinogen. Many other PAHs are considered 

to be probable or possible human carcinogens. IARC and 

NTP have classified specific PAH-containing chemical 

mixtures (e.g., soot, coke oven emissions, coal tars and coal 

tar pitches) as human carcinogens. OSHA has developed 

Polycyclic Aromatic Hydrocarbon Metabolites in this Report

Polycyclic Aromatic Hydrocarbon 

(CAS number)

Urinary hydroxylated metabolite 

(CAS number)

Fluorene (86-73-7) 

2-Hydroxyfluorene (2443-58-5) 

3-Hydroxyfluorene (6344-67-8) 

9-Hydroxyfluorene (484-17-3) 

Naphthalene (91-20-3) 1-Hydroxynapthalene (90-15-3) 

2-Hydroxynapthalene (135-19-3) 

Phenanthrene (85-01-8) 

1-Hydroxyphenanthrene (2433-56-9) 

2-Hydroxyphenanthrene 

3-Hydroxyphenanthrene (605-87-8) 

4-Hydroxyphenanthrene (7651-86-7) 

Pyrene (129-00-0) 1-Hydroxypyrene (5315-79-7) 
Fourth National Report on Human Exposure to Environmental Chemicals 435

 Polycyclic Aromatic Hydrocarbons 

criteria on the allowable levels of these chemicals in the 

workplace.

Information about external exposure (i.e., environmental 

levels) and health effects is available in reviews (Bosetti et 

al., 2007; Bostrom et al., 2002; Brandt and Watson 2003) 

and from ATSDR at: http://www.atsdr.cdc.gov/toxpro2.

html.

Biomonitoring Information

Measurement of urinary metabolites reflects recent exposure 

to PAHs. Some of the parent PAHs can produce more than 

one measurable urinary metabolite, as shown in the Table. 

The hydroxylated metabolites of PAHs are excreted in 

human urine both as free hydroxylated metabolites and as 

hydroxylated metabolites conjugated to glucuronic acid and 

sulfate. Urine metabolite profiles can vary depending on the 

PAH source(s), but also have been found to vary between 

individuals experiencing similar exposures within the same 

workplace (Grimmer et al., 1997; Jacob and Seidel 2002).

Finding a measurable amount of one or more metabolites 

in the urine does not mean that the levels of the PAH 

metabolites or the parent PAH cause an adverse health 

effect. Biomonitoring studies of urinary PAHs provide 

physicians and public health officials with reference values 

so that they can determine whether or not people have 

been exposed to higher levels of PAHs than are found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for polycyclic aromatic hydrocarbons 1995 

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp69.html. 5/26/09

Bosetti C, Boffetta P, La Vecchia C. Occupational exposures 

to polycyclic aromatic hydrocarbons, and respiratory and 

urinary tract cancers: a quantitative review to 2005. Ann Oncol 

2007;18:431-446.

Bostrom CE, Gerde P, Hanberg A, Jernstrom B, Johansson 

C, Kyrklund T, et al. Cancer risk assessment, indicators, and 

guidelines for polycyclic aromatic hydrocarbons in the ambient 

air. Environ Health Perspect 2002;110Suppl 3:451-488.

Brandt HCA, Watson WP. Monitoring human occupational and 

environmental exposures to polycyclic aromatic compounds. 

Ann Occup Hyg 2003;47(5):349-378.

Choi H, Jedrychowski W, Spengler J, Camann DE, Whyatt 

RM, Rauh V, et al., International studies of prenatal exposure 

to polycyclic aromatic hydrocarbons and fetal growth. Environ 

Health Perspect 2006;114(11):1744-1750.

Grimmer G, Jacob J, Dettbarn G, Naujack K-W. Determination of 

urinary metabolites of polycyclic aromatic hydrocarbons (PAH) 

for the risk assessment of PAH-exposed workers. Int Arch Occup 

Environ Health 1997;69:231-239.

International Programme on Chemical Safety (IPCS). 

Selected non-heterocyclic policyclic aromatic hydrocarbons. 

Environmental Health Criteria 202. 1998 [online].Available at 

URL: http://www.inchem.org/documents/ehc/ehc/ehc202.htm. 

5/26/09

Jacob J, Seidel A. Biomonitoring of polycyclic aromatic 

hydrocarbons in human urine. J Chromatogr B 2002;778(1-

2):31-47.

Lloyd J. Long-term mortality study of steelworkers. V. Respiratory 

cancer in coke plant workers. J Occup Med 1971;13:53-68.

Ramesh A, Walker SA, Hood DB, Guillen MD, Schneider K, 

Weyand EH. Bioavailability and risk assessment of orally ingested 

polycyclic aromatic hydrocarbons. Int J Toxicol 2004;23(5):301-

333.

Rehwagen M, Muller A, Massolo L, Herbarth O, Ronco A. 

Polycyclic aromatic hydrocarbons associated with particles in 

ambient air from urban and industrial areas. Sci Tot Environ 

2005;348:199-210.
 436 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Fluorene

CAS No. 86-73-7

Fluorene can be an intermediate in several chemical 

processes, and it is used to form polyradicals for resins and 

in manufacturing dyestuffs. Fluorene is frequently detected 

in the vapor phase of various PAH emission sources, 

including coal tar pitch, petroleum refineries, diesel 

exhaust fumes, and tobacco smoke, where it is the second 

most abundant PAH (Ding et al., 2005). Fluorene is present 

in air particulates resulting from vehicle emissions and 

combustion of coal and petroleum-based fuels (Fang et al., 

2006). IARC determined that fluorene was not classifiable 

with respect to human carcinogenicity.

Biomonitoring Information

Urinary levels of 2-hydroxyfluorene, 3-hydroxyfluorene, 

and 9-hydroxyfluorene reflect recent exposure. Mean levels 

of 2-hydroxyfluorene were significantly higher in Japanese 

smokers than non-smokers in one small study (Toriba et al., 

2003). By comparison, geometric mean and median urinary 

2-hydroxyfluorene levels in adults in this Report were 

similar to the mean levels in the smokers and somewhat 

higher than those in the non-smokers.

Finding a measurable amount of one or more urinary 

fluorene metabolites does not mean that the level causes 

an adverse health effect. Biomonitoring studies of urinary 

fluorene metabolites can provide physicians and public 

health officials with reference values so that they can 

determine whether or not people have been exposed to 

higher levels of fluorene than levels found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Urinary 2-Hydroxyfluorene 

Metabolite of Fluorene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 304 (262-354) 280 (242-319) 679 (561-815) 1850 (1430-2190) 2670 (2230-3130) 2521 

Age group 

6-11 years 03-04 209 (183-239) 228 (189-259) 341 (295-411) 576 (423-728) 763 (613-827) 338

12-19 years 03-04 281 (245-321) 292 (259-323) 502 (445-601) 1000 (753-1320) 1480 (1320-1930) 707

20 years and older 03-04 323 (272-383) 290 (247-334) 832 (653-1020) 2090 (1680-2460) 2920 (2410-3650) 1476 

Gender 

Males 03-04 385 (333-446) 338 (300-415) 900 (739-1150) 2120 (1770-2450) 2930 (2490-3390) 1213 

Females 03-04 243 (204-290) 226 (184-269) 490 (405-617) 1400 (907-1930) 2310 (1740-3070) 1308 

Race/ethnicity 

Mexican Americans 03-04 248 (215-286) 235 (203-293) 502 (412-580) 1100 (771-1330) 1640 (1250-2240) 629

Non-Hispanic blacks 03-04 432 (361-516) 381 (317-462) 856 (702-1270) 2200 (1830-2610) 2960 (2350-4460) 684

Non-Hispanic whites 03-04 308 (255-372) 280 (233-332) 728 (554-898) 1940 (1540-2390) 2920 (2400-3500) 1045 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 5.0. 
Fourth National Report on Human Exposure to Environmental Chemicals 437

 Polycyclic Aromatic Hydrocarbons 

Urinary 2-Hydroxyfluorene (creatinine corrected) 

Metabolite of Fluorene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 286 (256-320) 221 (200-249) 495 (429-629) 1510 (1150-1800) 2070 (1850-2390) 2521 

Age group 

6-11 years 03-04 221 (199-246) 217 (188-238) 305 (270-356) 462 (370-535) 695 (465-807) 338

12-19 years 03-04 213 (189-240) 189 (172-211) 310 (275-377) 649 (512-778) 937 (762-1320) 707

20 years and older 03-04 310 (274-350) 233 (203-269) 659 (494-835) 1730 (1420-1940) 2310 (1930-2590) 1476 

Gender 

Males 03-04 302 (271-337) 242 (218-272) 635 (494-758) 1510 (1200-1700) 1940 (1700-2310) 1213 

Females 03-04 271 (235-314) 208 (183-244) 415 (352-521) 1530 (991-1890) 2220 (1730-2590) 1308 

Race/ethnicity 

Mexican Americans 03-04 224 (197-255) 198 (178-227) 370 (306-432) 745 (562-1030) 1200 (745-1730) 629

Non-Hispanic blacks 03-04 308 (259-365) 249 (210-305) 609 (430-803) 1430 (939-1870) 1880 (1430-2500) 684

Non-Hispanic whites 03-04 304 (266-349) 226 (199-261) 581 (449-796) 1630 (1410-1940) 2310 (1940-2540) 1045 
 438 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Urinary 3-Hydroxyfluorene 

Metabolite of Fluorene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 134 (115-155) 111 (96.0-126) 253 (207-349) 959 (666-1300) 1620 (1390-1900) 2745 

03-04 126 (108-148) 103 (90.4-118) 302 (231-404) 1090 (934-1270) 1740 (1400-2070) 2502 

Age group 

6-11 years 01-02 106 (94.8-119) 106 (91.0-124) 174 (145-200) 287 (235-358) 385 (306-455) 387

03-04 89.2 (77.3-103) 92.3 (79.7-103) 151 (113-172) 238 (184-331) 343 (241-423) 336

12-19 years 01-02 129 (103-161) 113 (97.0-137) 222 (177-266) 542 (325-1070) 1210 (680-2130) 733

03-04 116 (100-134) 114 (94.7-133) 214 (181-269) 476 (317-748) 924 (609-1410) 701

20 years and older 01-02 138 (119-161) 111 (94.0-129) 311 (228-429) 1130 (823-1400) 1850 (1470-2080) 1625 

03-04 134 (112-160) 105 (86.5-125) 408 (300-537) 1240 (1050-1480) 1910 (1620-2290) 1465 

Gender 

Males 01-02 163 (137-194) 134 (115-155) 352 (242-481) 1110 (721-1500) 1850 (1390-2190) 1346 

03-04 165 (140-194) 133 (108-162) 458 (313-681) 1270 (1030-1530) 1920 (1580-2120) 1205 

Females 01-02 111 (95.0-130) 94.0 (83.0-108) 204 (169-250) 796 (498-1040) 1390 (1250-1670) 1399 

03-04 98.2 (81.2-119) 80.5 (66.7-101) 195 (163-272) 842 (530-1200) 1590 (1180-1800) 1297 

Race/ethnicity 

Mexican Americans 01-02 108 (87.1-134) 99.0 (81.0-119) 190 (144-255) 476 (302-641) 718 (476-1140) 662

03-04 93.4 (79.6-110) 83.4 (67.0-96.9) 190 (150-252) 520 (388-726) 1030 (688-1320) 622

Non-Hispanic blacks 01-02 203 (169-244) 162 (135-188) 449 (308-830) 1420 (1130-1780) 2350 (1520-3000) 692

03-04 195 (157-242) 160 (124-187) 482 (303-827) 1460 (1070-1800) 2110 (1580-2830) 683

Non-Hispanic whites 01-02 130 (108-157) 108 (93.0-127) 246 (202-352) 948 (621-1320) 1620 (1320-1990) 1207 

03-04 129 (106-155) 105 (87.6-124) 313 (237-464) 1200 (1010-1410) 1870 (1430-2220) 1035 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 2.0 and 5.0. 
Fourth National Report on Human Exposure to Environmental Chemicals 439

 Polycyclic Aromatic Hydrocarbons 

Urinary 3-Hydroxyfluorene (creatinine corrected) 

Metabolite of Fluorene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 125 (108-144) 94.4 (83.3-106) 220 (174-303) 754 (622-873) 1060 (909-1290) 2745 

03-04 119 (106-134) 86.6 (76.8-97.3) 256 (201-337) 856 (668-1060) 1330 (1130-1590) 2502 

Age group 

6-11 years 01-02 119 (103-137) 110 (96.7-121) 153 (135-197) 265 (206-377) 382 (254-631) 387

03-04 94.6 (84.3-106) 92.4 (83.1-98.5) 130 (115-154) 202 (168-282) 311 (197-435) 336

12-19 years 01-02 99.3 (81.6-121) 81.9 (74.2-92.6) 144 (109-197) 390 (214-700) 711 (372-1380) 733

03-04 88.1 (78.0-99.6) 79.0 (72.5-83.2) 137 (114-170) 319 (225-440) 586 (356-880) 701

20 years and older 01-02 131 (113-151) 94.4 (81.0-108) 279 (195-367) 862 (727-923) 1210 (1010-1350) 1625 

03-04 128 (113-146) 88.2 (76.8-104) 364 (242-484) 1020 (828-1240) 1500 (1290-1710) 1465 

Gender 

Males 01-02 132 (111-156) 100 (88.5-117) 260 (194-361) 745 (560-914) 1130 (862-1380) 1346 

03-04 129 (114-147) 95.8 (82.5-111) 338 (226-456) 833 (672-1010) 1220 (980-1510) 1205 

Females 01-02 119 (104-136) 88.9 (78.6-103) 179 (156-227) 777 (604-888) 1030 (923-1270) 1399 

03-04 110 (93.4-129) 81.7 (69.5-91.5) 183 (132-285) 920 (488-1270) 1460 (1130-1750) 1297 

Race/ethnicity 

Mexican Americans 01-02 101 (84.2-121) 84.0 (74.8-97.2) 159 (124-214) 364 (227-598) 604 (357-1230) 662

03-04 84.8 (73.1-98.4) 68.8 (60.0-80.2) 170 (119-213) 353 (319-435) 668 (353-1050) 622

Non-Hispanic blacks 01-02 143 (118-173) 110 (90.7-133) 316 (186-525) 849 (622-1230) 1240 (882-1430) 692

03-04 139 (113-169) 106 (93.1-118) 328 (211-488) 961 (580-1310) 1310 (961-1770) 683

Non-Hispanic whites 01-02 128 (108-152) 94.7 (83.4-109) 223 (171-323) 816 (642-914) 1150 (910-1410) 1207 

03-04 127 (110-146) 89.8 (79.1-104) 311 (212-418) 980 (768-1180) 1460 (1270-1700) 1035 
 440 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Urinary 9-Hydroxyfluorene 

Metabolite of Fluorene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 267 (234-305) 269 (233-313) 541 (463-620) 929 (839-1060) 1390 (1130-1600) 2504 

Age group 

6-11 years 03-04 209 (184-238) 216 (173-240) 331 (267-458) 594 (446-809) 853 (553-1500) 333

12-19 years 03-04 253 (216-297) 271 (215-324) 506 (413-560) 894 (773-988) 1210 (929-1510) 698

20 years and older 03-04 277 (240-320) 279 (237-335) 583 (476-656) 979 (842-1140) 1490 (1140-1770) 1473 

Gender 

Males 03-04 330 (291-374) 330 (285-372) 632 (583-709) 1090 (898-1370) 1720 (1360-2250) 1208 

Females 03-04 218 (188-253) 226 (191-253) 439 (357-521) 833 (697-973) 1100 (955-1310) 1296 

Race/ethnicity 

Mexican Americans 03-04 229 (200-261) 232 (197-274) 435 (362-492) 773 (561-1010) 1030 (849-1170) 614

Non-Hispanic blacks 03-04 380 (311-465) 357 (291-475) 709 (559-825) 1260 (1080-1600) 1880 (1560-2330) 679

Non-Hispanic whites 03-04 266 (226-313) 266 (228-324) 558 (453-659) 939 (824-1130) 1450 (1090-1770) 1048 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 5.0. 

Urinary 9-Hydroxyfluorene (creatinine corrected) 

Metabolite of Fluorene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 252 (230-276) 233 (205-266) 412 (371-461) 729 (609-905) 1100 (918-1390) 2504 

Age group 

6-11 years 03-04 223 (200-247) 208 (176-264) 343 (299-389) 548 (433-689) 866 (533-958) 333

12-19 years 03-04 192 (172-215) 182 (161-200) 323 (286-360) 484 (412-696) 738 (571-1110) 698

20 years and older 03-04 267 (242-294) 243 (219-280) 446 (392-490) 788 (641-994) 1280 (991-1560) 1473 

Gender 

Males 03-04 260 (238-283) 236 (209-269) 429 (382-480) 739 (591-952) 1300 (916-1800) 1208 

Females 03-04 244 (217-275) 227 (198-269) 396 (342-467) 717 (569-905) 1020 (905-1280) 1296 

Race/ethnicity 

Mexican Americans 03-04 209 (188-232) 195 (181-209) 335 (293-379) 541 (447-722) 793 (569-1440) 614

Non-Hispanic blacks 03-04 272 (226-326) 258 (208-307) 463 (349-568) 777 (628-920) 1040 (863-1300) 679

Non-Hispanic whites 03-04 263 (235-295) 244 (211-287) 439 (387-490) 773 (607-1020) 1290 (967-1700) 1048 
Fourth National Report on Human Exposure to Environmental Chemicals 441

 Polycyclic Aromatic Hydrocarbons 

References

Ding YS, Trommel JS, Yan Xj, Ashley D, Watson CH. 

Determination of 14 polycyclic aromatic hydrocarbons in 

mainstream smoke from domestic cigarettes. Environ Sci Technol 

2005;39:471-478.

Fang G-C, Wu Y-S, Chen J-C, Chang C-N, Ho T-T. characteristic 

of polycyclic aromatic hydrocarbon concentrations and source 

identification for fine and coarse particulates at Taichung 

Harbor near Taiwan Strait during 2004-2005. Sci Tot Environ 

2006;366:729-738.

Toriba A, Chetiyanukornkul T, Kizu R, Hayakawa K. 

Quantification of 2-hydroxyfluorene in human urine by columnswitching high performance liquid chromatography with 

fluorescence detection. Analyst 2003;128(6):605-610.
 442 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Naphthalene

CAS No. 91-20-3

Naphthalene is produced commercially from coal tar 

and petroleum. It is used in producing an assortment of 

chemicals: phthalate plasticizers, naphthalene sulfonates 

and dyes, the insecticide carbaryl, and synthetic leather 

tanning chemicals. Naphthalene is an intermediate in 

manufacturing several pharmaceuticals. Crystalline 

naphthalene has been used as a moth repellent. Naphthalene 

is the most abundant PAH in cigarette smoke (Ding 

et al., 2005), and it is present in fossil fuel smoke and 

exhaust fumes, especially from diesel and jet fuels. Nonoccupational exposure typically occurs through inhaling 

ambient and indoor air, and cigarette smoke. Naphthalene 

can be absorbed through the skin as a result of handling 

moth repellent or wearing clothes stored with moth 

repellent. Workers may be exposed via inhalation or dermal 

absorption in settings such as naphthalene production, coal 

coking operations, and wood treatment with creosote.

In the body, naphthalene metabolism is complex, leading 

to biologically reactive metabolites and other metabolites 

that are excreted in the urine. In studies of workers, 

naphthalene air concentrations were correlated with 1- 

and 2-hydroxynaphthalene urine concentrations (Bieniek 

1994; 1997). Both naphthalene and the insecticide carbaryl 

are metabolized to 1-hydroxynaphthalene, making it 

difficult to distinguish between these exposures in the 

general population (Meeker et al., 2007). In contrast, only 

naphthalene metabolism results in 2-hydroxynaphthalene 

in urine.

Humans can develop hemolytic anemia and jaundice after 

high dose naphthalene exposure by either inhalation or 

ingestion, or from skin exposure to clothing and bedding 

treated with naphthalene moth repellents (ATSDR, 2005). 

Exposure to naphthalene vapor can irritate the eyes and 

respiratory tract. High dose and chronic exposure in 

occupational settings can result in cataracts or lens opacities 

(ATSDR, 2005). OSHA has established a workplace 

standard. IARC considers naphthalene to be a possible 

human carcinogen, and NTP considers that it is reasonably 

anticipated to be a human carcinogen.

Biomonitoring Information

Urinary levels of 1-hydroxynaphthalene and 

2-hydroxynaphthalene (1-naphthol and 2-naphthol, 

respectively) reflect recent exposure. Levels similar to 

those reported in NHANES 2001-2002 and 2003-2004 

subsamples have been found in small studies of pre-school 

children, adolescents and non-occupationally exposed 

adults (Kang et al., 2002; Kim et al., 2003; Kuusimaki 

et al., 2004; Wilson et al., 2003). Smokers typically have 

urinary 1- and 2-hydroxynaphthalene levels that are about 

2 to 3 times higher than nonsmokers in both occupationally 

exposed and general populations (Campo et al., 2006; Nan 

et al., 2001; Serdar et al., 2003a, 2003b). Depending on 

the intensity of exposure, workers exposed to naphthalene 

have been found to have geometric mean urinary 1- and 

Urinary 1-Hydroxynaphthalene (1-Naphthol) 

Metabolite of Naphthalene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 2680 (2360-3050) 2260 (1980-2650) 7660 (6270-9420) 18500 (15500-20900) 26100 (23000-33600) 2595

Age group 

6-11 years 03-04 1540 (1360-1750) 1330 (1110-1680) 2790 (2180-3520) 5770 (4110-8200) 10500 (5870-17000) 340

12-19 years 03-04 1960 (1680-2280) 1670 (1500-1970) 4190 (3100-5400) 10500 (8430-14300) 20900 (13500-26100) 727

20 years and older 03-04 3020 (2580-3520) 2650 (2200-3200) 9420 (7320-11500) 20500 (16500-23400) 29400 (23400-37400) 1528

Gender 

Males 03-04 3170 (2820-3560) 2840 (2370-3390) 8790 (7130-11000) 19600 (16100-22200) 25800 (22500-30600) 1243

Females 03-04 2290 (1940-2720) 1840 (1500-2310) 6380 (4450-8810) 17900 (14000-21500) 28500 (21500-37400) 1352

Race/ethnicity 

Mexican Americans 03-04 1950 (1720-2190) 1650 (1370-2040) 4380 (3520-5300) 11600 (9040-15500) 20100 (14900-22500) 651

Non-Hispanic blacks 03-04 3340 (2800-3990) 2650 (2190-3460) 7840 (6520-10800) 20800 (17000-28600) 34700 (25400-48900) 695

Non-Hispanic whites 03-04 2800 (2410-3250) 2310 (1930-2840) 8630 (6820-11000) 19900 (15900-22600) 27600 (23400-35100) 1084

Limit of detection (LOD, see data analysis section) for Survey period 03-04 is 46.7. 
Fourth National Report on Human Exposure to Environmental Chemicals 443

 Polycyclic Aromatic Hydrocarbons 

2-hydroxynaphthalene levels that range from around 2 to 

100 times higher than the levels in this Report (Bieniek 

1997; Elovaara et al., 2006; Nan et al., 2001; Serdar et al., 

2003a).

Finding a measurable amount of 1- or 2-hydroxynaphthalene 

in the urine does not mean that the level causes an adverse 

health effect. Biomonitoring studies on levels of 1- and 

2-naphthalene provide physicians and public health officials 

with reference values so that they can determine whether 

people have been exposed to higher levels of naphthalene 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

Urinary 1-Hydroxynaphthalene (1-Naphthol) (creatinine corrected) 

Metabolite of Naphthalene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 2520 (2280-2790) 2100 (1870-2400) 6560 (5430-8180) 15100 (13500-17400) 21800 (18200-25400) 2595

Age group 

6-11 years 03-04 1630 (1430-1860) 1360 (1180-1740) 2770 (2260-3200) 5690 (3990-8950) 10200 (5690-16400) 340

12-19 years 03-04 1470 (1260-1710) 1200 (1020-1390) 2840 (2490-4080) 7560 (5470-9120) 10800 (9120-13400) 727

20 years and older 03-04 2900 (2590-3250) 2520 (2120-3060) 8210 (6450-9810) 16900 (14400-19800) 24200 (20000-27200) 1528

Gender 

Males 03-04 2490 (2250-2750) 2140 (1860-2590) 6560 (5500-8010) 13500 (12300-14400) 18300 (16600-20700) 1243

Females 03-04 2560 (2220-2950) 2040 (1730-2440) 6680 (5000-8850) 17500 (13500-21700) 24700 (19800-30600) 1352

Race/ethnicity 

Mexican Americans 03-04 1750 (1590-1930) 1500 (1260-1690) 3240 (2900-4250) 8550 (7150-12000) 17500 (13500-21400) 651

Non-Hispanic blacks 03-04 2370 (2020-2780) 2000 (1560-2420) 5900 (4440-7070) 13800 (8930-18700) 21100 (17100-27800) 695

Non-Hispanic whites 03-04 2770 (2460-3120) 2350 (1940-2900) 8030 (6330-9260) 16600 (14400-18500) 23600 (20000-26600) 1084
 444 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Urinary 2-Hydroxynaphthalene (2-Naphthol) 

Metabolite of Naphthalene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 2470 (2110-2890) 2280 (1930-2670) 5680 (4580-6830) 14700 (12800-19500) 26000 (22500-29700) 2748

03-04 3180 (2760-3670) 2960 (2500-3500) 7500 (6190-9690) 17300 (14500-22100) 25800 (22600-27700) 2575

Age group 

6-11 years 01-02 1690 (1560-1840) 1700 (1400-1950) 3010 (2580-3470) 5410 (3890-6700) 7720 (6300-9540) 387

03-04 2110 (1800-2470) 2140 (1790-2590) 3570 (3140-4380) 5580 (5050-6380) 9710 (5230-20000) 339

12-19 years 01-02 2220 (1700-2900) 2150 (1740-2530) 4390 (3150-6110) 11000 (6990-20400) 22500 (13900-28400) 735

03-04 3040 (2680-3460) 2910 (2510-3500) 5290 (4670-6590) 12400 (8530-16800) 17600 (15100-25900) 721

20 years and older 01-02 2620 (2220-3100) 2440 (1940-2950) 6380 (5110-8110) 17600 (14000-21100) 28100 (23300-33700) 1626

03-04 3360 (2860-3960) 3180 (2590-3960) 8770 (7210-11300) 19200 (16000-23200) 26600 (23400-28800) 1515

Gender 

Males 01-02 2750 (2360-3210) 2510 (2090-2970) 6060 (4820-7810) 16900 (11900-23000) 28100 (20800-35600) 1349

03-04 3520 (3090-4010) 3370 (2910-3880) 8520 (6960-10500) 18400 (15300-22600) 26100 (22200-27900) 1233

Females 01-02 2220 (1860-2660) 2060 (1650-2480) 5240 (3890-6440) 13900 (12300-17700) 25300 (19700-28300) 1399

03-04 2890 (2420-3450) 2600 (2140-3160) 6800 (5140-9210) 16600 (12700-21300) 23900 (22100-27600) 1342

Race/ethnicity 

Mexican Americans 01-02 2700 (2360-3080) 2710 (2350-3260) 5140 (4360-6150) 9640 (8150-10600) 14300 (10400-18700) 665

03-04 3130 (2710-3630) 3110 (2570-3850) 6740 (5600-8280) 14500 (10400-15600) 18000 (15500-20500) 648

Non-Hispanic blacks 01-02 3970 (3470-4540) 3460 (3100-4020) 9290 (6820-13200) 22800 (16000-29100) 33000 (25900-38700) 692

03-04 4690 (3830-5750) 4290 (3250-5540) 10300 (7670-13100) 21200 (17300-26100) 30100 (22300-40600) 690

Non-Hispanic whites 01-02 2190 (1760-2720) 1910 (1610-2420) 4970 (3710-6780) 14100 (10700-20200) 25900 (20700-30000) 1207

03-04 3080 (2580-3670) 2660 (2200-3530) 7640 (5890-10400) 18000 (14600-22900) 26100 (22900-27900) 1072

Limit of detection (LOD, see data analysis section) for Survey periods 01-02 and 03-04 are 2.4 and 31.1. 
Fourth National Report on Human Exposure to Environmental Chemicals 445

 Polycyclic Aromatic Hydrocarbons 

Urinary 2-Hydroxynaphthalene (2-Naphthol) (creatinine corrected) 

Metabolite of Naphthalene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 2310 (1980-2680) 1940 (1670-2300) 4730 (3820-5860) 11500 (9980-13100) 16700 (14100-19200) 2748

03-04 2990 (2670-3340) 2560 (2200-2970) 6340 (5010-7870) 14100 (11800-16300) 19900 (16000-23800) 2575

Age group 

6-11 years 01-02 1890 (1740-2070) 1830 (1720-1940) 3110 (2510-3470) 5040 (4380-5540) 6490 (5270-12400) 387

03-04 2240 (1890-2650) 2040 (1660-2440) 3540 (2840-3910) 5950 (4140-8510) 8720 (7560-12000) 339

12-19 years 01-02 1720 (1350-2190) 1510 (1340-1830) 2750 (2080-4070) 7180 (4070-10900) 11100 (7860-17400) 735

03-04 2280 (2060-2520) 2030 (1770-2350) 3780 (3200-4470) 7840 (6130-9110) 10500 (9100-12500) 721

20 years and older 01-02 2480 (2130-2880) 2080 (1680-2600) 5630 (4460-6940) 12400 (10900-13900) 17700 (15200-20600) 1626

03-04 3230 (2870-3640) 2910 (2360-3410) 7540 (6200-9100) 15600 (13100-17900) 21800 (17200-24000) 1515

Gender 

Males 01-02 2230 (1900-2610) 1860 (1630-2100) 4790 (3510-6120) 11400 (8950-14300) 15800 (13100-19200) 1349

03-04 2770 (2500-3060) 2360 (2130-2810) 6300 (5080-7360) 12800 (11300-14600) 16400 (14600-18300) 1233

Females 01-02 2380 (2050-2770) 1990 (1660-2560) 4730 (3790-6000) 11500 (10300-12800) 17400 (13700-21500) 1399

03-04 3210 (2760-3730) 2680 (2200-3260) 6430 (4740-8580) 16000 (11500-19900) 22500 (18100-25000) 1342

Race/ethnicity 

Mexican Americans 01-02 2520 (2230-2850) 2350 (2010-2950) 4650 (3970-5210) 7320 (6050-8090) 12000 (7820-15300) 665

03-04 2830 (2440-3280) 2570 (2200-3230) 5000 (4100-5940) 10300 (6790-13000) 13300 (11000-15500) 648

Non-Hispanic blacks 01-02 2790 (2390-3270) 2410 (2040-2770) 5980 (4840-6980) 11600 (9090-15300) 17400 (12200-23400) 692

03-04 3320 (2700-4090) 3060 (2310-3860) 7050 (5140-9410) 12800 (10200-16500) 19000 (15700-23400) 690

Non-Hispanic whites 01-02 2160 (1780-2620) 1740 (1440-2180) 4340 (3320-6090) 11900 (9930-14300) 16900 (13800-20600) 1207

03-04 3040 (2660-3460) 2480 (2110-3020) 7170 (5100-8950) 15500 (13300-17600) 21800 (17100-24000) 1072
 446 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

References

Agency for Toxic Substances and Disease Registry 

(ATSDR). Toxicological profile for naphthalene, 

1-methylnaphthalene, and 2-methylnaphthalene.

August 2005 (update) [online] Available at URL: http://www.

atsdr.cdc.gov/toxprofiles/tp67.html. 5/26/09

Bieniek G. The presence of 1-naphthol in the urine of industrial 

workers exposed to naphthalene. Occup Environ Med 

1994;51(5):357-359.

Bieniek G. Urinary napthols as an indicator of exposure to 

naphthalene. Scand J Work Environ Health 1997;23:414-420.

Campo L, Buratti M, Fustinoni S, Cirla PE, Martinotti I, Longhi 

O, et al. Evaluation of exposure to PAHs in asphalt workers by 

environmental and biological monitoring. Ann NY Acad Sci 

2006;1076:405-420.

Ding YS, Trommel JS, Yan Xj, Ashley D, Watson CH. 

Determination of 14 polycyclic aromatic hydrocarbons in 

mainstream smoke from domestic cigarettes. Environ Sci Technol 

2005;39:471-478.

Elovaara E, Mikkola J, Makela M, Paldanius B, Priha E. 

Assessment of soil remediation workers’ exposure to polycyclic 

aromatic hydrocarbons (PAH): Biomonitoring of naphthols, 

phenanthrols, and 1-hydroxypyrene in urine. Toxicol Lett 

2006;162:158-163.

Kang JW, Cho SH, Kim H, Lee CH. Correlation of urinary 

1-hydroxypyrene and 2-naphthol with total suspended particulates 

in ambient air in municipal middle-school students in Korea. 

Arch Environ Health 2002;57(4):377-382.

Kim YD, Lee CH, Nan HM, Kang JW, Kim H. Effects of genetic 

polymorphisms in metabolic enzymes on the relationships 

between 8-hydroxydeoxyguanosine levels in human leukocytes 

and urinary 1-hydroxypyrene and 2-naphthol concentrations. J 

Occup Health 2003;45(3):160-167.

Kuusimaki L, Peltonen Y, Mutanen P, Peltonen K, Savela K. 

Urinary hydroxy-metabolites of naphthalene, phenanthrene and 

pyrene as markers of exposure to diesel exhaust. Int Arch Occup 

Environ Health 2004;77(1):23-30.

Meeker JD, Barr DB, Serbar B, Rappaport SM, Hauser R. Utility of 

urinary 1-naphthol and 2-naphthol levels to assess environmental 

carbaryl and naphthalene exposure in an epidemiology study. J 

Expo Sci Eviron Epidemiol 2007;17(4):314-320.

Nan HM, Kim H, Lim HS, Choi JK, Kawamoto T, Kang JW, 

et al. Effects of occupation, lifestyle and genetic polymorphisms 

of CYP1A1, CYP2E1, GSTM1 and GSTT1 on urinary 

1-hydroxypyrene and 2-naphthol concentrations. Carcinogenesis 

2001;22(5):787-793.

Serdar B, Egeghy PP, Waidyanatha S, Gibson R, Rappaport SM. 

Urinary biomarkers of exposure to jet fuel (JP-8). Environ Health 

Perspect 2003a;111(14):1760-1764.

Serdar B, Waidyanatha S, Zheng Y, Rappaport SM. Simultaneous 

determination of urinary 1- and 2-naphthols, 3- and 9-phenanthrols, 

and 1-pyrenol in coke oven workers. Biomarkers 2003b;8(2):93-

109.
Fourth National Report on Human Exposure to Environmental Chemicals 447

 Polycyclic Aromatic Hydrocarbons 

Phenanthrene

CAS No. 85-01-8

Phenanthrene is used in manufacturing dyestuffs and 

explosives and in biological research. Sources of 

phenanthrene include diesel fuel exhaust, coal tar pitch and 

tobacco smoke. Phenanthrene has been found in particle 

emissions from natural gas combustion and municipal 

incinerator waste, and in the particulates present in ambient 

air pollution near high vehicular traffic and industrial or 

urban areas (ATSDR, 1995; Fang et al., 2006; Rehwagen 

et al., 2005). IARC determined that phenanthrene was not 

classifiable with respect to human carcinogenicity.

Biomonitoring Information

Urinary levels of 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 4-hydroxyphenanthrene reflect recent exposure. Geometric 

mean and median urine concentrations of 1- and 

3-hydroxyphenanthrene in a 1998 sample of German adults 

were about 2-fold higher than levels in the NHANES 

2001-2002 and 2003-2004 subsamples (Becker et al., 

2003). Children and adults in housing where coal tar 

flooring glue was applied had similar urinary 1-, 2-, 3-, and 

4-hydroxyphenanthrene levels compared to residents in 

houses without the glue; mean levels of these metabolites 

were higher than levels for similar age groups in this Report

(Heudorf and Angerer, 2001a). Smoking increases levels of 

urinary 2-, 3-, and 4-hydroxyphenanthrene (Becker et al., 

2003; Elovaara et al., 2006; Heudorf and Angerer 2001b; 

Jacob et al., 1999). Occupational PAH exposures have been 

associated with median urinary phenanthrene metabolite 

concentrations that range from 10 to 100 times higher than 

median values in the general population (Elovaara et al., 

2006; Gundel et al., 2000).

Finding a measurable amount of one or more urinary 

phenanthrene metabolites does not mean that the level 

causes an adverse health effect. Biomonitoring studies 

on levels of phenanthrene metabolites provide physicians 

and public health officials with reference values so that 

they can determine whether people have been exposed to 

higher levels of phenanthrene than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Urinary 1-Hydroxyphenanthrene 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 140 (125-158) 141 (130-154) 266 (229-312) 476 (426-539) 684 (581-763) 2741 

03-04 156 (140-173) 166 (150-179) 287 (263-321) 464 (423-508) 625 (538-745) 2496 

Age group 

6-11 years 01-02 119 (104-137) 121 (98.0-142) 228 (182-249) 357 (265-501) 501 (367-661) 387

03-04 138 (124-154) 131 (111-161) 222 (200-275) 397 (304-500) 615 (384-916) 328

12-19 years 01-02 133 (110-162) 131 (110-153) 238 (198-303) 431 (376-546) 579 (439-820) 733

03-04 158 (141-178) 171 (138-193) 300 (262-333) 470 (437-537) 654 (563-745) 692

20 years and older 01-02 145 (127-164) 145 (133-164) 274 (237-329) 499 (440-565) 713 (595-819) 1621 

03-04 157 (141-176) 167 (152-182) 296 (264-337) 469 (430-513) 625 (534-783) 1476 

Gender 

Males 01-02 150 (133-169) 145 (132-164) 284 (235-348) 501 (424-593) 713 (575-845) 1344 

03-04 176 (161-194) 182 (167-198) 321 (283-363) 492 (459-536) 662 (541-929) 1196 

Females 01-02 132 (115-152) 137 (121-151) 254 (221-297) 464 (390-520) 654 (538-769) 1397 

03-04 138 (122-156) 144 (126-164) 263 (240-294) 430 (404-469) 589 (489-680) 1300 

Race/ethnicity 

Mexican Americans 01-02 117 (90.8-152) 116 (88.0-147) 214 (157-306) 369 (254-583) 549 (342-847) 664

03-04 138 (120-158) 152 (129-175) 246 (213-291) 413 (311-492) 518 (352-896) 611

Non-Hispanic blacks 01-02 150 (127-179) 145 (126-170) 287 (243-327) 493 (423-629) 713 (568-975) 690

03-04 182 (152-217) 178 (149-212) 346 (274-418) 552 (459-645) 797 (606-1050) 679

Non-Hispanic whites 01-02 144 (125-166) 144 (131-162) 276 (241-330) 489 (436-552) 661 (550-793) 1204 

03-04 159 (140-180) 168 (151-186) 296 (265-330) 475 (421-539) 641 (528-843) 1046 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 3.5 and 5.0. 
 448 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Urinary 1-Hydroxyphenanthrene (creatinine corrected) 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 132 (118-147) 125 (113-141) 210 (191-231) 344 (310-385) 464 (404-539) 2741 

03-04 146 (138-155) 141 (133-150) 222 (205-244) 352 (330-384) 487 (416-546) 2496 

Age group 

6-11 years 01-02 133 (116-153) 126 (110-147) 188 (165-225) 344 (245-437) 467 (364-598) 387

03-04 145 (129-163) 138 (121-155) 205 (169-240) 315 (244-456) 477 (313-803) 328

12-19 years 01-02 103 (87.9-121) 97.3 (81.4-117) 158 (131-192) 240 (198-322) 354 (235-531) 733

03-04 119 (108-130) 115 (101-131) 176 (157-197) 275 (230-331) 345 (269-496) 692

20 years and older 01-02 137 (122-153) 132 (117-145) 223 (200-243) 351 (319-395) 476 (421-541) 1621 

03-04 151 (142-161) 147 (134-157) 237 (212-254) 365 (335-397) 500 (422-580) 1476 

Gender 

Males 01-02 122 (108-137) 116 (104-131) 194 (173-218) 321 (262-395) 455 (348-642) 1344 

03-04 138 (131-146) 130 (117-143) 201 (187-227) 335 (301-391) 437 (392-550) 1196 

Females 01-02 142 (125-160) 136 (118-156) 226 (199-256) 355 (323-399) 473 (421-541) 1397 

03-04 154 (142-168) 150 (138-160) 241 (212-269) 364 (323-425) 505 (418-635) 1300 

Race/ethnicity 

Mexican Americans 01-02 110 (88.6-136) 101 (85.5-131) 162 (138-203) 275 (187-452) 400 (268-755) 664

03-04 124 (111-140) 122 (107-136) 183 (159-242) 304 (246-392) 392 (318-437) 611

Non-Hispanic blacks 01-02 106 (88.7-127) 102 (92.4-111) 172 (141-203) 274 (224-356) 384 (308-598) 690

03-04 129 (112-148) 126 (108-143) 199 (173-242) 337 (272-400) 428 (374-522) 679

Non-Hispanic whites 01-02 142 (126-161) 137 (119-153) 228 (206-247) 363 (321-406) 476 (411-552) 1204 

03-04 157 (146-168) 150 (140-159) 241 (216-256) 372 (335-424) 515 (426-658) 1046 
Fourth National Report on Human Exposure to Environmental Chemicals 449

 Polycyclic Aromatic Hydrocarbons 

Urinary 2-Hydroxyphenanthrene 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 54.0 (46.0-63.5) 58.0 (50.0-68.0) 117 (102-140) 240 (201-271) 332 (299-377) 2742 

03-04 59.3 (52.5-66.9) 62.2 (55.4-69.7) 117 (105-129) 206 (180-235) 291 (252-336) 2512 

Age group 

6-11 years 01-02 40.5 (34.3-47.7) 46.0 (37.0-57.0) 87.0 (71.0-101) 170 (133-207) 257 (195-320) 387

03-04 45.3 (40.0-51.3) 48.1 (41.9-56.8) 72.7 (63.2-89.4) 135 (104-176) 225 (136-299) 337

12-19 years 01-02 49.5 (37.3-65.7) 52.0 (41.0-68.0) 108 (93.0-122) 210 (145-270) 281 (214-524) 733

03-04 58.0 (50.7-66.2) 62.5 (54.5-71.6) 104 (88.8-132) 198 (166-215) 258 (199-318) 707

20 years and older 01-02 56.8 (48.1-66.9) 60.0 (52.0-73.0) 126 (104-152) 249 (207-292) 342 (308-398) 1622 

03-04 61.5 (53.7-70.4) 64.9 (57.2-73.5) 125 (111-138) 216 (187-250) 310 (259-389) 1468 

Gender 

Males 01-02 62.1 (53.3-72.5) 67.0 (58.0-80.0) 136 (109-161) 274 (245-303) 367 (329-414) 1345 

03-04 72.3 (64.4-81.3) 71.6 (65.8-83.3) 138 (123-150) 240 (200-279) 337 (279-428) 1211 

Females 01-02 47.4 (39.1-57.5) 50.0 (41.0-60.0) 105 (88.0-129) 200 (171-240) 294 (236-357) 1397 

03-04 49.0 (42.4-56.6) 52.5 (45.3-58.7) 95.4 (84.1-110) 166 (146-202) 247 (202-291) 1301 

Race/ethnicity 

Mexican Americans 01-02 46.8 (32.7-66.8) 51.0 (36.0-73.0) 97.0 (72.0-140) 191 (122-332) 303 (187-652) 665

03-04 53.9 (46.7-62.1) 60.1 (50.8-68.6) 104 (89.5-115) 164 (144-187) 200 (187-219) 627

Non-Hispanic blacks 01-02 71.1 (58.0-87.1) 74.0 (66.0-90.0) 152 (124-182) 262 (217-311) 374 (284-560) 690

03-04 81.2 (68.1-96.7) 73.4 (61.8-101) 158 (125-199) 280 (219-374) 390 (289-574) 678

Non-Hispanic whites 01-02 53.1 (43.6-64.6) 57.0 (48.0-68.0) 117 (99.0-144) 242 (199-286) 333 (303-385) 1204 

03-04 58.2 (50.1-67.7) 60.7 (52.5-71.0) 115 (97.9-133) 209 (172-255) 299 (251-351) 1044 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 3.2 and 5.0. 
 450 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Urinary 2-Hydroxyphenanthrene (creatinine corrected) 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 50.6 (43.3-59.2) 52.5 (46.4-59.6) 91.4 (78.7-108) 164 (138-200) 233 (206-275) 2742 

03-04 55.4 (51.1-60.0) 52.3 (48.8-55.8) 85.8 (79.4-97.0) 150 (128-174) 212 (180-252) 2512 

Age group 

6-11 years 01-02 45.3 (38.8-52.8) 50.0 (40.0-57.8) 85.9 (69.6-100) 144 (105-217) 234 (138-397) 387

03-04 47.9 (43.6-52.7) 46.6 (41.0-51.4) 66.3 (60.3-72.8) 106 (81.0-125) 183 (108-295) 337

12-19 years 01-02 38.4 (29.6-49.7) 38.5 (30.6-48.7) 64.9 (52.4-84.0) 117 (86.7-167) 173 (128-305) 733

03-04 43.6 (39.3-48.5) 40.8 (37.7-45.0) 70.6 (55.8-84.7) 106 (88.2-123) 127 (115-176) 707

20 years and older 01-02 53.7 (46.2-62.4) 55.6 (49.4-62.7) 94.6 (84.1-112) 173 (145-201) 241 (209-287) 1622 

03-04 58.7 (53.6-64.2) 54.8 (50.7-60.9) 91.6 (83.5-105) 164 (139-182) 227 (183-291) 1468 

Gender 

Males 01-02 50.4 (43.3-58.5) 52.5 (47.2-59.2) 91.4 (78.6-103) 176 (140-208) 245 (206-349) 1345 

03-04 56.6 (52.5-61.0) 52.3 (48.1-57.1) 84.7 (79.2-96.4) 157 (132-180) 227 (184-284) 1211 

Females 01-02 50.9 (42.7-60.7) 52.8 (45.5-61.0) 91.6 (75.0-115) 158 (133-183) 214 (200-245) 1397 

03-04 54.3 (48.7-60.5) 52.3 (47.0-57.2) 88.1 (76.4-101) 146 (118-179) 202 (175-246) 1301 

Race/ethnicity 

Mexican Americans 01-02 43.7 (31.9-59.8) 44.0 (34.3-58.8) 80.8 (59.8-115) 146 (103-245) 245 (144-394) 665

03-04 48.8 (42.5-55.9) 50.1 (42.4-58.8) 79.5 (68.2-86.1) 124 (96.2-149) 155 (127-206) 627

Non-Hispanic blacks 01-02 50.2 (40.5-62.2) 49.7 (44.3-56.0) 87.7 (72.6-103) 174 (127-224) 257 (178-459) 690

03-04 57.6 (49.8-66.7) 53.1 (45.7-63.5) 90.3 (77.9-117) 152 (128-186) 218 (173-348) 678

Non-Hispanic whites 01-02 52.5 (43.8-62.9) 54.8 (47.7-61.9) 92.7 (80.5-113) 170 (140-204) 233 (202-293) 1204 

03-04 57.1 (51.7-63.0) 52.9 (49.1-57.2) 88.5 (79.2-102) 159 (128-187) 237 (180-295) 1044 
Fourth National Report on Human Exposure to Environmental Chemicals 451

 Polycyclic Aromatic Hydrocarbons 

Urinary 3-Hydroxyphenanthrene 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 105 (92.5-118) 105 (92.0-118) 200 (179-225) 401 (336-480) 649 (542-747) 2741 

03-04 115 (104-128) 118 (107-129) 219 (201-237) 424 (351-487) 647 (509-788) 2426 

Age group 

6-11 years 01-02 105 (91.1-122) 109 (82.0-138) 195 (160-231) 298 (245-346) 412 (319-545) 387

03-04 116 (99.9-134) 107 (93.0-135) 205 (170-223) 333 (241-435) 472 (322-881) 325

12-19 years 01-02 104 (87.3-125) 107 (90.0-122) 201 (165-231) 329 (255-445) 459 (331-631) 733

03-04 120 (103-141) 127 (107-149) 221 (195-262) 366 (327-424) 564 (391-730) 677

20 years and older 01-02 105 (91.7-119) 105 (89.0-118) 201 (180-231) 433 (366-515) 683 (597-806) 1621 

03-04 114 (103-128) 118 (105-130) 221 (203-243) 450 (353-505) 696 (511-885) 1424 

Gender 

Males 01-02 122 (107-138) 117 (106-132) 224 (188-278) 474 (372-597) 734 (597-1010) 1344 

03-04 137 (122-154) 135 (119-157) 251 (221-287) 487 (398-579) 754 (606-913) 1167 

Females 01-02 90.8 (77.7-106) 93.0 (80.0-108) 184 (155-207) 328 (291-399) 518 (434-649) 1397 

03-04 97.7 (86.5-110) 100 (86.6-114) 193 (170-210) 351 (287-445) 531 (447-647) 1259 

Race/ethnicity 

Mexican Americans 01-02 83.5 (64.1-109) 84.0 (64.0-111) 144 (117-198) 259 (193-430) 454 (253-1140) 664

03-04 92.7 (81.3-106) 92.8 (84.1-111) 164 (133-204) 317 (236-374) 436 (338-501) 576

Non-Hispanic blacks 01-02 145 (122-172) 135 (120-163) 281 (228-346) 516 (414-684) 957 (609-1410) 690

03-04 166 (141-195) 159 (137-193) 313 (249-399) 542 (458-670) 798 (579-1200) 686

Non-Hispanic whites 01-02 104 (90.8-120) 106 (92.0-120) 199 (177-224) 401 (331-495) 649 (518-747) 1204 

03-04 114 (100-129) 117 (104-128) 220 (201-237) 440 (332-509) 702 (505-915) 1010 

Limit of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 3.6 and 5.0. 
 452 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Urinary 3-Hydroxyphenanthrene (creatinine corrected) 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 01-02 98.0 (87.4-110) 86.5 (78.8-97.1) 158 (142-174) 299 (252-342) 428 (365-621) 2741 

03-04 108 (101-115) 99.5 (91.9-106) 172 (158-189) 321 (273-363) 497 (406-566) 2426 

Age group 

6-11 years 01-02 118 (103-135) 114 (94.9-131) 173 (150-201) 289 (238-368) 410 (308-544) 387

03-04 124 (110-138) 119 (110-129) 165 (145-202) 283 (231-402) 484 (269-710) 325

12-19 years 01-02 81.1 (70.1-93.8) 78.0 (66.7-89.4) 116 (96.5-144) 205 (153-275) 283 (198-511) 733

03-04 90.3 (81.5-100) 84.9 (76.1-93.9) 139 (116-160) 212 (193-231) 295 (225-429) 677

20 years and older 01-02 98.9 (88.3-111) 85.3 (78.3-96.6) 164 (147-183) 320 (273-356) 488 (379-774) 1621 

03-04 109 (102-117) 99.1 (91.7-106) 180 (161-198) 343 (282-385) 523 (417-608) 1424 

Gender 

Males 01-02 98.6 (87.7-111) 87.1 (79.5-98.2) 159 (138-188) 310 (245-368) 505 (356-761) 1344 

03-04 107 (98.2-116) 99.2 (87.4-109) 169 (154-184) 305 (261-343) 491 (383-592) 1167 

Females 01-02 97.5 (84.9-112) 86.4 (76.9-100) 158 (139-178) 292 (245-333) 410 (352-583) 1397 

03-04 109 (99.6-119) 100 (88.9-110) 176 (155-202) 328 (265-398) 497 (380-594) 1259 

Race/ethnicity 

Mexican Americans 01-02 78.2 (62.4-98.0) 70.8 (56.2-87.4) 130 (92.9-171) 224 (173-321) 333 (224-656) 664

03-04 83.8 (75.1-93.6) 79.5 (72.9-87.0) 137 (111-165) 224 (188-274) 305 (247-406) 576

Non-Hispanic blacks 01-02 102 (85.8-122) 91.9 (79.8-108) 160 (133-202) 296 (234-475) 673 (347-1260) 690

03-04 118 (103-135) 106 (90.5-126) 186 (156-219) 357 (257-439) 505 (384-772) 686

Non-Hispanic whites 01-02 103 (91.5-117) 89.4 (80.2-102) 167 (148-193) 324 (272-368) 447 (365-738) 1204 

03-04 112 (104-121) 103 (96.9-108) 183 (160-200) 346 (278-402) 544 (417-656) 1010 
Fourth National Report on Human Exposure to Environmental Chemicals 453

 Polycyclic Aromatic Hydrocarbons 

Urinary 4-Hydroxyphenanthrene 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 25.1 (22.6-27.9) 25.9 (22.5-29.6) 53.7 (47.4-59.7) 96.8 (85.0-116) 152 (118-176) 2443 

Age group 

6-11 years 03-04 25.2 (22.3-28.4) 26.3 (22.8-30.0) 45.7 (38.6-53.3) 95.5 (61.7-137) 138 (95.1-202) 321

12-19 years 03-04 23.7 (20.3-27.6) 25.8 (20.5-31.4) 49.9 (45.2-53.0) 77.4 (67.2-95.1) 123 (94.6-142) 683

20 years and older 03-04 25.3 (22.4-28.6) 25.8 (22.4-29.5) 54.8 (48.6-61.9) 101 (87.1-120) 163 (117-197) 1439 

Gender 

Males 03-04 30.0 (26.5-34.0) 29.6 (25.5-35.1) 60.4 (53.4-68.7) 110 (90.6-130) 169 (118-211) 1180 

Females 03-04 21.1 (18.7-23.8) 21.3 (18.3-25.3) 46.5 (41.6-53.3) 88.4 (73.5-103) 136 (106-157) 1263 

Race/ethnicity 

Mexican Americans 03-04 23.5 (20.9-26.3) 24.4 (21.4-29.4) 46.1 (40.1-53.0) 80.5 (60.9-94.1) 99.7 (80.2-154) 607

Non-Hispanic blacks 03-04 35.4 (29.6-42.3) 37.1 (29.8-46.1) 71.4 (60.3-83.3) 123 (104-145) 167 (133-215) 657

Non-Hispanic whites 03-04 24.4 (21.5-27.7) 25.2 (21.8-29.1) 51.5 (45.1-58.5) 97.9 (77.4-127) 163 (113-202) 1021 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 5.0. 

Urinary 4-Hydroxyphenanthrene (creatinine corrected) 

Metabolite of Phenanthrene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 23.3 (21.7-25.0) 22.7 (20.5-24.9) 42.0 (38.6-44.6) 74.3 (66.3-85.4) 114 (102-130) 2443 

Age group 

6-11 years 03-04 26.3 (23.7-29.2) 24.8 (21.6-28.6) 43.3 (35.2-48.8) 72.9 (56.3-113) 126 (79.3-173) 321

12-19 years 03-04 17.7 (15.9-19.8) 16.7 (15.7-18.4) 31.4 (26.0-37.1) 47.9 (40.7-54.1) 61.7 (51.7-86.0) 683

20 years and older 03-04 24.0 (22.0-26.2) 23.3 (21.1-25.4) 43.5 (39.4-48.1) 79.0 (66.8-100) 121 (104-138) 1439 

Gender 

Males 03-04 23.4 (21.6-25.4) 22.7 (20.3-24.9) 40.9 (35.9-45.7) 72.7 (61.5-86.8) 112 (100-126) 1180 

Females 03-04 23.2 (21.2-25.5) 22.8 (19.7-26.0) 42.5 (38.3-46.2) 75.1 (63.4-94.0) 119 (93.1-139) 1263 

Race/ethnicity 

Mexican Americans 03-04 21.2 (18.8-23.8) 20.7 (19.1-22.9) 35.9 (29.8-40.7) 59.0 (43.3-87.5) 83.4 (60.9-139) 607

Non-Hispanic blacks 03-04 25.0 (21.6-28.9) 25.3 (23.1-28.8) 42.0 (37.4-51.4) 75.0 (61.6-87.9) 102 (79.2-137) 657

Non-Hispanic whites 03-04 23.7 (21.5-26.2) 22.4 (19.4-25.4) 43.6 (38.8-47.3) 82.2 (68.5-101) 126 (103-143) 1021 
 454 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for polycyclic aromatic hydrocarbons 

[online] 1995. Available at URL: http://www.atsdr.cdc.gov/

toxprofiles/tp69.html. 5/26/09

Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German 

environmental survey 1998 (GerES III): environmental pollutants 

in the urine of the German population. Int J Hyg Environ Health 

2003; 206:15-24.

Elovaara E, Mikkola J, Makela M, Paldanius B, Priha E. 

Assessment of soil remediation workers’ exposure to polycyclic 

aromatic hydrocarbons (PAH): Biomonitoring of naphthols, 

phenanthrols, and 1-hydroxypyrene in urine. Toxicol Lett 

2006;162:158-163.

Fang G-C, Wu Y-S, Chen J-C, Chang C-N, Ho T-T. characteristic 

of polycyclic aromatic hydrocarbon concentrations and source 

identification for fine and coarse particulates at Taichung 

Harbor near Taiwan Strait during 2004-2005. Sci Tot Environ 

2006;366:729-738.

Gundel J, Schaller KH, Angerer J. Occupational exposure to 

polycyclic aromatic hydrocarbons in a fireproof stone producing 

plant: biological monitoring of 1-hydroxypyrene, 1-, 2-, 3- and 

4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 

3-hydroxybenzo-(a)-pyrene. Int Arch Occup Environ Health 

2000;73(4):270-274.

Heudorf U, Angerer J. Internal exposure to PAHs of children 

and adults living in homes with parquet flooring containing high 

levels of PAHs in the parquet glue. Int Arch Occup Environ 

Health 2001a;74(2):91-101.

Heudorf U, Angerer J. Urinary monohydroxylated phenanthrenes 

and hydroxypyrene--the effects of smoking habits and changes 

induced by smoking on monooxygenase-mediated metabolism. 

Int Arch Occup Environ Health. 2001b 74(3):177-83.

Jacob J, Grimmer G, Dettbarn G. Profile of urinary phenanthrene 

metabolites in smokers and non-smokers. Biomarkers 

1999;4(5):319-327.
Fourth National Report on Human Exposure to Environmental Chemicals 455

 Polycyclic Aromatic Hydrocarbons 

Pyrene

CAS No. 129-00-0

Pyrene has been used as a starting material for producing 

optical brighteners and dyes. Notable pyrene sources include 

domestic heating sources, particularly wood burning; 

gasoline fuel exhaust; coal tar and asphalt; and cigarette 

smoke. Pyrene is commonly found in PAH mixtures, and its 

urinary metabolite, 1-hydroxypyrene, has been used widely 

as an indicator of exposure to PAH chemicals, particularly 

in occupational exposure studies. IARC determined that 

pyrene was not classifiable as to its human carcinogenicity.

Biomonitoring Information

Urinary levels of 1-hydroxypyrene reflect recent exposure. 

The overall geometric mean of 1-hydroxypyrene levels in 

the NHANES 2003-2004 subsample was similar to that 

of general populations in other industrialized countries 

(Becker et al., 2003; Chuang et al., 1999; Goen et al., 1995; 

Heudorf and Angerer 2001a, 2001b; Yang et al., 2003). 

Higher levels have been noted in residents of industrialized 

and high traffic urban areas compared with rural or 

suburban settings, and the mean urinary 1-hydroxypyrene 

levels from the former group were somewhat higher than in 

the NHANES 2003-2004 subsample (Kanoh et al., 1993; 

Kuo et al., 2004; Yang et al., 2003). Variation also has been 

noted in the mean 1-hydroxypyrene urine levels between 

different industrialized countries (for example, South 

Korea or China, compared to the U.S.), which is attributable 

to such factors as ambient air pollution and residential 

heating and cooking sources (Huang et al., 2004; Kuo et 

al., 2004; Roggi et al., 1997; Siwinska et al., 1999; Yang 

et al., 2003). In general, smokers have about 2 to 4-fold 

higher urinary 1-hydroxypyrene levels than non-smokers 

(Goen et al., 1995; Heudorf and Angerer 2001b; Jacob et 

al., 1999). Environmental tobacco smoke may contribute to 

higher urinary 1-hydroxypyrene levels in exposed children 

(Chuang et al., 1999; Siwinska et al., 1999; Tsai et al., 

2003).

Numerous studies of workers with occupational exposure 

to excessive vehicular exhaust have found increased 

urinary 1-hydroxypyrene levels compared to non-exposed 

individuals (Kuusimaki et al., 2004; Merlo et al., 1998; Tsai 

et al., 2004). The highest urinary levels of 1-hydroxypyrene 

measured in occupational studies have been found in 

aluminum smelter and coke oven workers exposed to 

heated tar and coal tar products (Alexandrie et al., 2000; 

Goen et al., 1995; Jacob and Seidel, 2002; Lu et al., 2002; 

Serdar et al., 2003). Results in these workers have ranged 

from about 100 to more than 1000 times greater than nonexposed levels and the geometric mean values found in this 

Report. Tobacco smoking also was associated with levels 

about double those in nonsmoking workers (Campo et al., 

2006; Merlo et al., 1998; Mukherjee et al., 2004).

Finding a measurable amount of urinary 1-hydroxypyrene 

does not mean that the level of 1-hydroxypyrene causes 

an adverse health effect. Biomonitoring studies on levels 

of 1-hydroxypyrene provide physicians and public health 

officials with reference values so that they can determine 

whether people have been exposed to higher levels of pyrene 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.
 456 Fourth National Report on Human Exposure to Environmental Chemicals 

Polycyclic Aromatic Hydrocarbons 

Urinary 1-Hydroxypyrene 

Metabolite of Pyrene 

Geometric mean and selected percentiles of urine concentrations (in ng/L) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 89.2 (79.8-99.7) 91.3 (83.5-98.8) 189 (168-208) 389 (345-459) 569 (493-676) 2515 

Age group 

6-11 years 03-04 112 (96.9-130) 119 (99.0-143) 193 (163-229) 351 (233-484) 514 (336-680) 333

12-19 years 03-04 119 (103-137) 115 (98.0-145) 244 (213-274) 506 (359-608) 705 (636-788) 705

20 years and older 03-04 82.8 (73.0-93.8) 83.8 (75.6-92.4) 177 (155-203) 387 (337-437) 553 (483-644) 1477 

Gender 

Males 03-04 108 (96.0-122) 111 (98.7-121) 227 (197-265) 459 (387-518) 644 (526-811) 1214 

Females 03-04 74.0 (64.3-85.1) 75.3 (66.3-83.9) 158 (143-173) 334 (258-407) 502 (389-604) 1301 

Race/ethnicity 

Mexican Americans 03-04 89.4 (78.6-102) 92.4 (79.8-113) 173 (153-191) 331 (281-415) 495 (404-548) 623

Non-Hispanic blacks 03-04 128 (105-155) 126 (108-153) 296 (226-355) 553 (400-669) 699 (564-935) 681

Non-Hispanic whites 03-04 84.8 (73.5-97.9) 85.4 (75.6-97.3) 182 (156-214) 386 (336-462) 566 (470-749) 1050 

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 5.0. 

Urinary 1-Hydroxypyrene (creatinine corrected) 

Metabolite of Pyrene 

Geometric mean and selected percentiles of urine concentrations (in ng/g of creatinine) for the U.S. population from the National

Health and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample 

years (95% conf. interval) 50th 75th 90th 95th size 

Total 03-04 83.4 (77.4-90.0) 79.9 (72.6-86.9) 149 (133-167) 279 (236-343) 424 (352-474) 2515 

Age group 

6-11 years 03-04 119 (102-138) 112 (98.2-137) 185 (156-225) 336 (227-440) 475 (336-566) 333

12-19 years 03-04 89.4 (77.7-103) 81.6 (74.3-93.0) 146 (123-187) 269 (196-364) 364 (251-611) 705

20 years and older 03-04 79.1 (73.2-85.4) 73.5 (66.7-82.3) 142 (127-160) 278 (236-331) 424 (349-472) 1477 

Gender 

Males 03-04 84.8 (77.3-93.1) 82.8 (72.7-91.0) 163 (145-175) 290 (241-352) 416 (353-513) 1214 

Females 03-04 82.1 (73.5-91.7) 78.3 (69.2-86.8) 137 (119-165) 274 (215-350) 440 (313-479) 1301 

Race/ethnicity 

Mexican Americans 03-04 81.2 (73.9-89.2) 80.9 (70.4-91.7) 146 (122-167) 247 (221-301) 372 (321-460) 623

Non-Hispanic blacks 03-04 91.0 (77.7-107) 92.4 (76.6-106) 173 (145-211) 315 (227-433) 451 (301-680) 681

Non-Hispanic whites 03-04 83.3 (75.4-92.0) 77.9 (69.1-86.8) 148 (127-174) 287 (241-360) 438 (360-506) 1050 
Fourth National Report on Human Exposure to Environmental Chemicals 457

 Polycyclic Aromatic Hydrocarbons 

References

Alexandrie AK, Warholm M, Carstensen U, Axmon A, Hagmar 

L, Levin JO, et al. CYP1A1 and GSTM1 polymorphisms 

affect urinary 1-hydroxypyrene levels after PAH exposure. 

Carcinogenesis 2000;21(4):669-676.

Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German 

environmental survey 1998 (GerES III): environmental pollutants 

in the urine of the German population. Int J Hyg Environ Health 

2003; 206:15-24.

Campo L, Buratti M, Fustinoni S, Cirla PE, Martinotti I, Longhi 

O, et al. Evaluation of exposure to PAHs in asphalt workers by 

environmental and biological monitoring. Ann NY Acad Sci 

2006;1076:405-420.

Chuang JC, Callahan PJ, Lyu CW, Wilson NK. Polycyclic 

aromatic hydrocarbon exposures of children in low-income 

families. J Expo Anal Environ Epidemiol 1999;9(2):85-98.

Goen T, Gundel J, Schaller KH, Angerer J. The elimination 

of 1-hydroxypyrene in the urine of the general population and 

workers with different occupational exposures to PAH. Sci Total 

Environ 1995;163(1-3):195-201.

Heudorf U, Angerer J. Internal exposure to PAHs of children 

and adults living in homes with parquet flooring containing high 

levels of PAHs in the parquet glue. Int Arch Occup Environ 

Health 2001a;74(2):91-101.

Heudorf U, Angerer J. Urinary monohydroxylated phenanthrenes 

and hydroxypyrene--the effects of smoking habits and changes 

induced by smoking on monooxygenase-mediated metabolism. 

Int Arch Occup Environ Health. 2001b 74(3):177-183.

Huang W, Grainger J, Patterson DG, Turner WE, Caudill SP, 

Needham LL, et al. Comparison of 1-hydroxypyrene exposure in 

the US population with that in occupational exposure studies. Int 

Arch Occup Environ Health 2004;77:491-498.

Jacob J, Grimmer G, Dettbarn G. Profile of urinary phenanthrene 

metabolites in smokers and non-smokers. Biomarkers 

1999;4(5):319-327.

Jacob J, Seidel A. Biomonitoring of polycyclic aromatic 

hydrocarbons in human urine. J Chromatogr B 2002;778(1-

2):31-47.

Kanoh T, Fukuda M, Onozuka H, Kinouchi T, Ohnishi Y. Urinary 

1-hydroxypyrene as a marker of exposure to polycyclic aromatic 

hydrocarbons in environment. Environ Res 1993;62(2):230-241.

Kuo CT, Chen HW, Chen JL. Determination of 1-hydroxypyrene 

in children urine using column-switching liquid chromatography 

and fluorescence detection. J Chromatogr B 2004;805(2):187-

193.

Kuusimaki L, Peltonen Y, Mutanen P, Peltonen K, Savela K. 

Urinary hydroxy-metabolites of naphthalene, phenanthrene and 

pyrene as markers of exposure to diesel exhaust. Int Arch Occup 

Environ Health 2004;77(1):23-30.

Lu PL, Chen ML, Mao IF. Urinary 1-hydroxypyrene levels in 

workers exposed to coke oven emissions at various locations in a 

coke oven plant. Arch Environ Health 2002;57(3):255-261.

Merlo F, Andreassen A, Weston A, Pan CF, Haugen A, Valerio 

F, et al. Urinary excretion of 1-hydroxypyrene as a marker for 

exposure to urban air levels of polycyclic aromatic hydrocarbons. 

Cancer Epidemiol Biomarkers Prev 1998;7(2):147-155.

Mukherjee S, Palmer LJ, Kim JY, Aeschliman DB, Houk RS, 

Woodin MA, et al. Smoking status and occupational exposure 

affects oxidative DNA injury in boilermakers exposed to metal 

fume and residual oil fly ash. Cancer Epidemiol Biomarkers Prev 

2004;13(3):454-460.

Roggi C, Minoia C, Sciarra GF, Apostoli P, Maccarini L, 

Magnaghi S, et al. Urinary 1-hydroxypyrene as a marker of 

exposure to pyrene: an epidemiological survey on a general 

population group. Sci Total Environ 1997;199(3):247-254.

Serdar B, Waidyanatha S, Zheng Y, Rappaport SM. Simultaneous 

determination of urinary 1- and 2-naphthols, 3- and 9-phenanthrols, 

and 1-pyrenol in coke oven workers. Biomarkers 2003;8(2):93-

109.

Siwinska E, Mielzynska D, Bubak A, Smolik E. The effect of 

coal stoves and environmental tobacco smoke on the level of 

urinary 1-hydroxypyrene. Mutat Res 1999;445(2):147-153.

Tsai HT, Wu MT, Hauser R, Rodrigues E, Ho CK, Liu CL, et 

al. Exposure to environmental tobacco smoke and urinary 

1-hydroxypyrene levels in preschool children. Kaohsiung J Med 

Sci 2003;19(3):97-104.

Tsai PJ, Shih TS, Chen HL, Lee WJ, Lai CH, Liou SH. Urinary 

1-hydroxypyrene as an indicator for assessing the exposures of 

booth attendants of a highway toll station to polycyclic aromatic 

hydrocarbons. Environ Sci Technol 2004;38(1):56-61.

Yang M, Kim S, Lee E, Cheong HK, Chang SS, Kang D, et 

al. Sources of polycyclic aromatic hydrocarbon exposure in 

non-occupationally exposed Koreans. Environ Mol Mutagen 

2003;42(4):250-257.
 458 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Benzene

CAS No. 71-43-2

General Information

Benzene is a volatile chemical that is produced 

commercially from coal and petroleum sources. It is among 

the most abundantly produced chemicals in the U.S. and is 

used extensively as an industrial solvent, in the synthesis 

of numerous chemicals, and as an additive in unleaded 

gasoline (ATSDR, 2007).

Human exposure occurs primarily by inhaling benzene in 

ambient air (Hattemer-Frey et al., 1990; Wallace, 1996). 

Sources of benzene in the air may result from either natural 

(e.g., forest fires) or industrial sources. Among industrial 

sources, automobile emissions and vapor around gasoline 

filling stations contribute to benzene in air (ATSDR, 

2007). Tobacco smoke contributes to benzene in indoor 

air (Duarte-Davidson, et al., 2001), and tobacco smoke is 

estimated to account for about half of the total estimated 

exposure to benzene (ATSDR, 2007). Indoor sources 

for benzene, which include the offgassing of building 

materials, account for a significant portion of a nonsmoker’s benzene exposure (Wallace, 1996; Wallace et 

al., 1987). The consumption of food, drinking water, and 

beverages are considered negligible sources of exposure 

unless benzene contamination has occurred, such as from 

leaking underground fuel storage tanks (ATSDR, 2007; 

Wallace, 1996). In recent years, less than five percent of 

domestic wells used for drinking water in the U.S. have 

been found to contain detectable amounts of benzene 

(Rowe et al., 2007). Workplace exposure to benzene may 

result from production, use, or transportation of petroleum 

products.

Benzene is well absorbed after inhalational, oral, or dermal 

exposure. In the blood, benzene is distributed rapidly 

throughout the body, especially into the brain and fatty 

tissues, and can cross the placenta. Benzene is metabolized 

in the liver, and some metabolites may be distributed to 

the bone marrow, where additional metabolism may result 

in toxic effects on hematopoietic cells (ATSDR, 2007; 

Ross, 2000). The primary benzene metabolites are phenol, 

catechol, hydroquinone, 1,2,4-benzenetriol, and to a lesser 

extent, trans, trans-muconic acid, which are eliminated in 

urine as glucuronide and sulfate conjugates (Ross, 2000). 

Urinary S-phenylmercapturic and t,t-muconic acids are 

used for monitoring workplace exposure. A very small 

amount of unchanged benzene is eliminated in the breath.

Blood Benzene 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * .030 (<LOD-.050) .100 (.060-.140) .190 (.140-.290) .320 (.190-.480) 837

03-04 * .027 (.025-.031) .064 (.050-.084) .170 (.150-.190) .260 (.210-.320) 1345

Age group 

20-59 years 01-02 * .030 (<LOD-.050) .100 (.060-.140) .190 (.140-.290) .320 (.190-.480) 837

03-04 * .027 (.025-.031) .064 (.050-.084) .170 (.150-.190) .260 (.210-.320) 1345

Gender 

Males 01-02 * .030 (<LOD-.050) .110 (.060-.160) .230 (.150-.370) .370 (.210-.510) 403

03-04 .039 (.035-.043) .030 (.027-.035) .069 (.053-.084) .160 (.140-.180) .240 (.190-.320) 654

Females 01-02 * .030 (<LOD-.050) .100 (.060-.130) .180 (.120-.240) .250 (.170-.330) 434

03-04 * .025 (<LOD-.029) .057 (.040-.090) .180 (.150-.220) .290 (.220-.420) 691

Race/ethnicity 

Mexican Americans 01-02 * .030 (<LOD-.070) .070 (.030-.170) .140 (.060-.360) .230 (.130-.370) 227

03-04 * .027 (<LOD-.035) .041 (.034-.057) .077 (.058-.110) .130 (.084-.320) 254

Non-Hispanic blacks 01-02 * < LOD .060 (<LOD-.160) .180 (.090-.300) .250 (.160-.480) 137

03-04 .043 (.033-.058) .029 (<LOD-.054) .092 (.055-.140) .210 (.140-.290) .320 (.240-.460) 302

Non-Hispanic whites 01-02 * .030 (<LOD-.060) .110 (.070-.160) .210 (.140-.340) .330 (.190-.510) 411

03-04 * .028 (.025-.033) .068 (.053-.088) .180 (.150-.200) .280 (.210-.330) 687

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.024 and 0.024. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 459

 Volatile Organic Compounds (VOCs)

Accidental and intentional exposures to high concentrations 

of benzene vapor can lead rapidly to euphoria, central 

nervous system depression, cardiac arrhythmias, followed 

by unconsciousness and death (ATSDR, 2007). Workers 

have developed skin irritation following repeated dermal 

exposure and mucous membrane irritation following 

repeated vapor inhalation (ATSDR, 2007). Epidemiologic 

studies of workers in industries involving benzene have 

found that benzene exposure can cause bone marrow 

suppression and increases the risk of various leukemias 

(Savitz and Andrews, 1997). Supportive evidence for 

benzene carcinogenicity comes from animal studies 

and from in vitro studies demonstrating the clastogenic 

properties of benzene on blood forming cells (NTP, 1986; 

Ross, 2000). The background exposure levels for the 

general population have been estimated to be much lower 

than the estimated lowest effect level for benzene at which 

leukemia risk is increased (Duarte-Davidson, et al., 2001).

Workplace standards and guidelines for benzene have been 

established by OSHA and ACGIH, respectively. The U.S. 

EPA has established environmental and drinking water 

standards for benzene, and the FDA has established a 

bottled water standard. Benzene is classified as a known 

human carcinogen by IARC and by NTP. Information about 

external exposure (ie., environmental levels) and health 

effects is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html.

Biomonitoring Information

Levels of blood benzene reflect recent exposure. The 

median level of blood benzene observed in the NHANES 

2003-2004 subsample appear slightly lower than the 

median level in a nonrepresentative subsample of adults 

in NHANES III (1988-1994) (Ashley et al., 1994), as well 

for other previous studies of the U.S. general population 

(Bonanno et al., 2001; Buckley et al., 1997; Sexton et al., 

2005 and 2006; Lin et al., 2008), and studies from other 

countries (Brugnone et al., 1994; Navasumrit et al., 2005).

Smoking, residing, or working in urban areas and exposure 

to gasoline and petroleum products can result in blood 

benzene levels that are higher than those in the nonsmoking 

general population (Ashley et al., 1995; Carrer et al., 2000; 

Backer et al., 1997). The amount and duration of cigarette 

smoking increases the likelihood of higher blood benzene 

levels (Bonanno et al., 2001; Churchill et al., 2001; Lin 

et al., 2008). Workers exposed to gasoline fumes, such as 

garage mechanics, drivers, and street vendors, and workers 

exposed to solvent fumes have been found to have blood 

benzene levels as much as tenfold higher than levels in 

the general population (Brugnone, et al., 1994 and 1999; 

Moolenaar et al., 1997; Perbellini et al., 2002; Romieu et 

al., 1999).

Finding a measurable amount of benzene in blood does not 

mean that the level of benzene causes an adverse health 

effect. Biomonitoring studies of blood benzene can provide 

physicians and public health officials with reference values 

so that they can determine whether or not people have been 

exposed to higher levels of benzene than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for benzene update. 2007 [online]. Available 

at URL: http://www.atsdr.cdc.gov/toxprofiles/tp3.html. 4/20/09

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Ashley DL, Bonin MA, Hamar B, McGeehin MA. Removing 

the smoking confounder from blood volatile organic compounds 

measurements. Environ Res 1995;71:39-45.

Backer LC, Egeland GM, Ashley DL, Lawryk NJ, Weisel CP, 

White MC, et al. Exposure to regular gasoline and ethanol 

oxyfuel during refueling in Alaska. Environ Health Perspect 

1997;105(8):850-855.

Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate 

analysis on levels of selected metals, particulate matter, VOC, 

and household characteristics and activities from the Midwestern 

states NHEXAS. Appl Occup Environ Hyg 2001;6(9):859-874.

Brugnone F. Benzene in blood as a biomarker of low level 

occupational exposure. Sci Tot Environ. 1999;235:247.

Brugnone F, Perbellini L, Giuliari C, Cerpelloni M, Soave M. 

Blood and urine concentrations of chemical pollutants in the 

general population. Med Lav 1994;85(5):370-389.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, 

Needham LL. Environmental and biomarker measurements in 

nine homes in the lower Rio Grande Valley: multimedia results for 

pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-

732.

Carrer P, Maroni M, Alcini D, Cavallo D, Fustinoni S, Lovato 

L, et al. Assessment through environmental and biological 

measurements of total daily exposure to volatile organic 

compounds of office workers in Milan, Italy. Indoor Air 
 460 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

2000;10:258-268.

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures 

and blood volatile organic compound levels in a large populationbased sample. Arch Environ Health 2001;56(2):157-166.

Duarte-Davidson R, Courage C, Rushton L, Levy L. Benzene in 

the environment: an assessment of the potential risks to the health 

of the population. Occup Environ Med 2001;58(1):2-13.

Hattemer-Frey HA, Travis CC, Land ML. Benzene: Environmental 

partitioning and human exposure. Environ Res 1990;53:221-232.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Expo Sci Environ Epidemiol 2008;18(4):421-9.

Moolenaar RL, Brockton JH, Ashley DL, Middauth JP, Etzel RA. 

Blood benzene concentrations in workers exposed to oxygenated 

fuel in Fairbanks, Alaska. Int Arch Occup Environ Health 

1997;69:139-143.

National Toxicology Program (NTP). Toxicology and 

carcinogenesis studies of benzene (CAS No. 71-43-2) in F344/N 

rats and B6C3F1 mice (gavage studies). National Toxicology 

Program Tech Rep Series No. 289. 1986 [online]. Available at 

URL: http://ntp.niehs.nih.gov/go/reports. 4/20/09

Navasumrit P, Chanvaivit S, Intarasunanont P, Arayasiri M, 

Lauhareungpanya N, Parnlob V, et al. Environmental and 

occupational exposure to benzene in Thailand. Chem Biol 

Interact. 2005;153-154:75-83.

Perbellini L, Pasini F, Romani S, Princivalle A, Brugnone F. 

Analysis of benzene, toluene, ethylbenzene and m-xylene in 

biological samples from the general population. J Chromat B 

2002;778:198-210.

Romieu I, Ramirez M, Meneses F, Ashley DL, Lemire S, Colome 

S, et al. Environmental exposure to volatile organic compounds 

among workers in Mexico City as assessed by personal 

monitors and blood concentrations. Environ Health Perspect 

1999;107(7):511-515.

Ross D. The role of metabolism and specific metabolites in 

benzene-induced toxicity: evidence and issues. J Toxicol Environ 

Health A 2000;61(5-6):357-372.

Rowe BL, Toccalino PL, Moran MJ, Zogorski JS, Price CV. 

occurrence and potential human-health relevance of colatile 

organic compounds in drinking water from domestic wells in the 

United States. Environ Health Perspect 2007;115(11):1539-1546.

Savitz DA, Andrews KW. Review of epidemiologic evidence on 

benzene and lymphatic and hematopoietic cancers. Am J Ind Med 

1997 Mar;31(3):287-95.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran G, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 

years of age. Environ Health Perspect 2006;114(3):453-459.

Wallace L. Environmental exposure to benzene: an update. 

Environ Health Perspect 1996;104 Suppl 6:1129-1136.

Wallace L, Pellizzari E, Leaderer B, Zelon H, Sheldon L. 

Emissions of volatile organic compounds from building materials 

and consumer products. Atmos Environ 1987;21:385-393.
Fourth National Report on Human Exposure to Environmental Chemicals 461

 Volatile Organic Compounds (VOCs)

Chlorobenzenes

Chlorobenzene (Monochlorobenzene)

CAS No. 108-90-7

1,2-Dichlorobenzene (o-dichlorobenzene)

CAS No. 95-50-1

1,3-Dichlorobenzene (m-dichlorobenzene)

CAS No. 541-73-1

1,4-Dichlorobenzene (p-dichlorobenzene, 

Paradichlorobenzene) CAS No. 106-46-7

General Information

Chlorobenzene (monochlorobenzene) and the three 

dichlorobenzenes are halogenated aromatic hydrocarbons 

pirmarily used in industrial and chemical synthetic 

processes. Chlorobenzene has been used to produce DDT, 

phenol, and nitrobenzene. The dichlorobenzenes are also 

chemical intermediates in synthesis of dyes, pesticides, 

and other industrial products. The chlorobenzenes have 

sometimes been used as solvents for pesticides and auto 

parts degreasers (ATSDR, 2007). 1,4-Dichlorobenzene 

(1,4-DCB; para-dichlorobenzene) is used also as a moth 

repellent and as a deodorizer (ATSDR, 2007).

Ambient air is the primary source of chlorobenzene exposure 

for the general population. Indoor air levels of 1,4-DCB may 

exceed outdoor levels when moth repellents or deodorizers 

are in use (Wallace et al., 1987, 1991). Dietary sources 

are negligible (Schaum et al., 2003), and chlorobenzenes 

generally are not detected in drinking water or groundwater 

in the United States (USGS, 2006), but may be detected 

where industrial waste containing these chemicals has been 

discharged (IPCS, 2004). Chlorobenzenes volatilize from 

soil and water (ATSDR, 2007, 2008). People involved in 

the production or use of chlorobenzenes may be exposed 

by inhalation or dermal contact. Chlorobenzenes are well 

absorbed after inhalation and ingestion. 1,4-DCB is not 

appreciably absorbed through intact skin. Within a few 

hours following exposure, these chemicals are eliminated 

from tissues via oxidative hepatic metabolism followed by 

conjugation or oxidation. The major urinary metabolites 

are dichlorophenols (ATSDR, 2007, 2006).

Human health effects from chlorobenzenes at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. In humans, high 

air levels of 1,2- or 1,4-dichlorobenzenes cause eye and 

nasal irritation, and prolonged or repeated contact with 

concentrated solutions of either chemical may cause skin 

irritation or sensitization (Elovaara, 1998). Asthma and 

reduced pulmonary function have been associated with 

recent exposure to aromatic chemicals, including 1,4-DCB, 

but causation is unclear (Arif and Shah, 2007; Elliott et 

al., 2006). Laboratory animals exposed to high levels of 

chlorobenzene may demonstrate liver enlargement and 

serum transaminase elevations, renal tubular cell damage, 

and central nervous system depression. High doses of 1,2- 

or 1,3-dichlorbenzenes can result in centrilobular liver 

necrosis and decreased thyroid hormone levels and, among 

Blood Chlorobenzene (Monochlorobenzene) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1366

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1366

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 669

Females 03-04 * < LOD < LOD < LOD < LOD 697

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 300

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 694

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.011. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 462 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

male animals, renal tubular degeneration (ATSDR, 2007; 

Elovaara, 1998; NTP, 1987). 1,4-DCB is not as acutely 

hepatotoxic or thyrotoxic as the other dichlorobenzene 

isomers (den Besten et al., 1991, 1992; Stine et al., 1991). 

In animal studies, 1,4-DCB is not considered to be a 

reproductive or developmental toxicant (ATSDR, 2007, 

2008; Elovaara, 1998). Animals fed high doses of 1,4-DCB 

demonstrated an increased incidence of renal and hepatic 

tumors, but no evidence was found of mutagenicity or 

genotoxicity in vitro (NTP, 1987).

The U.S. EPA and the FDA regulate the levels of 1,2- 

or 1,4-dichlorobenzene in air and water and in bottled 

drinking water, respectively. U.S. EPA regulates the 

monochlorobenzene level in drinking water. NIOSH 

and ACGIH provide workplace guidelines for 1,2- and 

1,4-dichlorobenzenes and monochlorobenzene levels 

in air. IARC classified 1,4-dichlorobenze as a possible 

human carcinogen and NTP determined that it was 

reasonably anticipated to be a human carcinogen. However, 

IARC determined that the human carcinogenicity of 

1,2-dichlorobenzene and 1,3-dichlorobenzene was 

unclassifiable. Additional information about external 

exposure (i.e., environmental levels) and health effects 

is available from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html.

Biomonitoring Information

Levels of chlorobenzene, 1,2-dichlorobenzene, 

1,3-dichlorobenzene, and 1,4-dichlorobenzene in blood reflect recent exposure. Data from the NHANES 2003-2004 

subsample are shown in the tables for all the chlorobenzenes. 

In addition, the table for 1,4-dichlorobenzene shows data 

from the NHANES 2001-2002 subsample.

Generally, blood levels of chlorobenzene, 

1,2-dichlorobenzene, 1,3-dichlorobenzene were not 

detected in NHANES 2003-2004 and were detected in only 

less than 10% of the U.S. general population samples in 

earlier surveys (Ashley et al., 1994; Elliott et al., 2006). 

For 1,4-dichlorobenzene, a nonrepresentative sample of 

adults from the National Health and Nutrition Examination 

Survey (NHANES) III (1988–1994) demonstrated a median 

level of 1,4-DCB level of 0.33 μg/L (Hill et al., 1995), or 

equivalent to the 75th percentile of the NHANES 2003-2004 

subsample, and about three times higher than levels found 

in a sample of Midwestern adults and children (Bonanno 

et al., 2001). A small study of urban, low-income children 

monitored over a two year period reported that median 1,4-

DCB blood levels were slightly lower than NHANES III 

(Sexton et al., 2005, 2006). Ambient air and blood levels 

have been shown to correlate reasonably well (Lin et al., 

2008; Sexton et al., 2005). Residential construction and 

cleaning activities, including the recent use of toilet bowl 

deodorants, may contribute to elevated indoor air and blood 

levels of 1,4-DCB (Bonanno et al., 2001; Churchill et al., 

2001).

Finding a measurable amount of chlorobenzenes in the 

urine does not mean that the level of chlorobenzene causes 

an adverse health effect. Biomonitoring studies of urinary 

chlorobenzenes can provide physicians and public health 

officials with reference values so that they can determine 

Blood 1,2-Dichlorobenzene (o-Dichlorobenzene) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1327

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1327

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 647

Females 03-04 * < LOD < LOD < LOD < LOD 680

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 250

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 291

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 682

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.1. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 463

 Volatile Organic Compounds (VOCs)

whether people have been exposed to higher levels of 

chlorobenzenes than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.
 464 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Blood 1,3-Dichlorobenzene (m-Dichlorobenzene) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1334

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1334

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 659

Females 03-04 * < LOD < LOD < LOD < LOD 675

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 266

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 279

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 686

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.05. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Blood 1,4-Dichlorobenzene (Paradichlorobenzene) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD .300 (.190-.550) 1.19 (.610-2.90) 4.10 (1.40-7.60) 807

03-04 * < LOD .320 (.250-.400) 1.10 (.710-1.60) 3.30 (1.70-5.10) 1322

Age group 

20-59 years 01-02 * < LOD .300 (.190-.550) 1.19 (.610-2.90) 4.10 (1.40-7.60) 807

03-04 * < LOD .320 (.250-.400) 1.10 (.710-1.60) 3.30 (1.70-5.10) 1322

Gender 

Males 01-02 * < LOD .270 (.180-.530) .900 (.570-2.90) 3.60 (1.10-7.20) 390

03-04 * < LOD .320 (.250-.380) .770 (.580-1.20) 1.90 (1.20-4.00) 651

Females 01-02 * < LOD .360 (.190-.620) 1.20 (.620-3.90) 4.10 (1.68-8.30) 417

03-04 * < LOD .350 (.220-.450) 1.40 (.810-2.10) 4.10 (2.20-5.90) 671

Race/ethnicity 

Mexican Americans 01-02 .331 (.246-.446) .180 (<LOD-.260) .790 (.400-1.30) 6.00 (1.30-16.0) 16.0 (6.20-33.0) 217

03-04 .381 (.256-.566) .210 (.140-.400) .730 (.370-2.90) 6.20 (2.90-9.30) 10.0 (6.30-19.0) 262

Non-Hispanic blacks 01-02 .558 (.376-.827) .360 (.260-.560) 1.80 (.710-3.90) 6.30 (1.40-29.0) 15.0 (3.60-51.0) 136

03-04 .423 (.292-.613) .340 (.200-.480) .980 (.550-1.50) 4.10 (1.60-9.20) 11.0 (2.50-19.0) 297

Non-Hispanic whites 01-02 * < LOD .200 (<LOD-.380) .570 (.300-1.20) 1.19 (.570-3.70) 396

03-04 * < LOD .200 (.160-.260) .490 (.370-.720) .940 (.690-2.00) 658

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.12 and 0.12. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 465

 Volatile Organic Compounds (VOCs)

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for chlorobenzene. Atlanta GA [updated 

2008 August 08] Available at URL: http://www.atsdr.cdc.gov/

toxprofiles/tp131.html. 4/13/09

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for dichlorobenzenes update. Atlanta GA 

[updated 2007 October 19] Available at URL: http://www.atsdr.

cdc.gov/toxprofiles/tp10.html#bookmark09. 4/13/09

Arif AA, Shah SM. Association between personal exposure 

to volatile organic compounds and asthma among US adult 

population. Int Arch Occup Environ Health 2007;80(8):711-719.

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate 

analysis on levels of selected metals, particulate matter, VOC, 

and household characteristics and activities from the Midwestern 

states NHEXAS. Appl Occup Environ Hyg 2001;16(9):859-874.

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures 

and blood volatile organic compound levels in a large populationbased sample. Arch Environ Health 2001;56(2):157-166.

Den Besten C, Ellenbroek M, van der Ree MAE, Rietjens 

IMCM, van Bladeren PJ. The involvement of primary and 

secondary metabolism in the covalent bainding of 1,2- and 

1,4-dichlorobenzenes. Chem Biol Interact 1992;84:259-275.

Den Besten C, Vet JJRM, Besselink HT, Kiel FS, van Berke 

BJM, Beems R, et al. The liver, kidney, and thyroid toxicity of 

chlorinated benzenes. Toxicol Appl Pharmacol 1991;111:69-81.

Elliott L, Longnecker MP, Kissling GE, London SJ. Volatile 

organic compounds and pulmonary function in the Third National 

Health and Nutrition Examination Survey, 1988-1994. Environ 

Health Perspect 2006;114(8):1210-1214.

Elovaara E. 122. Dichlorobenzenes, The Nordic Expert Group 

for Criteria Documentation of Health Risks from Chemicals. 

The National Institute for Working Life. Stockholm, Sweden. 

1998. Availableat URL: https://gupea.ub.gu.se/dspace/

bitstream/2077/4199/1/ah1998_04.pdf . 4/13/09

Hill RH Jr, Ashley DL, Head SL, Needham LL, Pirkle JL. 

p-Dichlorobenzene exposure among 1,000 adults in the United 

States. Arch Environ Health 1995;50(4):277-280.

International Programme on Chemical Safety (IPCS). 

Chlorobenzenes other than hexachlorobenzene: environmental 

aspects (Cicads 60). Geneva, Switzerland. 2004. Available at 

URL: http://www.inchem.org/documents/cicads/cicads/cicad60.

htm. 4/13/09

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Expo Sci Environ Epidemiol. 2008 Jul;18(4):421-

429.

National Toxicology Program (NTP). Toxicology and 

carcinogenesis studies of 1,4-dichlorobenzene in F344/N rats and 

B6C3F1 mice (gavage studies), NTP TR 319, NIH Publication 

No. 87-2575 . Research Triangle Park NC. 1987. Available 

from: http://ntp.niehs.nih.gov:8080/cs.html?charset=iso-8859-

1&url=http%3A//ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr319.

pdf&qt=1%2C4-dichlorobenzene&col=020rpt&n=2&la=en. 

4/13/09

Schaum J, Schuda L, Wu C, Sears R, Ferrario J, Andrews K. A 

national survey of persistent, bioaccumulative, and toxic (PBT) 

pollutants in the United States milk supply. J Exp Anal Environ 

Epidemiol 2003;13:177-186.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 

years of age. Environ Health Perspect 2006;114(3):453-459.

Stine ER, Gunawardhana L, Sipes IG. The acute hepatotoxicity 

of the isomers of dichlorobenzene in Fischer-344 and SpragueDawley rats: isomer-specific and strain-specific differential 

toxicity. Toxicol Appl Pharmacol 1991;42:197-208.

United States Geological Survey (USGS). Volatile organic 

compounds in the nation’s ground water and drinking-water 

supply wells. Reston VA [updated 2006 August 28] Available 

from: http://pubs.usgs.gov/circ/circ1292/. 4/13/09

Wallace L, Pellizzari E, Hartwell T, et al. The TEAM study: 

personal exposures to toxic substances in air, drinking water, and 

breath of 400 residents of New Jersey, North Carolina, and North 

Dakota. Environ Res 1987;43:290–307.

Wallace L, Nelson W, Ziegenfus R, et al. The Los Angeles team 

study: personal exposures, indoor-outdoor air concentrations, 

and breath concentrations of 25 volatile organic compounds. J 

Exposure Anal Environ Epidemiol 1991;1:157–192.
 466 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

1,2-Dibromo-3-Chloropropane (DBCP)

CAS No. 96-12-8

General Information

1,2-Dibromo-3-chloropropane (DBCP) is a liquid soil 

fumigant used until 1985 when the U.S. Environmental 

Protection Agency (U.S. EPA) banned applications 

(ATSDR, 1992). DBCP volatilizes from soil into the air 

after application. Recent surveys of U.S. public drinking 

water supplies have not detected DBCP (USGS, 2006).

Exposure to the general population is rare. In the past, 

inhalational and dermal exposure occurred primarily in 

formulators and applicators. DBCP can be absorbed by 

ingestion, inhalation, and dermal routes. After absorption, 

DBCP is shown in animal studies to distribute widely into 

most tissues. Metabolites are excreted in urine, feces, and, 

to a limited extent, exhaled air (ATSDR, 1992; MacFarland 

et al., 1984).

In animal studies, large acute doses of DBCP produce 

lethargy, ataxia, and convulsions. High chronic doses in 

laboratory animals demonstrate kidney toxicity, testicular 

injury and reduced sperm production, and altered estrus 

cycles and infertility (ATSDR, 1992; Lag et al., 1989; Rao et 

al., 1982). Male workers exposed during DBCP production 

have demonstrated oligospermia or azoospermia; sperm 

count recovery occurred generally with less than 3 years of 

workplace exposure (Potashnik, 1983; Potashnik and YaniInbar, 1987; Whorton et al., 1979; Lipschultz et al., 1980). In 

general populations, epidemiologic investigations found no 

association between exposure to previously contaminated 

drinking water and birth rates, birth outcomes, gastric 

cancer, or leukemia (Whorton et al., 1989; Wong et al., 

1988).

An increased risk for certain cancers was found in several 

studies of workers exposed to DBCP (Olsen et al., 1995; 

Wesseling et al., 1996); however, these studies may have 

been confounded by other unmeasured exposures. Rodents 

that were administered DBCP developed tumors in the nasal 

cavity, lungs, and forestomach (NCI, 1978; NTP, 1982). 

The International Agency for Research on Cancer classified 

DBCP as a possible human carcinogen; the National 

Toxicology Program determined that DBCP was reasonably 

anticipated to be a human carcinogen. U.S. EPA established 

drinking water and other environmental standards and the 

Occupational Safety and Health Administration established 

workplace standards for DBCP. Information about external 

exposure (i.e., environmental levels) and health effects 

is available from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html.

Biomonitoring Information

Levels of DBCP in blood reflect recent exposure. In the 

general population, DBCP was not detected in the NHANES 

2003-2004 subsample, similar to other studies (Ashley 

et al. 1994; Churchill et al., 2001). Finding a measurable 

amount of DBCP in the blood does not mean that the level 

of DBCP causes an adverse health effect. Biomonitoring 

studies of DBCP in the blood can provide physicians and 

Blood 1,2-Dibromo-3-chloropropane (DBCP) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1170

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1170

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 568

Females 03-04 * < LOD < LOD < LOD < LOD 602

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 234

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 239

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 603

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.1. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 467

 Volatile Organic Compounds (VOCs)

public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of DBCP than are found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for 1,2-dibromo-3-chloropropane. 1992 

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp36.html. 7/3/08

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures 

and blood volatile organic compound levels in a large populationbased sample. Arch Environ Health 2001;56(2):157-166.

Lag M, Omichinski JG, Soderlund EJ, Brunborg G, Holme JA, 

Dahl JE, et al. Role of P-450 activity and glutathione levels in 

1,2-dibromo-3-chloropropane tissue distribution, renal necrosis 

and in vivo DNA damage. Toxicology 1989;56:273-288.

Lipshultz LI, Ross CE, Ehorton D, Milby T, Samith R, Joyner 

RE. Dibromochloropropane and its effect on testicular function 

in man. J Urol 1980;124:464-468.

MacFarland RT, Gandolfi AT, Sipes IC. Extra-hepatic GSHdependent metabolism of 1,2-dibromoethane (DBE) and 

1,2-dibromo-3-chloropropane (DBCP) in the rat and mouse. 

Drug Chem Toxicol 1984;7:213-227.

National Cancer Institute (NCI). Bioassay of 

dibromochloropropane for possible carcinogenicity (CAS no. 96-

12-8). Technical Report Series No. 28. 1978 [online]. Available 

at URL: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr028.pdf. 

7/3/08

National Toxicology Program (NTP). Carcinogenesis bioassay of 

1,2-dibromo-3-chloro-propane (CAS no. 96-12-8) inF344/N rats 

and B6C31F mice (inhalation studies). Technical Report Series 

No. 206. 1982 [online]. Available at URL: http://ntp.niehs.nih.

gov/ntp/htdocs/LT_rpts/tr206.pdf. 7/3/08

Olsen GW, Bodner KM, Stafford BA, Cartmill JB, Gondek 

MR. Update of the mortality experience of employees with 

occupational exposure to 1,2-dibromo-3-chloropropane (DBCP). 

Am J Ind Med 1995;28(3):399-410.

Potashnik G. A four-year reassessment of workers with 

dibromochloropropane-induced testicular dysfunction. 

Andrologia 1983;15(2):164-170.

Potashnik G, Yanai-Inbar I. Dibromochloropropane (DBCP): 

an 8-year reevaluation of testicular function and reproductive 

performance. Fertil Steril 1987;47(2):317-323.

Rao, K.S., J.D. Burek, F. Murray, John JA, Schwetz BA, Beyer 

JE, Parker CM. Toxicologic and reproductive effects of inhaled 

1,2-dibromo-3-chloropropane in male rabbits. Fund Appl Toxicol 

1982;2(5): 241-251.

United States Geological Survey (USGS). Volatile Organic 

Compounds in the Nation’s Ground Water and Drinking-Water 

Supply Wells. 2006 [online]. Available at URL: http://pubs.usgs.

gov/circ/circ1292/. 7/3/08

Wesseling C, Ahlbom A, Antich D, Rodriguez AC, Castro 

R. Cancer in banana plantation workers in Costa Rica. Int J 

Epidemiol 1996;25(6):1125-1131.

Whorton D, Milby TH, Krauss RM, Stubbs HA. Testicular 

function in DBCP exposed pesticide workers. J Occup Med 

1979;21(3):161-166.

Whorton DM, Wong O, Morgan RW, Gordon N. An 

epidemiologic investigation of birth outcomes in relation to 

dibromochloropropane contamination in drinking water in 

Fresno County, California, USA. Int Arch Occup Environ Health 

1989;61:403-407.

Wong O, Whorton MD, Gordon N, Morgan RW. An epidemiologic 

investigation of the relationship between DBCP contamination in 

drinking water and birth rates in Fresno County, California. Am J 

Public Health 1988;78:43-46.
 468 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

2,5-Dimethylfuran

CAS No. 625-86-5

General Information

2,5-Dimethylfuran is a volatile chemical found in tobacco 

smoke (Baggett et al., 1974) and in roasted coffee aroma 

(Wang et al., 1983). Exposure among the general population 

may occur through inhaling cigarette smoke and coffee 

aroma. 2,5-Dimethylfuran in blood and exhaled air has 

been used to determine smoking status (Ashley et al., 1996; 

Gordon et al., 2002; Perbellini et al., 2003). In addition, 

levels of 2,5-dimethylfuran found in blood provide a rough 

estimate of the number of cigarettes smoked per day (Ashley 

et al., 1995, 1996). After a person smokes cigarettes, 

2,5-dimethylfuran is absorbed from the respiratory tract 

and then rapidly eliminated from the blood (Egle and 

Gochberg, 1979; Gordon et al., 2002). 2,5-Dimethylfuran 

is also a human urinary metabolite of n-hexane. Workers 

exposed to n-hexane will eliminate 2,5-dimethylfuran, 

along with other metabolites, in their urine (ATSDR, 2007; 

Iwata et al., 1983; Mutti et al., 1984; Perbellini et al., 1981).

Human health effects from 2,5-dimethylfuran at low 

environmental doses or at biomonitored levels from 

low environmental exposures are unknown. Neither 

IARC or NTP has evaluated 2,5-dimethylfuran’s human 

carcinogenicity. 2,5-Dimethylfuran is not mutagenic by in 

vitro testing (Zeiger et al., 1992).

Biomonitoring Information

Levels of 2,5-dimethylfuran in blood reflect recent exposure 

and are generally undetectable among nonsmoking 

adults and in the general population. Ashley et al. (1995) 

and Perbellini et al. (2003) reported median blood 

2,5-dimethylfuran levels of 0.13 μg/L in smokers which 

were similar values to the 95th percentile in participants of 

NHANES 2003-2004 reflecting the U.S. population mix 

of nonsmokers and smokers. Levels of 2,5-dimethylfuran 

in blood increase generally with the number of cigarettes 

smoked per day (Ashley et al., 1995, 1996).

Finding a measurable amount of 2,5-dimethylfuran in 

blood does not mean that the level of 2,5-dimethylfuran

causes an adverse health effect. Biomonitoring studies of 

2,5-dimethylfuran in blood can provide physicians and 

public health officials with reference values so that they 

can determine whether people have been exposed to higher 

levels of 2,5-dimethylfuran than are found in the general 

population. Biomonitoring data can also help scientists 

plan and conduct research on exposure and health effects.

Blood 2,5-Dimethylfuran 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD .015 (<LOD-.031) .100 (.083-.110) .140 (.120-.180) 1221

Age group 

20-59 years 03-04 * < LOD .015 (<LOD-.031) .100 (.083-.110) .140 (.120-.180) 1221

Gender 

Males 03-04 * < LOD .019 (<LOD-.031) .094 (.071-.110) .130 (.110-.190) 602

Females 03-04 * < LOD < LOD .110 (.074-.120) .150 (.120-.210) 619

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD .012 (<LOD-.020) .038 (.013-.054) 237

Non-Hispanic blacks 03-04 * < LOD .041 (.018-.063) .110 (.079-.160) .170 (.099-.220) 261

Non-Hispanic whites 03-04 * < LOD .020 (<LOD-.041) .110 (.087-.120) .150 (.120-.210) 628

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.012. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 469

 Volatile Organic Compounds (VOCs)

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for n-hexane. 1999 [online]. Available at 

URL: http://www.atsdr.cdc.gov/toxprofiles/tp113.html. 4/14/09

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for n-hexane. Atlanta GA 2007 [online]. 

Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp113.

html. 4/14/09

Ashley DL, Bonin MA, Hamar B, McGeehin MA. Removing 

the smoking confounder from blood volatile organic compounds 

measurements. Environ Res 1995;71(1):39-45.

Ashley DL, Bonin MA, Hamar B, McGeehin M. Using the blood 

concentration of 2,5-dimethylfuran as a marker for smoking. Int 

Arch Occup Environ Health 1996;68(3):183-187.

Baggett MS, Morie GP, Simmons MW, Lewis JS. Quantitative 

determination of semivolatile compounds in cigarette smoke. J 

Chromatogr 1974;97(1):79-82.

Egle JL Jr, Gochberg BJ. Retention of inhaled 2-methylfuran and 

2,5-dimethylfuran. Am Ind Hyg Assoc J 1979;40(10):866-869.

Gordon SM, Wallace LA, Brinkman MC, Callahan PJ, Kenny 

DV. Volatile organic compounds as breath biomarkers for active 

and passive smoking. Environ Health Perspect 2002;110(7):689-

698.

Iwata M, Takeuchi Y, Hisanaga N, Ono Y. A study on biological 

monitoring of n-hexane exposure. Int Arch Occup Environ Health 

1983;51(3):253-260.

Mutti A, Falzoi M, Lucertini S, Arfini G, Zignani M, Lombardi 

S, Franchini I. n-Hexane metabolism in occupationally exposed 

workers. Br J Ind Med 1984;41(4):533-538.

Perbellini L, Brugnone F, Faggionato G. Urinary excretion of 

the metabolites of n-hexane and its isomers during occupational 

exposure. Br J Ind Med 1981;38:20-26.

Perbellini L, Princivalle A, Cerpelloni M, Pasini F, Brugnone 

f. Comparison of breath, blood and urine concentrations in the 

biomonitoring of environmental exposure to 1,3-butadiene, 

2,5-dimethylfuran, and benzene. Int Arch Occup Environ Health 

2003;76:461-466.

Wang TH, Shanfield, Zlatkis A. Analysis of trace volatile 

organic compounds in coffee by headspace concentration and 

gas chromatography-mass spectrometry. Chromatographia 

1983;17:411-417.

Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K. 

Salmonella mutagenicity tests: V. Results from the testing of 311 

chemicals. Environ Mol Mutagen 1992;19 supp. 21:2-141.
 470 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Ethylbenzene

CAS No. 100-41-4

General Information

Ethylbenzene is a flammable hydrocarbon found in crude oil. 

It is a high production chemical used largely to synthesize 

styrene and also as a solvent and an additive to automobile 

and aviation fuels. Automobile emission contributes a 

significant amount of ethylbenzene to outdoor air. Indoor 

sources of ethylbenzene include carpet adhesives and 

tobacco smoke. Ethylbenzene is ubiquitous in ambient air, 

with higher concentrations in areas with greater vehicular 

traffic. It undergoes biodegradation or photooxidation 

in air, water, and soil, and it does not bioaccumulate in 

aquatic food chains (ATSDR, 2007). Producing and using 

petroleum products are potential sources of workplace 

exposure to ethylbenzene.

The general population may be exposed to ethylbenzene 

through inhalation, particularly from motor vehicle 

emissions, self-service gasoline pump vapors, and 

cigarette smoke. Drinking water is contaminated rarely by 

leaking underground storage tanks containing petroleum 

products. Ethylbenzene is well absorbed by inhalation, 

oral, or dermal exposure routes. After absorption, 

ethylbenzene is metabolized rapidly by the liver. Mandelic 

and phenylglyoxylic acids are the predominant urinary 

metabolites and have been used to monitor workplace 

exposure (Knecht et al., 2000).

Human health effects from ethylbenzene at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Ethylbenzene can 

cause respiratory tract and eye irritation and dizziness at air 

concentrations that exceed workplace standards (ComettoMuniz and Cain, 1995). Much higher levels occurring with 

accidental exposures can produce central nervous system 

depression. Laboratory animals exposed to ethylbenzene for 

several weeks to months at air concentrations several times 

higher than occupational standards have shown respiratory 

irritation, increased liver weight, liver microsomal enzyme 

induction, and increased leukocyte counts (ATSDR, 2007). 

Chronic animal exposure studies have also demonstrated 

renal tubular, alveolar, and hepatic tumors with some 

evidence of gender-specific susceptibility (NTP, 1999).

The IARC classified ethylbenzene as a possible human 

carcinogen. OSHA and ACGIH established workplace 

standards and guidelines, respectively, for ethylbenzene. 

Blood Ethylbenzene 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 .034 (.029-.039) .030 (.030-.040) .050 (.050-.070) .090 (.070-.120) .140 (.090-.180) 879

03-04 .035 (.033-.037) .032 (.030-.036) .053 (.048-.057) .083 (.077-.088) .110 (.098-.120) 1299

Age group 

20-59 years 01-02 .034 (.029-.039) .030 (.030-.040) .050 (.050-.070) .090 (.070-.120) .140 (.090-.180) 879

03-04 .035 (.033-.037) .032 (.030-.036) .053 (.048-.057) .083 (.077-.088) .110 (.098-.120) 1299

Gender 

Males 01-02 .035 (.029-.041) .030 (<LOD-.040) .060 (.040-.070) .100 (.070-.150) .150 (.090-.220) 419

03-04 .037 (.034-.041) .036 (.031-.040) .057 (.051-.065) .086 (.078-.099) .110 (.094-.130) 625

Females 01-02 .033 (.028-.038) .030 (.030-.040) .050 (.040-.060) .080 (.060-.120) .130 (.070-.180) 460

03-04 .032 (.030-.034) .030 (.027-.033) .048 (.041-.053) .081 (.071-.089) .100 (.091-.120) 674

Race/ethnicity 

Mexican Americans 01-02 * .030 (<LOD-.040) .040 (.040-.060) .070 (.050-.110) .120 (.070-.210) 220

03-04 .031 (.027-.036) .029 (<LOD-.035) .044 (.035-.048) .064 (.051-.074) .091 (.066-.170) 253

Non-Hispanic blacks 01-02 .032 (.027-.038) .030 (<LOD-.040) .050 (.030-.070) .080 (.060-.130) .130 (.070-.240) 159

03-04 .032 (.027-.038) .030 (<LOD-.037) .050 (.037-.066) .079 (.065-.100) .110 (.084-.130) 281

Non-Hispanic whites 01-02 .035 (.029-.043) .030 (<LOD-.040) .060 (.050-.070) .090 (.070-.140) .150 (.090-.190) 432

03-04 .036 (.034-.038) .034 (.030-.038) .055 (.050-.061) .087 (.081-.092) .110 (.098-.130) 669

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.024 and 0.024. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 
Fourth National Report on Human Exposure to Environmental Chemicals 471

 Volatile Organic Compounds (VOCs)

The U.S. EPA established environmental and drinking 

water standards for ethylbenzene. Information about 

external exposure (i.e., environmental levels) and health 

effects is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html.

Biomonitoring Information

Levels of ethylbenzene in blood reflect recent exposure.

In a nonrepresentative subsample of adults in the National 

Health and Nutrition Examination Survey (NHANES) 

III (1988-1994), the median ethylbenzene level in blood 

was 0.060 μg/L (Ashley et al., 1994), which is similar to 

the geometric mean value reported for nonsmokers in the 

NHANES 1999-2000 subsample (Lin et al., 2008). The 

geometric mean level in participants 20 years and older 

in the NHANES 2001-2002 and 2003-2004 subsamples 

appear similar or slightly below these previously reported 

values, though differences in methodology and sampled 

populations may account for slight differences in levels. 

Also, approximately similar levels were observed in sample 

of southwestern U.S. residents (Buckley et al., 1997), but 

such levels were about two to three times higher than levels 

reported among low-income children in a Midwestern U.S. 

city (Sexton et al., 2005, 2006).

Smoking cigarettes increases blood ethylbenzene levels, 

but environmental tobacco smoke exposure appears not to 

increase blood ethylbenzene (Lin et al., 2008; Perbellini 

et al., 2002). Residents in high density urban areas and 

commuters may have ethylbenzene levels up to two times 

higher than the nonsmoking general population (Lemire et 

al., 2004). Street vendors and workers exposed to gasoline 

fumes can have blood ethylbenzene levels up to ten times 

higher than levels found in the general population (Mannino 

et al., 1995; Romieu et al., 1999). Workers in the petroleum 

industry and those with solvent exposure can have blood 

ethylbenzene levels that are several hundred times higher 

than those in the general population (Angerer and Wulf, 

1985; Kawai et al., 1992).

Finding a measurable amount of ethylbenzene in the blood 

does not mean that the level of ethylbenzene causes an 

adverse health effect. Biomonitoring studies of ethylbenzene 

in blood can provide physicians and public health officials 

with reference values so that they can determine whether 

people have been exposed to higher levels of ethylbenzene 

than are found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for ethylbenzene, draft. September 2007 

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp110.html#bookmark08. 4/15/09

Angerer J, Wulf H. Occupational chronic exposure to organic 

solvents.XI. Alkylbenzene exposure of varnish workers: Effects 

on hematopoietic system. Int Arch Occup Environ Health 

1985;56:307-321.

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, 

Needham LL. Environmental and biomarker measurements in 

nine homes in the lower Rio Grande Valley: multimedia results for 

pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-

732.

Cometto-Muniz JE, Cain WS. Relative sensitivity of the ocular 

trigeminal, nasal trigeminal and olfactory systems to airborne 

chemicals. Chemical Senses 1995;20(2):191-198.

Kawai T, Yasugi T, Mizunuma K, Horiguchi SI, Iguchi H, Uchida 

Y, et al. Comparative evaluation of urinalysis and blood analysis 

as means of detecting exposure to organic solvents at low 

concentrations. Int Arch Occup Environ Health 1992;64(4):223-

234.

Knecht U, Reske A, Woitowitz HJ. Biological monitoring of 

standardized exposure to ethylbenzene: evaluation of a biological 

tolerance (BAT) value. Arch Toxicol 2000;73(12):632-640.

Lemire S, Ashley D, Olaya P, Romieu I, Welch S, MenesesGonzalez F, Hernandez-Avila M. Environmental exposure of 

commuters in Mexico City to volatile organic compounds as 

assessed by blood concentrations, 1998. Salud Publica Mex 

004;46:32-38.

Lin YS, Egeghy PP, Rappaport SM.Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Expo Sci Environ Epidemiol 2008 Jul;18(4):421-9. 

Epub 2007 Dec 5.

Mannino DM, Schreiber J, Aldous K, Ashley D, Moolenaar R, 

Almaguer D. Human exposure to volatile organic compounds: a 

comparison of organic vapor monitoring badge levels with blood 

levels. Int Arch Occp Environ Health 1995;67:59-64.

National Toxicology Program (NTP). Toxicology and 

Carcinogenesis Studies of Ethylbenzene (CAS No. 100-41-4) 

in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1999 

[online]. Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/

LT_rpts/tr466.pdf. 4/15/09
 472 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Perbellini L, Pasini F, Romani S, Princivalle A, Brugnone F. 

Analysis of benzene, toluene, ethylbenzene and m-xylene in 

biological samples from the general population. J Chromat B 

2002;778:198-210.

Romieu I, Ramirez M, Meneses F, Ashley DL, Lemire S, Colome 

S, et al. Environmental exposure to volatile organic compounds 

among workers in Mexico City as assessed by personal 

monitors and blood concentrations. Environ Health Perspect 

1999;107(7):511-515.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 

years of age. Environ Health Perspect 2006;114(3):453-459.
Fourth National Report on Human Exposure to Environmental Chemicals 473

 Volatile Organic Compounds (VOCs)

Halogenated Solvents

Dichloromethane (Methylene chloride)

CAS No. 75-09-2

Trichloroethene (Trichloroethylene) CAS No. 79-01-6

Tetrachloroethene (Tetrachloroethylene, Perchloroethylene) CAS No. 127-18-4

General Information

Dichloromethane, trichloroethene, and tetrachloroethene 

are volatile halogenated short-chain hydrocarbons. 

Dichloromethane is used principally as a solvent in paint 

removers and thinners, as well as in other household 

products (cleaners, glues, and adhesives), and also as a 

degreasing agent. Trichloroethene is used primarily as an 

industrial degreaser, solvent, and in the synthesis of other 

chemicals. In the past, it was used in dry cleaning, food 

processing, household cleaners, and as a general anesthetic. 

Tetrachloroethene is used in dry cleaning, metal cleaning, the 

synthesis of other chemicals, and household products such 

as water repellants, silicone lubricants, and spot removers. 

All three of these halogenated solvents are produced and 

used in high volumes in the U.S., and have been detected in 

urban and ambient air and occasionally, soils, and drinking 

water most likely contaminated by industrial discharge 

(Moran et al., 2007; Rowe et al., 2007). Because of their 

volatility, these solvents do not persist in the soil or water 

following the discontinuation of contamination.

Inhalation is the most common exposure route for the general 

population including indoor sources from paints, adhesives, 

and cleaning solutions. Volatilization from contaminated 

water (eg., shower water) as well as the use of household 

products containing these solvents can result in higher indoor 

than outdoor air concentrations (ATSDR, 1997b; Martin et 

al., 2005). Nearby dry cleaning establishments, industries 

producing these solvents, and contaminated waste disposal 

sites can also contribute to human exposure (Armstrong and 

Green, 2004; ATSDR, 1997a, 1997b, and 2000; Schreiber 

et al., 1993; Wallace et al., 1991). Drinking water may 

contribute to exposure when underground drinking water 

supplies have been contaminated. Workers in industries 

such as dry cleaning, aircraft maintenance, electronics 

manufacturing, and chemical production may be exposed 

by inhalation or by dermal contact with the liquid solvents. 

The U.S. EPA has established drinking water standards and 

other environmental standards for all three solvents, and 

the FDA regulates tetrachloroethene and trichloroethene as 

indirect food additives. For all three solvents, workplace 

standards have been established by OSHA, and ACGIH 

has recommended occupational guidelines and biological 

exposure indices for monitoring workers.

All three solvents are well absorbed by ingestion and 

inhalation, and animal studies have demonstrated that liquid 

forms can be dermally absorbed. Following absorption, 

part of the solvent dose is excreted into expired air; for 

tetrachloroethene, about 97-99% of the dose is eliminated 

unmetabolized into expired air, though it has an elimination 

half-life of several days (ATSDR1997a; Monster et 

Blood Dichloromethane (Methylene chloride) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1165

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1165

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 568

Females 03-04 * < LOD < LOD < LOD < LOD 597

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 225

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 245

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 607

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.07. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 474 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

al., 1986). The retained solvent can undergo hepatic 

metabolism. Trichloroethene and tetrachloroethene are 

metabolized to trichloroacetic acid and tricholoroethanol, 

which are eliminated in the urine. Dichloromethane is 

partially metabolized to carbon monoxide and carbon 

dioxide. Elevated carboxyhemoglobin levels in blood 

have been reported following intentional dichloromethane 

overdose or exposure to air concentrations greatly 

exceeding occupational standards (ATSDR, 2000; Hughes 

and Tracy, 1993).

Human health effects from dichloromethane, 

tetrachloroethene, and trichloroethene at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Accidental or intentional high 

dose acute exposure by ingestion or inhalation of any of 

these solvents can result in loss of motor coordination, 

somnolence, and unconsciousness. Inhaling high doses 

of trichloroethene and tetrachloroethene may also 

produce cardiac arrhythmias attributed to enhanced 

sensitivity to catecholamines. High dose acute exposure 

to tetrachloroethene has resulted in reversible kidney 

impairment, and prolonged, low level exposure to either 

tetrachloroethene or trichloroethene has been associated 

with altered renal enzyme excretion and liver enlargement 

(ATSDR, 1997a, b). Chronic occupational exposure to 

any of these three solvents may be associated with mild 

degrees of neurological impairments, including reaction 

times, verbal skills, cognitive ability and motor function 

(Armstrong and Green, 2004).

Various epidemiologic studies of chronic tetrachloroethene 

exposure in dry cleaning workers found increased incidences 

of esophageal and cervical cancers and non-Hodgkins 

lymphoma, but confounding exposures (e.g., other 

solvents and trichloroethene) were likely (IPCS, 2006). 

In animals studies, tetrachloroethene and trichloroethene 

each induced kidney and liver tumors; tetrachloroethene 

also caused leukemia, and trichloroethene caused lung and 

testicular tumors (IARC, 1995). Animal studies of inhaled 

dichloromethane have reported increased incidences of 

lung and hepatocellular cancers, and in female animals, 

mammary gland tumors (NTP, 2004). Trichloroethene 

and tetrachloroethene are classified as probable human 

carcinogens by IARC, and dichloromethane is classified as a 

possible human carcinogen by IARC. All three are classified 

as reasonably anticipated to be human carcinogens by NTP. 

Additional information about these solvents is available 

from ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Blood Trichloroethene (Trichloroethylene) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD < LOD < LOD < LOD 922

03-04 * < LOD < LOD < LOD < LOD 1228

Age group 

20-59 years 01-02 * < LOD < LOD < LOD < LOD 922

03-04 * < LOD < LOD < LOD < LOD 1228

Gender 

Males 01-02 * < LOD < LOD < LOD < LOD 434

03-04 * < LOD < LOD < LOD < LOD 604

Females 01-02 * < LOD < LOD < LOD < LOD 488

03-04 * < LOD < LOD < LOD < LOD 624

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD < LOD < LOD 228

03-04 * < LOD < LOD < LOD < LOD 224

Non-Hispanic blacks 01-02 * < LOD < LOD < LOD < LOD 191

03-04 * < LOD < LOD < LOD < LOD 266

Non-Hispanic whites 01-02 * < LOD < LOD < LOD < LOD 441

03-04 * < LOD < LOD < LOD < LOD 644

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.012 and 0.012. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 475

 Volatile Organic Compounds (VOCs)

Biomonitoring Information

Levels of halogenated solvents in blood reflect recent 

exposure. In the NHANES 2003-2004 subsample, the level 

of blood tetrachloroethene for adults at the 75th percentile 

of the U.S. population appear similar to the levels at the 75th

percentile reported for non-smoking adults in a subsample 

of NHANES 1999-2000 participants (Lin et al., 2008) 

and were similar or slightly less that levels reported in a 

nonrepresentative subsample of the earlier NHANES III 

(1988-1994) (Ashley et al., 1994; Churchill et al., 2001). 

A recent study of low income, urban children in the 

Midwest reported slightly lower median tetrachloroethene 

levels (Sexton et al., 2005; Sexton et al., 2006) than the 

NHANES III levels (Ashley et al., 1994; Churchill et al., 

2001). Other population studies have reported similarly 

low tetrachloroethene levels (Begerow et al., 1996; 

Bonanno et al., 2001). Population studies in Italy and 

Germany have reported multifold higher tetrachloroethene 

and trichloroethene blood levels than the U.S. surveys 

(Brugnone et al., 1994; Hajimiragha et al., 1986). Blood 

levels of trichloroethene and dichloromethane were detected 

infrequently in previous U.S. surveys and were generally 

not detected in the NHANES 2003-2004 subsample.

Comparatively higher blood levels of tetrachloroethene and 

trichloroethene have been noted for urban and industrial 

residential settings than for rural settings (Barkley et 

al., 1980; Begerow et al., 1996; Brugnone et al., 1994). 

Residing near dry-cleaning facilities or storing recently 

dry-cleaned clothes at home can contribute to increased 

blood tetrachloroethene levels (Begerow et al., 1996; Popp 

et al., 1992). In contrast, tetrachloroethene blood levels in 

occupationally exposed workers have been reported to be 

many thousand times higher than the unexposed general 

population (Begerow et al., 1996; Furuki et al., 2000; 

Monster et al., 1983). The occupational biological exposure 

index associated with an 8-hour exposure of 25 ppm is 500 

μg/L tetrachloroethene in blood (ACGIH, 2007). Nonoccupational exposures are usually well below this level.

Finding a measurable amount of any of these solvents in 

blood does not mean that the level of the solvent causes 

an adverse health effect. Biomonitoring studies of blood 

halogenated solvents can provide physicians and public 

health officials with reference values so that they can 

determine whether or not people have been exposed to 

higher levels of halogenated solvents than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Blood Tetrachloroethene (Perchloroethylene) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD .050 (<LOD-.060) .100 (.070-.150) .190 (.130-.260) 978

03-04 * < LOD < LOD .076 (.060-.097) .140 (.091-.300) 1317

Age group 

20-59 years 01-02 * < LOD .050 (<LOD-.060) .100 (.070-.150) .190 (.130-.260) 978

03-04 * < LOD < LOD .076 (.060-.097) .140 (.091-.300) 1317

Gender 

Males 01-02 * < LOD .050 (<LOD-.060) .110 (.070-.170) .210 (.170-.340) 457

03-04 * < LOD < LOD .082 (.060-.140) .230 (.097-.410) 639

Females 01-02 * < LOD .050 (<LOD-.060) .100 (.070-.140) .150 (.100-.220) 521

03-04 * < LOD < LOD .069 (.050-.091) .120 (.085-.180) 678

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD .060 (<LOD-.070) .070 (.060-.230) 226

03-04 * < LOD < LOD .049 (<LOD-.097) .100 (.054-.180) 248

Non-Hispanic blacks 01-02 * < LOD < LOD .070 (.050-.110) .110 (.060-.190) 195

03-04 * < LOD < LOD .086 (.050-.220) .220 (.082-.360) 284

Non-Hispanic whites 01-02 * < LOD .050 (<LOD-.070) .110 (.090-.170) .210 (.150-.260) 487

03-04 * < LOD < LOD .072 (.060-.091) .140 (.085-.330) 686

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.048 and 0.048. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 476 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

References

ACGIH. TLVs and BEIs Based on the documentation of the 

threshold limit values for chemical substances and physical agents 

and biological exposure indices. 2007. Signature Publications. 

Cincinnati OH. p.104.

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for trichloroethylene update. 1997b

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp19.html. 4/22/09

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for tetrachloroethylene update. 1997a

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp18.html. 4/22/09

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for Methylene chloride update. 2000 

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp14.html. 4/22/09

Armstrong SR, Green LC. Chlorinated hydrocarbon solvents. 

Clin Occup Environ Med 2004;4(3):481-496.

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Barkley J, Bunch J, Bursey JT, Castillo N, Cooper SD, Davis 

JM, et al. Gas chromatography mass spectrometry computer 

analysis of volatilie halogenated hydrocarbons in man and his 

environment—a multimedia environmental study. Biomed Mass 

Spectrom 1980;7(4):139-147.

Begerow J, Jermann E, Keles T, Freier I, Ranft U, Dunemann 

L. Internal and external tetrachloroethene exposure of persons 

living in differently polluted areas of Northrhine-Westphalia 

(Germany). Zentralbl Hyg Umweltmed. 1996;198(5):394-406.

Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate 

analysis on levels of selected metals, particulate matter, VOC, 

and household characteristics and activities from the Midwestern 

states NHEXAS. Appl Occup Environ Hyg 2001;16(9):859-874.

Brugnone F, Perbellini L, Guiliari C, Cerpelloni M, Soave M. 

Blood and urine concentrations of chemical pollutants in the 

general population. Med Lav 1994;8(5):370-389.

Churchill JA, Ashley DL, Kaye WE. Recent chemical exposures 

and blood volatile organic compound levels in a large populationbased sample. Arch Environ Health 2001;56(2):157-166.

Furuki K, Ukai H, Okamoto S, Takada S, Kawai T, Miyama Y, 

Mitsuyoshi K, et al. Monitoring of occupational exposure to 

tetrachloroethene by analysis for unmetabolized tetrachloroethene 

in blood and urine in comparison with urinalysis for trichloroacetic 

acid. Int Arch Occup Environ Health. 2000;73(4):221-227.

Hughes NJ, Tracey JA. A case of methylene chloride (nitromors) 

poisoning, effects on carboxyhaemoglobin levels. Hum Exp 

Toxicol 1993;12(2):159-60.

International Programme on Chemical Safety (IPCS). 

Concise International Chemical Assessment Document 

68-Tetrachloroethene. 2006 [online]. Available at URL: http://

www.inchem.org/documents/cicads/cicads/cicad68.htm. 4/22/09

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Exp Sci Environ Epidemiol 2008;18:421-429.

Martin SA, Simmons MB, Ortiz-Serrano M, Kendrick C, Gallo 

A, Campbell J, et al. Environmental exposure of a community 

to airborne trichloroethylene. Arch Environ Occup Health 

2005;60(6):341-316.

Monster AC. Biological monitoring of chlorinated hydrocarbon 

solvents. J Occup Med 1986;28:583-588.

Monster AC, Regouin-Peeters W, Van Schijndel A, van der 

Tuin J. Biological monitoring of occupational exposure to 

tetrachloroethene. Scand J Work Environ Health 1983;9:273-281.

Moran MJ, Zogorski JS, Squillace PJ. Chlorinated solvents 

in groundwater of the United States. Environ Sci Technol 

2007;41:74-81.

National Toxicology Program (NTP). Report on Carcinogens, 

11th ed. 2004. [online]. Available at URL: http://ntp.niehs.nih.

gov/ntp/roc/eleventh/profiles/s066dich.pdf. 4/22/09

Popp W, Muller G, Baltes-Schmitz B, Wehner B, Vahrenholz C, 

Schmieding W, et al. concentrations of tetrachloroethene in blood 

and trichloroacetic acid in urine in workers and neighbours of 

dry-cleaning shops. Int Arch Occup Environ Health 1992;63:393-

395.

Rowe BL, Toccalino PL, Moran MJ, Zogorski JS, Price CV. 

Occurrence and potential human-health relevance of volatile 

organic compounds in drinking water from domestic wells in the 

United States. Environ Health Perspect 2007;115(11):1539-1546.

Schreiber JS, House S, Prohonic E, Smead G, Hudson C, Styk M, 

et al. An investigation of indoor air contamination in residences 

above dry cleaners. Risk Anal 1993;13(3):335-344.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 
Fourth National Report on Human Exposure to Environmental Chemicals 477

 Volatile Organic Compounds (VOCs)

years of age. Environ Health Perspect 2006;114(3):453-459.

Wallace L, Nelson W, Ziegenfus R, Pellizzari E, Michael L, 

Whitmore R, et al. The Los Angeles TEAM Study: Personal 

exposures, indoor-outdoor air concentrations, and breath 

concentrations of 25 volatile organic compounds. J Exp Anal 

Environ Epidemiol 1991;1(2):157-192.
 478 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Other Halogenated Solvents

Dibromomethane CAS No. 74-95-3

1,1-Dichloroethane

CAS No. 75-34-3

1,2-Dichloroethane (Ethylene dichloride)

CAS No. 107-06-2

1,1-Dichloroethene (Vinylidene chloride)

CAS No. 75-34-3

cis-1,2-Dichloroethene CAS No. 156-59-2

trans-1,2-Dichloroethene CAS No. 156-60-5

1,2-Dichloropropane CAS No. 78-87-5

1,1,1-Trichloroethane (Methyl chloroform)

CAS No. 71-55-6

1,1,2-Trichloroethane CAS No. 79-00-5

1,1,2,2-Tetrachloroethane CAS No. 79-34-5

Tetrachloromethane (Carbon tetrachloride)

CAS No. 56-23-5

General Information

The halogenated solvents are volatile organic chemicals 

consisting of a hydrocarbon chain or one hydrocarbon 

substituted with one or more chlorine or bromine atoms. 

Most of these chemicals are used as degreasers and 

solvents in various products such as paints. In the past, 

1,1,1-trichloroethane was used as a dry cleaning agent, 

insect fumigant, and solvent in consumer products; more 

recently, its U.S. production has been restricted because 

of its principal use in manufacturing hydrofluorocarbons 

(Armstrong, et al., 2004; ATSDR, 2006b). Production 

of 1,1,2,2-tetrachloroethane in the U.S. has ceased, and 

currently, it is only used as a chemical intermediate in the 

production of several other halogenated solvents (ATSDR, 

2006a). 1,1,2-trichloroethane, 1,2-dichloroethane and 

1,1-dichloroethene are used in the synthesis of other 

chemicals, such as polyvinylidene. Tetrachloromethane 

use as a solvent and fumigant has been discontinued due 

to toxicity concerns, and its other major use, production 

of chlorofluorocarbon refrigerants, has been restricted 

as a result of regulations of ozone-depleting chemicals 

(ATSDR, 2005).

These volatile halogenated solvents may be released into 

the air from facilities that produce or use them, from 

contaminated waste water, or from hazardous waste sites. 

In surveys of U.S. drinking water, 1,1,1-trichloroethane was 

one of the most frequently detected chlorinated solvents; 

detected in less than 10 percent of domestic wells (Moran et 

al., 2007; Rowe et al., 2007). When 1,1,1-trichlorethane was 

available in consumer products, indoor air concentrations 

Blood Dibromomethane 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1355

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1355

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 666

Females 03-04 * < LOD < LOD < LOD < LOD 689

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 292

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 693

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.03. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 479

 Volatile Organic Compounds (VOCs)

could exceed outdoor air concentrations (Wallace, et 

al., 1991). Because of their volatility, these halogenated 

solvents generally do not persist in soil or water. Workers 

involved in the production or use of these solvents may be 

exposed by inhalation or by dermal contact with the liquid 

solvents.

Inhalation is the most common exposure route for the 

general population, including indoor sources from such 

as paints, adhesives, cleaning solutions, and aerosolized 

insecticide sprays; from industries producing these solvents; 

and from contaminated waste disposal sites (Armstrong et 

al., 2004; ATSDR, 2006a and 2001). Drinking water may 

contribute to exposure due to contaminated underground 

drinking water supplies. In general, these solvents are well 

absorbed by inhalation, dermal, or oral exposure. After 

absorption, small amounts may be exhaled in expired air, 

and the remaining amount rapidly distributed to tissues. 

1,1,1-Trichloroethane is exceptional in that most of a dose 

is exhaled unchanged in expired air and less than 10 percent 

of a dose is metabolized (Monster, et al., 1979). Fatty 

tissues can transiently accumulate these solvents, which are 

slowly released back into the blood stream. Many of these 

halogenated solvents are metabolized to more water soluble 

metabolites that can be excreted in the urine. Hepatic 

transformation of tetrachloromethane may lead to the 

generation of reactive intermediate metabolites which may 

be responsible for liver toxicity (Weber et al., 2003). Other 

halogenated solvents may undergo similar metabolism to 

reactive intermediates that contribute to toxicity (Casciola 

and Ivanetich, 1984; IPCS, 2003; Raucy et al., 1993).

Human health effects from these solvents at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Acute exposure to 

massive doses by either inhalation or ingestion can cause 

central nervous system depression and unconsciousness, 

cardiac dysrhythmias, and hepatic and renal injury. Eye 

and respiratory tract irritation may occur with exposure to 

high vapor concentrations of most of these solvents, and 

allergic contact dermatitis has been reported following 1, 

2-dichloroethane dermal exposure (Baruffini et al., 1989). 

Exposures to vapor concentrations exceeding occupational 

standards have been associated with fatigue, headache, 

delayed reactions, and neuropsychological impairment 

(ATSDR, 2001; Bowler et al., 2003). Epidemiologic 

studies of workers exposed to various halogenated solvents 

have found occasional associations between exposure and 

reduced fertility and spontaneous abortion in women (FigaTalamanca, 2006). In animal studies, reproductive toxicity 

has not been consistently demonstrated in the absence of 

maternal toxicity (IPCS, 1990, 1992, and 1993).

Experimental animals exposed chronically to high doses 

of each of these solvents developed tumors of the liver, 

lung, and kidney. In addition, lymphoid and hematopoietic 

tumors were observed with 1,2-dichloroethane and 

1,1,1-trichloroethane; mammary gland tumors were 

observed with tetrachloromethane, 1,2-dichloroethane, 

and 1,1-dichloroethene. IARC has determined that the 

dichloroethanes and tetrachloromethane are possible human 

carcinogens; the other halogenated solvents in this section 

are not classifiable regarding human carcinogenicity. 

NTP has determined that tetrachloromethane and 

Blood 1,1-Dichloroethane

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1367

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1367

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 670

Females 03-04 * < LOD < LOD < LOD < LOD 697

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 300

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 695

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.01. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 480 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

1,2-dichloroethane are reasonably anticipated to be human 

carcinogens. With the exception of dibromomethane, the 

U.S. EPA has established drinking water standards and other 

environmental criteria. The FDA regulates several of these 

solvents in bottled water and as indirect food additives. 

Occupational standards and guidelines are available 

for most of these chemicals from OSHA and ACGIH, 

respectively. Further information on the halogenated 

solvents is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html.

Biomonitoring Information

Levels of halogenated solvents in blood reflect recent 

exposure. Except for tetrachloromethane in the NHANES 

2003-2004 subsample, the other ten halogenated 

solvents were detectable in less that a few percent of the 

participants. In a non-representative sample of adults in 

NHANES III (1988-1994), blood levels were also nondetectable or detected in <10% of samples, except for 

1,1,1-trichloroethane which was detected in a majority 

of samples with a median of 0.13 μg/L (Ashley et al., 

1994; Churchill et al., 2001). 1,1,1-Trichloroethane was 

not detected in children who underwent periodic blood 

testing as part of an environmental exposure study (Sexton 

et al., 2005 and 2006). In a study of German residents, 

1,1,1-trichloroethane levels were of similar magnitude to 

the NHANES III study (Hajimiragha et al., 1986).

Finding a measurable amount of any of these halogenated 

solvents in blood does not mean that the level of the solvent 

causes an adverse health effect. Biomonitoring studies of 

blood halogenated solvents can provide physicians and 

public health officials with reference values so that they 

can determine whether or not people have been exposed to 

higher levels of halogenated solvents than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

Blood 1,2-Dichloroethane (Ethylene dichloride) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1346

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1346

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 661

Females 03-04 * < LOD < LOD < LOD < LOD 685

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 289

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 689

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.01. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 481

 Volatile Organic Compounds (VOCs)

Blood 1,1-Dichloroethene (Vinylidene chloride) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1367

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1367

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 670

Females 03-04 * < LOD < LOD < LOD < LOD 697

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 300

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 695

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.009. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Blood cis-1,2-Dichloroethene 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1366

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1366

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 669

Females 03-04 * < LOD < LOD < LOD < LOD 697

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 300

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 694

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.01. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 482 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Blood trans-1,2-Dichloroethene

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1367

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1367

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 670

Females 03-04 * < LOD < LOD < LOD < LOD 697

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 300

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 695

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.01. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Blood 1,2-Dichloropropane 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1364

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1364

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 667

Females 03-04 * < LOD < LOD < LOD < LOD 697

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 300

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 692

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.008. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 483

 Volatile Organic Compounds (VOCs)

Blood 1,1,1-Trichloroethane (Methyl chloroform) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1345

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1345

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 660

Females 03-04 * < LOD < LOD < LOD < LOD 685

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 289

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 688

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.048. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Blood 1,1,2-Trichloroethane 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1354

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1354

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 664

Females 03-04 * < LOD < LOD < LOD < LOD 690

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 297

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 686

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.01. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 484 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Blood 1,1,2,2-Tetrachloroethane 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1235

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1235

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 613

Females 03-04 * < LOD < LOD < LOD < LOD 622

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 250

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 282

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 606

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.01. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 

Blood Tetrachloromethane (Carbon tetrachloride) 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD .010 (<LOD-.010) .010 (<LOD-.140) .020 (.010-.050) 742

03-04 * < LOD < LOD < LOD < LOD 1362

Age group 

20-59 years 01-02 * < LOD .010 (<LOD-.010) .010 (<LOD-.140) .020 (.010-.050) 742

03-04 * < LOD < LOD < LOD < LOD 1362

Gender 

Males 01-02 * < LOD .010 (<LOD-.010) .010 (<LOD-.140) .010 (.010-.040) 364

03-04 * < LOD < LOD < LOD < LOD 667

Females 01-02 * < LOD .010 (<LOD-.010) .010 (<LOD-.090) .040 (.010-.080) 378

03-04 * < LOD < LOD < LOD < LOD 695

Race/ethnicity 

Mexican Americans 01-02 * < LOD < LOD .010 (<LOD-.750) .020 (.010-.050) 193

03-04 * < LOD < LOD < LOD < LOD 266

Non-Hispanic blacks 01-02 * < LOD .010 (<LOD-.010) .010 (<LOD-.020) .010 (<LOD-.020) 132

03-04 * < LOD < LOD < LOD < LOD 299

Non-Hispanic whites 01-02 * < LOD .010 (<LOD-.010) .010 (<LOD-.140) .030 (.010-.080) 366

03-04 * < LOD < LOD < LOD < LOD 692

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.01 and 0.005. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 485

 Volatile Organic Compounds (VOCs)

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for carbon tetrachloride. Atlanta GA. 2005 

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp30.html. 4/21/09

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for 1,2-dichloroethane update. Atlanta 

GA. 2001 [online]. Available at URL: http://www.atsdr.cdc.gov/

toxprofiles/tp38.html. 4/21/09 

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for 1,1,1-trichloroethane update. Atlanta 

GA. 2006b [online}. Available at URL: http://www.atsdr.cdc.

gov/toxprofiles/tp70.html. 4/21/09

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for 1,1,2,2-tetracholoroethane draft. Atlanta 

GA. 2006a [online]. Available at URL: http://www.atsdr.cdc.gov/

toxprofiles/tp93.html#bookmark08. 4/21/09

Armstrong SR, Green LC. Chlorinated hydrocarbon solvents. 

Clin Occup Environ Med 2004;4(3):481-496, vi.

Baruffini A, Cirla AM, Pisati G, Ratti R, Zedda S. Allergic 

contact dermatitis from 1,2-dichloropropane. Contact Dermatitis 

1989;20(5):379-380.

Bell BP, Franks P, Hildreth N, et al. Methylene chloride exposure 

and birthweight in Monroe County, New York. Environ Res 

1991:55:31-39.

Bove FJ, Fulcomer MC, Klotz JB, Esmart J, Dufficy EM, Savrin 

JE. Public drinking water contamination and birth outcomes.Am 

J Epidemiol 1995 May 1;141(9):850-62.

Bowler RM, Gysens S, Hartney C. Neuropsychological effects 

of ethylene dichloride exposure. Neurotoxicology 2003;24(4-

5):553-562.

Casciola LA, Ivanetich KM. Metabolism of chloroethanes by rat 

liver nuclear cytochrome P-450. Carcinogenesis 1984;5(5):543-

548.

Costas K, Knorr RS, Condon SK. A case-control study of 

childhood leukemia in Woburn, Massachusetts: the relationship 

between leukemia incidence and exposure to public drinking 

water. Sci Total Environ 2002;300(1-3):23-35.

Croen LA, Shaw GM, Sanbonmatsu L, et al. 1997. Maternal 

residential proximity to hazardous waste sites and risk for selected 

congenital malformations. Epidemiology 1997;8:347-354.

Eskenazi B, Fenster L, Hudes M, Wyrobek AJ, Katz DF, Gerson 

J, et al. A study of the effect of perchloroethylene exposure on the 

reproductive outcomes of wives of dry cleaning workers. Am J 

Ind Med 1991a; 20:593-600.

Eskenazi B, Wyrobek AJ, Fenster L, Katz DF, Sadler M, Lee J, et 

al. A study of the effect of perchloroethylene exposure on semen 

quality in dry cleaning workers. Am J Ind Med 1991b;20:575- 

591.

Figa-Telemanca I. Occupational risk factors and reproductive 

health of women. Occup Med (Lond) 2006;56(8):521-531.

Hajimiragha H, Ewers U, Jansen-Rosseck R, Brockhaus A. 

Human exposure to volatile halogenated hydrocarbons from 

the general environment. Int Arch Occup Environ Health. 

1986;58(2):141-150.

Hill RH Jr, Ashley DL, Head SL, Needham LL, Pirkle JL. 

p-Dichlorobenzene exposure among 1,000 adults in the United 

States. Arch Environ Health 1995;50(4):277-280.

International Programme on Chemical Safety (IPCS). 

Concise International Chemical Assessment Document 51. 

1,1-Dicholoroethene (vinylidene chloride). 2003 [online]. 

Available at URL: http://www.inchem.org/documents/cicads/

cicads/cicad51.htm. 4/21/09

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 146. 1,3-Dichloropropene, 

1,2-Dichloropropane & Mixtures. 1993 [online]. Available at 

URL: http://www.intox.org/databank/documents/chemical/

dichlorp/ehc146.htm. 4/21/09

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 136. 1,1,1-Trichloroethane. 1992 

[online]. Available at URL: http://www.inchem.org/documents/

ehc/ehc/ehc136.htm. 4/21/09

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 100. Vinylidene chloride. 1990 

[online]. Available at URL: http://www.inchem.org/documents/

ehc/ehc/ehc100.htm. 4/21/09

Monster AC, Boersma G, Steenweg H. Kinetics of 

tetrachloroethylene in volunteers: influence of exposure 

concentration and work load. Int Arch Occup Environ Health 

1979;42:303-309.

Moran MJ, Zogorski JS, Squillace PJ. Chlorinated solvents 

in groundwater of the United States. Environ Sci Technol 

2007;41:74-81.

Raucy JL, Kraner JC, Lasker JM. Bioactivation of halogenated 

hydrocarbons by cytochrome P4502E1. Crit Rev Toxicol 

1993;23(1):1-20.

Rodenbeck SE, Sanderson LM, Rene A. Maternal exposure to 

trichloroethylene in drinking water and birth-weight outcomes. 

Arch Environ Health 2000;55(3):188-194.

Rowe BL, Toccalino PL, Moran MJ, Zogorski JS, Price CV. 
 486 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Occurrence and potential human-health relevance of volatile 

organic compounds in drinking water from domestic wells in the 

United States. Environ Health Perspect 2007;115(11):1539-1546.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran G, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 

years of age. Environ Health Perspect 2006;114(3):453-459.

Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism 

of action of haloalkanes: carbon tetrachloride as a toxicological 

model. Crit Rev Toxicol 2003;33(2):105-136.

Windham GC, Shusterman D, Swan SH, Fenster L, Eskenazi B. 

Exposure to organic solvents and adverse pregnancy outcome. 

Am J Ind Med. 1991;20(2):241-259.
Fourth National Report on Human Exposure to Environmental Chemicals 487

 Volatile Organic Compounds (VOCs)

Hexachloroethane

CAS No. 67-72-1

General Information

Hexachloroethane is a solid that sublimates at room 

temperature. It is primarily used in combination with 

zinc or titanium oxides in military pyrotechnic or smoke 

generating devices, as an agent to degas or purify molten 

ores, as an ignition and explosive suppressant, and as a 

vulcanizing agent. Hexachloroethane is no longer produced 

in the U. S., and usage has declined since the 1970’s 

(ATSDR, 1997). In the past, hexachloroethane was used 

as an ingredient in some pesticides, in fire extinguisher 

fluids, and as a veterinary antihelminthic (ATSDR, 1997). 

Hexachloroethane can enter the atmosphere from emissions 

during its production and use, or as a byproduct from the 

chlorination of other hydrocarbons. Hexachloroethane 

is relatively persistent in the environment and has been 

detected a low levels in ambient air and rarely in drinking 

water systems (USGS, 2006).

For the general population, hexachloroethane exposure is 

infrequent and occurs by inhaling contaminated air. A less 

common pathway is the ingestion of contaminated drinking 

water. Workers in metal and alloy refining or pyrotechnic 

and smoke device production may be exposed to larger 

amounts. Hexachloroethane is absorbed by inhalation, 

dermal and ingestion routes, and it is preferentially 

distributed to fat, kidney and liver. Metabolism in the 

liver results in formation of trichloroacetic acid and 

trichloroethanol, which are excreted in urine (ATSDR, 

1997). A small portion of unmetabolized hexachloroethane 

is excreted in the feces.

Human health effects from hexachloroethane at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. Workers exposed to 

hexachloroethane reported irritation of the skin and mucous 

membranes, but no changes were noted in pulmonary 

function tests or in serum tests of renal, pancreatic, and liver 

function (Selden et al., 1994, Selden et al., 1997). Animals 

exposed to high air levels of hexachloroethane developed 

ataxia, facial twitching, tremors, and pneumonitis (Weeks 

et al., 1979). In feeding studies, animals developed 

dose-related abnormalities of the liver (enlargement, 

transaminase elevation, centrilobular necrosis) and 

kidney (tubular nephrosis and nephrocalcinosis) (ATSDR, 

1997). Animal carcinogenicity studies show inconsistent 

evidence of hepatocellular carcinomas (NCI, 1978), an 

increased incidence of renal tumors in males (NTP, 1989), 

and no clear evidence of mutagenicity or genotoxicity. 

Hexachloroethane does not appear to be a reproductive or 

developmental toxicant in animal studies (ATSDR, 1997).

Hexachloroethane is classified as a possible human 

carcinogen by IARC and is reasonably anticipated to be a 

human carcinogen by NTP. The U.S. EPA has established 

drinking water and other environmental regulations for 

hexachloroethane. Workplace standards and guidelines 

for hexachloroethane have been established by OSHA and 

ACGIH, respectively. Information about external exposure 

(ie., environmental levels) and health effects is available 

from ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Blood Hexachloroethane 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1366

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1366

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 669

Females 03-04 * < LOD < LOD < LOD < LOD 697

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 267

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 300

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 694

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.011. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
 488 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Biomonitoring Information

Levels of hexachloroethane in the blood reflect recent 

exposure. Blood levels were not detectable in the NHANES 

2003-2004 subsample as has been the case in several other 

general population studies (Ashley et al., 1994; Buckley et 

al., 1997; Foster, 1995; Selden et al., 1993).

Finding a measureable amount of hexachloroethane in 

blood does not mean that the level of hexachloroethane 

causes an adverse health effect. Biomonitoring studies 

of blood hexachloroethane can provide physicians and 

public health officials with reference values so that they 

can determine whether or not people have been exposed 

to higher levels of hexachloroethane than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for hexachloroethane. 1997 [online]. 

Available from URL: http://www.atsdr.cdc.gov/toxprofiles/tp97.

html. 4/21/09

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, 

Needham LL, Akland G. Environmental and biomarker 

measurements in nine homes in the lower Rio Grande Valley: 

multimedia results for pesticides, metals, PAHs, and VOCs. 

Environ Int 1997;23:705-732.

Foster WG. The reproductive toxicology of Great Lakes 

contaminants. Environ Health Perspect 1995;103 Suppl 9:63-9.

National Cancer Institute (NCI). Bioassay of hexachloroethane 

for possible carcinogenicity (CAS No. 67-72-1). NCI-CG-TR-68. 

Tech Report Ser No. 68. U.S. DHEW. Publ. No. (NIH) 78-1318. 

Bethesda MD. 1978. Available at URL: http://ntp.niehs.nih.gov/

ntp/htdocs/LT_rpts/tr068.pdf. 4/21/09

National Toxicology Program (NTP). Toxicology and 

carcinogenesis studies of hexachloroethane (CAS No.67-72-1) 

in F344/N rats (gavage studies). Tech Report Ser No. 361. NIH 

Publication No. 89-2816. Research Triangle Part, NC: National 

Toxicology Program. Research Triangle Park NC, 1989 [online]. 

Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/

tr361.pdf. 4/21/09

Selden A, Kvamlof A, Bodin L, et al. Health effects of low 

level occupational exposure to hexachloroethane. J Occup Med 

Toxicol 1994;3(10):73-79.

Selden A, Nygren M, Kvarnlof A, Sundell K, Spangberg O. 

Biological monitoring of hexachloroethane. Int Arch Occup 

Environ Health 1993;65(1 Suppl):S111-S114.

Selden AI, Nygren Y, Westberg HB, Bodin LS. Hexachlorobenzene 

and octachlorostyrene in plasma of aluminium foundry workers 

using hexachloroethane for degassing. Occup Environ Med 

1997;54(8):613-618.

United States Geological Survey (USGS). Volatile organic 

compounds in the nation’s ground water and drinking-water 

supply wells. Reston VA. 2006 [online]. Available at URL: http://

pubs.usgs.gov/circ/circ1292/. 4/21/09

Weeks MH, Angerhofer RA, Bishop R, Thomasino J, Pope CR. 

The toxicity of hexachloroethane in laboratory animals. Am Ind 

Hyg Assoc J 1979;40:187-199.
Fourth National Report on Human Exposure to Environmental Chemicals 489

 Volatile Organic Compounds (VOCs)

Methyl tert-Butyl Ether (MTBE)

CAS No. 1634-04-4

General Information

Methyl tert-butyl ether (MTBE) was added to reformulated 

gasoline to boost octane and to reduce carbon monoxide 

exhaust emissions in high smog areas of the United 

States in the1980s. Because of concerns for groundwater 

contamination and water quality, MTBE was banned or its 

usage was limited in several states. Ethanol has replaced 

MTBE as an additive to reformulated gasoline (U.S. DOE, 

2003 and 2006; U.S. EPA, 2000). MTBE contamination 

of groundwater has been more common in urban 

areas (Squillace et al., 2004) and in areas near leaking 

underground storage tanks (Rowe et al., 2007). MTBE also 

has been detected in ambient air near blending facilities, 

in cities where MTBE is used in reformulated gasoline, 

and in the breathing zone during consumer refueling at 

service stations (IPCS, 1998). MBTE is also used in small 

amounts as a laboratory solvent and as a pharmaceutical 

agent (ATSDR, 1996).

The general population is exposed to MBTE primarily by 

inhalation of contaminated air. Contaminated water is a less 

common source though exposure can occur by ingestion or 

inhalation of vaporized MTBE from water (IPCS, 1998). 

Workplace exposure to MTBE may occur in the production, 

transportation, and use of petrochemicals. MTBE is well 

absorbed after inhalational, oral, or dermal exposure and 

is rapidly cleared from the blood with an estimated halflife of several hours (Dekant et al., 2001). Most MTBE 

absorbed by the body is metabolized by the liver and then 

eliminated in urine, primarily as 2-hydroxyisobutyrate with 

tert-butyl alcohol and 2-methyl-1,2-propanediol as minor 

urinary metabolites (Amberg et al., 1999; Amberg et al., 

2001). Depending upon the dose, more than one third of 

inhaled MTBE may be excreted in exhaled air (ATSDR, 

1996; Nihlen et al., 1998).

Human health effects from MTBE at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Following the introduction of 

MTBE reformulated gasoline, complaints of respiratory 

tract irritation, headache, nausea, and dizziness prompted 

several population surveys, epidemiologic studies, and 

experimental human volunteer studies that provided little 

evidence of an association between MTBE exposure and 

health complaints (ATSDR, 1996). Based upon high dose 

animal studies, MTBE has been considered to be a skin and 

Blood Methyl tert-butyl ether (MTBE) 

Geometric mean and selected percentiles of blood concentrations (in pg/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 16.4 (4.77-56.7) 27.7 (7.29-64.9) 73.8 (35.5-127) 132 (64.0-278) 188 (109-339) 672

03-04 11.0 (5.98-20.1) 10.0 (4.60-25.1) 45.0 (16.0-98.0) 110 (70.0-180) 170 (110-340) 1307

Age group 

20-59 years 01-02 16.4 (4.77-56.7) 27.7 (7.29-64.9) 73.8 (35.5-127) 132 (64.0-278) 188 (109-339) 672

03-04 11.0 (5.98-20.1) 10.0 (4.60-25.1) 45.0 (16.0-98.0) 110 (70.0-180) 170 (110-340) 1307

Gender 

Males 01-02 16.9 (4.96-57.7) 27.9 (6.82-64.6) 75.0 (35.5-131) 132 (54.9-307) 167 (109-417) 334

03-04 12.2 (6.29-23.6) 11.0 (4.80-29.0) 55.0 (18.0-110) 130 (79.0-200) 200 (110-470) 641

Females 01-02 16.0 (4.12-61.8) 26.6 (5.93-74.6) 72.7 (32.6-132) 142 (73.5-255) 194 (92.3-336) 338

03-04 9.88 (5.62-17.4) 8.90 (4.30-23.0) 38.0 (14.0-85.0) 94.0 (58.0-160) 140 (90.0-250) 666

Race/ethnicity 

Mexican Americans 01-02 23.3 (4.96-110) 33.4 (2.92-187) 91.3 (26.1-255) 225 (80.6-339) 273 (182-358) 166

03-04 11.6 (5.35-25.3) 12.0 (3.80-29.0) 32.0 (14.0-80.0) 80.0 (38.0-190) 160 (74.0-220) 245

Non-Hispanic blacks 01-02 14.9 (6.11-36.4) 26.4 (3.11-55.6) 52.6 (30.0-86.8) 87.4 (38.6-155) 120 (70.0-155) 119

03-04 9.63 (4.83-19.2) 10.0 (3.50-28.0) 32.8 (11.0-85.0) 77.0 (36.0-160) 140 (61.0-210) 285

Non-Hispanic whites 01-02 16.0 (4.13-62.4) 27.9 (4.71-74.6) 72.7 (33.3-132) 132 (59.6-249) 165 (92.8-366) 333

03-04 11.5 (5.51-23.8) 11.0 (4.00-33.5) 59.0 (14.0-120) 120 (73.0-230) 180 (110-430) 673

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.232 and 2.0. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 
 490 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

eye irritant (IPCS, 1998). Animal studies of carcinogenicity 

have been inconclusive (ATSDR, 1996). MTBE does 

not appear to be a reproductive or developmental in 

animal studies (IPCS, 1998). Methyl tert-butyl ether is 

unclassifiable as a human carcinogen by IARC. The U.S. 

EPA has established standards and guidelines for MTBE 

in water and air, and ACGIH has adopted guidelines 

for workplace air exposure. Information about external 

exposure (i.e., environmental levels) and health effects 

is available from ATSDR at: http://www.atsdr.cdc.gov/

toxpro2.html.

Biomonitoring Information

Levels of MTBE in blood reflect recent exposure. In the 

NHANES 2003-2004 subsample, MTBE was detectable 

in most of the population; the geometric mean was 11.0 

pg/mL for the total population. In a subsample of adults 

in NHANES 1999-2000, Lin et al. (2008) found geometric 

mean blood levels of MTBE to be 17 and 15 pg/mL in 

smokers and non-smokers, respectively. In a small study 

of U.S. automobile drivers when MTBE was used as a fuel 

additive, blood levels were about 100 times higher than 

those in the NHANES subsamples (White et al., 1995). 

Commuters in urban areas with high vehicular traffic had 

median blood MTBE blood levels that were more than 

tenfold higher than those in the U.S. general population 

(Lemire et al., 2004). Workers exposed to oxygenated 

gasoline fumes and vehicle exhaust had levels that were 

by 10 to 100 times higher than general population levels 

(Mannino et al., 1995; Moolenaar et al., 1994; Romieu 

et al., 1999; White et al., 1995), depending in part on the 

concentration of MTBE in the gasoline.

Finding a measurable amount of MTBE in blood does not 

mean that the level of MTBE causes an adverse health 

effect. Biomonitoring studies of blood MTBE can provide 

physicians and public health officials with reference values 

so that they can determine whether or not people have been 

exposed to higher levels of MTBE than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for methyl tert-butyl ether. 1996 [online]. 

Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp91.

html#bookmark07. 4/21/09

Amberg A, Rosner E, Dekant W. Biotransformation and kinetics 

of excretion of methyl-tert-butyl ether in rats and humans. 

Toxicol Sci 1999;51(1):1-8.

Amberg A, Rosner E, Dekant W. Toxicokinetics of methyl tertbutyl ether and its metabolites in humans after oral exposure. 

Toxicol Sci 2001;61(1):62-67.

Dekant W, Bernauer U, Rosner E, Amberg A. Biotransformation 

of MTBE, ETBE, and TAME after inhalation or ingestion in rats 

and humans. Res Rep Health Eff Inst 2001;102:29-71.

International Programme on Chemical Safety (IPCS). 

Environmental Health Criteria 206. Methyl Tertiary-Butyl Ether. 

Geneva, Switzerland.1998 [online]. Available at URL: http://

www.inchem.org/documents/ehc/ehc/ehc206.htm. 4/21/09

Lemire S, Ashley D, Olaya P, Romieu I, Welch S, MenesesGonzalez F, Hernandez-Avila M. Environmental exposure of 

commuters in Mexico City to volatile organic compounds as 

assessed by blood concentrations, 1998. Salud Publica Mex 

2004;46:32-38.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Expo Sci Environ Epidemiol 2008;18(4):421-429.

Mannino DM, Schreiber J, Aldous K, Ashley D, Moolenaar R, 

Almaguer D. Human exposure to volatile organic compounds: a 

comparison of organic vapor monitoring badge levels with blood 

levels. Int Arch Occup Environ Health. 1995;67(1):59-64.

Moolenaar RL, Heffline BJ, Ashley DL, Middaugh JP, Etzel 

RA. Methyl tertiary butly ether in human blood after exposure 

to oxygenated fuel in Fairbanks, Alaska. Arch Environ Health 

1994;49(5):402-409.

Nihlen A, Lof A, Johanson G. Experimental exposure to methyl 

tertiary-butyl ether. I. Toxicokinetics in humans. Toxicol Appl 

Pharmacol 1998;148:274-280.

Romieu I, Ramirez M, Meneses F, Ashley D, Lemire S, Colome 

S, et al. Environmental exposure to volatile organic compounds 

among workers in Mexico City as assessed by personal 

monitors and blood concentrations. Environ Health Perspect 

1999;107(7):511-515.

Rowe BL, Toccalino PL, Moran MJ, Zogorski JS, Price CV. 

Occurrence and potential human-health relevance of volatile 

organic compounds in drinking water from domestic wells in the 

United States. Environ Health Perspect 2007;115(11):1539-1546.

Squillace PJ, Moran MJ, Price CV. VOCs in shallow groundwater 

in new residential/commercial areas of the United States. Environ 

Sci Technol 2004;38(20):5327-5338.

United States Environmental Protection Agency (U.S. EPA). 

Advance notice of proposed rulemaking to control MTBE in 

gasoline. Regulatory Announcement. Office of Transportation 

and Air Quality. Federal Register: March 24, 2000 (Volume 65, 
Fourth National Report on Human Exposure to Environmental Chemicals 491

 Volatile Organic Compounds (VOCs)

Number 58) [online]. Available at URL: http://www.epa.gov/

EPA-TOX/2000/March/Day-24/t7323.htm. 4/21/09

United States Department of Energy (U.S. DOE). Status and 

impact of state MTBE ban. 2003 [online]. Available at URL:

http://www.eia.doe.gov/oiaf/servicerpt/mtbeban/. 4/21/09

United States Department of Energy (U.S. DOE). Eliminating 

MTBE in gasoline in 2006. 2006 [online]. Available at URL: http://

www.eia.doe.gov/pub/oil_gas/petroleum/feature_articles/2006/

mtbe2006/mtbe2006.pdf. 4/21/09

White MC, Johnson CA, Ashley DL, Buchta TM, Pelletier DJ. 

Exposure to methyl tertiary-butyl ether from oxygenated gasoline 

in Stamford, Connecticut. Arch Environ Health. 1995;50(3):183-

189.
 492 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Nitrobenzene

CAS No. 98-95-3

General Information

Nitrobenzene is a synthetic aromatic chemical made from 

benzene and used to manufacture aniline, which is in turn, 

is used to make some types of polyurethanes. Nitrobenzene 

is also used in the synthesis of other chemicals, including 

pesticides, dyes, and explosives and as a solvent in 

petroleum refining. Less common or discontinued 

applications include use in shoe polish, special lubricating 

oils, and as an almond flavoring. Environmental sources 

for nitrobenzene include emissions from its production or 

use and the atmospheric chemical reaction of benzene with 

nitrogen oxides. Nitrobenzene was detected infrequently at 

low levels in ambient air taken in urban, rural and waste 

disposal areas in the 1970s and 1980s (IPCS, 2003). 

Nitrobenzene was rarely detected in surface and industrial 

effluent water and was not detected in soil and sediment 

specimens obtained from selected locations in the United 

States (IPCS, 2003).

The general population can be exposed infrequently to 

nitrobenzene in contaminated air and water. Workers may 

be exposed to nitrobenzene during its use or production. 

Nitrobenzene is absorbed after dermal, inhalational, or oral 

exposure and then metabolized to various intermediates. 

About 10 to 20 percent of a dose is eliminated in the urine 

as p-nitrophenol, which is used in biological monitoring 

of occupational exposures. A smaller fraction of a dose is 

eliminated in urine as p-aminophenol (Astier, 1992; IARC, 

1996). The nitroreduced metabolites of nitrobenzene may 

mediate some toxic effects (e.g., methemoglobinemia or 

carcinogenicity) (IPCS, 2003).

Human health effects from nitrobenzene at low 

environmental doses or at biomonitored levels from low 

environmental exposures are unknown. People having 

accidental exposures to large amounts of nitrobenzene 

have developed methemoglobinemia, hemolytic anemia, 

and toxic hepatitis (IARC, 1996). In animals treated with 

high doses of nitrobenzene, methemoglobinemia, testicular 

atrophy and reduced sperm counts, and increased liver and 

kidney weights were observed (NTP, 2002). In animals 

exposed to high concentrations of nitrobenzene in air, 

multiple tumors were observed, depending on gender, 

including lung, thyroid, mammary gland, liver, and kidney 

tumors (Cattley et al., 1994; NTP, 2002). Nitrobenzene is 

classified by IARC as a possible human carcinogen and by 

NTP as reasonably anticipated to be human carcinogen. 

The U.S. EPA has established environmental standards 

for nitrobenzene. Workplace standards and guidelines for 

nitrobenzene have been established by OSHA and ACGIH, 

respectively. The ACGIH recommends biological exposure 

indices to monitor workplace exposure. Information about 

external exposure (ie., environmental levels) and health 

effects is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html.

Biomonitoring Information

Levels of nitrobenzene in blood reflect recent exposure. In 

Blood Nitrobenzene 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 03-04 * < LOD < LOD < LOD < LOD 1066

Age group 

20-59 years 03-04 * < LOD < LOD < LOD < LOD 1066

Gender 

Males 03-04 * < LOD < LOD < LOD < LOD 529

Females 03-04 * < LOD < LOD < LOD < LOD 537

Race/ethnicity 

Mexican Americans 03-04 * < LOD < LOD < LOD < LOD 206

Non-Hispanic blacks 03-04 * < LOD < LOD < LOD < LOD 205

Non-Hispanic whites 03-04 * < LOD < LOD < LOD < LOD 564

Limit of detection (LOD, see Data Analysis section) for Survey year 03-04 is 0.3. 

# Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 493

 Volatile Organic Compounds (VOCs)

the NHANES 2003-2004 subsample, nitrobenzene was not 

detected. Finding a measureable amount of nitrobenzene in 

blood does not mean that the level of nitrobenzene causes 

an adverse health effect. Biomonitoring studies of blood 

nitrobenzene can provide physicians and public health 

officials with reference values so that they can determine 

whether or not people have been exposed to higher levels 

of nitrobenzene than levels found in the general population. 

Biomonitoring data can also help scientists plan and 

conduct research on exposure and health effects.

References

Astier A. Simultaneous high-performance liquid chromatographic 

determination of urinary metabolites of benzene, nitrobenzene, 

toluene, xylene and styrene. J Chromatogr 1992;573(2):318-22.

Cattley RC, Everitt JI, Gross EA, Moss OR, Hamm TE Jr, 

Popp JA. Carcinogenicity and toxicity of inhaled nitrobenzene 

in B6C3F1 mice and F344 and CD rats. Fundam Appl Toxicol 

1994;22(3):328-40. Erratum in: Fundam Appl Toxicol 

1995;25(1):159.

International Agency for Research on Cancer (IARC). IARC 

Monographs on the Evaluation of Carcinogenic Risks to Humans. 

Volume 65. Printing Processes and Printing inks, Carbon black 

and Some Nitro Compounds. Summary of Data Reported and 

Evaluation 1996 [online]. Available at URL: http://monographs.

iarc.fr/ENG/Monographs/vol65/volume65.pdf. 4/21/09

International Programme on Chemical Safety-INCHEM (IPCS). 

Environmental Health Criteria 230. Nitrobenzene. 2003 [online]. 

Available at URL: http://www.inchem.org/documents/ehc/ehc/

ehc230.htm. 4/21/09

National Toxicology Program (NTP). Report on Carcinogens 

Background Document for Nitrobenzene. 2002 [online]. 

Available at URL: http://ntp.niehs.nih.gov/ntp/newhomeroc/

roc11/NBPub.pdf. 4/21/09
 494 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Styrene

CAS No. 100425

General Information

Styrene is a high production, hydrocarbon chemical used to 

manufacture of polystyrene resins, which are widely used in 

plastic packaging, disposal cups and containers, insulation, 

adhesives, and in composite materials such as fiberglass. It 

is also used to produce synthetic rubber and latex. Because 

styrene is synthesized largely from ethylbenzene, it may be 

present in products made from styrene. Styrene is commonly 

detected in urban air, especially near industrial sites where 

it is produced and used, and in high motor vehicle traffic 

areas. Air concentrations of styrene may be greater indoors 

than outdoors, as a result of emissions from photocopiers 

and laser printers, cigarette smoke, and consumer products 

in the home (ATSDR, 2007; Wallace et al., 1987). Styrene 

does not persist in the aquatic or soil environments because 

of its volatility and is rarely detected in U.S. groundwater 

or drinking water supplies (USGS, 2006).

For the general population, inhalation of styrene is the 

primary exposure route. Trace amounts can be ingested 

when styrene migrates from packaging into foods. Styrene 

is well absorbed by inhalation, ingestion or dermal routes. 

Workplace exposure may occur during the production of 

styrene or products derived from styrene. After absorption, 

styrene is metabolized within hours by the liver. The 

main urinary excretion products are mandelic acid and 

phenylglyoxylic acid, which have been used in monitoring 

workplace exposure (ATSDR, 2007; Brugnone et al., 

1993; Ramsey et al., 1980). The U.S. EPA has established 

a drinking water and other environmental standards for 

styrene. Workplace standards and guidelines for styrene 

have been established by OSHA and ACGIH, respectively. 

The ACGIH recommends biological exposure indices to 

monitor workplace exposure.

Human health effects from styrene at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Eye and upper respiratory tract 

irritation occur after several hours of exposure to air 

concentrations that exceed the occupational standard for 

workers. Several studies of chronic occupational exposure 

to styrene reported neurological effects, including altered 

color vision, vestibular dysfunction, impaired hearing 

and altered performance on neuropsychological and 

neurophysiological tests (ATSDR, 2007). Various studies 

of workers with styrene exposure have not provided 

Blood Styrene 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD .080 (.050-.100) .130 (.090-.200) .200 (.140-.260) 950

03-04 * < LOD .050 (.044-.061) .089 (.081-.097) .120 (.110-.130) 1245

Age group 

20-59 years 01-02 * < LOD .080 (.050-.100) .130 (.090-.200) .200 (.140-.260) 950

03-04 * < LOD .050 (.044-.061) .089 (.081-.097) .120 (.110-.130) 1245

Gender 

Males 01-02 * < LOD .080 (.050-.110) .140 (.100-.230) .220 (.140-.340) 445

03-04 * < LOD .056 (.045-.068) .089 (.081-.100) .120 (.095-.150) 608

Females 01-02 * < LOD .070 (.050-.100) .120 (.090-.180) .180 (.120-.260) 505

03-04 * < LOD .048 (.040-.060) .090 (.074-.100) .110 (.097-.140) 637

Race/ethnicity 

Mexican Americans 01-02 * < LOD .050 (.030-.070) .090 (.070-.110) .120 (.090-.470) 225

03-04 * < LOD < LOD .049 (.033-.066) .062 (.048-.100) 241

Non-Hispanic blacks 01-02 * .040 (<LOD-.080) .100 (.040-.180) .180 (.110-.350) .300 (.170-1.00) 192

03-04 * < LOD .060 (.047-.077) .100 (.077-.130) .130 (.110-.160) 264

Non-Hispanic whites 01-02 * .030 (<LOD-.050) .080 (.050-.110) .130 (.090-.210) .200 (.130-.260) 462

03-04 * < LOD .056 (.046-.067) .096 (.083-.110) .130 (.110-.140) 646

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.03 and 0.03. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 495

 Volatile Organic Compounds (VOCs)

clear evidence of an increased risk for reproductive or 

developmental effects, or cancer (ATSDR, 2007), but 

increased serum prolactin levels have been correlated with 

levels of its urinary metabolite (Mutti et al., 1984) and 

levels of styrene in blood (Luderer et al., 2004) in both 

male and female workers.

Animal carcinogenicity studies have shown variable 

results, including lung tumors in mice and no increase in 

tumor incidence in rats (IARC, 2002). Styrene-7, 8-oxide, 

a biological metabolite of styrene and also a chemical used 

in making fragrances and epoxy resins, is classified as a 

probable human carcinogen by IARC and is reasonably 

anticipated to be human carcinogen by NTP. Styrene 

is classified as a possible human carcinogen by IARC. 

Additional information about external exposure (ie., 

environmental levels) and health effects is available from 

ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Levels of styrene in blood reflect recent exposure. In 

NHANES 2003-2004 subsample, levels of styrene in blood 

are of a similar range to those found in a non-representative 

sample of adults in NHANES III (1988-1994) (Ashley et 

al., 1994; Churchill et al., 2001). Other small studies of the 

U.S. general population have reported similar or slightly 

higher blood styrene levels (Bonanno et al., Buckley, et al., 

1997; Sexton et al., 2005 and 2006). Blood styrene levels 

can be three to fourfold higher in smokers than nonsmokers 

(Ashley et al., 1995; Bonanno et al., 2001), but exposure to 

environmental tobacco smoke or vehicle exhaust in urban 

areas has not been associated with higher blood styrene 

levels (Bonanno et al., 2001; Romieu et al., 1999). Workers 

exposed to styrene can have blood levels that are 25 times 

higher than those in the general population (Brugnone et 

al., 1993; Triebig et al., 1985).

Finding a measureable amount of styrene in blood does 

not mean that the level of styrene causes an adverse health 

effect. Biomonitoring studies of blood styrene can provide 

physicians and public health officials with reference values 

so that they can determine whether or not people have been 

exposed to higher levels of styrene than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for styrene draft. Atlanta GA. September 

2007 [online]. Available at URL: http://www.atsdr.cdc.gov/

toxprofiles/tp53.html. 4/15/08

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Ashley DL, Bonin MA, Hamar B, McGeehin MA. Removing 

the smoking confounder from blood volatile organic compounds 

measurements. Environ Res 1995;71:39-45.

Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate 

analysis on levels of selected metals, particulate matter, VOC, 

and household characteristics and activities from the Midwestern 

states NHEXAS. Appl Occup Environ Hyg 2001;6(9):859-874.

Brugnone F, Perbellini L, Wang GZ, Maranelli G, Raineri E, 

De Rosa E, et al. Blood styrene concentrations in a “normal” 

population and in exposed workers 16 hours after the end of the 

workshift. Int Arch Occup Environ Health 1993;65(2):125-130.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, 

Needham LL. Environmental and biomarker measurements in 

nine homes in the lower Rio Grande Valley: multimedia results for 

pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-

732.

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures 

and blood volatile organic compound levels in a large populationbased sample. Arch Environ Health 2001;56(2):157-166.

International Agency for Research on Cancer (IARC). IARC 

Monographs on the Evaluation of Carcinogenic Risks to 

Humans. Volume 82. Some Traditional Herbal Medicines, 

Some Mycotoxins, Naphthalene and Styrene Summary of Data 

Reported and Evaluation. Lyon, France. 2002 [online]. Available 

at URL: http://monographs.iarc.fr/ENG/Monographs/vol82/

volume82.pdf. 4/15/08

Luderer U, Tornero-Velez R, Shay T, Rappaport S, Heyer N, 

Echeverria D. Temporal association between serum prolactin 

concentration and exposure to styrene. Occup Environ Med. 

2004:61(4):325-333.

Mutti A, Vescovi PP, Falzoi M, Arfini G, Valenti G, Franchini 

I. Neuroendocrine effects of styrene on occupationally exposed 

workers. Scand J Work Environ Health. 1984;10(4):225-228.

Ramsey JC, Young JD, Karbowski RJ, Chenoweth MB, McCarty 

LP, Braun WH. Pharmacokinetics of inhaled styrene in human 

volunteers. Toxicol Appl Pharmacol 1980;53:54-63.

Romieu I, Ramirez M, Meneses F, Ashley D, Lemire S, Colome 

S, et al. Environmental exposure to volatile organic compounds 

among workers in Mexico City as assessed by personal 

monitors and blood concentrations. Environ Health Perspect 

1999;107(7):511-515.
 496 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran G, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 

years of age. Environ Health Perspect 2006;114(3):453-459.

Triebig G, Schaller K-H, Valentin H. Investigations on 

neurotoxicity of chemical substances at the workplace. VII. 

Longitudinal study with determination of nerve conductions 

velocities in persons occupationally exposed to styrene. Int Arch 

Occup Environ Health. 1985;56:239-247.

United States Geological Survey (USGS). Volatile organic 

compounds in the nation’s ground water and drinking-water 

supply wells. Reston VA. 2006 [online]. Available at URL: http://

pubs.usgs.gov/circ/circ1292/. 4/15/08

Wallace LA, Pellizzari ED, Hartwell TD, Sparacino C, Whitmore 

R, Sheldon L, et al. The TEAM study: personal exposures to toxic 

substances in air, drinking water, and breath of 400 residents of 

New Jersey, North Carolina, and North Dakota. Environ Res 

1987;43:290-307.
Fourth National Report on Human Exposure to Environmental Chemicals 497

 Volatile Organic Compounds (VOCs)

Toluene

CAS No. 108-88-3

General Information

Toluene (methylbenzene) is a flammable, liquid, aromatic 

hydrocarbon. It is a high production chemical isolated 

from crude oil. Toluene is used widely as a solvent and to 

synthesize chemicals such as benzene, trinitrotoluene, and 

toluene diisocyanate. As with other aromatic solvents, it is 

a minor component of gasoline, and additives containing 

toluene are used as octane boosters. Toluene is detected 

frequently in urban air, especially in high motor traffic areas 

and near industrial areas or hazardous waste sites (ATSDR, 

2000; Mukund et al., 1996). Indoor air levels of toluene can 

exceed outdoor levels, largely due to consumer products 

(e.g., nail polish solvent, adhesive glues, paints, and paint 

thinner) and cigarette smoke (ATSDR, 2000; Gordon et al., 

1999). Toluene does not persist in soil due to its volatility 

and is not detected commonly in U.S. groundwater and 

drinking water supplies (USGS, 2006).

The general population is exposed to toluene mainly by 

breathing contaminated air. Workplace exposure to toluene 

may occur during the production and use of petrochemicals 

and solvents. Toluene is well absorbed by inhalation, 

dermal, and oral exposure routes. After absorption, toluene 

is metabolized rapidly by hepatic microsomal enzymes, 

and the major urinary excretion product is hippuric acid. 

Other urinary metabolites include ortho- and para-cresol, 

S-benzylmercapturic acid, and S-para-toluylmercapturic 

acid.

Human health effects from toluene at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Humans exposed to high levels 

of toluene in air for a short time can show central nervous 

system depression (lassitude, stupor, and coma). Persons 

with short term exposures to toluene at levels higher than 

workplace air standards have shown poor performance 

on cognitive tests, neurobehavioral impairment, and eye 

and upper respiratory tract irritation (ATSDR, 2000). 

Its distinctive aromatic smell is detectable well below 

workplace air standards. Chronic solvent inhalant abuse, 

usually involving toluene and other volatile hydrocarbons, 

has resulted in permanent brain damage with dementia 

(Filley et al., 2004). Chronic occupational exposures at 

levels exceeding workplace standards have damaged 

hearing and possibly color vision (Lomax et al., 2004). In 

animal studies, prenatal toluene exposure impaired fetal 

Blood Toluene 

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 .156 (.122-.198) .160 (.120-.220) .340 (.260-.430) .670 (.480-.950) 1.06 (.700-1.43) 954

03-04 .114 (.100-.129) .096 (.087-.110) .220 (.180-.260) .430 (.380-.550) .680 (.560-.880) 1336

Age group 

20-59 years 01-02 .156 (.122-.198) .160 (.120-.220) .340 (.260-.430) .670 (.480-.950) 1.06 (.700-1.43) 954

03-04 .114 (.100-.129) .096 (.087-.110) .220 (.180-.260) .430 (.380-.550) .680 (.560-.880) 1336

Gender 

Males 01-02 .165 (.130-.209) .170 (.120-.230) .360 (.260-.520) .780 (.580-1.06) 1.22 (.850-1.43) 450

03-04 .128 (.112-.148) .110 (.096-.130) .250 (.190-.310) .500 (.380-.660) .730 (.590-1.10) 647

Females 01-02 .147 (.114-.190) .150 (.110-.220) .320 (.240-.390) .550 (.400-.740) .810 (.530-1.63) 504

03-04 .101 (.086-.118) .085 (.070-.100) .190 (.150-.230) .410 (.340-.500) .580 (.480-.750) 689

Race/ethnicity 

Mexican Americans 01-02 .136 (.106-.176) .140 (.080-.210) .270 (.210-.340) .550 (.400-.980) .990 (.500-1.30) 219

03-04 .084 (.074-.096) .076 (.064-.091) .120 (.100-.170) .280 (.170-.410) .400 (.310-.620) 253

Non-Hispanic blacks 01-02 .137 (.089-.210) .150 (.070-.200) .310 (.200-.460) .690 (.390-1.19) 1.15 (.660-1.69) 194

03-04 .105 (.077-.144) .095 (.070-.130) .200 (.130-.330) .440 (.290-.620) .620 (.480-.710) 297

Non-Hispanic whites 01-02 .165 (.125-.217) .170 (.120-.240) .350 (.270-.450) .710 (.450-1.12) 1.14 (.710-1.63) 467

03-04 .123 (.110-.139) .100 (.092-.120) .240 (.210-.280) .500 (.400-.590) .750 (.590-.940) 685

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.025 and 0.025. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 
 498 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

growth and skeletal development, and altered behavioral 

development in the offspring (ADSDR, 2000; Jones and 

Balster, 1997). Evidence for human reproductive effects 

is inconclusive, and reports of developmental effects have 

been reported mainly in children exposed in utero by 

maternal solvent abuse (Bukowski, 2001). Epidemiologic 

studies of workers exposed to toluene (or toluene together 

with other solvents) have not demonstrated increased risks 

for cancer, and animal studies have not demonstrated 

an increased incidence of tumors (IARC, 1999). IARC 

determined that toluene was not classifiable with regard 

to human carcinogenicity. The U.S. EPA has established 

a drinking water and other environmental standards for 

toluene. The FDA has established a bottle water standard 

and level for toluene as an indirect food additive. OSHA 

and ACGIH established workplace standards and 

guidelines, respectively, for toluene. Information about 

external exposure (i.e., environmental levels) and health 

effects is available from ATSDR at: http://www.atsdr.cdc.

gov/toxpro2.html.

Biomonitoring Information

Levels of blood toluene reflect recent exposure. A 

nonrepresentative sample of adults in NHANES III (1988-

1994) had geometric mean and median blood toluene 

levels, respectively, of 0.52 and 0.28 μg/L (Ashley et 

al., 1994; Churchill et al., 2001), generally higher than 

comparable levels in NHANES 2001-2002 and 2003-2004. 

Similar median blood toluene levels have been reported in 

U.S. children (Sexton et al., 2005, 2006) and in studies of 

adults without occupational exposure (Backer et al., 1997; 

Bonanno et al., 2001; Buckley et al., 1997). Population 

studies in Italy and Mexico have reported median blood 

toluene levels that were about twice as high as those 

in the U.S. (Brugnone et al., 1994; Carrer et al., 2000; 

Lemire et al., 2004; Perbellini et al., 2002). Geometric 

mean blood toluene levels were 0.191 and 0.669 ng/mL 

in non-smoking and smoking adults, respectively, from a 

subsample of NHANES 1999-2000 participants (Lin et al., 

2008). Other studies have reported blood toluene levels 

that were approximately four times higher in smokers 

than non-smokers (Ashley et al., 1995; Bonanno et al., 

2001; Brugnone et al., 1994; Perbellini et al., 2002), but 

environmental tobacco smoke exposure has not been 

associated with elevated blood toluene levels (Carrer et al., 

2000; Sexton et al., 2005). Exposure to gasoline fumes can 

increase blood toluene levels during self-service refueling 

(Backer et al., 1997). Vehicle exhaust and gasoline fumes 

in such occupational settings as gas stations, automobile 

repair shops, and street vending can result in blood toluene 

levels that are two to three times higher than background 

levels (Mannino et al., 1995; Romieu et al., 1999).

Finding a measureable amount of toluene in blood does 

not mean that the level of toluene causes an adverse health 

effect. Biomonitoring studies of blood toluene can provide 

physicians and public health officials with reference values 

so that they can determine whether or not people have been 

exposed to higher levels of toluene than levels found in 

the general population. Biomonitoring data can also help 

scientists plan and conduct research on exposure and health 

effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for toluene update. September 2000 

[online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/

tp56.html. 4/26/09

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Ashley DL, Bonin MA, Hamar B, McGeehin MA. Removing 

the smoking confounder from blood volatile organic compounds 

measurements. Environ Res 1995;71:39-45.

Backer LC, Egeland GM, Ashley DL, Lawryk NJ, Weisel CP, 

White MC, et al. Exposure to regular gasoline and ethanol 

oxyfuel during refueling in Alaska. Environ Health Perspect 

1997;105(8):850-855.

Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate 

analysis on levels of selected metals, particulate matter, VOC, 

and household characteristics and activities from the Midwestern 

states NHEXAS. Appl Occup Environ Hyg 2001;6(9):859-874.

Brugnone F, Perbellini L, Giuliari C, Cerpelloni M, Soave M. 

Blood and urine concentrations of chemical pollutants in the 

general population. Med Lav 1994;85(5):370-389.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, 

Needham LL. Environmental and biomarker measurements in 

nine homes in the lower Rio Grande Valley: multimedia results for 

pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-

732.

Bukowski JA. Review of the epidemiological evicdence relating 

toluene to reproductive outcomes. Regul Toxicol Pharmacol 

2001;33(2):147-156.

Carrer P, Marconi M, Alcini D, Cavallo D, Fustinoni S, Lovato 

L, et al., Assessment through environmental and biological 

measurements of total daily exposure to volatile organic 

compounds of office workers in Milan, Italy. Indoor Air 

2000;10:258-268.

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures 
Fourth National Report on Human Exposure to Environmental Chemicals 499

 Volatile Organic Compounds (VOCs)

and blood volatile organic compound levels in a large populationbased sample. Arch Environ Health 2001;56(2):157-166.

Filley CM, Halliday W, Kleinschmidt-DeMasters BK. The 

effects of toluene on the central nervous system. J Neuropathol 

Exp Neurol 2004;63(1):1-12.

Gordon SM, Callahan PJ, Nishioka MG, Brinkman MC, 

O’Rourke MK, Lebowitz MD, et al. Residential environmental 

measurements in the National Human Exposure Assessment 

Survey (NHEXAS) pilot study in Arizona: preliminary results for 

pesticides and VOCs. J Exp Anal Environ Epidemiol 1999;9:456-

470.

International Agency for Research on Cancer (IARC). IARC 

Monographs on the Evaluation of Carcinogenic Risks to 

Humans. Volume 71. Re-Evaluation of Some Organic Chemicals, 

Hydrazine and Hydrogen Peroxide. Summary of Data Reported 

and Evaluation 1999 [online]. Available at URL: http://

monographs.iarc.fr/ENG/Monographs/vol71/volume71.pdf. 

4/27/09

Jones HE, Balster RL. Neurobehavioral consequences of 

intermittent prenatal exposure to high concentrations of toluene. 

Neurotoxicol Teratol 1997;19(4):305-313.

Lemire S, Ashley D, Olaya P, Romieu I, Welch S, MenesesGonzalez F, et al. Environmental exposure of commuters in 

Mexico City to volatile organic compounds as assessed by blood 

concentrations, 1998. Salud Publica Mex 2004;46:32-38.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Expo Sci Environ Epidemiol 2008;18(4):421-429.

Lomax FB, Ridgway P, Meldrum M. Does occupational exposure 

to organic solvents affect colour discrimination? Toxicol Rev 

2004;23(2):91-121.

Mannino DM, Schreiber J, Aldous K, Ashley D, Moolenaar R, 

Almaguer D. Human exposure to volatile organic compounds: a 

comparison of organic vapor monitoring badge levels with blood 

levels. Int Arch Occup Environ Health 1995;67:59-64.

Mukund R, Kelly TJ, Spicer CW. Source attribution of ambient 

air toxic and other VOCs in Columbus, Ohio. Atmospheric 

Environment 1996;30(20):3457-3470.

Perbellini L, Pasini F, Romani S, Princivalle A, Brugnone F. 

Analysis of benzene, toluene, ethylbenzene and m-xylene in 

biological samples from the general population. J Chromat B 

2002;778:198-210.

Romieu I, Ramirez M, Meneses F, Ashley DL, Lemire S, Colome 

S, et al. Environmental exposure to volatile organic compounds 

among workers in Mexico City as assessed by personal 

monitors and blood concentrations. Environ Health Perspect 

1999;107(7):511-515.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran G, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 

years of age. Environ Health Perspect 2006;114(3):453-459.

United States Geological Survey (USGS). Volatile organic 

compounds in the nation’s ground water and drinking-water 

supply wells. 2006 [online]. Available at URL: http://pubs.usgs.

gov/circ/circ1292/. 4/26/09
 500 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Xylenes

CAS No. 1330-20-7

o-xylene CAS No. 95-47-6

m-xylene CAS No. 108-38-3

p-xylene CAS No. 106-42-3

General Information

Xylenes are aromatic chemicals that exist in three isomeric 

forms: o-, m-, and p-xylene. Commercial production results 

in mixed xylenes, which contain these three isomers, in 

addition to ethylbenzene and trace amounts of several 

non-xylene hydrocarbons. Specific xylene isomers are 

produced from mixed xylene and are used to synthesize 

other chemicals. Mixed xylenes are used widely as gasoline 

additives; as solvents in manufacturing and laboratory 

processes; in glues, adhesives, printing inks, paint thinners, 

and sealants; and as carrier solvents for delivery of some 

pesticides. Indoor air sources of xylene include building 

and consumer products, such as adhesives and paints, and 

also tobacco smoke (ATSDR, 2007). The most important 

route of exposure for the general population is inhaling 

volatized xylenes, although dermal contact with liquids 

containing xylene may also contribute. Workplace exposure 

to xylenes may occur when producing, transporting, and 

using petrochemicals and industrial solvents.

Following inhalational, dermal, or oral exposure, xylenes 

are well absorbed and then rapidly and widely distributed 

throughout the body tissues, especially adipose tissue. A 

fraction of an absorbed xylene dose is excreted unchanged 

in exhaled air, and about 90% of a dose is metabolized 

by the liver and then eliminated in urine over several 

days. Methylhippuric acids are the predominant urinary 

metabolites and have been used to monitor workplace 

exposures.

Human health effects from xylenes at low environmental 

doses or at biomonitored levels from low environmental 

exposures are unknown. Among humans, accidental 

exposure to high levels of xylene in air can cause eye and 

mucous membrane irritation, dyspnea, and central nervous 

system effects, such as headaches, dizziness, forgetfulness, 

delayed reaction times, and poor coordination (ATSDR, 

2007). Epidemiologic studies of cancer and xylene exposure 

have been inconclusive and are limited by small numbers, 

lack of exposure measurements, and the concomitant 

Blood o-Xylene

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 * < LOD .070 (.050-.080) .100 (.080-.130) .130 (.110-.180) 981

03-04 * < LOD .051 (<LOD-.057) .072 (.066-.079) .090 (.081-.097) 1365

Age group 

20-59 years 01-02 * < LOD .070 (.050-.080) .100 (.080-.130) .130 (.110-.180) 981

03-04 * < LOD .051 (<LOD-.057) .072 (.066-.079) .090 (.081-.097) 1365

Gender 

Males 01-02 * < LOD .070 (.050-.090) .110 (.080-.140) .150 (.110-.180) 465

03-04 * < LOD .057 (.050-.060) .074 (.068-.084) .096 (.084-.110) 667

Females 01-02 * < LOD .060 (.050-.080) .100 (.070-.130) .120 (.100-.180) 516

03-04 * < LOD < LOD .067 (.059-.076) .085 (.074-.095) 698

Race/ethnicity 

Mexican Americans 01-02 * < LOD .060 (<LOD-.080) .090 (.080-.110) .120 (.090-.270) 227

03-04 * < LOD .052 (<LOD-.067) .074 (.067-.080) .100 (.075-.130) 265

Non-Hispanic blacks 01-02 * < LOD .050 (<LOD-.070) .100 (.080-.110) .110 (.100-.160) 197

03-04 * < LOD < LOD .065 (.055-.078) .084 (.068-.100) 301

Non-Hispanic whites 01-02 * < LOD .070 (.050-.090) .110 (.080-.140) .140 (.110-.180) 483

03-04 * < LOD .052 (<LOD-.058) .073 (.066-.082) .090 (.081-.100) 694

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.049 and 0.049. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 

< LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. 

* Not calculated: proportion of results below limit of detection was too high to provide a valid result. 
Fourth National Report on Human Exposure to Environmental Chemicals 501

 Volatile Organic Compounds (VOCs)

exposure to other solvents (IARC, 1999). Animal studies 

involving high doses showed hepatic enzyme induction, 

liver enlargement, increased kidney weight and renal 

cytochrome P450 content, as well as neurobehavioral 

effects and altered catecholamine levels in the brain 

(ATSDR 2007). Pregnant animals that inhaled high doses 

had increased fetal resorptions and offspring with skeletal 

abnormalities and decreased body weight (ATSDR 2007). 

Neurobehavioral effects resulted in laboratory animals 

exposed during gestation to xylene concentrations in the 

air that were about five times higher than U.S. occupational 

standards (Hass et al., 1997,1995). Animals exposed to 

high doses of technical grade xylene by gavage did not 

demonstrate an increase in the incidence of tumors (NTP, 

1986).

Workplace standards for xylene levels in air have been 

established by OSHA, and ACGIH recommends a biological 

exposure index to monitor workplace exposure. The U.S. 

EPA has established a drinking water standard and other 

environmental standards for xylene. FDA has established 

a bottled drinking water standard. IARC has determined 

that xylene is not classifiable with regard to its human 

carcinogenicity. Information about external exposure (i.e., 

environmental levels) and health effects is available from 

ATSDR at: http://www.atsdr.cdc.gov/toxpro2.html.

Biomonitoring Information

Levels of blood xylenes reflect recent exposure. The mand p- xylene isomers usually are measured together and 

reported as m/p-xylene; the o-xylene isomer is measured 

and reported separately. In the NHANES 2001-2002 and 

2003-2004 subsamples, blood o-xylene was nondetectable 

in a majority of the participants, whereas the median blood 

m/p-xylene levels were similar to the earlier NHANES 

III results. In a nonrepresentative subsample of adults in 

NHANES III (1988-1994), the median blood levels of 

o-xylene and m/p-xylene were 0.11 μg/L and 0.19 μg/L, 

respectively (Ashley et al., 1994). These results were 

roughly similar to geometric mean levels of nonsmokers 

reported in a subsample of NHANES 1999-2000 (Lin et al., 

2008) and in other studies of the U.S. general population 

(Bonanno et al., 2001; Buckley et al., 1997; Hamar et al., 

1996), and to levels in adults in other countries (Lemire et 

al., 2002). Blood o-xylene levels in U.S. children were two 

to three times lower than adult levels (Sexton et al., 2005, 

2006). Smokers can have blood o- and m/p-xylene levels 

that are each about twice as high as those for nonsmokers 

(Ashley et al., 1995; Bonanno et al., 2001; Lin et al., 2008).

Blood m- and p-Xylene

Geometric mean and selected percentiles of blood concentrations (in ng/mL) for the U.S. population from the National Health 

and Nutrition Examination Survey. 

Geometric Selected percentiles 

Survey mean ( 95% confidence interval) Sample

years# (95% conf. interval) 50th 75th 90th 95th size

Total 01-02 .156 (.124-.198) .150 (.110-.200) .280 (.190-.430) .500 (.370-.690) .670 (.500-.890) 962

03-04 .136 (.123-.150) .130 (.120-.150) .200 (.190-.210) .280 (.260-.300) .340 (.310-.400) 1346

Age group 

20-59 years 01-02 .156 (.124-.198) .150 (.110-.200) .280 (.190-.430) .500 (.370-.690) .670 (.500-.890) 962

03-04 .136 (.123-.150) .130 (.120-.150) .200 (.190-.210) .280 (.260-.300) .340 (.310-.400) 1346

Gender 

Males 01-02 .155 (.121-.200) .140 (.110-.190) .280 (.180-.440) .510 (.350-.700) .700 (.500-.890) 455

03-04 .149 (.134-.166) .140 (.130-.170) .220 (.200-.230) .290 (.270-.320) .380 (.300-.490) 654

Females 01-02 .157 (.124-.199) .150 (.110-.220) .270 (.190-.410) .480 (.360-.650) .650 (.460-.890) 507

03-04 .124 (.112-.138) .130 (.110-.140) .180 (.160-.200) .270 (.240-.300) .340 (.290-.390) 692

Race/ethnicity 

Mexican Americans 01-02 .134 (.097-.184) .130 (.090-.180) .240 (.150-.370) .400 (.290-.540) .540 (.380-1.10) 223

03-04 .132 (.109-.160) .120 (.110-.150) .180 (.140-.230) .250 (.220-.320) .360 (.260-.490) 257

Non-Hispanic blacks 01-02 .147 (.107-.202) .140 (.090-.220) .280 (.160-.460) .470 (.330-.850) .590 (.420-1.08) 198

03-04 .117 (.094-.146) .120 (.099-.140) .170 (.140-.220) .270 (.210-.330) .330 (.260-.450) 297

Non-Hispanic whites 01-02 .163 (.124-.214) .160 (.110-.220) .300 (.190-.480) .520 (.370-.740) .700 (.510-.960) 468

03-04 .141 (.128-.155) .140 (.130-.150) .210 (.190-.220) .290 (.270-.310) .350 (.330-.400) 690

Limits of detection (LOD, see Data Analysis section) for Survey years 01-02 and 03-04 are 0.034 and 0.034. 

# Survey period 2001-2002 is a one-third subsample of 20-59 year olds; Survey period 2003-2004 is a one-half subsample of 20-59 year olds. 
 502 Fourth National Report on Human Exposure to Environmental Chemicals 

Volatile Organic Compounds (VOCs)

Workers who are exposed to vehicle exhaust can have oand m/p-xylene blood levels that are each about two to three 

times higher than levels in the general population (Backer 

et al., 1997; Mannino et al., 1995; Romieu et al., 1999).

Finding a measurable amount of any of the xylenes in blood 

does not mean that the level of xylene causes an adverse 

health effect. Biomonitoring studies of blood xylenes 

can provide physicians and public health officials with 

reference values so that they can determine whether or 

not people have been exposed to higher levels of xylenes 

than levels found in the general population. Biomonitoring 

data can also help scientists plan and conduct research on 

exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 

Toxicological profile for xylene. 2007 [online]. Available at URL:

http://www.atsdr.cdc.gov/toxprofiles/tp71.html#bookmark07. 

7/1/08

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten 

JV. Blood concentrations of volatile organic compounds in a 

nonoccupationally exposed US population and in groups with 

suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Ashley DL, Bonin MA, Hamar B, McGeehin MA. Removing 

the smoking confounder from blood volatile organic compounds 

measurements. Environ Res 1995;71:39-45.

Backer LC, Egeland GM, Ashley DL, Lawryk NJ, Weisel CP, 

White MC, et al. Exposure to regular gasoline and ethanol 

oxyfuel during refueling in Alaska. Environ Health Perspect 

1997;105(8):850-855.

Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate 

analysis on levels of selected metals, particulate matter, VOC, 

and household characteristics and activities from the Midwestern 

states NHEXAS. Appl Occup Environ Hyg 2001;6(9):859-874.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, 

Needham LL. Environmental and biomarker measurements in 

nine homes in the lower Rio Grande Valley: multimedia results for 

pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-

732.

Hamar GB, McGeehin MA, Phifer BL, Ashley DL. Volatile 

organic compound testing of a population living near a hazardous 

waste site. J Exp Anal Environ Epidemiol 1996;6(2):247-255.

Hass U, Lund SP, Simonsen L. Long-lasting neurobehavioral 

effects of prenatal exposure to xylene in rats. Neurotoxicology 

1997;18(2):547-551.

Hass U, Lund SP, Simonsen L, Fries AS. Effects of prenatal 

exposure to xylene on postnatal development and behavior in 

rats. Neurotoxicol Teratol 1995;17(3):341-349.

International Agency for Research on Cancer (IARC). Volume 

71.Re-Evaluation of Some Organic Chemicals, Hydrazine and 

Hydrogen Peroxide. 1999 [online]. Available at URL: http://

monographs.iarc.fr/ENG/Monographs/vol71/volume71.pdf.

7/1/08

Lemire S, Ashley D, Olaya P, Romieu I, Welch S, MenesesGonzalez F, Hernandez-Avila M. Environmental exposure of 

commuters in Mexico City to volatile orgnic compounds as 

assessed by blood concentrations, 1998. Salud Publica Mex 

004;46:32-38.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels 

of volatile organic compounds in air and blood from the general 

population. J Expo Sci Environ Epidemiol 2008;18(4):421-429.

Mannino DM, Schreiber J, Aldous K, Ashley D, Moolenaar R, 

Almaguer D. Human exposure to volatile organic compounds: a 

comparison of organic vapor monitoring badge levels with blood 

levels. Int Arch Occp Environ Health 1995;67:59-64.

National Toxicology Program (NTP). Toxicology and 

carcinogenesis studies of xylenes (mixed) (60% m-xylene, 14% 

p-xylene, 9% o-xylene, and 17% ethylbenzene) (CAS No. 1330-

20-7) in F344/N rats and B6C3Fl mice (gavage studies). 1986 

[online]. Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/

LT_rpts/tr327.pdf. 7/1/08

Romieu I, Ramirez M, Meneses F, Ashley DL, Lemire S, Colome 

S, et al. Environmental exposure to volatile organic compounds 

among workers in Mexico City as assessed by personal 

monitors and blood concentrations. Environ Health Perspect 

1999;107(7):511-515.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, 

Ramachandran G, et al. Children’s exposure to volatile organic 

compounds as determined by longitudinal measurements in 

blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, 

Ashley DL. Using biologic markers in blood to assess exposure 

to multiple environmental chemicals for inner-city children 3-6 

years of age. Environ Health Perspect 2006;114(3):453-459.
Fourth National Report on Human Exposure to Environmental Chemicals 503

 Appendix A. Procedure to Estimate Percentiles

Appendix A. Procedure to Estimate 

Percentiles

Including percentiles whose estimate falls on a value 

that is repeated multiple times in the dataset

A common practice to calculate confidence intervals from 

survey data is to use large-sample normal approximations. 

Ninety-five percent confidence intervals on point estimates 

of percentiles are often computed by adding and subtracting 

from the point estimate a quantity equal to twice its 

standard error. This normal approximation method may 

not be adequate, however, when estimating the proportion 

of subjects above or below a selected value, especially 

when the proportion is near 0.0 or 1.0 or when the effective 

sample size is small. In addition, confidence intervals 

on proportions deviating from 0.5 are not theoretically 

expected to be symmetric around the point estimate. 

Further, adding and subtracting a multiple of the standard 

error to an estimate near 0.0 or 1.0 can lead to impossible 

confidence limits (i.e., proportion estimates below 0.0 or 

above 1.0). The approach used for the Report data tables 

(and for previous Reports) produces asymmetric confidence 

intervals consistent with skewed (nonnormal) biologic data 

distributions.

The method we use to estimate percentiles and their 

confidence limits for the Report data tables and for previous 

reports is adapted from a method proposed by Woodruff 

(1952) for percentile estimation and a method described 

by Korn and Graubard (1998) for estimating confidence 

intervals for proportions. This method essentially involves 

first obtaining an empirical point estimate of the desired 

percentile by creating a rank ordered listing of the sampled 

observations along with their sampling weights. From this 

listing and the sampling weights, it is possible to determine 

an empirical percentile estimate for the target population. 

After this point estimate of the percentile has been obtained, 

the fraction of results below the estimate is calculated. The 

fraction below the point estimate should be very close to the 

proportion corresponding to the desired percentile, but can 

deviate from this proportion depending on the frequency 

of non-unique sampled observations in the vicinity of 

the empirical percentile estimate and depending on the 

sampling weight associated with the sampled observation. 

For example, when measuring some compounds as part of 

NHANES there may be multiple results below a common 

limit of detection (LOD) or multiple results with identical 

measured values due to the reporting limitations of the 

instrument. This phenomenon coupled with the sampling 

weight assigned to each measured result and with the 

limitations of statistical software can lead to difficulties 

in accurately estimating some percentiles and their 

corresponding confidence limits because an exact percentile 

may fall within a large group of results with identical 

measured values. We circumvented this potential problem 

for the Report data tables by adding a unique, negligibly 

small number to each measured result. This small number 

was later subtracted from the percentile estimate without 

affecting the percentile estimate and without altering any of 

the original measured results.

By adding a unique, negligibly small number to each 

sampled observation, it was possible to associate a single 

sampled observation with the percentile estimate and thus 

to minimize the difference between the fraction below the 

point estimate and the proportion corresponding to the 

desired percentile. However, due to sample weighting, it 

is still possible to obtain a different point estimate (which 

will only differ by the difference between numerically 

adjacent analyte values) depending on how the data are 

sorted before adding the unique number to each result. 

We circumvented this potential problem by replacing 

actual sample weights with an average sample weight 

where the average is computed across subjects in the same 

demographic domain who have identical measured results. 

We computed standard error estimates in a separate step 

using the original (unaltered) data. Clopper-Pearson 95% 

confidence intervals around the estimated proportion are 

obtained using the method described by Korn and Graubard 

(1998).

We describe below how SAS Proc Univariate and SUDAAN 

can be used to carry out this method of percentile and 

confidence interval estimation. SAS code for calculating 

these confidence intervals can be downloaded from http://

www.cdc.gov/exposurereport. In the narrative that follows, 

the term ‘demographic domain’ refers to a demographic 

group of interest, for example non-Hispanic blacks. The 

term ‘set of subsample weights’ refers to the sampling 

weights that correspond to the variable for which percentiles 

will be estimated, for example the set of subsample weights 

associated with total blood mercury measurements. The 

term ‘analyte’ refers to the biological or chemical compound 

measured in a group of subjects and for which percentiles 

are to be estimated.
 504 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix A. Procedure to Estimate Percentiles

Procedure to calculate percentile estimates and their confidence intervals

Step 1: Obtain a percentile estimate using the original (unaltered data):

Create a separate file with original data (ORIG_DATA). Use SAS (SAS Institute Inc. 1999) Proc Univariate (with 

default percentile definition equivalent to option PCTLDEF = 5 and with the Freq option variable equal to the 

original subsample sampling weight) to obtain a point estimate of the percentile (PTLE_ORIG) of an analyte’s 

original results for the demographic domain of interest, for example, the 90th percentile of blood lead results for 

children aged 1-5 years.

Step 2: Obtain a percentile estimate using the altered data:

Create a separate file for use with altered data (ALTR_DATA). Sort the data by analyte measured value separately 

for each particular demographic domain and set of subsample weights. Use SAS Proc Means to compute the 

average sampling weight (WTAVE) for each unique measured result. For each unique measured result, use a 

counter from 1 to the total number of subjects with identical values to create a unique integer to associate with 

each measured observation. Each of these numbers should then be divided by 1,000,000,000 and added to the 

corresponding measured observation. This will result in each measured observation having an additional fractional 

amount beyond the fourth decimal as long as there are less than 10,000 subjects with the same measured result. 

Use SAS Proc Univariate (again with default percentile definition equivalent to option PCTLDEF = 5 but now 

with the Freq option variable equal to WTAVE) to obtain a point estimate of the percentile (PTLE_ALTR) of an 

analyte’s altered results for the demographic domain of interest.

Step 3: Sort the data in the ORIG_DATA file by the stratum (sdmvstra) and primary sampling unit (sdmvpsu) variables. 

Use SUDAAN (SUDAAN Users Manual, 2001) Proc Descript with Taylor Linearization DESIGN = WR (i.e., 

sampling with replacement), with proper NEST statement, and with the original subsample sampling weight 

variable to estimate the proportion (P_ORIG) of subjects with results below the percentile estimate (PTLE_

ORIG) obtained in Step 1 and discard P_ORIG but retain the standard error (SEMEAN_ORIG) associated with 

PTLE_ORIG.

Step 4: Sort the data in the ALTR_DATA file by the stratum (sdmvstra) and primary sampling unit (sdmvpsu) variables. 

Use SUDAAN (SUDAAN Users Manual, 2001) Proc Descript with Taylor Linearization DESIGN = WR (i.e., 

sampling with replacement), with proper NEST statement, and with the average sampling weight variable 

(WTAVE) to estimate the proportion (P_ALTR) of subjects with results below the percentile estimate (PTLE_

ALTR) obtained in Step 2 and keep P_ALTR but discard the standard error (SEMEAN_ALTR) associated with 

PTLE_ALTR. Compute the degrees-of-freedom adjusted effective sample size. 

(1) ndf =((tnum/tdenom)2)P_ALTR(1 – P_ALTR)/(SEMEAN_ORIG2)

where tnum and tdenom are 0.975 critical values of the Student’s t distribution with degrees of freedom equal to 

the actual sample size minus 1 and the number of primary sampling units (PSUs) minus the number of strata, 

respectively. Note: the degrees of freedom for tdenom can vary with the demographic domain of interest (e.g., 

males).

Step 5: After obtaining an estimate of P_ALTR (i.e., the proportion obtained in Step 4), compute the Clopper-Pearson 

95% confidence interval (PL(x,ndf), PU(x,ndf)) as follows:

(2) PL(x,ndf) = v1

Fv1,v2 (0.025)/(v2 + v1Fv1,v2(0.025)) & PU(x,ndf) = v3Fv3,v4 (0.975)/(v4 + v3Fv3,v4(0.975))

 

where x is equal to P_ALTR times ndf, v1 = 2x, v2 = 2(ndf - x + 1), v3 = 2(x + 1), v4 = 2(ndf - x), and Fd1,d2(β) is 

the β quantile of an F distribution with d1

 and d2 degrees of freedom. (Note: If ndf is greater than the actual sample 

size or if P_ALTR is equal to zero, then the actual sample size should be used.) This step will produce a lower and 

an upper limit for the estimated proportion obtained in Step 4.
Fourth National Report on Human Exposure to Environmental Chemicals 505

 Appendix A. Procedure to Estimate Percentiles

Step 6: Use SAS Proc Univariate (again with default percentile definition equivalent to option PCTLDEF = 5 and with 

the Freq option variable equal to WTAVE) to determine the analyte values that correspond to the desired percentile 

(proportion) and the lower and upper proportion limits obtained in Step 5. Round these results to 2 or 3 decimals 

depending on the significant figures associated with the original measured values.

 

Example:

To estimate the 75th percentile of blood lead in children age 1-5 years in the 2003-2004 survey, create two separate files: 

name one ORIG_DATA and the other ALTR_DATA. For the ORIG_DATA file use SAS Proc Univariate with the Freq 

option and the subsample sampling weight (or in this case the full sample sampling weight because blood lead is the 

analyte of interest) to get a weighted point estimate of the analyte value that corresponds to the 75th percentile (PTLE_

ORIG). For this example the value is 2.5 μg/dL.

Sort the results in the ALTR_DATA file by analyte measured value. Use SAS Proc Means to compute the average sampling 

weight (WTAVE) for each unique analyte measured value. For each unique measured result, use a counter from 1 to the 

total number of subjects with identical values to create a unique integer to associate with each measured observation. 

Divide each counter value by 1,000,000,000 and add this amount to the corresponding measured observation. For this 

altered data file (ALTR_DATA) use SAS Proc Univariate with the Freq option and WTAVE to get a weighted point estimate 

of the analyte value that corresponds to the 75th percentile (PTLE_ALTR). For this example the value is also 2.5 μg/dL.

For the ORIG_DATA file use SUDAAN to estimate the weighted proportion (P_ORIG) of subjects with results below 

the value of PTLE_ORIG (which can differ from 0.75 depending on the number of results with identical values; for this 

example the proportion is 0.7374) and the standard error (SEMEAN_ORIG) associated with P_ORIG (for this example 

SEMEAN_ORIG = 0.0237).

For the ALTR_DATA file use SUDAAN to estimate the weighted proportion of subjects (P_ALTR) with results below 

the value of PTLE_ALTR (which should also be very close to 0.75 regardless of the number of original results with 

identical values; for this example the proportion is 0.7497). Then obtain a confidence interval on P_ALTR by computing 

the weighted Clopper-Pearson 95% confidence limits (equation 2 above) using the degrees-of-freedom adjusted effective 

sample size as described in equation 1 above. For this example the effective sample size is 283.911 resulting in lower and 

upper confidence limits of 0.6951 and 0.7990, respectively. Then use SAS Proc Univariate (with the Freq option variable 

equal to WTAVE) to determine the analyte values corresponding to the weighted 69.5th and 79.9th percentiles. These point 

estimates are the lower and upper confidence limits on the 75th percentile estimate. Round the 75th percentile estimate and 

its confidence limits to 2 or 3 decimals depending on the significant figures associated with the original measured values. 

For this example the rounded point estimate is 2.5 μg/dL with lower and upper confidence limits of 2.3 and 2.8 μg/dL, 

respectively.

Note: Previous reports of the analyses of 1999-2000 data (in the Second National Report on Human Exposure to 

Environmental Chemicals) used a jackknife method (available within SUDAAN) for variance estimation that was based 

on replicate weights. To better address multiple 2-year data sets and to combine 2-year data sets into 4-year data sets, 

NCHS developed a new approach based on masked variance units that uses a Taylor series (linearization) method that 

is also available in SUDAAN. The two methods produce very similar, but not identical, variance estimates. In the Third 

National Report on Human Exposure to Environmental Chemicals and in the current Report data tables, all variance 

estimates (1999-2000, 2001-2002, 2003-2004) were calculated using the Taylor series (linearization) method within 

SUDAAN.
 506 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix B. Changes and Edits to Results Released in the Third Report

Appendix B. Changes and Edits to Results 

Released in the Third Report

Some biomonitoring results from earlier NHANES survey 

periods require corrections due to analytical issues. 

Corrections can include changes in specific data tables or 

the removal of data tables in this Report, as compared to 

the previous Third National Report on Human Exposure to 

Environmental Chemicals. The following chemical tables 

are affected:

1. The data for beta-hexachlorocyclohexane serum levels 

(lipid adjusted and whole weight) in the Third National 

Report on Human Exposure to Environmental Chemicals

for the NHANES survey period 2001-2002 should have 

been adjusted by multiplying each data point by a factor 

of 1.5528. The data for this chemical in the current Report 

have had this adjustment applied. This adjustment was 

needed due to a misassignment of the concentration of a 

purchased standard material.

2. Urinary 2,4-dichlorophenol and 2,5-dichlorophenol were 

presented in the Third National Report on Human Exposure 

to Environmental Chemicals for the years 1999-2002 and

have been removed from this Report due to matrix-based 

calibration biases. Data Tables for these two chemicals in 

the 2003-2004 survey period will be included in the next 

release of the Report.

3. Improvements in analytical methods have resulted in 

dropping data for some urinary Polycyclic Aromatic Hydrocarbon (PAH) metabolites. For the 1999-2000 survey 

period, urinary data for 2-hydroxyfluorene, 3-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 

3-hydroxyphenanthrene, and 1-hydroxypyrene have been 

removed from the Data Tables in the current Report. The data 

from 1999-2000 for these specific analytes are not in agreement with current methods -- specifically interferences in 

some analytical peaks have been detected with newer analytic methods and newer techniques have shown that deconjugation in the analytical method was not complete for some 

PAHs. For the 1999-2002 period, data for urinary metabolites of 1-Hydroxybenz[a]anthracene, 3-hydroxybenz[a]

anthracene, 9-Hydroxybenz[a]anthracene, 1-Hydroxybenzo[c]phenanthrene, 2-Hydroxybenzo[c]phenanthrene, 

3-Hydroxybenzo[c]phenanthrene, 1-Hydroxychrysene, 

2-Hydroxychrysene, 3-Hydroxychrysene, 4-Hydroxychrysene, 6-Hydroxychrysene and 3-Hydroxybenzo[a]pyrene 

have been removed and are not planned for future Reports. 

Improvements in analytical methods have found uncertainties due to interferences in accurate mass detection in the 

previous method. In addition, data for 3-Hydroxybenzo[a]

pyrene in the 2001-2002 survey period has been removed 

due to an interference in a purchased reagent used in the 

deconjugation step of the analytical method.

Data for three additional PAH urinary metabolites 

have been removed for the 1999-2002 survey period. 

Urinary 9-hydroxyphenanthrene has been removed 

due to degradation during the deconjugation step of 

the analytical method. Urinary 9-hydroxyphenanthrene 

will not be reported in future survey periods. Urinary 

9-hydroxyfluorene has been removed due to an incomplete 

deconjugation step revealed by improved methods. Data 

for urinary 9-hydroxyfluorene is reported in the 2003-

2004 survey period. Urinary 4-hydroxyphenanthrene has 

been removed as a result of infrequent interferences in the 

analytical method, which were detected by an improved 

analytical method. Urinary 4-Hydroxyphenanthrene is

reported in the 2003-2004 survey period.

Data for three urinary PAH metabolites from the 2001-

2002 survey are under current evaluation and do not 

appear in this release of the Report: 1-hydroxynaphthalene, 

2-hydroxyfluorene, and 1-hydroxypyrene.
Fourth National Report on Human Exposure to Environmental Chemicals 507

 Appendix C. References for Biomonitoring Analytical Methods 

Appendix C. References for Biomonitoring 

Analytical Methods

Acrylamide Adducts 

Vesper HW, Bernert JT, Ospina M, Meyers T, Ingham 

L, Smith A, et al. Assessment of the relation between 

biomarkers for smoking and biomarkers for acrylamide 

exposure in humans. Cancer Epidemiol Biomarkers Prev 

2007;16(11):2471-2478.

Vesper HW, Slimani N, Hallmans G, Tjonneland A, Agudo 

A, Benetou V, et al. Cross-sectional study on acrylamide 

hemoglobin adducts in subpopulations from the European 

Prospective Investigation into Cancer and Nutrition (EPIC) 

study. J Agric Food Chem 2008; 56 (15):6046–6053.

Cotinine

Bernert JT, McGuffey JE, Morrison MA, Pirkle JL. 

Comparison of serum and salivary cotinine measurements 

by a sensitive high-performance liquid chromatography/

tandem mass spectrometry method as an indicator 

of exposure to tobacco smoke among smokers and 

nonsmokers. J Anal Toxicol 2000;24:333-339.

Bernert JT, Turner WE, Pirkle JL, Sosnoff CS, Akins 

JR, Waldrep MK, et al. Development and validation of a 

sensitive measurement of serum cotinine in both smokers 

and nonsmokers by liquid chromatography/atmospheric 

pressure ionization tandem mass spectrometry. Clin Chem 

1997;43:2281-2291.

N,N-Diethyl-meta-toluamide (DEET)

Olsson AO, Baker SE, Nguyen JV, Romanoff LC, Udunka 

SO, Walker RD, et al. A liquid chromatography-tandem 

mass spectrometry multiresidue method for quantification 

of specific metabolites of organophosphorus pesticides, 

synthetic pyrethroids, selected herbicides, and DEET in 

human urine. Anal Chem 2004;76(9):2453-2461.

Disinfection By-Products (Trihalomethanes)

Blount BC, Kobelski RJ, McElprang DO, Ashley DL, 

Morrow JC, Chambers DM, et al. Quantification of 31 

volatile organic compounds in whole blood using solidphase microextraction and gas chromatography-mass 

spectrometry. J Chromatogr B Analyt Technol Biomed Life 

Sci 2006;832: 292-301.

Environmental Phenols

Ye X, Kuklenyik Z, Needham LL, Calafat AM. Automated 

on-line column-switching HPLC-MS/MS method with 

peak focusing for the determination of nine environmental 

phenols in urine. Anal Chem 2005;77:5407-5413.

Fungicides

Hill RH Jr, Shealy DB, Head SL, Williams CC, Bailey SL, 

Gregg M, et al. Determination of pesticide metabolites in 

human urine using isotope dilution technique and tandem 

mass spectrometry. J Anal Toxicol 1995;19(5):323-329.

Bravo R, Caltabiano LM, Fernandez C, Smith KD, Gallegos 

M, Whitehead RD, et al. Quantification of phenolic 

metabolites of environmental chemicals in human urine 

using gas chromatography-tandem mass spectrometry 

and isotope dilution quantification. J Chromatog B 

2005;820(2):229-236.

Herbicides

Bravo R, Caltabiano LM, Fernandez C, Smith KD, Gallegos 

M, Whitehead RD, et al. Quantification of phenolic 

metabolites of environmental chemicals in human urine 

using gas chromatography-tandem mass spectrometry 

and isotope dilution quantification. J Chromatog B 

2005;820(2):229-236.

Hill RH Jr, Shealy DB, Head SL, Williams CC, Bailey SL, 

Gregg M, et al. Determination of pesticide metabolites in 

human urine using isotope dilution technique and tandem 

mass spectrometry. J Anal Toxicol 1995;19(5):323-329.

Olsson AO, Baker SE, Nguyen JV, Romanoff LC, Udunka 

SO, Walker RD, et al. A liquid chromatography-tandem 

mass spectrometry multiresidue method for quantification 

of specific metabolites of organophosphorus pesticides, 

synthetic pyrethroids, selected herbicides, and DEET in 

human urine. Anal Chem 2004;76(9):2453-2461.

Insecticides and Pesticides

 Carbamate Insecticides

Bravo R, Caltabiano LM, Fernandez C, Smith KD, Gallegos 

M, Whitehead RD, et al. Quantification of phenolic 

metabolites of environmental chemicals in human urine 

using gas chromatography-tandem mass spectrometry 

and isotope dilution quantification. J Chromatog B 

2005;820(2):229-236.

Hill RH Jr, Shealy DB, Head SL, Williams CC, Bailey SL, 

Gregg M, et al. Determination of pesticide metabolites in 

human urine using isotope dilution technique and tandem 

mass spectrometry. J Anal Toxicol 1995;19(5):323-329.
 508 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix C. References for Biomonitoring Analytical Methods

Organochlorines Pesticides

Barr JB, Maggio VL, Barr DB, Turner WE, Sjödin A, 

Sandau CD, et al. New high-resolution mass spectrometric 

approach for the measurement of polychlorinated biphenyls 

and organochlorine pesticides in human serum. J Chromatog 

B 2003;794:137-148.

Hill RH Jr, Shealy DB, Head SL, Williams CC, Bailey SL, 

Gregg M, et al. Determination of pesticide metabolites in 

human urine using isotope dilution technique and tandem 

mass spectrometry. J Anal Toxicol 1995;19(5):323-329.

Turner WE, DiPietro E, Lapeza CR, Jr., Green V, Gill 

J, Patterson DG Jr., et al. Universal automated cleanup 

system for the isotope-dilution high-resolution mass 

spectrometric analysis of PCDDs, PCDFs, coplanar PCBs, 

PCB congeners, and persistent pesticides from the same 

serum sample. Organohalogen Compounds 1997;31:26-31.

Organophosphate Insecticides: Dialkyl 

 Phosphate Metabolites

Bravo R, Caltabiano LM, Weerasekera G, Whitehead 

RD, Fernandez C, Needham LL, et al. Measurement 

of dialkyl phosphate metabolites of organophosphorus 

pesticides in human urine using lyophilization with gas 

chromatography-tandem mass spectrometry and isotope 

dilution quantification. J Expo Anal Environ Epidemiol 

2004;14:249-259.

Bravo R, Driskell WJ, Whitehead RD Jr, Needham LL, 

Barr DB. Quantitation of dialkyl phosphate metabolites 

of organophosphate pesticides in human urine using GCMS-MS with isotopic internal standards. J Anal Toxicol 

2002;26:245-252.

Organophosphate Insecticides: Specific 

 Metabolites

Bravo R, Caltabiano LM, Fernandez C, Smith KD, Gallegos 

M, Whitehead RD, et al. Quantification of phenolic 

metabolites of environmental chemicals in human urine 

using gas chromatography-tandem mass spectrometry 

and isotope dilution quantification. J Chromatog B 

2005;820(2):229-236.

Hill RH Jr, Shealy DB, Head SL, Williams CC, Bailey SL, 

Gregg M, et al. Determination of pesticide metabolites in 

human urine using isotope dilution technique and tandem 

mass spectrometry. J Anal Toxicol 1995;19(5):323-329.

Olsson AO, Baker SE, Nguyen JV, Romanoff LC, Udunka 

SO, Walker RD, et al. A liquid chromatography-tandem 

mass spectrometry multiresidue method for quantification 

of specific metabolites of organophosphorus pesticides, 

synthetic pyrethroids, selected herbicides, and DEET in 

human urine. Anal Chem 2004;76(9):2453-2461.

Pyrethroid Pesticides 

Olsson AO, Baker SE, Nguyen JV, Romanoff LC, Udunka 

SO, Walker RD, et al. A liquid chromatography-tandem 

mass spectrometry multiresidue method for quantification 

of specific metabolites of organophosphorus pesticides, 

synthetic pyrethroids, selected herbicides, and DEET in 

human urine. Anal Chem 2004;76(9):2453-2461.

Metals 

Caldwell KL, Hartel J, Jarrett J, Jones RL. Inductively 

coupled plasma mass spectrometry to measure multiple 

toxic elements in urine in NHANES 1999-2000. Atomic 

Spectroscopy. 2005;26(1):1-7.

Chen HP, Paschal DC, Miller DT, Morrow JC. Determination 

of total and inorganic mercury in whole blood by online digestion with flow injection. Atomic Spectroscopy 

1998;19:176-179.

Jarrett JM, Jones RL, Caldwell KL, Verdon CP. Total urine 

arsenic measurements using inductively coupled plasma 

mass spectrometry with a dynamic reaction cell. Atomic 

Spectroscopy 2007;28(4):113-122.

Miller, DT, Paschal DC, Gunter EW, Stroud PE, D’Angelo 

J. Determination of lead in blood using electrothermal 

atomization atomic absorption spectrometry with a L’vov 

platform and matrix modifier. Analyst 1987;112:1701-

1704.

Paschal DC, Ting BG, Morrow JC, Pirkle JL, Jackson RJ, 

Sampson EJ, et al. Trace metals in urine of United States 

residents: reference range concentrations. Environ Res 

1998;76:53-59.

Stoeppler M, Brandt K. Determination of cadmium in 

whole blood and urine by electrothermal atomic-absorption 

spectrophotometry. Fresnius A Anal Chem 1980;300:372-

380.

Verdon CP, Caldwell KL, Fresques MR, Jones RL. 

Determination of seven arsenic compounds in urine by 

HPLC-ICP-DRC-MS: a CDC population biomonitoring 

method. Anal Bioanal Chem 2008;393(3):939-947.
Fourth National Report on Human Exposure to Environmental Chemicals 509

 Appendix C. References for Biomonitoring Analytical Methods 

Perchlorate

Valentin-Blasini L, Blount BC, Delinsky A. Quantification 

of iodide and sodium-iodide symporter inhibitors in human 

urine using ion chromatography tandem mass spectrometry. 

J Chrom A 2007;1155(1):40-46.

Valentin-Blasini L, Mauldin JP, Maple D and Blount 

BC. Analysis of perchlorate in human urine using 

ion chromatography and electrospray tandem mass 

spectrometry. Anal Chem 2005;77(8):2475-2481.

Perfluorochemicals

Kuklenyik Z, Needham LL, Calafat AM. Measurement 

of 18 perfluorinated organic acids and amides in human 

serum using on-line solid-phase extraction. Anal Chem 

2005;77:6085-6091.

Phthalates

Blount BC, Milgram KE, Silva M, Malek N, Reidy J, 

Needham LL, et al. Quantitative detection of eight phthalate 

metabolites in human urine using HPLC-APCI-MS/MS. 

Anal Chem 2000;72:4127-4134.

Silva MJ, Malek NA, Hodge CC, Reidy JA, Kato K, 

Barr DB, et al. Improved quantitative detection of 11 

urinary phthalate metabolites in humans using liquid 

chromatography-atmospheric pressure chemical ionization 

tandem mass spectrometry. J Chromatog B 2003;789:393-

404.

Silva MJ, Slakman AR, Reidy JA, Preau JLJ, Herbert AR, 

Samandar E, et al. Analysis of human urine for 15 phthalate 

metabolites using automated solid-phase extraction. J 

Chromatog B 2004;805:161-167.

Phytoestrogens

Valentin-Blasini L, Blount BC, Rogers HS, Needham LL. 

HPLC-MS/MS method for the measurement of seven 

phytoestrogens in human serum and urine. J Expo Anal 

Environ Epidemiol 2000;10:799-807.

Kuklenyik Z, Ye X, Reich JA, Needham LL, Calafat AM. 

Automated on-line and off-line solid phase extraction 

methods for measuring isoflavones and lignans in urine. J 

Chromatogr Sci 2004; 42:495-500.

Polybrominated Diphenyl Ethers and 

2,2’,4,4’,5,5’-Hexabromobiphenyl

Sjödin A, Jones RS, Lapeza CR, Focant J-F, McGahee 

EE III, Patterson DG. Semiautomated high-throughput 

extraction and cleanup method for the measurement of 

polybrominated diphenyl ethers, polybrominated biphenyls, 

and polychlorinated biphenyls in human serum. Anal Chem 

2004;76:1921-1927.

Polychlorinated Biphenyls, Polychlorinated Dibenzo-pdioxins, Dibenzofurans

Barr JB, Maggio VL, Barr DB, Turner WE, Sjödin A, 

Sandau CD, et al. New high-resolution mass spectrometric 

approach for the measurement of polychlorinated biphenyls 

and organochlorine pesticides in human serum. J Chromatog 

B 2003;794:137-148.

Patterson DG Jr., Alexander LR, Turner WE, Isaacs SG, 

Needham LL. The development and application of a 

high resolution mass spectrometry method for measuring 

polychlorinated dibenzo-p-dioxins and dibenzofurans 

in serum. In: Clement RE, Sui KM, Hill HH Jr., eds. 

Instrumentation for trace organic monitoring. Chelsea, MI: 

Lewis Publishers; 1990. pp. 119-53.

Patterson DG Jr., Hampton L, Lapeza CR Jr., Belser 

WT, Green V, Alexander L, et al. High resolution gas 

chromatographic/high resolution mass spectrometric 

analysis of human serum on a whole weight and lipid basis 

for 2,3,7,8 TCDD. Anal Chem 1987;59:2000-2005.

Patterson, DG Jr., Wong L-Y, Turner WE, Caudill SP, 

DiPietro ES, McClure PC, et al. Levels in the U.S. population 

of those persistent organic pollutants (2003-2004) included 

in the Stockholm Convention or in other Long-Range Tran 

boundary Air Pollution Agreements. Environ Sci Technol 

2009;43(4):1211-1218.

Turner WE, DiPietro E, Cash TP, McClure PC, Patterson 

DG Jr., Shirkhan H. An improved SPE extraction and 

automated sample cleanup method for serum PCDDs, 

PCDFs, and coplanar PCBs. Organohalogen Compounds 

1994;19:31-35.

Turner WE, DiPietro E, Lapeza CR, Jr., Green V, Gill 

J, Patterson DG Jr., et al. Universal automated cleanup 

system for the isotope-dilution high-resolution mass 

spectrometric analysis of PCDDs, PCDFs, coplanar PCBs, 

PCB congeners, and persistent pesticides from the same 

serum sample. Organohalogen Compounds 1997;31:26-31.

Polycyclic Aromatic Hydrocarbons

Li Z, Romanoff LC, Young KJ, Blakely NC III, Wei RW, 

Needham LL, et al. Biomonitoring of human exposure to 
 510 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix C. References for Biomonitoring Analytical Methods

polycyclic aromatic hydrocarbons (PAH) and diesel exhaust 

by measurement of urinary biomarkers. Epidemiology 

2004;15(4):S75.

Romanoff LC, Li Z, Young KJ, Blakely NC III, Patterson 

DG, Sandau CD. Automated solid-phase extraction method 

for measuring urinary polycyclic aromatic hydrocarbon 

metabolites in human biomonitoring using isotope-dilution 

gas chromatography high-resolution mass spectrometry. J 

Chromatog B 2006;835:47-54.

Smith CJ, Huang WL, Walcott CJ, Turner WE, Grainger 

J, Patterson DG Jr. Quantification of monohydroxy-PAH 

metabolites in urine by solid-phase extraction with isotope 

dilution GC-HRMS. Anal Bioanal Chem 2002;372:216-

220.

Volatile Organic Compounds

Blount B.C, Kobelski R.J, McElprang D.O, Ashley D.L, 

Morrow J.C, Chambers D.M, et al. Quantification of 31 

volatile organic compounds in whole blood using solidphase microextraction and gas chromatography-mass 

spectrometry. J Chromatogr B Analyt Technol Biomed Life 

Sci 2006;832: 292-301.
Fourth National Report on Human Exposure to Environmental Chemicals 511

 Appendix D. Limit of DetectionTable Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

Acrylamide Adducts 

Acrylamide blood pmol/g 

hemoglobin

3.0

Glycidamide blood pmol/g 

hemoglobin

4.0

Cotinine serum ng/mL 0.05 0.05 0.015N,N-Diethyl-meta -toluamide (DEET) urine μg/L 0.449 0.1

Disinfection By-Products (Trihalomethanes)

Bromodichloromethane blood pg/mL 0.233 0.62

Dibromochloromethane (Chlorodibromomethane) blood pg/mL 0.271 0.62Tribromomethane (Bromoform) blood pg/mL 0.596 1.5

Trichloromethane (Chloroform) blood pg/mL 2.37 2.11

Appendix D. Limit of Detection Table

The analytical limit of detection (LOD) for each of the different chemical measurements is presented in the table below. The LOD is the level at which the measurement has a 95% probability of being greater than zero (Taylor, 1987). For most chemicals, the LOD is constant for each sample analyzed. However, for dioxins, furans, PCBs, organochlorine insecticides, and some other pesticides, each individual sample has its own LOD. These analyses have an individual LOD for each sample, mostly because the sample volume available for analysis differed for each sample. A higher sample volume results in a lower LOD and a better ability to detect low levels.For chemicals with sample-specific LODs, we report in the table the maximum LOD among the samples analyzed. In general, the averageLOD for these samples is about 40-50% of the maximum LOD. If a geometric mean or percentile estimate is less than the maximum LOD, it is noted in the results tables, and we do not report a number for that estimate. This conservative approach is to assure high confidence in all number reported in the results tables. As analytical methods improve, LODs will often change. For this reason, LOD results are reported by survey periods (e.g., 1999-2000, 2001-2002, 2003-2004).Reference: Taylor JK. Quality Assurance of Chemical Measurements. Chelsea (MI): Lewis Publishing. 1987.
 512 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix D. Limit of DetectionTable Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

Environmental Phenol

s

 Bisphenol A (2,2-bis [4-Hydroxyphenyl] propane) urine μg/L 0.4 Benzophenone-3 (2-Hydroxy-4-methoxybenzophenone) urine μg/L 0.3

 4-tert -Octylphenol (4-[1,1,3,3-Tetramethylbutyl] phenol) urine μg/L 0.2

 Triclosan (2,4,4’-Trichloro-2’-hydroxyphenyl ether) urine μg/L 2.3Fungicides and Metabolites Pentachlorophenol urine μg/L 0.25 0.5

 ortho -Phenylphenol urine μg/L 0.3 0.3

Herbicides and Metabolites

Acetochlor mercapturate urine μg/L 0.1Alachlor mercapturate urine μg/L 1.18Atrazine mercapturate urine μg/L 0.791 0.3 2,4-Dichlorophenoxyacetic acid urine μg/L 0.952 0.2 Metolachlor mercapturate urine μg/L 0.2

 2,4,5-Trichlorophenoxyacetic acid urine μg/L 1.2 0.1

Insecticides and Metabolite

s

 Carbamates

 Carbofuranphenol urine μg/L 0.4 0.4

 2-Isopropoxyphenol urine μg/L 1.1 0.4

 Organochlorines and Metabolite

s

 Aldrin serum ng/g of lipid 5.94 7.8 o,p'-Dichlorodiphenyltrichloroethane serum ng/g of lipid 20.7 17.4 7.8 p,p'-Dichlorodiphenyltrichloroethane (DDT) serum ng/g of lipid 20.7 17.4 7.8

p,p'-Dichlorodiphenyldichloroethene (DDE) serum ng/g of lipid 18.6 8.3 7.8

 Dieldrin serum ng/g of lipid 10.5 7.8 Endrin serum ng/g of lipid 5.09 7.8

 Hexachlorobenzene serum ng/g of lipid 118 31.4 7.8 beta -Hexachlorocyclohexane serum ng/g of lipid 9.36 6.76 7.8

gamma -Hexachlorocyclohexane (Lindane) serum ng/g of lipid 14.5 10.5 7.8

 Heptachlor epoxide serum ng/g of lipid 14.6 10.5 7.8 Mirex serum ng/g of lipid 14.6 10.5 7.8

trans -Nonachlor serum ng/g of lipid 14.5 10.5 7.8

 Oxychlordane serum ng/g of lipid 14.5 10.5 7.8

 2,4,5-Trichlorophenol urine μg/L 0.9 0.9 2,4,6-Trichlorophenol urine μg/L 1 1.3
Fourth National Report on Human Exposure to Environmental Chemicals 513

 Appendix D. Limit of DetectionTable

Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

 Diethylphosphate (DEP) urine μg/L 0.2 0.2 0.1 Dimethylphosphate (DMP) urine μg/L 0.58 0.5 0.5 Diethylthiophosphate (DETP) urine μg/L 0.09 0.1 0.2 Dimethylthiophosphate (DMTP) urine μg/L 0.18 0.4 0.5 Diethyldithiophosphate (DEDTP) urine μg/L 0.05 0.1 0.1 Dimethyldithiophosphate (DMDTP) urine μg/L 0.08 0.1 0.1 3-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one/ol urine μg/L 0.2

 2-(Diethylamino)-6-methylpyrimidin-4-ol/one urine μg/L 0.2

 2-Isopropyl-4-methyl-6-hydroxypyrimidine urine μg/L 7.2 0.7 Malathion dicarboxylic acid urine μg/L 2.64 para -Nitrophenol urine μg/L 0.8 0.1 3,5,6-Trichloro-2-pyridinol urine μg/L 0.4 0.4

 Pyrethroid Pesticide Metabolite

s

cis -3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid urine μg/L 0.1 0.1

 cis -3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid urine μg/L 0.1 0.1 trans -3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid urine μg/L 0.4 0.4

 4-Fluoro-3-phenoxybenzoic acid urine μg/L 0.2 0.2 3-Phenoxybenzoic acid urine μg/L 0.1 0.1

Metals

 Antimony urine μg/L 0.04 0.04 0.07

 Arsenic, Total urine μg/L 0.74

 Arsenic (V) Acid urine μg/L 1.0

 Arsenobetaine urine μg/L 0.4

 Arsenocholine urine μg/L 0.6 Arsenous (III) Acid urine μg/L 1.2 Dimethylarsinic Acid urine μg/L 1.7 Monomethylarsonic Acid urine μg/L 0.9 Trimethylarsine oxide urine μg/L 1.0 Barium urine μg/L 0.12 0.12 0.31

 Organophosphorus Insecticides: Dialkyl Phosphate Metabolite

s

 Organophosphorus Insecticides: Specific Insecticides and Metabolites
 514 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix D. Limit of DetectionTable Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

Metals (continued)

 Beryllium urine μg/L 0.13 0.13 0.13

 Cadmium blood μg/L 0.3 0.3 0.14 Cadmium urine μg/L 0.06 0.06 0.06 Cesium urine μg/L 0.14 0.14 0.2 Cobalt urine μg/L 0.07 0.07 0.08 Lead blood μg/dL 0.3 0.3 0.28 Lead urine μg/L 0.1 0.1 0.33 Mercury, Inorganic blood μg/L 0.42 Mercury, Total blood μg/L 0.14 0.14 0.2 Mercury urine μg/L 0.14 0.14 0.14 Molybdenum urine μg/L 0.8 0.8 1.5 Platinum urine μg/L 0.04 0.04 0.07 Thallium urine μg/L 0.02 0.02 0.02 Tungsten urine μg/L 0.04 0.04 0.04 Uranium urine μg/L 0.004 0.004 0.005

Perchlorate urine μg/L 0.05 0.05Perfluorinated Com

pounds

 Perfluorobutane sulfonic acid (PFBuS) serum μg/L 0.4

 Perfluorodecanoic acid (PFDeA) serum μg/L 0.3

 Perfluorododecanoic acid (PFDoA) serum μg/L 1.0

 Perfluoroheptanoic acid (PFHpA) serum μg/L 0.3

 Perfluorohexane sulfonic acid (PFHxS) serum μg/L 0.3

 Perfluorononanoic acid (PFNA) serum μg/L 0.1

 Perfluorooctanoic acid (PFOA) serum μg/L 0.1

 Perfluorooctane sulfonic acid (PFOS) serum μg/L 0.4 Perfluorooctane sulfonamide (PFOSA) serum μg/L 0.2 2-(N-Ethyl-perfluorooctane sulfonamido) acetic acid (Et-PFOSA-AcOH) serum μg/L 0.4 2-(N-Methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) serum μg/L 0.6 Perfluoroundecanoic acid (PFUA) serum μg/L 0.3

Phthalate Metabolites Mono-benzyl phthalate (MBzP) urine μg/L 0.8 0.3 0.1 Mono-isobutyl phthalate (MiBP) urine μg/L 1.0 0.3

 Mono-n-butyl phthalate (MnBP) urine μg/L 0.9 1.1 0.4 Mono-cyclohexyl phthalate (MCHP) urine μg/L 0.9 0.3 0.2
Fourth National Report on Human Exposure to Environmental Chemicals 515

 Appendix D. Limit of DetectionTable

Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

Phthalate Metabolites (continued) Mono-ethyl phthalate (MEP) urine μg/L 1.2 0.9 0.4 Mono-2-ethylhexyl phthalate (MEHP) urine μg/L 1.2 1.0 0.9 Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) urine μg/L 1.0 0.3 Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) urine μg/L 1.1 0.5 Mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) urine μg/L 0.3 Mono-isononyl phthalate (MiNP) urine μg/L 0.8 0.8 1.0 Mono-methyl phthalate (MMP) urine μg/L 0.2 1.0

 Mono-(3-carboxypropyl) phthalate (MCPP) urine μg/L 0.4 0.2 Mono-n-octyl phthalate (MOP) urine μg/L 0.9 1.0 1.0Phytoestrogens and Metabolite

s

 Daidzein urine μg/L 0.5 1.6 1.6 O-Desmethylangolensin urine μg/L 0.2 0.4 0.4 Enterodiol urine μg/L 0.8 1.5 1.5 Enterolactone urine μg/L 0.6 1.9 1.9 Equol urine μg/L 3.0 3.3 3.3 Genistein urine μg/L 0.3 0.8 0.8 2,2',4-Tribromodiphenyl ether (BDE 17) serum ng/g of lipid 1.0 2,4,4'-Tribromodiphenyl ether (BDE 28) serum ng/g of lipid 0.8 2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) serum ng/g of lipid 4.2 2,3',4,4'-Tetrabromodiphenyl ether (BDE 66) serum ng/g of lipid 1.0 2,2',3,4,4'-Pentabromodiphenyl ether (BDE 85) serum ng/g of lipid 2.4 2,2’,4,4’,5-Pentabromodiphenyl ether (BDE 99) serum ng/g of lipid 5.0 2,2',4,4',6-Pentabromodiphenyl ether (BDE 100) serum ng/g of lipid 1.4 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE 153) serum ng/g of lipid 2.2

 2,2',4,4',5,6'-Hexabromodiphenyl ether (BDE 154) serum ng/g of lipid 0.8

 2,2',3,4,4',5',6-Heptabromodiphenyl ether (BDE 183) serum ng/g of lipid 1.7 2,2',4,4',5,5'-Hexabromobiphenyl (BB 153) serum ng/g of lipid 0.8Polychlorinated Biphenyls, Non-Dioxin-Like 2,4,4'-Trichlorobiphenyl (PCB 28) serum ng/g of lipid 32.4 1.7 2,2'3,5'-Tetrachlorobiphenyl (PCB 44) serum ng/g of lipid 0.4 2,2',4,5'-Tetrachlorobiphenyl (PCB 49) serum ng/g of lipid 0.4 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) serum ng/g of lipid 12.5 12.4 0.8 2,3',4,4'-Tetrachlorobiphenyl (PCB 66) serum ng/g of lipid 12.4 12.4 0.8 2,4,4',5-Tetrachlorobiphenyl (PCB 74) serum ng/g of lipid 12.4 10.5 0.8 2,2',3,4,5'-Pentachlorobiphenyl (PCB 87) serum ng/g of lipid 10.5 0.4

Polybrominated Diphenyl Ethers and Polybrominated Biphenyl
 516 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix D. Limit of DetectionTable Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

Polychlorinated Biphenyls, Non-Dioxin-Like (continued) 2,2',4,4',5-Pentachlorobiphenyl (PCB 99) serum ng/g of lipid 12.5 10.5 0.6 2,2',4,5,5'-Pentachlorobiphenyl (PCB 101) serum ng/g of lipid 25.7 10.5 0.6 2,3,3',4',6-Pentachlorobiphenyl (PCB 110) serum ng/g of lipid 10.5 0.8

 2,2',3,3',4,4'-Hexachlorobiphenyl (PCB 128) serum ng/g of lipid 12.4 10.5 0.4 2,2',3,4,4',5' and 2,3,3',4,4',6-Hexachlorobiphenyl (PCB 138 & 158) serum ng/g of lipid 41.1 10.5 0.4 2,2',3,4',5,5'-Hexachlorobiphenyl (PCB 146) serum ng/g of lipid 12.4 10.5 0.4 2,2',3,4',5',6-Hexachlorobiphenyl (PCB 149) serum ng/g of lipid 10.5 0.4

 2,2',3,5,5',6-Hexachlorobiphenyl (PCB 151) serum ng/g of lipid 10.5 0.4

 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) serum ng/g of lipid 55.6 10.5 1.1 2,2',3,3',4,4',5-Heptachlorobiphenyl (PCB 170) serum ng/g of lipid 17.2 10.5 0.4 2,2',3,3',4,5,5'-Heptachlorobiphenyl (PCB 172) serum ng/g of lipid 12.5 10.5 0.4 2,2',3,3',4,5',6'-Heptachlorobiphenyl (PCB 177) serum ng/g of lipid 12.5 10.5 0.4 2,2',3,3',5,5',6-Heptachlorobiphenyl (PCB 178) serum ng/g of lipid 12.4 10.5 0.4 2,2',3,4,4',5,5'-Heptachlorobiphenyl (PCB 180) serum ng/g of lipid 28.2 10.5 0.4 2,2',3,4,4',5',6-Heptachlorobiphenyl (PCB 183) serum ng/g of lipid 12.4 10.5 0.4 2,2',3,4',5,5',6-Heptachlorobiphenyl (PCB 187) serum ng/g of lipid 12.4 10.5 0.4 2,2',3,3',4,4',5,5'-Octachlorobiphenyl (PCB 194) serum ng/g of lipid 10.5 0.4

 2,2',3,3',4,4',5,6-Octachlorobiphenyl (PCB 195) serum ng/g of lipid 28.1 0.7

 2,2',3,3',4,4',5,6' and 2,2',3,4,4',5,5',6-Octachlorobiphenyl (PCB 196 & 203) serum ng/g of lipid 10.5 0.4 2,2',3,3',4,5,5',6-Octachlorobiphenyl (PCB 199) serum ng/g of lipid 10.5 0.4

 2,2',3,3',4,4',5,5',6-Nonachlorobiphenyl (PCB 206) serum ng/g of lipid 28.1 0.7

 2,2',3,3',4,4',5,5',6,6'-Decachlorobiphenyl (PCB 209) serum ng/g of lipid 0.7

 Coplanar Polychlorinated Biphenyls 3,4,4',5-Tetrachlorobiphenyl (PCB 81) serum pg/g of lipid 68.4 26.8 13.1 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) serum pg/g of lipid 23.2 10.8 13.9 3,3',4,4',5,5'-Hexachlorobiphenyl (PCB 169) serum pg/g of lipid 27.0 11.0 15.9 Mono-ortho -substituted Polychlorinated Biphenyls 2,3,3',4,4'-Pentachlorobiphenyl (PCB 105) serum ng/g of lipid 12.4 10.5 0.4 2,3',4,4',5-Pentachlorobiphenyl (PCB 118) serum ng/g of lipid 12.5 10.5 0.6 2,3,3',4,4',5-Hexachlorobiphenyl (PCB 156) serum ng/g of lipid 12.5 10.5 0.4 2,3,3',4,4',5'-Hexachlorobiphenyl (PCB 157) serum ng/g of lipid 12.5 10.5 0.4 2,3',4,4',5,5'-Hexachlorobiphenyl (PCB 167) serum ng/g of lipid 12.4 10.5 0.4 2,3,3’,4,4’,5,5’-Heptachlorobiphenyl (PCB 189) serum ng/g of lipid 10.5 0.4

Polychlorinated Dibenzo-p -dioxins, Dibenzofurans, and Dioxin-Like Polychlorinated Biphenyls
Fourth National Report on Human Exposure to Environmental Chemicals 517

 Appendix D. Limit of DetectionTable

Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

 Polychlorinated Dibenzofurans 1,2,3,4,6,7,8-Heptachlorodibenzofuran (HpCDF) serum pg/g of lipid 13.5 7.0 8.6 1,2,3,4,7,8,9-Heptachlorodibenzofuran (HpCDF) serum pg/g of lipid 7.0 8.6 1,2,3,4,7,8-Hexachlorodibenzofuran (HxCDF) serum pg/g of lipid 12.7 6.5 7.4 1,2,3,6,7,8-Hexachlorodibenzofuran (HxCDF) serum pg/g of lipid 12.6 6.1 7.9 1,2,3,7,8,9-Hexachlorodibenzofuran (HxCDF) serum pg/g of lipid 12.7 6.0 8.3 2,3,4,6,7,8-Hexachlorodibenzofuran (HxCDF) serum pg/g of lipid 12.9 5.8 8.2 1,2,3,4,6,7,8,9-Octachlorodibenzofuran (OCDF) serum pg/g of lipid 35.6 21.0 12.0 1,2,3,7,8-Pentachlorodibenzofuran (PeCDF) serum pg/g of lipid 13.2 5.8 7.1 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) serum pg/g of lipid 12.7 5.5 6.8 2,3,7,8-Tetrachlorodibenzofuran (TCDF) serum pg/g of lipid 11.9 5.2 6.0 Polychlorinated Dibenzo-p -dioxins

 1,2,3,4,6,7,8-Heptachlorodibenzo-p -dioxin (HpCDD) serum pg/g of lipid 55.9 10.3 13.0

 1,2,3,4,7,8-Hexachlorodibenzo-p -dioxin (HxCDD) serum pg/g of lipid 9.0 11.9 1,2,3,6,7,8-Hexachlorodibenzo-p -dioxin (HxCDD) serum pg/g of lipid 20.1 9.1 12.3 1,2,3,7,8,9-Hexachlorodibenzo-p -dioxin (HxCDD) serum pg/g of lipid 20.3 9.3 12.3 1,2,3,4,6,7,8,9-Octachlorodibenzo-p -dioxin (OCDD) serum pg/g of lipid 329.0 319.0 218.0

 1,2,3,7,8-Pentachlorodibenzo-p -dioxin (PeCDD) serum pg/g of lipid 14.2 6.0 4.5

 2,3,7,8-Tetrachlorodibenzo-p -dioxin (TCDD) serum pg/g of lipid 12.1 5.8 3.8

Polycyclic Aromatic Hydrocarbon Metabolites

 2-Hydroxyfluorene urine ng/L 5.0

 3-Hydroxyfluorene urine ng/L 2.0 5.0

 9-Hydroxyfluorene urine ng/L 5.0 1-Hydroxynaphthalene (1-Naphthol) urine ng/L 46.7 2-Hydroxynaphthalene (2-Naphthol) urine ng/L 2.4 31.1 1-Hydroxyphenanthrene urine ng/L 3.5 5.0 2-Hydroxyphenanthrene urine ng/L 3.2 5.0 3-Hydroxyphenanthrene urine ng/L 3.6 5.0 4-Hydroxyphenanthrene urine ng/L 5.0 1-Hydroxypyrene urine ng/L 5.0
 518 Fourth National Report on Human Exposure to Environmental Chemicals 

Appendix D. Limit of DetectionTable Chemical Matrix Units 1999-2000 2001-2002 2003-200

4

Volatile Organic Compounds (VOCs)

 Benzene blood ng/mL 0.024 0.024

 Chlorobenzene (Monochlorobenzene) blood ng/mL 0.011

 1,2-Dibromo-3-chloropropane (DBCP) blood ng/mL 0.1

 Dibromomethane blood ng/mL 0.03 1,2-Dichlorobenzene (

o -Dichlorobenzene) blood ng/mL 0.1

 1,3-Dichlorobenzene (

m -Dichlorobenzene) blood ng/mL 0.05

 1,4-Dichlorobenzene (Paradichlorobenzene) blood ng/mL 0.12 0.12 1,1-Dichloroethane blood ng/mL 0.01 1,2-Dichloroethane (Ethylene dichloride) blood ng/mL 0.01 1,1-Dichloroethene (Vinylidene chloride) blood ng/mL 0.009

cis -1,2-Dichloroethene blood ng/mL 0.01trans -1,2-Dichloroethene blood ng/mL 0.01

 Dichloromethane (Methylene chloride) blood ng/mL 0.07 1,2-Dichloropropane blood ng/mL 0.008

 2,5-Dimethylfuran blood ng/mL 0.012 Ethylbenzene blood ng/mL 0.024 0.024

 Hexachloroethane blood ng/mL 0.011

 Methyl tert -butyl ether (MTBE) blood pg/mL 0.232 2.0

 Nitrobenzene blood ng/mL 0.3

 Styrene blood ng/mL 0.03 0.03 1,1,2,2-Tetrachloroethane blood ng/mL 0.01

 Tetrachloroethene (Perchloroethylene) blood ng/mL 0.048 0.048

 Tetrachloromethane (Carbon tetrachloride) blood ng/mL 0.01 0.005

 Toluene blood ng/mL 0.025 0.025

 1,1,1-Trichloroethane (Methyl chloroform) blood ng/mL 0.048 1,1,2-Trichloroethane blood ng/mL 0.01

 Trichloroethene (Trichloroethylene) blood ng/mL 0.012 0.012

 o -Xylene blood ng/mL 0.049 0.049

m - and 

p -Xylene blood ng/mL 0.034 0.034
Fourth National Report on Human Exposure to Environmental Chemicals 519

 Appendix E. Abbreviations

Appendix E. Abbreviations Used in Text

ACGIH American Conference of Governmental Industrial Hygienists

ATSDR Agency for Toxic Substances and Disease Registry

CDC Centers for Disease Control and Prevention

DHHS Department of Health and Human Services

FAO/WHO Food and Agriculture Organization of the United Nations

FDA Food and Drug Administration

IARC International Agency for Research on Cancer

IOM Institute of Medicine

IPCS International Programme on Chemical Safety

NAS National Academy of Sciences 

NCEH National Center of Environmental Health

NCHS National Center for Health Statistics

NHANES National Health and Nutrition Examination Survey

NIOSH National Institute of Occupational Safety and Health

NRC National Research Council of the NAS

NTP National Toxicology Program

OSHA Occupational Safety and Health Administration

U.S. United States

USDA U.S. Department of Agriculture

U.S.EPA U.S. Environmental Protection Agency

USGS U.S. Geological Survey

WHO World Health Organization
Centers for Disease Control and Prevention

National Center for Environmental Health

Division of Laboratory Sciences

Mail Stop F-20

4770 Buford Highway, NE

Atlanta, GA 30341-3724

Telephone: (toll free) 1-800-CDC-INFO (1-800-232-4636)

Email: CDCINFO@cdc.gov

Website: http://www.cdc.gov/exposurereport