MIREX AND CHLORDECONE i

*** Version 1.0

Toxicological Profile for

Mirex and Chlordecone

October 2020
MIREX AND CHLORDECONE ii

DISCLAIMER

Use of trade names is for identification only and does not imply endorsement by the Agency for Toxic 

Substances and Disease Registry, the Public Health Service, or the U.S. Department of Health and Human 

Services.
MIREX AND CHLORDECONE iii

FOREWORD 

This toxicological profile is prepared in accordance with guidelines* developed by the Agency for Toxic 

Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The 

original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised 

and republished as necessary. 

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects 

information for these toxic substances described therein. Each peer-reviewed profile identifies and 

reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is 

also presented, but is described in less detail than the key studies. The profile is not intended to be an 

exhaustive document; however, more comprehensive sources of specialty information are referenced. 

The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile 

begins with a relevance to public health discussion which would allow a public health professional to 

make a real-time determination of whether the presence of a particular substance in the environment 

poses a potential threat to human health. The adequacy of information to determine a substance's health 

effects is described in a health effects summary. Data needs that are of significance to the protection of 

public health are identified by ATSDR.

Each profile includes the following:

(A) The examination, summary, and interpretation of available toxicologic information and 

epidemiologic evaluations on a toxic substance to ascertain the levels of significant 

human exposure for the substance due to associated acute, intermediate, and chronic 

exposures; 

(B) A determination of whether adequate information on the health effects of each substance 

is available or in the process of development to determine levels of exposure that present 

a significant risk to human health of acute, intermediate, and chronic health effects; and

(C) Where appropriate, identification of toxicologic testing needed to identify the types or 

levels of exposure that may present significant risk of adverse health effects in humans.

The principal audiences for the toxicological profiles are health professionals at the Federal, State, and 

local levels; interested private sector organizations and groups; and members of the public. 

This profile reflects ATSDR’s assessment of all relevant toxicologic testing and information that has been 

peer-reviewed. Staffs of the Centers for Disease Control and Prevention and other Federal scientists have 

also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel 

and was made available for public review. Final responsibility for the contents and views expressed in 

this toxicological profile resides with ATSDR.

Patrick N. Breysse, Ph.D., CIH Christopher M. Reh, Ph.D. 

Director, National Center for Environmental Health and Associate Director

Agency for Toxic Substances and Disease Registry Agency for Toxic Substances and Disease Registry 

Centers for Disease Control and Prevention Centers for Disease Control and Prevention
MIREX AND CHLORDECONE iv

*Legislative Background

The toxicological profiles are developed under the Comprehensive Environmental Response, Compensation, and 

Liability Act of 1980, as amended (CERCLA or Superfund). CERCLA section 104(i)(1) directs the Administrator 

of ATSDR to “...effectuate and implement the health related authorities” of the statute. This includes the 

preparation of toxicological profiles for hazardous substances most commonly found at facilities on the CERCLA 

National Priorities List (NPL) and that pose the most significant potential threat to human health, as determined by 

ATSDR and the EPA. Section 104(i)(3) of CERCLA, as amended, directs the Administrator of ATSDR to prepare a 

toxicological profile for each substance on the list. In addition, ATSDR has the authority to prepare toxicological 

profiles for substances not found at sites on the NPL, in an effort to “...establish and maintain inventory of 

literature, research, and studies on the health effects of toxic substances” under CERCLA Section 104(i)(1)(B), 

to respond to requests for consultation under section 104(i)(4), and as otherwise necessary to support the 

site-specific response actions conducted by ATSDR.
MIREX AND CHLORDECONE v 

VERSION HISTORY 

Date Description

October 2020 Final toxicological profile released

May 2019 Draft for public comment toxicological profile released

August 1995 Final toxicological profile released
MIREX AND CHLORDECONE vi

CONTRIBUTORS & REVIEWERS 

CHEMICAL MANAGER TEAM

Obaid Faroon, D.V.M., Ph.D. David W. Wohlers, Ph.D.

Lisa Ingerman, Ph.D., DABT

Laura McIlroy, B.S.

ATSDR, Office of Innovation and Analytics, SRC, Inc., North Syracuse, NY

Toxicology Section, Atlanta, GA

REVIEWERS

Interagency Minimal Risk Level Workgroup: 

Includes ATSDR; National Center for Environmental Health (NCEH); National Institute for 

Occupational Safety and Health (NIOSH); U.S. Environmental Protection Agency (EPA); National 

Toxicology Program (NTP). 

Additional reviews for science and/or policy: 

ATSDR, Office of Community Health and Hazard Assessment; ATSDR, Office of Capacity 

Development and Applied Prevention Science; ATSDR, Office of Science; NCEH, Division of 

Laboratory Science; NCEH, Division of Environmental Health Science and Practice; EPA, National 

Center for Environmental Assessment.

PEER REVIEWERS

1. Rogene Henderson, Ph.D., Applied Life Sciences and Toxicology, Lovelace Respiratory 

Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, New Mexico

2. Lucio Costa, PharmD., Department of Environmental and Occupational Health Sciences, 

Department of Neurological Surgery, University of Washington, Seattle, WA, USA and 

Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy

3. Luc Multigner, M.D., Ph.D., Directeur de Recherche Inserm, Inserm U1085 – IRSET, Institut de 

Recherche sur la santé, l'environnement et le travail, 9 Avenue du Professeur Léon Bernard, 

Rennes and Faculté de Médecine, Campus de Fouillole, Pointe à Pitre Cedex, Guadeloupe 

These experts collectively have knowledge of toxicology, chemistry, and/or health effects. All reviewers 

were selected in conformity with Section 104(I)(13) of the Comprehensive Environmental Response, 

Compensation, and Liability Act, as amended. 

ATSDR scientists review peer reviewers’ comments and determine whether changes will be made to the 

profile based on comments. The peer reviewers’ comments and responses to these comments are part of 

the administrative record for this compound. 

The listing of peer reviewers should not be understood to imply their approval of the profile's final 

content. The responsibility for the content of this profile lies with ATSDR.
MIREX AND CHLORDECONE vii

CONTENTS

DISCLAIMER..............................................................................................................................................ii

FOREWORD...............................................................................................................................................iii

VERSION HISTORY...................................................................................................................................v

CONTRIBUTORS & REVIEWERS...........................................................................................................vi

CONTENTS................................................................................................................................................vii

LIST OF FIGURES .....................................................................................................................................ix

LIST OF TABLES........................................................................................................................................x

CHAPTER 1. RELEVANCE TO PUBLIC HEALTH ................................................................................1

1.1 OVERVIEW AND U.S. EXPOSURES .........................................................................................1

1.2 SUMMARY OF HEALTH EFFECTS...........................................................................................1

1.3 MINIMAL RISK LEVELS (MRLs) ..............................................................................................9

CHAPTER 2. HEALTH EFFECTS...........................................................................................................13

2.1 INTRODUCTION........................................................................................................................13

2.2 DEATH ........................................................................................................................................78

2.3 BODY WEIGHT..........................................................................................................................79

2.4 RESPIRATORY...........................................................................................................................80

2.5 CARDIOVASCULAR .................................................................................................................81

2.6 GASTROINTESTINAL...............................................................................................................82

2.7 HEMATOLOGICAL ...................................................................................................................83

2.8 MUSCULOSKELETAL ..............................................................................................................84

2.9 HEPATIC.....................................................................................................................................84

2.10 RENAL.....................................................................................................................................88

2.11 DERMAL .................................................................................................................................89

2.12 OCULAR..................................................................................................................................90

2.13 ENDOCRINE ...........................................................................................................................91

2.14 IMMUNOLOGICAL................................................................................................................93

2.15 NEUROLOGICAL...................................................................................................................93

2.16 REPRODUCTIVE....................................................................................................................97

2.17 DEVELOPMENTAL..............................................................................................................100

2.18 OTHER NONCANCER .........................................................................................................104

2.19 CANCER................................................................................................................................105

2.20 GENOTOXICITY ..................................................................................................................109

2.21 MECHANISMS OF ACTION................................................................................................113

CHAPTER 3. TOXICOKINETICS, SUSCEPTIBLE POPULATIONS, BIOMARKERS, CHEMICAL 

INTERACTIONS.............................................................................................................121

3.1 TOXICOKINETICS...................................................................................................................121

3.1.1 Absorption...........................................................................................................................121

3.1.2 Distribution .........................................................................................................................124

3.1.3 Metabolism..........................................................................................................................129

3.1.4 Excretion .............................................................................................................................131

3.1.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models...........135

3.1.6 Animal-to-Human Extrapolations.......................................................................................135

3.2 CHILDREN AND OTHER POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE...136

3.3 BIOMARKERS OF EXPOSURE AND EFFECT .....................................................................138

3.3.1 Biomarkers of Exposure......................................................................................................139

3.3.2 Biomarkers of Effect...........................................................................................................140
MIREX AND CHLORDECONE viii

3.4 INTERACTIONS WITH OTHER CHEMICALS .....................................................................141

CHAPTER 4. CHEMICAL AND PHYSICAL INFORMATION ..........................................................145

4.1 CHEMICAL IDENTITY............................................................................................................145

4.2 PHYSICAL AND CHEMICAL PROPERTIES.........................................................................145

CHAPTER 5. POTENTIAL FOR HUMAN EXPOSURE......................................................................147

5.1 OVERVIEW...............................................................................................................................147

5.2 PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL ................................................152

5.2.1 Production ...........................................................................................................................152

5.2.2 Import/Export......................................................................................................................154

5.2.3 Use ......................................................................................................................................154

5.2.4 Disposal...............................................................................................................................155

5.3 RELEASES TO THE ENVIRONMENT...................................................................................156

5.3.1 Air .......................................................................................................................................157

5.3.2 Water...................................................................................................................................158

5.3.3 Soil ......................................................................................................................................160

5.4 ENVIRONMENTAL FATE ......................................................................................................161

5.4.1 Transport and Partitioning...................................................................................................161

5.4.2 Transformation and Degradation ........................................................................................167

5.5 LEVELS IN THE ENVIRONMENT.........................................................................................171

5.5.1 Air .......................................................................................................................................172

5.5.2 Water...................................................................................................................................172

5.5.3 Sediment and Soil ...............................................................................................................174

5.5.4 Other Media ........................................................................................................................176

5.6 GENERAL POPULATION EXPOSURE..................................................................................180

5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ..............................................193

CHAPTER 6. ADEQUACY OF THE DATABASE...............................................................................198

6.1 Information on Health Effects....................................................................................................198

6.2 Identification of Data Needs.......................................................................................................201

6.3 Ongoing Studies.........................................................................................................................208

CHAPTER 7. REGULATIONS AND GUIDELINES ............................................................................209

CHAPTER 8. REFERENCES .................................................................................................................211

APPENDICES

APPENDIX A. ATSDR MINIMAL RISK LEVEL WORKSHEETS ....................................................A-1

APPENDIX B. LITERATURE SEARCH FRAMEWORK FOR MIREX AND CHLORDECONE.....B-1

APPENDIX C. USER’S GUIDE.............................................................................................................C-1

APPENDIX D. QUICK REFERENCE FOR HEALTH CARE PROVIDERS.......................................D-1

APPENDIX E. GLOSSARY ................................................................................................................... E-1

APPENDIX F. ACRONYMS, ABBREVIATIONS, AND SYMBOLS ..................................................F-1
MIREX AND CHLORDECONE ix

LIST OF FIGURES 

1-1. Graph of Health Effects Found in Animals Following Oral Exposure to Mirex .................................. 2

1-2. Graph of Health Effects Found in Animals Following Oral Exposure to Chlordecone ....................... 4

1-3. Summary of Sensitive Targets of Mirex – Oral .................................................................................. 10

1-4. Summary of Sensitive Targets of Chlordecone – Oral ....................................................................... 11

2-1. Overview of the Number of Studies Examining Mirex Health Effects .............................................. 17

2-2. Overview of the Number of Studies Examining Chlordecone Health Effects ................................... 18

2-3. Levels of Significant Exposure to Mirex – Oral ................................................................................. 48

2-4. Levels of Significant Exposure to Chlordecone – Oral ...................................................................... 71

3-1. Proposed Metabolic Pathways for Chlordecone ............................................................................... 131

5-1. Number of NPL Sites with Mirex Contamination ............................................................................ 147

5-2. Number of NPL Sites with Chlordecone Contamination ................................................................. 148

6-1. Summary of Existing Health Effects Studies on Mirex By Route and Endpoint ............................. 199

6-2. Summary of Existing Health Effects Studies on Chlordecone By Route and Endpoint ................... 200
MIREX AND CHLORDECONE x

LIST OF TABLES

1-1. Minimal Risk Levels (MRLs) for Mirex ............................................................................................10

1-2. Minimal Risk Levels (MRLs) for Chlordecone..................................................................................12

2-1. Results of Epidemiological Studies Evaluating Associations Between Mirex and Health Outcomes19

2-2. Results of Epidemiological Studies Evaluating Associations Between Chlordecone and Health 

Outcomes............................................................................................................................................25

2-3. Levels of Significant Exposure to Mirex – Oral.................................................................................28

2-4. Levels of Significant Exposure to Chlordecone – Oral ......................................................................53

2-5. Levels of Significant Exposure to Mirex – Dermal............................................................................76

2-6. Levels of Significant Exposure to Chlordecone – Dermal .................................................................77

2-7. In Vivo Genotoxicity of Mirex and Chlordecone in Orally-Exposed Animals.................................110

2-8. Genotoxicity of Mirex and Chlordecone In Vitro.............................................................................111

4-1. Chemical Identity of Mirex and Chlordecone ..................................................................................145

4-2. Physical and Chemical Properties of Mirex and Chlordecone .........................................................146

5-1. Concentrations of Mirex in Aquatic Organisms...............................................................................163

5-2. Lowest Limit of Detection for Mirex Based on Standards...............................................................171

5-3. Lowest Limit of Detection for Chlordecone Based on Standards....................................................171

5-4. Geometric Mean and Selected Percentiles of Mirex (Lipid Adjusted) 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 (NHANES) 1999–2004..................................183

5-5. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex (Lipid Adjusted) Pooled 

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 (NHANES) 2005–

2010 ..................................................................................................................................................185

5-6. Geometric Mean and Selected Percentiles of Mirex (Whole Weight) Serum Concentrations (in 

ng/g of Serum or Parts per Billion) for the U.S. Population from the 

National Health and Nutrition Examination Survey (NHANES) 1999–2004..................................188

5-7. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex (Whole Weight) Pooled 

Serum Concentrations (in ng/g of Serum or Parts per Billion) for the U.S. Population from the 

National Health and Nutrition Examination Survey (NHANES) 2005–2010..................................190
MIREX AND CHLORDECONE xi

7-1. Regulations and Guidelines Applicable to Mirex and Chlordecone.................................................209
MIREX AND CHLORDECONE 1

CHAPTER 1. RELEVANCE TO PUBLIC HEALTH

1.1 OVERVIEW AND U.S. EXPOSURES

Mirex and chlordecone are structurally similar highly-chlorinated derivatives of cyclopentadiene. The 

only structural difference between mirex and chlordecone is that mirex has two bridgehead chlorine atoms 

where chlordecone has a carbonyl oxygen atom. Mirex was commercially introduced in the United States 

in 1959 for use in pesticide formulations and as an industrial fire retardant. In the 1960s, mirex was 

commonly used to control fire ants in southern States. Mirex was banned for use in the United States in 

1978, except for use on pineapples until stocks on hand were exhausted. Chlordecone was mainly 

registered for use in the United States to control banana root borer, although it was also used to control 

other pests. All registered products containing chlordecone were effectively canceled in 1978.

People living in areas surrounding hazardous waste sites may be exposed to mirex or chlordecone 

primarily via dermal contact with, or ingestion of, contaminated soil since these compounds bind to soil 

particles. The other major means of exposure for people living near hazardous waste sites is ingestion of 

indigenous wildlife since mirex and chlordecone are bioconcentrated in fish and animals. Ingestion of 

mirex or chlordecone from drinking water is unlikely because of their limited solubility in water (Kenaga 

1980). Similarly, inhalation exposure to mirex or chlordecone following volatilization from contaminated 

media is not likely to be a major route of exposure since these chemicals are essentially nonvolatile. For 

the general population, the most likely route of exposure to mirex or chlordecone is via ingestion of 

contaminated food because these chemicals have been observed to persist in soil for decades following 

cessation of application as pesticides. Both of these chemicals are excreted very slowly and 

bioaccumulate in the body after exposure.

1.2 SUMMARY OF HEALTH EFFECTS 

Mirex. Animal studies indicate that mirex exposure may result in a variety of adverse health effects in 

exposed populations. The primary organs affected by mirex in experimental animals include the liver, 

kidneys, selected developmental endpoints, and thyroid (see Figure 1-1). In the liver, mirex causes 

adaptive changes similar to those seen with other chlorinated hydrocarbon insecticides as well as 

decreased hepatobiliary function and decreased glycogen storage. In the kidneys, increases in 

glomerulosclerosis and proteinuria have been observed. Ocular lesions include the development of 

cataracts in the eyes of the young if exposure occurs during a critical period immediately after birth. In 

the thyroid, an increase in cystic follicles or a collapse of follicles has been observed. Decreased fertility 
MIREX AND CHLORDECONE 2

1. RELEVANCE TO PUBLIC HEALTH

and marked developmental toxicity have been observed following exposure to mirex. Mirex exposure 

results in testicular atrophy and reproductive failure. Adverse developmental effects seen in fetuses 

and/or young animals following maternal and/or early postnatal exposure to mirex include cataracts, 

cardiovascular disturbances, visceral anomalies, increased resorptions, and increased stillbirths. Also, 

mirex is a liver carcinogen in animals.

Figure 1-1. Graph of Health Effects Found in Animals Following Oral Exposure to 

Mirex
MIREX AND CHLORDECONE 3

1. RELEVANCE TO PUBLIC HEALTH

Chlordecone. The primary targets of chlordecone toxicity in experimental animals include the liver, 

kidneys, nervous system, reproductive system, endocrine system, and selected developmental endpoints 

(see Figure 1-2). Studies in humans exposed occupationally to chlordecone demonstrate toxic effects on 

the nervous system, liver, and reproductive system. Tremors, unfounded anxiety or irritability, blurring 

of vision, headache, and increases in cerebrospinal fluid pressure were found in workers exposed to high 

levels of chlordecone during its manufacture. In addition, several workers exhibited liver effects such as 

hepatomegaly, evidence of increased microsomal enzyme activity, mild inflammatory changes, and fatty 

degeneration. Reproductive toxicity consisted of decreased sperm and sperm motility. Studies in animals 

have supported these findings and, in addition, have demonstrated adverse effects of chlordecone on the 

kidney and thermoregulation. Animal studies also show effects on the female estrous cycle, uterus, and 

ovaries and decreased viability and development of fetuses. Liver cancer has also been observed in 

animal studies. Animal studies have also demonstrated the potential for greatly potentiated hepatotoxicity 

of haloalkanes such as carbon tetrachloride after exposure to chlordecone. The effects observed in 

occupationally-exposed workers and treated animals were related to chlordecone levels much higher than 

environmentally-relevant levels.

Neurological Effects

Mirex. Animal studies have demonstrated lethargy, weakness, diarrhea, hyperexcitability, tremors, and 

convulsions as a result of mirex exposure (Chu et al. 1981a; Curtis and Hoyt 1984; Fujimori et al. 1983; 

Gaines and Kimbrough 1970; Kendall 1974; Larson et al. 1979a; Mehendale 1981).

Chlordecone. Strong evidence for neurotoxicity of chlordecone has been obtained in human studies. 

Interviews of workers exposed to high levels of chlordecone during its manufacture revealed a high 

percentage of workers with histories of tremors, unfounded nervousness or anxiety, and visual difficulties 

(Cannon et al. 1978). The tremors were characterized as resembling intention tremors and occurred 

mainly in the upper extremities (Taylor 1982, 1985). In more severe cases, the lower extremities were 

involved and gait disturbances were apparent. Peripheral nerve biopsies of the more severely affected 

workers showed decreased numbers of small myelinated and unmyelinated axons in the absence of 

significant myelin abnormalities (Martinez et al. 1978). Although mood and memory disturbances were 

reported by many workers, testing revealed active encephalopathy in only one subject (Taylor 1982, 

1985). Reports of blurring of vision were found to be associated with an opsoclonus-like phenomenon, in 

which rapid random eye movements followed horizontal saccades (Taylor 1982, 1985). This was 

attributed to a loss of inhibitory control of saccadic activity. Headaches were also reported by a number 
MIREX AND CHLORDECONE 4

1. RELEVANCE TO PUBLIC HEALTH

of workers (Taylor 1982, 1985). Cerebrospinal fluid pressure was elevated in three of these individuals, 

and relief of cerebrospinal fluid pressure resulted in amelioration of the headaches (Sanborn et al. 1979).

Figure 1-2. Graph of Health Effects Found in Animals Following Oral Exposure to 

Chlordecone
MIREX AND CHLORDECONE 5

1. RELEVANCE TO PUBLIC HEALTH

Studies in animals have shown similar effects (tremor, exaggerated startle response, gait disturbances) 

(e.g., Aldous et al. 1984; Cannon and Kimbrough 1979; EPA 1986a; Klingensmith and Mehendale 1982a; 

Larson et al. 1979b; NCI 1976; Squibb and Tilson 1982a). 

Hepatic Effects

Mirex. Although human data on the hepatic effects of mirex are minimal, animal studies have shown that 

the liver undergoes both adaptive and toxic changes following oral exposure. The primary toxic effects of 

mirex are inhibition of hepatobiliary excretion (Berman et al. 1986; Davison et al. 1976; Mehendale 1976, 

1977a; Teo and Vore 1991) and depletion of hepatic glycogen stores (Elgin et al. 1990; Ervin and 

Yarbrough 1983; Fujimori et al. 1983; Jovanovich et al. 1987; Kendall 1979). A 28-day study in 

Sprague-Dawley rats reported a decrease in hepatic microsomal aniline hydroxylase. Histopathological 

findings in this study included fatty vacuolation, panlobular ballooning of hepatocytes, moderate lobular 

pattern with perinuclear clear zone, and perivenous cytoplasmic ballooning with anisokaryosis in liver 

(Chu et al. 1980a, 1981b). A 21-month study in Sprague-Dawley rats reported a decrease in hepatic 

microsomal aniline hydroxylase. Histopathological findings in this study included panlobular 

cytoplasmic vacuolation with loss of basophilia, fatty infiltration, and anisokaryosis in liver (Chu et al. 

1981c). F344/N male and female rats fed mirex doses (males: 0.007, 0.07, 0.7, 1.8, 3.8 mg/kg/day; 

females: 0.007, 0.08, 0.7, 2.0, 3.9 mg/kg/day) for 2 years developed histopathological changes, which 

included hepatocytomegaly with eosinophilic cytoplasm observed in males and females at 

>0.7 mg/kg/day. Fatty metamorphosis (cytoplasmic vacuoles consistent with intracellular fat 

accumulation) and necrosis of hepatocytes (focal and centrilobular) were increased in males and females 

at >0.7 mg/kg/day. Dilation of the sinusoids (by blood or proteinaceous material) was observed in males 

at >0.7 mg/kg/day and in females only at the highest dose tested (NTP 1990).

Chlordecone. Guzelian et al. (1980) evaluated liver function in a group of 32 male workers involved in 

the manufacture of chlordecone who exhibited signs or symptoms of chlordecone toxicity and blood 

chlordecone levels ≥600 ng/mL. Twenty of the 32 patients exhibited liver enlargement; common 

histopathological findings on liver biopsy included proliferation of the smooth endoplasmic reticulum, 

increased microsomal enzyme activity, increased serum alkaline phosphatase, lipofuscin accumulation, 

mild inflammatory changes, mild portal fibrosis, fatty infiltration, and/or paracrystalline mitochondrial 

inclusions. Normal results were obtained for serum bilirubin, albumin, globulin, prothrombin time, 

cholesterol, γ-glutamyl transpeptidase, alanine aminotransferase (ALT), and aspartate aminotransferase 

(AST). Sulfobromophthalein clearance was normal (sulfobromophthalein clearance is an indicator of 
MIREX AND CHLORDECONE 6

1. RELEVANCE TO PUBLIC HEALTH

liver function). Within 2–3 years following cessation of exposure, livers appeared normal in size and 

ultrastructural changes had resolved. The study authors considered the hepatic changes to largely 

represent adaptive responses to chlordecone. The results of animal studies support these findings and 

indicate that oral exposure to chlordecone at doses as low as 0.5–5 mg/kg/day may also result in 

decreased hepatobiliary function (Curtis and Hoyt 1984; Curtis and Mehendale 1979; Curtis et al. 1979, 

1981; Mehendale 1977b, 1981; Teo and Vore 1991); decreased hepatic glycogen (Fujimori et al. 1983); 

and increased serum nonprotein nitrogen compounds and enzymes, and decreased serum triglycerides and 

low-density lipoprotein (LDL) cholesterol (Chetty et al. 1993a, 1993b).

Reproductive Effects

Mirex. No studies are available to assess the reproductive effects of mirex in humans. Oral studies in 

animals suggest that both male and female reproductive systems are adversely affected by mirex. 

Reported effects in males include decreased fertility (Khera et al. 1976), decreased seminal vesicle weight 

(Dai et al. 2001), and decreased sperm count and testicular degeneration (Yarbrough et al. 1981). 

Reported effects in females include increased resorptions and failure of pregnancy (Grabowski and Payne 

1980; Khera et al. 1976); decreased ovarian and uterine weights and reduced blood flow to the ovaries, 

uterus, and fetuses (Buelke-Sam et al. 1983); decreased numbers of litters (Gaines and Kimbrough 1970); 

and decreases in mating and litter size (Chu et al. 1981b). Male and female mice treated for 30 days prior 

to mating, and then for an additional 90 days, experienced decreased number of litters per producing pair 

and decreased litter size (Ware and Good 1967).

Chlordecone. Available studies involving human exposure to chlordecone suggest that adverse 

reproductive effects can occur in males as a result of occupational exposure to chlordecone (Guzelian 

1982a; Taylor 1982, 1985; Taylor et al. 1978). Abnormal spermatogenesis has been observed among 

workers exposed at a chemical plant (Guzelian 1982a, 1982b). Chlordecone has demonstrated an 

estrogen-like action in animals (Huber 1965; Uphouse et al. 1984).

Mammalian studies indicate that testicular atrophy can occur at low doses of chlordecone in the diet for 

3 months; doses were well below the level that causes overt maternal toxicity (Larson et al. 1979b). 

Intermediate-duration dietary exposure of female mice at chlordecone doses as low as 2–5 mg/kg/day

resulted in persistent estrus (Huber 1965; Swartz et al. 1988). Chlordecone is well known for its 

estrogenic effects on mammalian reproductive organs when administered by oral (Hammond et al. 1978) 

or parenteral (Johnson et al. 1990; Pinkston and Uphouse 1988; Sierra and Uphouse 1986) routes. The 
MIREX AND CHLORDECONE 7

1. RELEVANCE TO PUBLIC HEALTH

effects of neonatal exposure to chlordecone on reproductive function in rats and mice are similar to those 

seen with prenatal exposure. Multiple injections of chlordecone to neonatal female rats increased 

uterotropic response (Gellert 1978); uterine weights increased in a dose-related manner (Gellert 1978; 

Hammond et al. 1979). Parenteral administration of a daily dose of chlordecone to 1-day-old female 

mouse pups produced cellular proliferation and hypertrophy in the entire reproductive tract and 

keratinization of the vagina within 4 days of treatment in a dose-dependent manner (Eroschenko and 

Mousa 1979).

Renal Effects. Studies in animals indicated an increase in the severity of renal lesions in rats following 

chronic-duration oral exposures to both mirex (NTP 1990) and chlordecone (Larson et al. 1979b).

Endocrine Effects.

Mirex. Result of studies in rats indicate that mirex is toxic to the thyroid. Reversible reduction in colloid 

density, a thickening of follicular epithelium, and angular collapse of the follicles, but no effect on serum 

levels of triiodothyronine (T3) or thyroxine (T4), were reported in rats following repeated oral exposure 

to mirex for ≥28 days (Chu et al. 1980b, 1981a, 1981b). In other studies, ultrastructural analyses of 

thyroids from rats treated for 28 days showed dilation of the rough endoplasmic reticulum and increased 

numbers of columnar cells with irregularly-shaped lysosomal bodies, dilation of cisternae, and increased 

vacuolization (Singh et al. 1982, 1985). Similar effects were observed following dietary exposure for 

148 days (Chu et al. 1981a). Dietary exposure for 2 years also resulted in an increase in cystic follicles in 

male rats (NTP 1990). Studies in animals also indicate that the adrenal gland hypertrophies and releases 

increased levels of corticosterone in response to mirex exposure (Ervin and Yarbrough 1985; Jovanovich 

et al. 1987; Williams and Yarbrough 1983). Other studies in animals have demonstrated increased 

adrenal weight; increased cholesterol, lipid, and protein content (Williams and Yarbrough 1983); 

increased adrenal weight and increased serum adrenocorticotropic hormone (Ervin and Yarbrough 1985; 

Jovanovich et al. 1987); and decreased body fats (Jovanovich et al. 1987).

Chlordecone. Increased relative adrenal weight was observed following a single oral dose of chlordecone 

in rats (Swanson and Wooley 1982). Enlargement of the adrenal gland, with hyperplasia and hypertrophy 

of the cortical cells, was observed in a 30-day dietary study in rats (Cannon and Kimbrough 1979); 

decreased adrenal lipid was observed in a 90-day dietary study in rats (Larson et al. 1979b). Consistent 

with a corticosterone-induced increase in lipid utilization, decreased body fat was observed following 

dietary exposure of rats for 15–20 days (Klingensmith and Mehendale 1982a; Mehendale et al. 1977, 
MIREX AND CHLORDECONE 8

1. RELEVANCE TO PUBLIC HEALTH

1978) or exposure of mice for 33 days (Fujimori et al. 1983). In contrast to the absence of mirex-induced 

effects on the adrenal medulla, oral exposure to chlordecone for 8 days resulted in a decrease in the 

medullary content of epinephrine in rats (Baggett et al. 1980).

Developmental Effects

Mirex. One human study provides suggestive evidence that gestational exposure to mirex may disrupt 

reproductive hormones in boys (Araki et al. 2018). Animal studies demonstrated that prenatal exposure 

to mirex can induce a high incidence of dysrhythmias that can persist into the postnatal period 

(Grabowski 1983). These effects were sufficiently severe to cause some fetal deaths (Grabowski and 

Payne 1983a). Cataracts and other lesions of the lens were induced in young animals exposed to mirex 

during a critical period (between postpartum days 1 and 8) (Chernoff et al. 1979a; Gaines and Kimbrough 

1970; Rogers and Grabowski 1984; Scotti et al. 1981).

Chlordecone. Gestational exposure of rats and mice to chlordecone resulted in increased stillbirths and 

decreased postnatal viability (Chernoff and Kavlock 1982; Chernoff and Rogers 1976; EPA 1986a; Gray 

and Kavlock 1984; Gray et al. 1983; Kavlock et al. 1985; Seidenberg and Becker 1987; Seidenberg et al. 

1986), decreased fetal or neonatal weight and/or skeletal ossification (Chernoff and Kavlock 1982; 

Chernoff and Rogers 1976; EPA 1986a; Gray and Kavlock 1984; Kavlock et al. 1985, 1987a; Seidenberg 

et al. 1986), and anomalies and malformations such as enlarged renal pelvis, undescended testes, enlarged 

cerebral ventricles, clubfoot, fused vertebrae or ribs, and encephalocele (Chernoff and Rogers 1976; 

Kavlock et al. 1985). Anovulation and persistent vaginal estrus were observed in female offspring of 

maternal rats given chlordecone during gestation (Gellert and Wilson 1979). Gestational exposure also 

resulted in subtle neurological changes in the offspring later in life (Rosecrans et al. 1982; Seth et al. 

1981; Squibb and Tilson 1982b).

Body Weight Effects

Mirex. Animal studies show decreases in serum glucose (Chu et al. 1981b; Ervin and Yarbrough 1983; 

Fujimori et al. 1983; Jovanovich et al. 1987; Robinson and Yarbrough 1978a; Williams and Yarbrough 

1983; Yarbrough et al. 1981) and decreases in body weight or body weight gain (Buelke-Sam et al. 1983; 

Byrd et al. 1981; Chadwick et al. 1977; Chernoff et al. 1979b, 1979b; Chu et al. 1981a; Curtis and Hoyt 

1984; Davison et al. 1976; Elgin et al. 1990; Fujimori et al. 1983; Jovanovich et al. 1987; Khera et al. 
MIREX AND CHLORDECONE 9

1. RELEVANCE TO PUBLIC HEALTH

1976; Larson et al. 1979a; Mehendale et al. 1973; NTP 1990; Ritchie and Ho 1982; Rogers and 

Grabowski 1984; Villeneuve et al. 1977).

Chlordecone. Workers exposed to high levels of chlordecone at a facility where it was manufactured 

experienced an unexplained weight loss (Cannon et al. 1978), with losses of up to 60 pounds in 4 months 

in at least one individual (Taylor et al. 1978). Animal studies have also demonstrated weight loss that in 

some cases was quite large (Albertson et al. 1985; Cannon and Kimbrough 1979; Chernoff and Kavlock 

1982; Chernoff and Rogers 1976; Curtis and Hoyt 1984; Curtis and Mehendale 1979; EPA 1986a; 

Fabacher and Hodgson 1976; Huang et al. 1980; Kavlock et al. 1987a; Klingensmith and Mehendale 

1982a; Larson et al. 1979b; Mehendale et al. 1977, 1978; Pryor et al. 1983; Seidenberg et al. 1986; 

Simmons et al. 1987; Smialowicz et al. 1985; Swanson and Wooley 1982; Uzodinma et al. 1984). 

Consistent with the results for mirex, loss of body fat (Fujimori et al. 1983; Klingensmith and Mehendale 

1982a; Mehendale et al. 1977, 1978) and decreased serum glucose levels (Fujimori et al. 1983) were seen.

Cancer. Studies in mice and rats have demonstrated the ability of mirex to cause liver tumors (Innes et 

al. 1969; NTP 1990; Ulland et al. 1977), adrenal gland pheochromocytomas (NTP 1990), and rare renal 

tumors (NTP 1990). A study in mice and rats also showed the ability of chlordecone to increase liver 

tumors (NCI 1976). The U.S. Department of Health and Human Services categorized both mirex and 

chlordecone (Kepone) as reasonably anticipated to be human carcinogens (NTP 2016a, 2016b). EPA has 

classified chlordecone as likely to be carcinogenic to humans (IRIS 2009). Mirex has not been assessed 

for carcinogenicity by EPA (IRIS 1992). The International Agency for Research on Cancer (IARC 1979) 

has classified mirex and chlordecone as Group 2B substances (possibly carcinogenic to humans).

1.3 MINIMAL RISK LEVELS (MRLs)

No data were available from which to derive inhalation MRLs for mirex. As presented in Figure 1-3, 

available data have identified the liver, developmental endpoints, reproductive endpoints, and endocrine 

system as sensitive targets of mirex toxicity following oral exposure. No acute- or intermediate-duration 

oral MRLs were derived for mirex due to inadequacy of available data (see Appendix A). The oral 

database was considered adequate for derivation of a chronic-duration oral MRL for mirex. The MRL 

value is summarized in Table 1-1 and discussed in detail in Appendix A.
MIREX AND CHLORDECONE 10

1. RELEVANCE TO PUBLIC HEALTH

Figure 1-3. Summary of Sensitive Targets of Mirex – Oral

The liver, developmental endpoints, reproductive endpoints, and endocrine system are the most 

sensitive targets of mirex. 

Numbers in circles are the lowest LOAELs (mg/kg/day) for all health effects in animals; no reliable doseresponse data were available for humans.

Table 1-1. Minimal Risk Levels (MRLs) for Mirexa

Exposure duration MRL Critical effect Point of departure

Uncertainty and 

modifying factors Reference

Inhalation exposure (ppm)

Acute Insufficient data for MRL derivation

Intermediate Insufficient data for MRL derivation

Chronic Insufficient data for MRL derivation

Oral exposure (mg/kg/day)

Acute Insufficient data for MRL derivation

Intermediate Insufficient data for MRL derivation

Chronic 0.0003 Liver lesions NOAEL: 0.075 UF: 100

MF: 3

NTP 1990

aSee Appendix A for additional information.

MF = modifying factor; NOAEL = no-observed-adverse-effect level; UF = uncertainty factor
MIREX AND CHLORDECONE 11

1. RELEVANCE TO PUBLIC HEALTH

No data were available from which to derive inhalation MRLs for chlordecone. As presented in

Figure 1-4, available data have identified the liver, endocrine system, kidney, and neurological endpoints

as sensitive targets of chlordecone toxicity following oral exposure. The oral database was considered 

adequate for derivation of acute-, intermediate-, and chronic-duration oral MRLs for chlordecone. The 

MRL values are summarized in Table 1-2 and discussed in detail in Appendix A.

Figure 1-4. Summary of Sensitive Targets of Chlordecone – Oral

The liver, endocrine system, kidney, and neurological system are the most sensitive targets of 

chlordecone.

Numbers in circles are the lowest LOAELs (mg/kg/day) for all health effects in animals; no reliable doseresponse data were available for humans.
MIREX AND CHLORDECONE 12

1. RELEVANCE TO PUBLIC HEALTH

Table 1-2. Minimal Risk Levels (MRLs) for Chlordeconea

Exposure duration MRL Critical effect Point of departure

Uncertainty and 

modifying factors Reference

Inhalation exposure (ppm)

Acute Insufficient data for MRL derivation

Intermediate Insufficient data for MRL derivation

Chronic Insufficient data for MRL derivation

Oral exposure (mg/kg/day)

Acute 0.01 Neurological 

effects

NOAEL: 1.25 100 EPA 1986a

Intermediate 0.003 Neurological 

and male 

reproductive 

effects

NOAEL: 0.26 100 Linder et al. 

1983

Chronic 0.0009 Renal effects NOAEL: 0.089 100 Larson et al. 

1979b

aSee Appendix A for additional information.

NOAEL = no-observed-adverse-effect level
MIREX AND CHLORDECONE 13

CHAPTER 2. HEALTH EFFECTS

2.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective on the toxicology of mirex and 

chlordecone. It contains descriptions and evaluations of toxicological studies and epidemiological 

investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic 

data to public health.

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile.

Mirex and chlordecone are structurally similar insecticides that are derivatives of cyclopentadiene. The 

only structural difference is that mirex has two bridgehead chlorine atoms where chlordecone has a 

carbonyl oxygen atom. As suggested by this similarity in structure, these two chemicals share some 

similarities in their toxicity profiles. However, the toxicity profiles of these two chemicals differ in a 

number of aspects. Therefore, each chemical will be discussed separately below.

To help public health professionals and others address the needs of persons living or working near hazardous 

waste sites, the information in this section is organized by health effect. These data are discussed in terms of 

route of exposure (inhalation, oral, and dermal) and three exposure periods: acute (≤14 days), intermediate 

(15–364 days), and chronic (≥365 days).

As discussed in Appendix B, a literature search was conducted to identify relevant studies examining health 

effect endpoints. Figure 2-1 for mirex and Figure 2-2 for chlordecone provide overviews of the database of 

studies in humans or experimental animals included in this chapter of the profile. These studies evaluate the 

potential health effects associated with inhalation, oral, or dermal exposure to mirex or chlordecone, but may 

not be inclusive of the entire body of literature.

The epidemiological database for mirex and chlordecone consists of a small number of studies reporting 

effects in chlordecone workers and general population studies examining possible associations between 

biomarkers of mirex or chlordecone exposure (serum, cord blood, or breast milk levels) and adverse health 

outcomes. Occupational exposure may have involved the inhalation, oral, and dermal routes, whereas oral 

exposure is the presumed route of exposure for the general population observational studies. The results of 

the observational studies should be interpreted cautiously due to the study limitations. For a number of 
MIREX AND CHLORDECONE 14

2. HEALTH EFFECTS

studies, mirex was detected in <50% of the blood samples; in one study (Everett and Matheson 2010), mirex 

was only detected in approximately 8% of the blood samples. Several studies compared groups with 

mirex/chlordecone levels above the limit of detection to those with levels below the limit of detection. 

Additionally, the observational studies measured exposure at a single point in time, which may not be 

reflective of past exposures. Most of the studies adjusted for some potential confounders such as age, sex, 

body mass index, alcohol consumption, etc. A small number of studies statistically adjusted for exposure to 

other chlorinated pesticides (e.g., DDT and hexachlorobenzene) and polychlorinated biphenyls (PCBs). The 

observational studies do not establish causality between mirex/chlordecone exposure and a health outcome. 

In addition to these limitations, the small number of studies examining a particular health outcome limits the 

interpretation of the study findings. The results of the observational studies for mirex and chlordecone are 

presented in Tables 2-1 and 2-2, respectively. 

Animal inhalation studies are not available for mirex or chlordecone. Animal oral studies are presented in 

Table 2-3 and Figure 2-3 for mirex and Table 2-4 and Figure 2-4 for chlordecone. Animal dermal studies 

are presented in Table 2-5 for mirex and Table 2-6 for chlordecone.

Levels of significant exposure (LSEs) for each route and duration are presented in tables and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. 

LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that 

evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress 

or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, 

or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a 

considerable amount of judgment may be required in establishing whether an endpoint should be 

classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be 

insufficient data to decide whether the effect is indicative of significant dysfunction. However, the 

Agency has established guidelines and policies that are used to classify these endpoints. ATSDR believes 

that there is sufficient merit in this approach to warrant an attempt at distinguishing between "less 

serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is 

considered to be important because it helps the users of the profiles to identify levels of exposure at which 

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not 

the effects vary with dose and/or duration, and place into perspective the possible significance of these 

effects to human health. Levels of exposure associated with cancer (Cancer Effect Levels, CELs) are 

indicated in Table 2-3 and Figure 2-3 for mirex and Table 2-4 and Figure 2-4 for chlordecone.
MIREX AND CHLORDECONE 15

2. HEALTH EFFECTS

A User's Guide has been provided at the end of this profile (see Appendix C). This guide should aid in 

the interpretation of the tables and figures for LSEs and MRLs.

Mirex. Human data regarding potential health effects of mirex exposure are limited to assessment of 

possible associations between mirex blood levels and selected health outcomes. No data were located 

regarding occupational exposure to mirex.

As illustrated in Figure 2-1, human studies related to mirex predominantly evaluated reproductive, 

developmental, and cancer endpoints, as well as diabetes. The human data do not provide exposureresponse data for mirex. Available animal data suggest the following sensitive targets of mirex toxicity:

• Developmental endpoint: Particularly sensitive developmental effects following prenatal and/or 

early postnatal exposure to mirex in animals were cardiac dysrhythmias, cataracts, and other 

lesions of the lens.

• Reproductive endpoint: Studies in animals suggest that both male and female reproductive 

systems are adversely affected by mirex, indicated by histopathologic effects on reproductive 

organs and decreased fertility resulting from mirex treatment of either males or females.

• Hepatic endpoint: In the liver, mirex causes adaptive changes similar to those seen with other 

chlorinated hydrocarbon insecticides as well as decreased hepatobiliary function, decreased 

glycogen storage, and histopathologic lesions.

• Renal endpoint: Increases in glomerulosclerosis and proteinuria have been observed in the 

kidneys of mirex-treated animals.

• Endocrine endpoint: Adverse effects were observed in the thyroid and adrenal glands of mirextreated animals.

• Cancer: The carcinogenicity of mirex has been demonstrated, particularly in the liver of both 

male and female rats and mice.

Chlordecone. Within a single cohort of 133 men exposed to chlordecone during its production in the 

mid-1970s, as many as 76 experienced neurological symptoms. Other effects in some workers included 

oligospermia and liver enlargement. There were no measurements of chlordecone levels in the working 

environment. Industrial hygiene was poor at the facility; therefore, chlordecone exposure may have 

included inhalation, oral, and/or dermal routes. Other human data regarding potential health effects is 

limited to assessments of possible associations between chlordecone blood levels, placental levels, and/or 

levels in maternal milk in studies of a population in Guadeloupe, French West Indies, where chlordecone 

had been used on banana plantations.
MIREX AND CHLORDECONE 16

2. HEALTH EFFECTS

As illustrated in Figure 2-2, human studies related to chlordecone predominantly evaluated reproductive, 

developmental, and neurological endpoints. The human data do not provide exposure-response data for 

chlordecone. Available human and animal data suggest the following sensitive targets of chlordecone 

toxicity:

• Hepatic endpoint: Some people involved in the production of chlordecone exhibited liver effects 

such as hepatomegaly, evidence of increased microsomal enzyme activity, mild inflammatory 

changes, and fatty degeneration.

• Renal endpoint: Increased severity of selected kidney lesions have been observed in rats 

chronically exposed to chlordecone.

• Endocrine endpoint: Chlordecone treatment of animals resulted in effects on the adrenal gland 

that included increased weight, depletion of epinephrine, hyperplasia, loss of adrenal lipid, and 

histopathologic lesions.

• Neurological endpoint: Tremors, unfounded anxiety or irritability, blurring of vision, headache, 

and increases in cerebrospinal fluid pressure were found in workers exposed to high levels of 

chlordecone during its manufacture.

• Reproductive endpoint: Some men involved in the production of chlordecone exhibited decreases 

in sperm count and motility. Adverse effects on the reproductive system have been demonstrated 

in male and female animals exposed to chlordecone.

• Developmental endpoint: Effects such as increased stillbirths, decreased postnatal viability, 

delayed skeletal ossification, selected anomalies and malformations, and subtle neurological 

changes have been associated with gestational exposure to chlordecone in animals.
MIREX AND CHLORDECONE 17

2. HEALTH EFFECTS

*Includes studies discussed in Chapter 2. A total of 161 studies include those finding no effect. Most studies examined multiple endpoints.

Figure 2-1. Overview of the Number of Studies Examining Mirex Health Effects 

Most studies examined the potential body weight, hepatic, and developmental effects of mirex

More studies evaluated health effects in animals than humans (counts represent studies examining endpoint)
MIREX AND CHLORDECONE 18

2. HEALTH EFFECTS

*Includes studies discussed in Chapter 2. A total of 198 studies include those finding no effect. Most studies examined multiple endpoints.

Figure 2-2. Overview of the Number of Studies Examining Chlordecone Health Effects 

Most studies examined the potential body weight, hepatic, and neurological effects of chlordecone

More studies evaluated health effects in animals than humans (counts represent studies examining endpoint)
MIREX AND CHLORDECONE 19

2. HEALTH EFFECTS

Table 2-1. Results of Epidemiological Studies Evaluating Associations Between 

Mirex and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Endocrine Effects

Han et al. 2019

Population-based, case-control 

study using 186 thyroid disease 

patients and 186 controls (without a 

history of thyroid disease) matched 

for age and residential area in 

eastern China

Serum mirex/chlordecone level 

(LOD ≤9.75 ng/L); median 

levels were 2.11 μg/kg lipid for 

cases and 1.55 μg/kg lipid for 

controls; categorized by quartile

Thyroid disease 

risk

↔

Reproductive Effects

Grindler et al. 2015

Cross-sectional survey using 

NHANES data from 1999–2008

Primary analysis: menopausal 

women (>30 years of age) with a 

laboratory assessment of 

endocrine-disrupting chemicals

Secondary analysis: 225 women 

45–55 years of age

Serum mirex level

Minimum: 0.50 ng/g

Median: 3.89 ng/g

90th percentile: 9.46 ng/g

Maximum: 2,960 ng/g

Menopause in 

women >30 years 

of age

↑

Menopause in 

women 45–

55 years of age

↑

Lebel et al. 1998

Case-control study of 86 women 

with endometriosis and 70 controls

Serum mirex level (LOD 0.02–

0.03 μg/L); mirex was 

measurable in 56% of subjects

Cases: 3.4 μg/kg lipids 

Controls: 3.1 μg/kg lipids 

Endometriosis ↔

Upson et al. 2013

Population-based, case-control 

study of endometriosis among 18–

49-year-old enrollees of a health 

care system in Washington State 

(248 surgically-confirmed 

endometriosis cases and 

538 population-based controls)

Serum mirex level (LOD 

10 pg/g; median mirex level 

15.47 pg/g); categorized into 

three groups:

All endometriosis:

Low: ≤10 pg/g

Middle: >10.0–15.47 pg/g

High: >15.47 pg/g

Ovarian endometriosis:

Low: ≤10 pg/g

Middle: >10.0–15.47 pg/g

High: >15.47 pg/g

All endometriosis ↑ (high group)

Ovarian 

endometriosis

↔
MIREX AND CHLORDECONE 20

2. HEALTH EFFECTS

Table 2-1. Results of Epidemiological Studies Evaluating Associations Between 

Mirex and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Developmental Effects

Araki et al. 2018

Prospective birth cohort (Hokkaido 

Study Sapporo Cohort) of 

232 pregnant women (23–

35 weeks of gestation) who 

presented at an obstetrics and 

gynecology hospital between July 

2002 and October 2005, lived in the 

Sapporo City area, planned to 

deliver at the facility, and provided 

maternal serum and cord blood 

samples for analysis of maternal 

organochlorine pesticide levels and 

cord blood levels of selected 

steroid and reproductive hormones

Maternal serum mirex level 

(LOD 0.5 pg/g wet weight).

Minimum: 0.88 pg/g

25th percentile: 4.11 pg/g

50th percentile: 6.04 pg/g

75th percentile: 8.53 pg/g

Maximum: 30.11 pg/g

Testosterone ↓

Cortisol ↓

Cortisone ↓

Prolactin ↓

Testosteroneandrostenedione 

ratio

↓

Androstenedione 

– DHEA ratio

↓

DHEA ↑

FSH ↑

AA-G ratio ↑

FSH-inhibin B 

ratio

↑

Denham et al. 2005

Population-based cohort of 

138 Akwesasne Mohawk Indian 

girls 10–16.9 years of age

Serum mirex level (LOD 

0.02 ppb)

Referent: <0.02 ppb

Low: 0.02–0.03 ppb

High: 0.04–1.17 ppb

Menarcheal status ↔

Fenster et al. 2006

Longitudinal birth cohort study of 

the health of pregnant women 

(n=385) and their children living in 

Salinas Valley, California, and 

enrolled in CHAMACOS; the study 

evaluated possible associations 

between in utero organochlorine 

pesticide exposure (including 

mirex) and fetal growth and length 

of gestation

Presence of detectable mirex 

maternal blood (LOD range 

0.01–0.69 ng/g lipid)

Detected in 85.9% of blood 

samples from 384 women 

(mean level of 0.3 ng/g lipid; 

range 0.04–15.9 ng/g lipid)

Gestation length ↔

Birth weight ↔

Crown-heel length ↔

Fernandez et al. 2007

Nested case-control study of 

48 newborns diagnosed with 

cryptorchidism and/or hypospadias 

and 114 boys without 

malformations matched by 

gestational age, date of birth, and 

parity; subjects were identified at 

Granada University Hospital in 

Granada, Spain 

Presence of detectable mirex in 

placental sample (LOD in the 

range of 0.1–3 ng/mL, not 

otherwise specified in study 

report)

Detected in 12/48 cases (mean 

level of 1.4 ng/mL [SD 1.0]; 

range 1.0–3.0 ng/mL) and 

18/114 controls (mean level of 

3.7 ng/mL [SD 3.7]; range 1.0–

15.0 ng/mL)

Urogenital 

malformations

↑
MIREX AND CHLORDECONE 21

2. HEALTH EFFECTS

Table 2-1. Results of Epidemiological Studies Evaluating Associations Between 

Mirex and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Guo et al. 2014

A total of 81 pairs of mothers and 

newborns enrolled at four hospitals 

in four different cities in China; the 

study evaluated possible 

associations between mirex in 

maternal serum and birth weight 

and between mirex in newborn cord 

serum and birth weight

Maternal serum mirex detected 

in 47/71 samples:

Mean 0.36 ng/g lipid

Median 0.23 ng/g lipid

Minimum <0.4 pg/Ml (LOD)

Maximum 66.36 ng/g lipid)

Birth weight ↔a

Cord serum mirex detected in 

13/60 samples:

Mean 0.27 ng/g lipid

Median <LOD

Minimum <LOD

Maximum 23.94 ng/g lipid)

Birth weight ↔b

Hjermitslev et al. 2020

A total of 482 mother-child pairs 

from the prospective mother-child 

cohort study of pregnant women of 

the ACCEPT program in Greenland

Maternal serum mirex (LOD not 

reported)

Median: 2.70 ng/g lipid; range: 

0.45–120 ng/g lipid)

Birth weight ↔

Gestation age at 

birth

↓

Puertas et al. 2010

Population-based randomlysampled birth cohort (n=104) 

recruited between 2000 and 2002 

in Granada, Spain, and evaluated 

for cognitive development at 4 

years of age

Placental mirex (presence or 

absence, based on LOQ of 

1 ng/mL)

Referent: <1 ng/mL in 

77/104 placentas

High: ≥1 ng/mL in 

27/104 placentas

Median: 1.4 ng/mL; range 0.5–

19.1 ng/mL

Working memory ↓

Quantitative 

functions

↓

Other Noncancer Effects

Aminov et al. 2016

Cross-sectional study of an adult 

Native-American (Mohawk) 

population (224 men and 

377 women, 18–84 years of age; 

41 men and 70 women diabetics)

Serum mirex level (MDL 

0.02 ppb)

Serum mirex <MDL in 16.1% of 

subjects (mean 0.12±0.15 ppb; 

range <MDL–1.67 ppb); 

categorization by quartile

Diabetes risk ↔ 

Codru et al. 2007

Cross-sectional study of an adult 

Native-American (Mohawk) 

population (352 subjects; 

134 males and 218 females ≥30 

years of age; 71 diabetics)

Serum mirex level (MDL 

0.02 ppb)

86.4% of subjects had 

measurable serum mirex levels 

(mean 0.13±0.16 ppb)

Diabetes risk ↔ 
MIREX AND CHLORDECONE 22

2. HEALTH EFFECTS

Table 2-1. Results of Epidemiological Studies Evaluating Associations Between 

Mirex and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Everett and Matheson 2010

Cross-sectional study of 

3,364 participants in 1999–2004 

NHANES survey

Serum mirex level (maximum 

LOD 14.6 ng/g lipid adjusted); 

mirex blood level was above 

the maximum limit of detection 

in 7.7% of participants

Total diabetes risk ↔

Pre-diabetes risk ↔

Rosenbaum et al. 2017

Cross-sectional study of 

548 residents of Anniston, Alabama 

included in the Anniston 

Community Health Survey (68% 

female; mean age 53.6±16.2 years; 

56% white, 44% African American, 

59% met criteria for metabolic 

syndrome)

Exposure: Serum mirex level 

(LOD not specified)

Categorized by quintile (parts 

per trillion, ppt):

Q1: 1.30–24.24 ppt

Q2: 24.25–48.44 ppt

Q3: 48.45–74.16 ppt

Q4: 74.17–128.96 ppt

Q5: 128.97–2,574.40 ppt

Metabolic 

syndrome risk

↔

Son et al. 2010

Selected participants in a 

community-based health survey in 

South Korea; included 40 subjects 

with fasting blood glucose level 

≥126 mg/dL or who were taking 

antidiabetic medication (considered 

type 2 diabetes cases) and 40 ageand sex-matched subjects with 

mean fasting plasma glucose of 

87.7±9.3 mg/dL; average age of 

55.6 years; 52.5% males

Median serum concentration of 

mirex by wet weight 

categorized by tertile:

T1: 6.6 pg/g

T2: 11.7 pg/g

T3: 27.8 pg/g

Diabetes risk ↑ (T3)

Lipid-standardized median 

serum concentration of mirex 

by tertile:

T1: 1.0 ng/g lipid

T2: 2.0 ng/g lipid

T3: 4.5 ng/g lipid

Diabetes risk ↔

Cancer Effects

Itoh et al. 2009

Case-control study of 403 breast 

cancer patients and 403 matched 

pairs at four hospitals in Japan

Lipid-adjusted serum mirex 

concentration; categorized by 

quartile median:

Q1: 1.4 ng/g lipid

Q2: 1.9 ng/g lipid

Q3: 2.4 ng/g lipid

Q4: 3.5 ng/g lipid

Breast cancer ↓
MIREX AND CHLORDECONE 23

2. HEALTH EFFECTS

Table 2-1. Results of Epidemiological Studies Evaluating Associations Between 

Mirex and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Koutros et al. 2015a, 2015b

Nested case-control study using 

data from the population-based 

Janus Serum Bank cohort of 

Norway. Subjects were 149 cases 

of metastatic prostate cancer with 

no history of cancer (except 

nonmelanoma skin cancer) and 

were diagnosed at least 2 years 

after serum collection and 

314 controls matched by region, 

date of blood draw, and age at 

blood draw

Plasma level of mirex (LOD not 

specified); median levels were 

1.8 ng/g lipid (range 0.1–

37.1 ng/g lipid) for cases and 

1.7 ng/g lipid (range 0.1–

18.3 ng/g lipid) for controls; 

categorized by quartile to 

approximate equal numbers of 

cases per quartile

Prostate cancer ↔

Moysich et al. 1998

Subset of 154 cases and 

192 community controls (ages 41–

85 years) from a case-control study 

of postmenopausal breast cancer in 

western New York

Serum mirex based on LOD 

(0.06–0.99 ng/g):

<LOD

>LOD

Post-menopausal 

breast cancer (all 

subjects)

↔

Post-menopausal 

breast cancer 

(never lactated 

subjects)

↔

Post-menopausal 

breast cancer (ever 

lactated subjects)

↔

Sawada et al. 2010

Nested case-control study using 

data from the Japan Public Health 

Center-based Prospective Study. 

Nested case-control subjects were 

201 newly-diagnosed prostate 

cancer cases and 2 controls for 

each case

Plasma level of lipid-adjusted 

mirex (LOD 3.0 pg/g wet) 

categorized by quartile:

Q1: <3.1 pg/g lipid-adjusted

Q2: 3.1–4.0 pg/g lipidadjusted

Q3: 4.1–5.9 pg/g lipidadjusted

Q4: ≥6.0 pg/g lipid-adjusted

Prostate cancer ↔

Spinelli et al. 2007

Population-based case-control 

study in British Columbia, Canada, 

including 422 pretreatment nonHodgkin’s lymphoma cases and 

460 controls

Exposure: Mirex in serum 

(lipid-adjusted) categorized by 

low or high concentration:

Low: ≤1.43 ng/g

High: >1.43–60.46 ng/g

Non-Hodgkin 

lymphoma

↑
MIREX AND CHLORDECONE 24

2. HEALTH EFFECTS

Table 2-1. Results of Epidemiological Studies Evaluating Associations Between 

Mirex and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Wielsoe et al. 2017

Seventy-seven breast cancer 

cases and 84 controls from the 

general population of Inuit women 

from Greenland

Serum mirex (LOD 0.04 or 

0.01 μg/L); median levels were 

25 μg/kg lipid (range 11.15–

74.92 μg/kg lipid) for cases and 

22.65 μg/kg lipid (range 6.08–

47.79 μg/kg lipid) for controls; 

categorized by tertile

Breast cancer ↑ (by serum 

level)

↔ (by tertile)

aSamples with detection rate >50%, but <80% stratified into three groups using LOD and median concentration of 

detected samples as cut points. bSamples with detection rate >20%, but <50% stratified by the LOD value into two groups.

↑ = association; ↓ = inverse association; ↔ = no association; ACCEPT = Adapting to Climate Change, Environmental 

Pollution and Dietary Transition; CHAMACOS = Center for the Health Assessment of Mothers and Children of 

Salinas; DHEA = dehydroepiandrosterone; FSH = follicle-stimulating hormone; LOD = limit of detection or level of 

detection; LOQ = limit of quantitation; MDL = method detection limit; NHANES = National Health and Nutrition 

Examination Survey; Q = quartile; SD = standard deviation; T = tertile
MIREX AND CHLORDECONE 25

2. HEALTH EFFECTS

Table 2-2. Results of Epidemiological Studies Evaluating Associations Between 

Chlordecone and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Cardiovascular Effects

Saunders et al. 2014

Subpopulation of 779 pregnant 

women in the TIMOUN prospective 

mother-child cohort study 

(Guadeloupe, French West Indies) 

between November 2004 and 

December 2007

Serum chlordecone level (LOD 

0.06 μg/L)

Q1: <0.17 μg/L; referent

Q2: 0.17–0.38 μg/L

Q3: 0.39–0.80 μg/L

Q4: >0.80 μg/L

Hypertensive 

disorders during 

pregnancy

↓ (Q3 and Q4)

Pre-eclampsia ↔

Endocrine Effects

Emeville et al. 2013

Population-based, cross-sectional 

study using a random sample of 

277 healthy, non-obese, middleaged men from the French West 

Indies

Serum chlordecone level (LOD 

0.06 μg/L)

Geometric mean: 0.40 μg/L

90th percentile: 1.74 μg/L

Maximum: 44.1 μg/L

Blood steroid 

hormone levels

↔

Han et al. 2019

Population-based, case-control 

study using 186 thyroid disease 

patients and 186 controls (without a 

history of thyroid disease) matched 

for age and residential area in 

eastern China

Serum mirex/chlordecone level 

(LOD ≤9.75 ng/L); median 

levels were 2.11 μg/kg lipid for 

cases and 1.55 μg/kg lipid for 

controls; categorized by quartile

Thyroid disease ↔

Developmental Effects

Boucher et al. 2013

Subpopulation of 141 pregnant 

women in the TIMOUN prospective 

mother-child cohort study 

(Guadeloupe, French West Indies) 

between November 2004 and 

December 2007

Chlordecone cord blood level 

(LOD 0.06 μg/L):

Referent: <0.06 μg/L (LOD)

Low: 0.07–0.24 μg/L

High: 0.24–3.91 μg/L 

ASQ score for 

fine motor 

function

↓ (boys)

Cordier et al. 2015

Subpopulation of 111 pregnant 

women in TIMOUN prospective 

mother-child cohort study 

(Guadeloupe, French West Indies) 

between November 2004 and 

December 2007

Chlordecone cord blood level 

(LOD 0.06 μg/L):

Referent: <0.06 μg/L (LOD)

Low: 0.06–0.31 μg/L

High: ≥0.31 μg/L

Chlordecone in maternal milk 

samples at 3 months 

postdelivery (LOD 0.34 μg/L):

TSH levels at 3 

months of age

↑ (males)

↔ (females)

Free T3 ↔ (males)

↔ (females)

Free T4 ↔ (males)

↑ (females)

Fine motor 

development at 

18 months of age

↓ (boys)

↔ (girls)
MIREX AND CHLORDECONE 26

2. HEALTH EFFECTS

Table 2-2. Results of Epidemiological Studies Evaluating Associations Between 

Chlordecone and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Referent: <0.5 μg/L

Low: 0.5–0.9 μg/L

High: ≥0.9 μg/L

Cordier et al. 2019

Subpopulation of 116 children 

(7 years of age) in TIMOUN 

prospective mother-child cohort 

study (Guadeloupe, French West 

Indies) between November 2004 

and December 2007

Chlordecone in cord blood 

(LOD 0.05 μg/L)

Mean: 0.1 μg/L; range <LOD–

7.4 μg/L (detected in 70.2% of 

104 samples)

Feminine play ↔

Masculine play ↔

Chlordecone in 7-year-old 

childhood blood sample (LOD 

0.02 μg/L)

Mean: 0.04 μg/L; range <LOD–

1.0 μg/L (detected in 70.8% of 

89 samples)

Feminine play ↔

Masculine play ↔

Costet et al. 2015

Subpopulation of 222 pregnant 

women in the TIMOUN prospective 

mother-child cohort study 

(Guadeloupe, French West Indies) 

between November 2004 and 

December 2007 

Chlordecone cord blood level 

(LOD 0.06 μg/L):

Referent: <0.06 μg/L (LOD)

Low: 0.06–0.306 μg/L

High: ≥0.306 μg/L

Body mass index 

in boys at 

3 months

↑

Body mass index 

in girls at 

3 months

↑

Dallaire et al. 2012

Subpopulation of up to 153 infants 

of women in the TIMOUN 

prospective mother-child cohort 

study (Guadeloupe, French West 

Indies) who were pregnant between 

November 2004 and December 

2007

Chlordecone cord blood level 

(LOD 0.06 μg/L):

Referent: <0.06 μg/L (LOD)

Low: >0.06–0.31 μg/L

High: >0.31 μg/L

Novelty preference 

on the Fagan Tests 

of Infant 

Intelligence

↑ (high group)

Risk of obtaining 

low scores on the 

fine motor 

development scale

↑ (detectable 

chlordecone 

levels)

Hervé et al. 2016

Subpopulation of 593 pregnant 

women in the TIMOUN prospective 

mother-child cohort study 

(Guadeloupe, French West Indies) 

between November 2004 and 

December 2007 

Chlordecone cord blood level 

(LOD 0.02 μg/L):

Referent: <0.08 μg/L

Low: 0.08–0.20 μg/L

Medium: 0.20–0.41 μg/L

High: ≥0.41 μg/L

Gestational age ↔
MIREX AND CHLORDECONE 27

2. HEALTH EFFECTS

Table 2-2. Results of Epidemiological Studies Evaluating Associations Between 

Chlordecone and Health Outcomes

Reference, study type, and

population

Exposure Outcome 

evaluated

Result

Kadhel et al. 2014

Subpopulation of 818 pregnant 

women in the TIMOUN prospective 

mother-child cohort study 

(Guadeloupe, French West Indies) 

between November 2004 and 

December 2007 

Chlordecone maternal blood 

level (LOD 0.06 μg/L):

Q1: <0.14 μg/L; referent

Q2: 0.14–0.28 μg/L

Q3: 0.29–0.51 μg/L

Q4: 0.52–0.97 μg/L

Q5: >0.98 μg/L

Gestation length ↓

Preterm birth ↑

Rouget et al. 2019

Subpopulation of pregnant women 

and their newborn from the 

TIMOUN prospective mother-child 

cohort study (Guadeloupe, French 

West Indies) between November 

2004 and December 2007 for 

whom maternal blood samples 

(n=843) and/or cord blood samples 

(n=668) were available for 

evaluation of chlordecone

Exposure: Chlordecone 

maternal blood level (LOD 0.02 

μg/L):

T1: <0.22 μg/L; referent

T2: 0.22–<0.59 μg/L

T3: ≥0.59 μg/L

Risk of 

malformations

↔

Chlordecone cord blood level 

(LOD 0.02 μg/L):

T1: <0.10 μg/L; referent

T2: 0.10–<0.32 μg/L

T3: ≥0.32 μg/L

Risk of 

malformations

↔

Risk of 

undescended 

testes

↔

Other Noncancer Effects

Saunders et al. 2014

Subpopulation of 779 pregnant 

women in the TIMOUN prospective 

mother-child cohort study 

(Guadeloupe, French West Indies) 

between November 2004 and 

December 2007

Exposure: Serum chlordecone 

level (LOD 0.06 μg/L)

Q1: <0.17 μg/L; referent

Q2: 0.17–0.38 μg/L

Q3: 0.39–0.80 μg/L

Q4: >0.80 μg/L

Diabetes during 

pregnancy

↔

Cancer Effects

Multigner et al. 2010

Population-based case-control 

study of 623 prostate cancer cases 

and 671 controls in Guadeloupe, 

French West Indies

Plasma chlordecone level (LOD 

0.25 μg/L):

Q1: ≤0.25 μg/L (LOD); referent

Q2: >0.25–0.47 μg/L

Q3: >0.47–0.96 μg/L

Q4: >0.96 μg/L

Prostate cancer ↑ (Q4)

Prostate cancer 

(family history of 

prostate cancer)

↑ (Q4)

Prostate cancer 

(past residence in 

western 

countries)

↑ (Q4)

↑ = association; ↓ = inverse association; ↔ = no association; ASQ = Ages and Stages Questionnaire; LOD = limit of 

detection or level of detection; Q = quartile or quintile; T= tertile; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid 

stimulating hormone
MIREX AND CHLORDECONE 28

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

ACUTE EXPOSURE

1 Rat

(SpragueDawley)

36 M

8 days

ad lib

(F)

0, 17 BI, HP Endocr 17

Baggett et al. 1980

2 Rat

(SpragueDawley)

5–11 M

3 days

1 time/day 

(GO)

0, 50 OF Hepatic 50 Impaired biliary excretion 

of glucuronide conjugates; 

increased bile flow

Berman et al. 1986

3 Rat

(CD) 

6–7 F

GDs 5, 5–9, 

5–14 

1, 5, or 

10 days

1 time/day

(GO)

0, 10 BW, DX, OF, 

OW

Bd wt 10 35–52% decrease in 

maternal weight gain

Cardio 10 Significant decrease of 

maternal cardiac output 

and heart weight

Hepatic 10 Significant increase in 

maternal liver weight

Immuno 10 32% decrease in maternal 

spleen weight

Repro 10 Decreased blood flow to 

ovaries, uterus, and 

fetuses; decreased 

ovarian and uterine weight

Develop 10 Decreased pup viability 

and pup weight; increased 

resorptions; fetal edema

Buelke-Sam et al. 1983
MIREX AND CHLORDECONE 29

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

4 Rat

[CRLCOBS;CD

(SD)]

20–30 F

GDs 5–14 or 

6–15

1 time/day

(GO)

0, 10 BW, DX, LE, 

OW

Death 10 24–25% maternal 

mortality

Bd wt 10 >30% depressed maternal

body weight

Repro 10 Decreased gravid uterine 

weight

Develop 10 >59% fetuses with edema; 

increased prenatal 

mortality; >20% decrease 

in pup body weight

Byrd et al. 1981

5 Rat

(CD)

10–38 F

GDs 7–16

1 time/day 

(GO)

0, 5, 7, 9.5, 

19, 38

BW, DX, LE Death 9.5 16% maternal mortality

Bd wt 7 9.5 36% decrease in maternal 

weight gain

Develop 5 7 9.5 Delayed ossification; 

edematous live fetuses 

(7 mg/kg); enlarged 

cerebral ventricles and 

undescended testes 

(9.5 mg/kg)

Chernoff et al. 1979b

6 Rat

(LongEvans)

10–45 F

PPDs 1–4

1 time/day 

(GO)

1, 2.5, 5, 10 BW, DX, LE, 

OP

Develop 10 F 35–36% mortality and 

cataracts in pups

Chernoff et al. 1979b

7 Rat

(LongEvans)

3–20 F

Once

GD 1, 2, 3, 4, 

5, 6, 7, 8, 10, 

or 14

(GO)

0, 10, 15 OP Develop 10 Cataracts in pups at 

postnatal days 12–14

Chernoff et al. 1979b
MIREX AND CHLORDECONE 30

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

8 Rat

(SpragueDawley)

4 or 8 NS

14 days

ad lib

(F)

0, 0.6, 6 BW, OF, OW Bd wt 6

Hepatic 6 Disruption of liver cord 

cells; focal stasis; central 

or midzonal hepatocellular 

necrosis

Davison et al. 1976

9 Rat

(Wistar)

7–29 M

7–29 F

3–7 days

ad lib

(F)

0, 4, 1,500, 

2,000

BI, BW, OW Bd wt 4 1,500 16–17% decrease in body 

weight gain

Hepatic 4 1,500 Decreased hepatic 

glycogen; increased lipid 

accumulation

Elgin et al. 1990

10 Rat

(SpragueDawley)

5–20 M

Once

(GO)

0, 100 BC, BI, BW,

HE, OF, OW

Hemato 100 12% decreased 

hematocrit

Hepatic 100 Significantly decreased 

hepatic glycogen

Other 

noncancer

100 Decreased blood glucose

Ervin and Yarbrough 1983

11 Rat

(SpragueDawley)

3–11 M

Once

(GO)

0, 100 BC, BW, OW Endocr 100 88% increase in serum 

adrenocorticotropic 

hormone

Ervin and Yarbrough 1985

12 Rat

(Sherman)

NS M, F

Once

(GO; corn oil)

NS LE Death 740 M

600 F

LD50

LD50 >3,000 mg/kg with 

peanut oil as vehicle

Gaines 1969
MIREX AND CHLORDECONE 31

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

13 Rat

(Sherman)

10 F

Once

(GO)

8 dose 

levels; lowest 

dose tested: 

50 mg/kg

LE Death 365 LD50

Gaines and Kimbrough 1970

14 Rat

(LongEvans)

3–11 F

GDs 8.5–

15.5 or 6.5–

15.5

1 time/day 

(GO)

0, 5, 6, 7, 10 DX, OF Develop 5 First-degree heart block in 

fetuses; decreased 

number of litters at 

10 mg/kg/day

Grabowski and Payne 1980

15 Rat

(LongEvans)

NS F

GDs 8.5–

15.5

1 time/day 

(GO)

0, 6 DX Develop 6 36% edematous fetuses

Grabowski 1981

16 Rat

(LongEvans)

NS F

GDs 8.5–

15.5 or 15.5–

21.5

1 time/day 

(GO)

0, 0.1, 0.25, 

0.5, 1, 1.5, 3, 

6

DX, FX Develop 0.1 Cardiac arrhythmia

Grabowski 1983

17 Rat

(LongEvans)

8–17 F

GDs 8.5–

15.5

1 time/day 

(GO)

0, 6 BW, DX Develop 6 23% stillborn pups; 

dyspnea; cardiac rhythm 

blockade

Grabowski and Payne 1983a

18 Rat

(LongEvans)

9–13 F

GDs 8.5–

15.5

1 time/day

(GO)

0, 6 DX Develop 6 First degree heart block in 

fetuses; 14% increased 

fetal mortality

Grabowski and Payne 1983b
MIREX AND CHLORDECONE 32

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

19 Rat

(SpragueDawley)

6 M

Once

(GO)

0, 50 BC, BI, OF Hepatic 50 Increased bile flow rate

Hewitt et al. 1986a

20 Rat

(Wistar)

10–29 M

10–29 F

7 days

ad lib

(F)

0, 4 BC, BI, OF, 

OW

Hepatic 4 Two-fold increase in liver 

weight; increased 

cholesterol and 

triglycerides

Jovanovich et al. 1987

21 Rat

(Wistar)

7 F

4 days

(F)

0, 2,100 BC, BI, BW, 

OW

Bd wt 2,100 30% lower mean body 

weight; 77% reduction in 

body fat

Hepatic 2,100 Two-fold increase in liver 

weight and serum 

triglycerides; 25% 

decreased in liver 

glycogen and glucose

Endocr 2,100 Two-fold increase in 

adrenal weight

Other 

noncancer

2,100 Reduced food intake; 88% 

reduction in serum 

glucose

Jovanovich et al. 1987

22 Rat

(Mai-Wistar)

50 M

Once

(GO)

0, 200 BI, OF Hepatic 200 Hepatic glycogen 

depletion; periportal 

liposis; degeneration of 

endoplasmic reticulum

Kendall 1979

23 Rat

(Wistar)

18–20 F

GDs 6–15

1 time/day 

(GO)

0, 1.5, 3, 6, 

12.5

LE, OF Death 6 4/20 maternal rats died

Repro 12.5 Pregnancy failure in 45% 

of dams

Khera et al. 1976
MIREX AND CHLORDECONE 33

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

24 Rat

(Wistar)

20 M

10 days

1 time/day 

(GO)

0, 1.5, 3, 6 OF Repro 3 6 Significantly decreased 

fertility

Khera et al. 1976

25 Rat

(SpragueDawley)

3 M

Once

(GO)

0, 10 BI Hepatic 10

Klingensmith and Mehendale 1983a

26 Rat

(SpragueDawley)

3 M

Once

(GO)

0, 20 BI, OF Hepatic 20 Induction of P450b and 

P450e mRNAs in liver

Kocarek et al. 1991

27 Rat

(CD-1)

8 M, 8 F

5 days

1 time/day 

(GO)

0, 5, 10, 25, 

50

LE, CS, GN Death 50 2/8 females died

Mehendale et al. 1973

28 Rat

(SpragueDawley

3–4 M

3 days

1 time/day 

(GO)

0, 50 OF Hepatic 50 Suppressed biliary 

excretion; increased bile 

flow

Mehendale 1977a

29 Rat

(SpragueDawley)

6 F

1 days

1 or 2 times

(GO)

0, 1.2, 3.6, 

12, 36, 60, 

90, 120, 180, 

240

BI, OF Hepatic 240 Increased serum ALT

Mitra et al. 1990

30 Rat

(SpragueDawley)

6 M

3 days

1 time/day 

(GO)

0, 0.5, 2, 10 BC, BI, HP, 

OW

Hepatic 10 Swollen hepatocytes

Renal 10

Plaa et al. 1987
MIREX AND CHLORDECONE 34

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

31 Rat

(SpragueDawley)

5–12 M

Once

(GO)

0, 8 BC, BI, OF,

OW

Hepatic 8

Other 

noncancer

8 Decreased blood glucose

Robinson and Yarbrough 1978a

32 Rat

(LongEvans)

NS F

GDs 8–15

1 time/day 

(GO)

0, 6 BI, DX, HP Develop 6 F Cataracts in 49.6% of 

fetuses; 14% fetal 

mortality on GD 21

Rogers and Grabowski 1983

33 Rat

(LongEvans)

3–12 F

PPDs 1–4

1 time/day 

(GO)

0, 10 BW HP BI Develop 10 F 10–20% decrease in pup 

weight; cataracts

Rogers and Grabowski 1984

34 Rat

(LongEvans)

5–7 F

GDs 8–15

1 time/day

(GO)

0, 6 BC, DX, HE Develop 6 Decrease in fetal 

hematocrit and plasma 

glucose

Rogers et al. 1984

35 Rat

(Sherman)

NS

PPDs 1–4

1 time/day 

(GO)

0, 5 DX, HP, OP Develop 5 Neonatal cortical 

degeneration and necrosis 

in lens of eye

Scotti et al. 1981

36 Rat

(SpragueDawley)

7–10 F

Once

(GO)

0, 100 BC, BI, OF Hepatic 100 Decreased hepatic 

glutathione

Sunahara and Chiesa 1992
MIREX AND CHLORDECONE 35

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

37 Rat

(SpragueDawley)

4–8 F

3 days

1 time/day

(GO)

0, 12.5, 25, 

50

BI, OF Hepatic 12.5 Decreased hepatic ion 

transport

Teo and Vore 1990

38 Rat

(SpragueDawley)

5–8 M

3 days

1 time/day 

(GO)

0, 50 BI, BW, OF, 

OW

Hepatic 50 Decreased biliary function; 

decreased bile flow; 

decreased concentration 

and secretion of bile acid

Teo and Vore 1991

39 Rat

(SpragueDawley)

6 M

14 days

1 time/day 

(GO)

0, 0.1, 1.0, 

10

BC, BI, BW,

FI, HE, HP,

OW

Bd wt 10 55% decrease in body 

weight gain

Hemato 10

Hepatic 1 Significantly increased 

relative liver weight; 

significantly increased 

serum lactic 

dehydrogenase 

Villeneuve et al. 1977

40 Rat

(SpragueDawley)

5–7 M

Once

(GO)

0, 20, 50, 

100, 150

BI, OW Hepatic 50 Two-fold increase in liver 

weight

Other 

noncancer

20 Increased serum 

corticosterone

Williams and Yarbrough 1983

41 Mouse

(CD-1)

10–25 F

PPDs 1–4

1 time/day 

(GO)

0, 1.5, 3.0, 

6.0, 9.0

DX Develop 6 32% pup mortality

Chernoff et al. 1979b
MIREX AND CHLORDECONE 36

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

42 Mouse

(CD-1)

NS

PPDs 1–4

1 time/day 

(GO)

0, 1.5, 3.0, 

6.0, 9.0

DX Develop 1.5 3 11–14% lower pup weight 

at 1.5 mg/kg/day; 

cataracts in pups at 

3 mg/kg/day; decreased 

pup viability at 

6 mg/kg/day

Chernoff et al. 1979b

43 Mouse

(CD-1)

24–25 F

GDs 8–12

1 time/day 

(GO)

0, 7.5 BW, DX, MX Develop 7.5 Increased mortality.

Decreased pup weight on 

LDs 1 and 3

Chernoff and Kavlock 1982

44 Mouse

(C57BL/6)

23–32 M

2 days

1 time/day 

(GO)

0, 30 BC, BI Hepatic 30 Elevated serum ALT and 

AST

Fouse and Hodgson 1987

45 Mouse

(ICR)

15 M

14 days

1 time/day 

(GO)

0, 10, 25, 50 BW, FI, LE, 

WI

Death 10 12/15 rats died

Bd wt 10 >10% decrease in body 

weight

Other 

noncancer

10 20% decrease in plasma 

glucose; decreased food 

and water consumption

Fujimori et al. 1983

46 Mouse

(ICR)

3–8 M

PPDs 54 and 

58

(GO)

0, 10, 25 BC, BI Hepatic 10 25 Decreased hepatic 

glycogen

Other 

noncancer

10 25 Decreased serum glucose 

and lactate; decreased 

free fatty acids

Fujimori et al. 1983

47 Mouse

(CD-1)

NS F

GDs 8–12

1 time/day 

(G)

0, 7.5 BH, BW, DX, 

FX, MX, OF, 

OW, TG

Develop 7.5 56% increased mortality in 

pups

Gray et al. 1983
MIREX AND CHLORDECONE 37

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

48 Mouse

(Swiss 

Webster)

6–16 M

Once

(GO)

0, 10, 50, 

250

HP, OW Hepatic 50 Slight hepatocyte 

vacuolization and loss of 

basophilic staining

Renal 50

Hewitt et al. 1979

49 Dog

(Mongrel)

1–5 M

Once

(GO)

125, 250, 

500, 750, 

1,000, 1,250, 

1,500

LE Death 1,250 3/5 dogs died

Larson et al. 1979a

INTERMEDIATE EXPOSURE

50 Rat

(SpragueDawley)

4–5 M

15s days

ad lib

(F)

0, 0.95 BC, BI, HP, 

OW

Hepatic 0.95 Decreased hepatobiliary 

function

Bell and Mehendale 1985

51 Rat

(CD)

17–21 F

PPDs 1–46

ad lib

(F)

0, 2 DX, OP Develop 2 Cataracts, outlined lenses, 

increased still births, 10–

19% decreased postnatal 

growth

Chernoff et al. 1979a

52 Rat

(CD)

21–24 F

GD 4–

PPD 46

ad lib

(F)

0, 2 DX Develop 2 Decreased postnatal 

viability; increased 

stillbirths, cataracts, and 

outlined lenses

Chernoff et al. 1979a
MIREX AND CHLORDECONE 38

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

53 Rat

(SpragueDawley)

10 M

28 days

ad lib

(F)

0, 0.086 BC, BI, BW, 

CS, FI, HE, 

HP

Bd wt 0.086

Hemato 0.086

Hepatic 0.086

Renal 0.086

Endocr 0.086

Other 

noncancer 

0.086

Chu et al. 1980b

54 Rat

(SpragueDawley)

5 M, 5 F

28 days

ad lib

(F)

0, 6.2 BC, BW, CS, 

FI, HE, HP, 

OF, OW

Bd wt 6.2

Hepatic 6.2 >34% increased liver 

weight; histopathologic 

liver lesions (e.g., 

hepatocellular 

hypertrophy, 

anisokaryosis, fatty 

vacuolation)

Endocr 6.2 Thyroid lesions (e.g., 

reduced colloid density 

with collapse of follicles, 

increased epithelial 

height)

Chu et al. 1980c
MIREX AND CHLORDECONE 39

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

55 Rat

(SpragueDawley)

15 M, 20 F

M: 91 days 

premating, 

15 days

mating

(106 days)

F: 91 days 

premating,

15 days

mating, 

gestation, 

lactation

(148 days)

ad lib (F)

Premating 

and mating:

0, 0.49, 0.98, 

2, 3

BC, BW, DX, 

FI, GN, HE, 

HP, MX, OF, 

OW

Hemato 2

Hepatic 0.49 Dose-related increased 

incidence and severity of 

histopathologic liver 

lesions

Endocr 0.49 Dose-related increased 

incidence and severity of 

histopathologic thyroid 

lesions

Neuro 2 3 Hypoactivity, irritability, 

tremors

Repro 0.49 Dose-related decreased 

numbers of females 

exhibiting sperm in vaginal 

smears; dose-related 

decreased litter size

Develop 0.49 Cataracts in 4/10 female 

pups (0/14 controls) at 

0.25 mg/kg/day; 

significantly decreased 

21-day pup survival at 

1 mg/kg/day

Chu et al. 1981b
MIREX AND CHLORDECONE 40

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

56 Rat

(SpragueDawley)

10M

28 d 

ad lib

(F)

0, 0.25, 2.5 BC, BW, CS, 

EA, GN, HE,

HP, LE, OW

Hemato 2.5

Hepatic 0.25 Liver lesions (fatty 

infiltration, cytoplasmic 

vacuolation, anisokaryosis 

and necrosis of 

hepatocytes)

Endocr 0.25 Thyroid lesions (thickening 

of follicular epithelium; 

loss of colloid and 

collapse of follicles)

Other 

noncancer

0.25 Decreased serum glucose

Chu et al. 1981a

57 Rat

(SpragueDawley)

3–11 M

15 days

(F)

0, 1.6, 8.2 BW, CS, OF Bd wt 1.6 8.2 39% decreased mean 

body weight gain

Hepatic 1.6 Impaired biliary excretion

Neuro 1.6 8.2 Lethargy

Curtis and Hoyt 1984

58 Rat

(SpragueDawley)

5–6 M

15 days

ad lib

(F)

0, 0.9 BC, BW, CS, 

HP, OW

Hepatic 0.9

Curtis et al. 1981

59 Rat

(SpragueDawley)

5 M

15 days

ad lib

(F)

0, 0.88 BW, CS, EA, 

FI, HP, OF, 

OW

Bd wt 0.88

Hepatic 0.88

Curtis and Mehendale 1980
MIREX AND CHLORDECONE 41

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

60 Rat

(SpragueDawley)

8 NS

28 days

ad lib

(F)

0, 0.6, 6 BW, HP, OF Bd wt 6 15% lower mean final 

body weight than controls

Hepatic 0.6 Disruption of liver cord 

cells; focal bile stasis; 

central or midzonal 

hepatocellular necrosis

Davison et al. 1976

61 Rat

(ZivacMiller)

15–30 NS

NS

5–

6 days/week

1 time/day 

(GO)

5, 12.5, 25 BH, CS Neuro 5 Decrease in operant 

behavior

Dietz and McMillan 1979

62 Rat

(Sherman)

10 F

90 days

ad lib

(F)

5.7, 11, 17, 

23, 28

LE Death 5.7 LDLO

Gaines and Kimbrough 1970

63 Rat

(Sherman)

10 M, 10 F

166 days

ad lib

(F)

M: 0, 0.04–

0.09, 0.21–

0.48, 1.3–3.1

F: 0.06–0.1, 

0.31–0.49, 

1.8–2.8

BI, HP, OF, 

OW

Hepatic 0.48 1.3 Bile stasis; decreased 

hepatic glycogen, 

multinucleation

Gaines and Kimbrough 1970
MIREX AND CHLORDECONE 42

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

64 Rat

(Sherman)

10 M, 10 F

2-generation

repro

ad lib

(F)

M: 0, 1.3–3.1 

F: 0, 1.8–2.8, 

0.31–0.49

DX, OF Repro 0.31 1.8 Decreased number of 

litters and number of live 

births from mirex-treated 

maternal rats only

Develop 0.31 1.8 Cataracts, decreased live 

births, increased mortality 

through weaning among 

pups from mirex-treated 

maternal rats only

Gaines and Kimbrough 1970

65 Rat

(Charles 

River)

10 M, 10 F

13 weeks

ad lib

(F)

0, 0.43, 1.7, 

6.9, 28, 110

LE, CS, BW, 

HE, HP

Death 110 M: 50% mortality

F: 100% mortality

Bd wt 28 110 M: 33–34% lower mean 

final body weight than 

controls

Hemato 6.9 28 Decreased hemoglobin

Hepatic 1.7 6.9 Hepatocellular vacuolation

Renal 110

Neuro 28 110 Hyperexcitability, tremors, 

convulsions

Larson et al. 1979a

66 Rat

(SpragueDawley)

5M

<30 days

ad lib

(F)

0, 10 CS, OF, OW Gastro 10 Diarrhea

Hepatic 10 Impaired biliary excretion

Neuro 10 Lethargy

Mehendale 1981

67 Rat

(SpragueDawley)

10 M

28 days

ad lib

(F)

0, 0.67, 6.7 HP Endocr 0.67 6.7 Increase in large 

irregularly shaped 

lysosomes in the thyroid

Singh et al. 1982
MIREX AND CHLORDECONE 43

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

68 Rat

(SpragueDawley)

10 M

28 days

ad lib

(F)

0, 0.67, 6.7 OF Endocr 0.67 Dilation of rough 

endoplasmic reticulum 

cisternae of thyroid in 

weanling rats

Singh et al. 1985

69 Rat

(LongEvans)

3–5 M

61–113 days

ad lib

(F)

0, 1.2 NX Neuro 1.2

Thorne et al. 1978

70 Rat

(SpragueDawley)

10 M

28 days

ad lib

(F)

0, 0.043, 

0.43, 4.3, 6.5

BC Hemato 6.5

Hepatic 6.5

Endocr 0.43 4.3 Significantly decreased 

serum thyroid T3

Repro 4.3 6.5 Hypocellularity of the 

seminiferous tubules; 

testicular degeneration

Yarbrough et al. 1981

71 Mouse

(CD-1)

3 M

21 days

(G)

0, 5 BW, OW Bd wt 5

Hepatic 5 >2-fold increase in mean 

absolute liver weight

Repro 5 27% decrease in mean 

absolute seminal vesicle 

weight

Dai et al. 2001

72 Mouse

(ICR)

15 M

15 days

1 time/day

(GO)

0, 10 LE Death 10 100% mortality

Fujimori et al. 1983
MIREX AND CHLORDECONE 44

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

73 Mouse

(SwissWebster)

6 M

15 days

ad lib

(F)

0, 1.9 BW, OW, FI,

HP, BC, BI

Bd wt 1.9

Hepatic 1.9

Mehendale et al. 1989

74 Mouse

(BALB/c) 

(CFW)

43–50 M

43–50 F

120 days

ad lib

(F)

0, 0.94 OR Repro 0.94

Ware and Good 1967

75 Mouse

(BALB/c)

102–108 M, 

102–108 F

120 days

ad lib

(F)

0, 0.65 OR Repro 0.94

Ware and Good 1967

76 Dog

(Beagle)

2 M, 2 F

13 weeks

ad lib

(F)

0, 0.19, 0.95, 

4.8

HE, UR, HP,

BW

Bd wt 0.95 4.8 58–74% decrease in body 

weight gain

Hemato 0.95 4.8 Increased hematocrit and 

leukocyte count

Hepatic 0.95 4.8 Increased serum alkaline 

phosphatase, impaired 

biliary excretion

Renal 4.8

Larson et al. 1979a

77 Gerbil

(Mongolian)

4–5 M

15 days

ad lib

(F)

0, 0.9 BC, BI Hepatic 0.9

Cai and Mehendale 1990
MIREX AND CHLORDECONE 45

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

CHRONIC EXPOSURE

78 Rat

(SpragueDawley)

10 M, 10 F

21 months

ad lib

(F)

0, 0.073, 

0.37

BC, BW, CS, 

FI, GN, HE, 

HP, LE, OW

Bd wt 0.37

Hemato 0.37

Hepatic 0.37

Chu et al. 1981c

79 Rat

(F344/N)

First study: 

52 M, 52 F

Second 

study: 52 F

2 years

ad lib

(F)

First study:

Combined 

sexes: 0, 

0.007, 0.075, 

0.75, 1.95, 

3.85

Second 

study:

F: 0, 3.9, 7.7

BW, CS, FI, 

GN, HP, LE

Death 1.95 63% mortality in males

Bd wt 1.95 3.85 Up to 17–18% lower mean 

body weight

Hepatic 0.075b 0.75 Focal and centrilobular 

necrosis; fatty 

metamorphosis; dilation of 

sinusoids

Renal 0.075 0.75 Increased incidence of 

epithelial hyperplasia of 

the renal pelvis at 

0.75 mg/kg/day; increased 

severity of nephrotoxicity

at 1.95 mg/kg/day

Cancer 0.75 CEL: neoplastic liver 

nodules in males, 

mononuclear cell leukemia 

in females 

NTP 1990
MIREX AND CHLORDECONE 46

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

80 Rat

(CD)

20 or 26 M

20 or 26 F

18 months

followed by 

6 months of

recovery

ad lib

(F)

0, 3.6, 7.2 BW, GN, HP, 

LE

Death 7.2 Decreased survival of 

males and females after 

treatment week 52

Bd wt 7.2

Hepatic 3.6 Megalocytosis in the liver 

of 14/26 males and 

8/26 females; no 

incidences among controls

Cancer 7.2 CEL: neoplastic nodules in 

the liver of 7/26 males

(0/20 controls); 

hepatocellular carcinoma 

in 4/26 males

Ulland et al. 1977
MIREX AND CHLORDECONE 47

2. HEALTH EFFECTS

Table 2-3. Levels of Significant Exposure to Mirex – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

81 Mouse

(C57BL/6 x 

C3H/ANF) 

(C57BL/6 x 

AKR)

18 M, 18 F

21 days by 

gavage, in 

food until 

terminal 

sacrifice at 

weeks 59–70

0, 4.8 (TWA) LE Death 4.8 100% mortality; 11% in 

controls

Cancer 4.8 CEL: hepatomas in males 

and females of both 

mouse strains

Innes et al. 1969

aThe number corresponds to entries in Figure 2-3; differences in levels of health effects and cancer effects between male and females are not indicated in 

Figure 2-3. Where such differences exist, only the levels of effect for the most sensitive gender are presented. bUsed to derive a chronic-duration oral minimal risk level (MRL) of 0.0003 mg/kg/day for mirex; dose divided by an uncertainty factor of 100 (10 for extrapolation 

from animals to humans, and 10 for human variability) and modifying factor of 3 (to protect for developmental toxicity); see Appendix A for more detailed 

information regarding the MRL.

ad lib = ad libitum; ALT = alanine aminotransferase; AST = aspartate aminotransferase; Bd wt or BW = body weight; BC = serum (blood) chemistry; 

BH = behavioral; BI = biochemical changes; Cardio = cardiovascular; CEL = cancer effect level; CS = clinical signs; Develop = developmental; 

DX = developmental toxicity; EA = enzyme activity; Endocr = endocrine; (F) = feed; F = female(s); FI = food intake; FX = fetal toxicity; (G) = gavage-not specified;

GD = gestation day; (GF) = gavage or diet; GN = gross necropsy; (GO) = gavage-oil; HE = hematology; Hemato = hematological; HP = histopathology; 

Immuno = immunological; LD = lactation day; LD50 = lethal dose, 50% kill; LDL0 = lowest lethal dose; LE = lethality; LOAEL = lowest-observed-adverse-effect 

level; M = male(s); MX = maternal toxicity; Neuro = neurological; NOAEL = no-observed-adverse-effect level; NS = not specified; OF = organ function; 

OP = ophthalmology;; OW = organ weight; PPD = postpartum day; Repro = reproductive; RNA = ribonucleic acid; T3 = triiodothyronine; TG = teratogenicity; 

TWA = time-weighted average; UR= urinalysis; WI = water intake 
MIREX AND CHLORDECONE 48

2. HEALTH EFFECTS

Figure 2-3. Levels of Significant Exposure to Mirex – Oral

Acute (≤14 days)
MIREX AND CHLORDECONE 49

2. HEALTH EFFECTS

Figure 2-3. Levels of Significant Exposure to Mirex – Oral

Acute (≤14 days)
MIREX AND CHLORDECONE 50

2. HEALTH EFFECTS

Figure 2-3. Levels of Significant Exposure to Mirex – Oral

Intermediate (15–364 days)
MIREX AND CHLORDECONE 51

2. HEALTH EFFECTS

Figure 2-3. Levels of Significant Exposure to Mirex – Oral

Intermediate (15–364 days)
MIREX AND CHLORDECONE 52

2. HEALTH EFFECTS

Figure 2-3. Levels of Significant Exposure to Mirex – Oral

Chronic (≥365 days)
MIREX AND CHLORDECONE 53

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

ACUTE EXPOSURE

1 Rat

(SpragueDawley)

14 M

Once

(GO)

0, 50 BH, BW, CS Bd wt 50 11% weight loss

Neuro 50 Tremors; splaying of legs

Albertson et al. 1985

2 Rat

(SpragueDawley)

4–5 M

Once

(GO)

0, 25, 50, 

100

CS, BI Neuro 50 100 Mild tremors

Aldous et al. 1984

3 Rat

(SpragueDawley)

3–15 M

10 days

1 time/day

(GO)

0, 2.5, 5, 10 BI, CS Neuro 5 10 Mild tremors

Aldous et al. 1984

4 Rat

(SpragueDawley)

15–68 M

8 days

(F)

0, 17 HP, BI Bd wt 17 Depletion of body fat

Endocr 17 Depletion of epinephrine 

in adrenal medulla

Neuro 17 Tremor, hyperexcitability

Baggett et al. 1980

5 Rat

(CD)

26–42 F

GDs 7–16 

1 time/day

(GO)

0, 2, 6, 10 BW, DX, LE, 

OW

Death 10 19% maternal mortality

Bd wt 2 15% decrease in maternal 

body weight gain

Develop 6 10 Increased number of 

fetuses with enlarged 

renal pelvis, edema, 

undescended testes, or 

enlarged cerebral 

ventricles; reduced fetal 

weight, reduced 

ossification

Chernoff and Rogers 1976
MIREX AND CHLORDECONE 54

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

6 Rat

(LongEvans)

5 F

4 days

1 time/day

(GO)

0, 15 DX, LE Death 15 40% mortality

Develop 15

Chernoff et al. 1979b

7 Rat

(SpragueDawley)

3–7 M

Once

(GO)

0, 5 BC, BI, BW,

OF, OW

Hepatic 5

Davis and Mehendale 1980

8 Rat

(SpragueDawley)

6 M

10 days

1 time/day

(GO)

0, 2.5, 5, 10 BI Neuro 10 25 Decreased dopamine 

binding and uptake; 

decreased norepinephrine 

uptake

Desaiah 1985

9 Rat

(SpragueDawley)

4 NS

10 days

(F)

0, 2.5, 5, 10 BI Neuro 2.5 >20% decreased total 

brain calmodulin

Desaiah et al. 1985

10 Rat

(SpragueDawley)

50 M

Once

(GO)

0, 72–98 CS, OF Musc/skel 72–98 Muscle weakness

Neuro 72–98 Tremors; hyperexcitability; 

abnormal gait

Egle et al. 1979

11 Rat

(NS)

6 NS

Once

(G)

0, 40 BH, BI, HP Neuro 40 Tremors

End et al. 1981
MIREX AND CHLORDECONE 55

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

12 Rat

(Fischer344)

10–14 M

10 days

1 time/day

(GO)

0, 0.625, 

1.25, 2.5, 5, 

10

BC, BW, OF, 

OW

Bd wt 5 10 10% lower mean terminal 

body weight 

Hepatic 5 10 Increased serum alkaline 

phosphatase, ALT, AST

Renal 5 10 Increased blood urea 

nitrogen

Endocr 5 10 38% increased relative 

adrenal weight

Immuno 5 10 Decreased spleen and 

thymus weights, leukocyte 

counts, natural killer cell 

activity, and Concanavalin 

A responsiveness

Neuro 1.25b 2.5 Increased startle response

Other 

noncancer

5 10 Decreased serum 

cholesterol and glucose

EPA 1986a

13 Rat

(Fischer 

344)

24 F

GDs 7–16

1 time/day

(GO)

0, 10 DX, LE Develop 10 84% decreased PPD 3 

pup survival

EPA 1986a

14 Rat

(Sherman)

NS M

NS F

Once

(GO)

NS CS, LE Death 125 LD50

Gaines 1969

15 Rat

(SpragueDawley)

NS F

GDs 14–20

1 time/day

(GO)

0, 15 BI, DX, OF, 

OW 

Develop 15 Anovulation and persistent 

vaginal estrus in offspring

Gellert and Wilson 1979
MIREX AND CHLORDECONE 56

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

16 Rat

(SpragueDawley)

4–6 M

Once

(GO)

0, 15.2 BI Hepatic 15.2

Glende and Lee 1985

17 Rat

(SpragueDawley)

3 M

3 days

1 time/day

(GO)

0, 10, 25, 50 BH, BI Neuro 25 50 Decreased Na+-

K+ATPase; decreased 

oligomycin sensitive 

Mg2+ATPase (25 mg/kg); 

increased activity; tremor; 

exaggerated startle 

response; abnormal gait 

(50 mg/kg)

Jordan et al. 1981

18 Rat

(SpragueDawley)

5 M

5 days

(F)

0, 9.7 BC, BW, CS, 

FI, OF, OW

Bd wt 9.7

Hepatic 9.7

Neuro 9.7 Tremors; exaggerated 

startle response

Klingensmith and Mehendale 1982a

19 Rat

(SpragueDawley)

6 M

3 days

1x/d

(GO)

0, 8.3, 16.7, 

25

BI Cardio 8.3 Decreased 45Ca-uptake 

and Ca2+ ATPase activity

Kodavanti et al. 1990a

20 Rat

(Wistar)

10 M, 10 F

Once

(GO)

LE Death 132 M

126 F

LD50

Larson et al. 1979b

21 Rat

(SpragueDawley)

4–6 M

2–3 days

1 time/day

(GO)

0, 10, 25, 50 CS, HP Musc/skel 10 25 Increased Mg2+ ATPase 

activity in muscle 

sarcoplasmic reticulum

Neuro 25 Tremors

Mishra et al. 1980
MIREX AND CHLORDECONE 57

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

22 Rat

(SpragueDawley)

6 M

3 days

1 time/day

(GO)

0, 0.5, 2, 10 BC, BI, HP, 

OW

Hepatic 10

Renal 10

Plaa et al. 1987

23 Rat

(Fischer 

344)

8–10 M

Once

(GO)

LE Death 91.3 M LD50

Pryor et al. 1983

24 Rat

(Fischer 

344)

10 M

10 days

1 time/day

0, 0.625, 

1.25, 2.5, 5, 

10

BC, CS, OW Bd wt 5 10 19% decrease in body 

weight

Hemato 5 10 Decreased neutrophils

Neuro 5 10 Tremors 

Smialowicz et al. 1985

25 Rat

(SpragueDawley)

8–10 F

Once

(GO)

0, 35, 55, 75 BW, CS, OF,

OW

Bd wt 75 12% decrease in body 

weight

Endocr 35 Increased relative adrenal 

weight

Immuno 75 Decreased thymus weight

Neuro 35 Tremors; exaggerated 

startle response

Repro 35 Persistent estrus

Other 

noncancer

35 55 Decrease in colonic 

temperature

Swanson and Woolley 1982

26 Rat

(SpragueDawley)

5–8 M

3 days

1 time/day

(GO)

0, 18.75 BI, BW, OF,

OW

Bd wt 18.75

Hepatic 18.75 Increased bile flow; 

decreased bile acid 

concentration and 

secretory rate

Teo and Vore 1991
MIREX AND CHLORDECONE 58

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

27 Mouse

(ICR)

7 M

2–4 days

1 time/day

(GO)

0, 25, 50 CS Neuro 25 Severe tremors; motor 

incoordination

Chang-Tsui and Ho 1979

28 Mouse

(ICR)

NS M

2–3 days

1 time/day

(GO)

0, 50 BI Neuro 50 Decreased dopamine and 

norepinephrine uptake; 

decreased dopamine 

binding

Chang-Tsui and Ho 1980

29 Mouse 

(CD-1)

25 F

GDs 8–12

1 time/day

(GO)

0, 20 LE, CS Death 20 16% mortality

Bd wt 20 61% decrease in maternal 

body weight gain

Develop 20 Decreased survival and 

body weight of pups on 

PPDs 1 and 3

Chernoff and Kavlock 1982

30 Mouse

(CD-1)

12–26 F

GDs 7–16

10 days

1 time/day

(GO)

0, 2, 4, 8, 12 BW, DX, MX,

OW

Develop 8 12 Increased fetal deaths; 

increased club foot

Chernoff and Rogers 1976

31 Mouse

(CD-1)

NS F

PPDs 1–4

1 time/day

(GO)

0, 6, 18, 24 DX, LE Death 24 4 of 9 maternal mice died

Develop 18 64% pup mortality; 100% 

pup mortality at 

24 mg/kg/day

Chernoff et al. 1979b

32 Mouse

(ICR)

10 M

12 days

1 time/day

(GO)

0, 25, 50 CS, LE Death 25 100% mortality

Neuro 25 Mild tremors

Desaiah et al. 1980a
MIREX AND CHLORDECONE 59

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

33 Mouse

(C57BL/6)

13–32 M

2 days

1 time/day

(GO)

0, 30 BC, BI, CS Hepatic 30

Fouse and Hodgson 1987

34 Mouse

(ICR)

5–9 M

1–11 days

1 time/day

(GO)

0, 10, 25, 50 BH, BI Neuro 10 Motor incoordination

Fujimori et al. 1982a

35 Mouse

(ICR)

3–8 M

4 days

1 time/day

(GO)

0, 10, 25 BC, BI Hepatic 25 Decreased hepatic 

glycogen

Other 

noncancer

25 Decreased serum glucose 

and lactate

Fujimori et al. 1983

36 Mouse

(ICR)

6–12 M

5 or 8 days

1 time/day

(GO)

0, 25 BH, BI Neuro 25 Decreased striatal 

dopamine synthesis 

uptake and release

Fujimori et al. 1986

37 Mouse

(CD-1)

NS F

GDs 8–12

1 time/day

(G)

0, 20 BH, BW, DX, 

FX, MX, OF, 

OW, TG

Develop 20 Decreased postnatal 

viability

Gray et al. 1983

38 Mouse

(ICR)

4–5 M

Once

(GO)

0, 25 BH, BI Neuro 25 Increased brain calcium in 

mice 6–8 weeks old; 

decreased brain calcium 

in adults

Hoskins and Ho 1982

39 Mouse

(ICR)

3–4 M

8 days

1 time/day

(GO)

0, 25 BH, BI Neuro 25 Tremors

Hoskins and Ho 1982
MIREX AND CHLORDECONE 60

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

40 Mouse

(ICR)

15 M

2–14 days

1 time/day

(GO)

0, 10, 25, 50 BH, BI, CS Bd wt 10 10–15% decrease in 

maternal weight gain

Neuro 10 Decreased motor 

coordination; tremors

Huang et al. 1980

41 Mouse

(CD-1)

15–40 F

Once

GD 8

(GO)

0, 110, 125 DX, LE Death 110 25% mortality

Develop 125 Increased resorptions and 

malformations; decreased 

viable litters

Kavlock et al. 1985

42 Mouse

(ICR/SIM)

27–28 F

GDs 8–12

1 time/day

(GO)

0, 24 BW, DX, LE Death 24 18% mortality

Bd wt 24 85% decrease in maternal 

weight gain

Develop 24 Decreased fetal survival 

and neonatal weight gain; 

increased still births

Seidenberg et al. 1986

43 Mouse

(CD-1)

6–15 F

2 weeks

5 days/week

1 time/day

(GO)

0, 2, 4, 8 OF Repro 2 Induction of persistent 

vaginal estrus

Swartz et al. 1988

44 Rabbit

(NS)

NS

Once

(GO)

LE Death 71 LD50

Larson et al. 1979b

45 Dog

(NS)

NS

Once

(GO)

LE Death 250 LD50

Larson et al. 1979b
MIREX AND CHLORDECONE 61

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

INTERMEDIATE EXPOSURE

46 Rat

(SpragueDawley)

4–5 M

15 days

(F)

0, 0.95, 2.4, 

4.7, 9.5

BI, CS Neuro 2.4 4.7 Tremors

Agarwal and Mehendale 1984a

47 Rat

(Fischer344)

25 F

105 days

(F)

0, 0.11, 0.68 BI, BW Bd wt 0.68

Endocr 0.68

Ali et al. 1982

48 Rat

(Sherman)

24–25 M,

22–25 F

3 months

(F)

M: 0, 1.17-

1.58

F: 0, 1.62-

1.71

BW, CS, DX, 

HP, OF, OW

Bd wt

1.62 F

1.17 M 13% lower mean body 

weight gain

Hepatic 1.17 M

1.62 F

Focal necrosis

Endocr 1.17 M

1.62 F

Reversible hyperplasia of 

adrenal cortex

Neuro 1.17 M

1.62 F

Tremor, hyperactivity, 

exaggerated startle 

response

Repro 1.17 M 1.62 F Decreased number of 

litters born to control 

males mated to 

chlordecone-treated 

females

Develop 1.17 M

1.62 F

Cannon and Kimbrough 1979
MIREX AND CHLORDECONE 62

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

49 Rat

(SpragueDawley)

6 M

15 days

(F)

0, 0.086, 

0.86, 4.3, 8.6

BC, BI, BW, 

OF, OW

Hepatic 0.86 4.3 Significantly increased 

serum nonprotein nitrogen 

compounds and enzymes

Other 

noncancer

8.6 Decreased serum 

triglycerides, LDL, and 

cholesterol

Chetty et al. 1993a

50 Rat

(SpragueDawley)

10 M

28 days

(F)

0, 0.086 BC, BI, BW, 

CS, FI, HP

Bd wt 0.086

Hemato 0.086

Hepatic 0.086

Renal 0.086

Chu et al. 1980b

51 Rat

(SpragueDawley)

3–11 M

15 days

(F)

0, 1.6, 8.2 BH, BI, BW, 

CS, OF, OW

Bd wt 1.6 8.2 99% decrease in body 

weight gain

Hepatic 1.6 Impaired biliary excretion

Increases in liver weight, 

serum ALT, and AST at 

5 mg/kg/day

Neuro 1.6 8.2 Tremors and 

hypersensitivity to sound 

and touch

Curtis and Hoyt 1984

52 Rat

(SpragueDawley)

20 M

15 days

(F)

0, 0.8, 4, 12 BI, BW, CS, 

FI, GN, OF, 

OW

Bd wt 0.8 4. 63% lower body weight 

gain

Neuro 4 12 Tremors; hyperexcitability

Curtis and Mehendale 1979
MIREX AND CHLORDECONE 63

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

53 Rat

(ZivacMiller)

1–5 M, 3 F

90 days

5–

6 days/week

1 time/day

(GO)

1, 5, 10 BH, CS, LE Neuro 1 Decrease in operant 

behavior; tremors

Dietz and McMillan 1979

54 Rat

(SpragueDawley)

4–5 M

15 days

(F)

0, 0.86 BI, BW, FI, 

HP, OW, WI

Bd wt 0.86

Faroon and Mehendale 1990

55 Rat

(SpragueDawley)

5 M

15 or 

20 days

(F)

0, 9.7 BH, BW, CS, 

FI, OW

Bd wt 9.7 48–49% decrease in body 

weight gain

Hepatic 9.7

Neuro 9.7 Progressively increased 

constant tremors

Other 

noncancer

9.7 36% decrease in 

epididymal fat

Klingensmith and Mehendale 1982a

56 Rat

(Wistar)

5 M, 5 F

3–9 months 

during a 

2-year study

(F)

M: 0, 0.083, 

0.42, 0.83, 

2.10, 4.2, 6.7

F: 0, 0.097, 

0.48, 0.97, 

2.4, 4.8, 7.8

BC, BW, CS, 

FI, HP, OW, 

UR

Bd wt 0.97 M

0.83 F

2.1 M

2.4 F

Up to 20% lower mean 

body weight

Up to 24% lower mean 

body weight 

Hemato 7.8 M

6.7 F

Hepatic 0.97 M

0.83 F

2.4 M

2.1 F

Congestion in liver of 

3/5 males and 2/5 females 

at 3 months

Endocr 6.7 M

0.83 F 2.4 F

Loss of adrenal lipid in 

2/5 females at 3 months
MIREX AND CHLORDECONE 64

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

Neuro 0.83 M

0.97 F

2.1 M

2.4 F

Tremors (earlier onset and 

increased severity with 

increasing dose) up to 

6 months, regressing 

thereafter; incidences by 

sex not reported

Repro 0.83 M 2.1 M Testicular atrophy in 

4/5 males at 3 months

Other 

noncancer

0.83 M

2.4 F

2.1 M Increased metabolic rate 

in males at 9 months

Larson et al. 1979b

57 Rat

(SpragueDawley)

10 M

90 days

(F)

0, 0.26, 0.83, 

1.67

CS, DX, OF Neuro 0.26c 0.83 Hyperexcitability; mild 

tremors at 0.83 and 

1.67 mg/kg/day

Repro 0.26c 0.83 46–48% decreased sperm 

motility and viability; 19% 

decreased epididymal 

sperm concentration

Develop 1.67

Linder et al. 1983

58 Rat

(SpragueDawley)

4 F

16 days

(F)

0, 3.95, 8.54, 

11.63

BI, BW, CS, 

FI, OW

Bd wt 3.95 Dose-related depressed 

body weight gain (28–

78% less than controls)

Neuro 3.95 Tremors; hypersensitivity 

to noise and stress

Mehendale et al. 1978
MIREX AND CHLORDECONE 65

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

59 Rat

(SpragueDawley)

5 M

30–35 days

(F)

0, 10 BH, CS, LE, 

OF, OW

Death 10 2/5 died

Bd wt 10 Significantly decreased 

body weight gain

Hepatic 10 Impaired biliary function

Neuro 10 Tremors, hyperactivity, 

exaggerated startle 

response

Mehendale 1981

60 Rat

(SpragueDawley)

4–5 M

15 days

(F)

0, 4 OF Hepatic 4 Decreased hepatobiliary 

function

Mehendale 1990

61 Rat

(SpragueDawley)

4 M

15 days

(F)

0, 0.88 BC Hepatic 0.88

Mehendale et al. 1991

62 Rat

(Fischer 

344)

9–10 M

15 weeks 

5 days/week

1 time/day

(GO)

0, 2.8, 4.1, 

7.1, 11.2

BH, CS, LE Death 4.1 6/10 died

Bd wt 2.8 >10% decrease in body 

weight gain

Neuro 2.8 4.1 Increased startle response

Other 

noncancer

7.1 Increased body 

temperature

Pryor et al. 1983

63 Rat

(Fischer344)

8–12 M

90 days

(F)

0, 1.0, 3.0 BH, CS Neuro 1.0 Exaggerated startle 

response

Squibb and Tilson 1982a
MIREX AND CHLORDECONE 66

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

64 Mouse

(ICR)

15 M

33 days

1 time/day

(GO)

0, 10, 25, 50 BI, CS, GN, 

LE

Death 10 100% mortality

Gastro NS Mild diarrhea

Neuro 10 Tremors; decreased motor 

coordination

Other 

noncancer

10 Decreased adipose tissue; 

decreased plasma 

glucose

Fujimori et al. 1983

65 Mouse

(BALB/c)

24–36 M, 

24–36 F

5 months 

(1 month 

premating 

and through 

production of 

two litters

(F)

0, 0.94, 1.9 OF Repro 0.94 36% decrease in second 

litters

Good et al. 1965

66 Mouse

(BALB/c)

4–70 M,F

2–12 months

(F)

1.9, 5.6, 7.5, 

11, 13, 15, 

19

BW, HP, LE, 

OW

Death 11 12% mortality in adults; 

100% mortality in juveniles

Bd wt 7.5 11 Decreased body weight in 

juveniles and adults

Hepatic 7.5 Focal necrosis, cellular 

hypertrophy, hyperplasia, 

congestion; liposphere 

formation and decreased 

numbers of mitochondria

Neuro 1.9 5.6 Tremor

Repro 7.5 Increased estrus

Huber 1965

67 Mouse

(BALB/c)

14 M,14 F

160 days

(F)

0, 7.5 OF Repro 7.5 Persistent vaginal estrus; 

reversible reproductive 

failure

Huber 1965
MIREX AND CHLORDECONE 67

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

68 Mouse

(BALB/c)

8 M, 8 F

130 days

(F)

0, 1.9, 5.6, 7 OF Repro 1.9 8% decrease in litter size 

and 19% increase in pairdays to litter; constant 

estrus at 3.9 mg/kg/day

Develop 1.9 7 Decreased postnatal 

survival

Huber 1965

69 Mouse

(SwissWebster)

6 M

15 days

(F)

0, 1.9 BC, BI, BW, 

FI, HP, OW

Bd wt 1.9

Hepatic 1.9

Mehendale et al. 1989

70 Mouse

(CD-1)

6 F

4 weeks

5 days/week

1 time/day

(GO)

0, 8 BH, CS Neuro 8 Slight tremors; increased 

reactivity to noise

Swartz and Schutzmann 1986

71 Mouse

(CD-1)

6–22 F

4 or 6 weeks

5 days/week

1 time/day

(GO)

0, 2, 4, 8 OF Repro 2 Increased ovulation; 

persistent vaginal estrus

Swartz et al. 1988

72 Gerbil

(Mongolian)

4–5 M

15 days

(F)

0, 5.4 BC, BI Hepatic 5.4

Cai and Mehendale 1990

73 Gerbil

(Mongolian)

4–5 M

15 days

(F)

0, 5.4 BI, HP Hepatic 5.4

Cai and Mehendale 1991a
MIREX AND CHLORDECONE 68

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

CHRONIC EXPOSURE

74 Rat

(SpragueDawley)

4–10 M

21 months

(GO)

0, 0.07 BI, BW, HE, 

HP

Hemato 0.07

Chu et al. 1981c

75 Rat

(Wistar)

40 M, 40 F

Up to 2 years

(F)

0, 0.089, 

0.45, 0.89, 

2.2, 4.5, 7.1

BC, BW, CS, 

FI, HE, HP, 

OW, UR

Death 2.2 Decreased survival in 

females; 100% mortality in 

both sexes at 2.5 and 

4.0 mg/kg/day treated for 

25 and 17 weeks, 

respectively

Bd wt 0.89 2.2 >10% decreased body 

weight gain at 1 and 

2 years

Cardio 2.2 No effect among survivors 

at 1 and 2 years

Hemato 0.89 2.2 Depressed hematocrit 

levels at 1 and 2 years

Hepatic 0.45 0.89 Fatty changes in liver at 

1 and 2 years

Renal 0.089d 0.45 Proteinuria and 

increased severity of 

glomerulosclerosis at 

1 and 2 years

Neuro 0.89 2.2 Tremor; observed as 

early as weeks 2–3 at 

the two highest dose 

levels

Larson et al. 1979b
MIREX AND CHLORDECONE 69

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

76 Rat

(OsborneMendel)

44–50 M

45–49 F

80 weeks

(F)

M: 0, 0.56, 

1.7

F: 0, 1.4, 

2.0

CS, HE, 

HP, LE

Death 1.7 M

2.0 F

Decreased survival 

among males and 

females

Hemato 0.56 M

1.4 F

Anemia

Hepatic 0.56 M

1.4 F

Fatty infiltration and 

liver degeneration

Dermal 0.56 M

1.4 F

Dermatitis

Neuro 0.56 M

1.4 F

Tremors

Cancer 1.7 M

2.0 F

CEL: hepatocellular 

carcinoma

NCI 1976

77 Mouse

(B6C3F1)

48–49 M

49–50 F

80 weeks

(F)

M: 0, 3.4, 3.9

F: 0, 3.5, 6.9

CS, LE Death 3.4 M Decreased survival in 

males

Hepatic 3.4M

3.5 F

Hepatocellular hyperplasia

Neuro 3.4M

3.5 F

Tremors

Cancer 3.4M

3.5 F

CEL: hepatocellular 

carcinoma

NCI 1976
MIREX AND CHLORDECONE 70

2. HEALTH EFFECTS

Table 2-4. Levels of Significant Exposure to Chlordecone – Oral

Figure 

keya

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

78 Dog

(beagle)

2 M, 2 F

124–

128 weeks

(F)

0, 0.047, 

0.24, 01.2

BC, BW, HP, 

OW

Neuro 1.2

Larson et al. 1979b

aThe number corresponds to entries in Figure 2-4; differences in levels of health effects and cancer effects between male and females are not indicated in 

Figure 2-4. Where such differences exist, only the levels of effect for the most sensitive gender are presented. bUsed to derive an acute-duration Minimal Risk Level (MRL) of 0.01 mg/kg/day for chlordecone; dose divided by an uncertainty factor of 100 (10 for extrapolation 

from animals to humans and 10 for human variability); see Appendix A for more detailed information regarding the MRL. cUsed to derive an intermediate-duration MRL of 0.003 mg/kg/day; dose divided by an uncertainty factor of 100 (10 for extrapolation from animals to humans and 

10 for human variability); see Appendix A for more detailed information regarding the MRL. dUsed to derive a chronic-duration MRL of 0.0009 mg/kg/day for chlordecone; dose divided by an uncertainty factor of 100 (10 for extrapolation from animals to 

humans and 10 for human variability); see Appendix A for more detailed information regarding the MRL.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATPase = adenosinetriphosphatase; BC = serum (blood) chemistry; Bd wt or BW = body 

weight; BH = behavioral; BI = biochemical changes; Cardio = cardiovascular; CEL = cancer effect level; CS = clinical signs; Develop = developmental; 

DX = developmental toxicity; Endocr = endocrine; (F) = feed; F = female(s); FI = food intake; FX = fetal toxicity; (G) = gavage, not specified; 

Gastro = gastrointestinal; GD = gestation day; (GO) = gavage, oil; GN = gross necropsy; HE = hematology; Hemato = hematological; HP = histopathology; 

Immuno = immunological; LD50 = lethal dose, 50% kill; LDL = low-density lipoprotein; LE = lethality; LOAEL = lowest-observed-adverse-effect level; M = male(s); 

Musc/skel = musculoskeletal; MX = maternal toxicity; Neuro = neurological; NOAEL = no-observed-adverse-effect level; NS = not specified; OF = organ function; 

OW = organ weight; PPD = post-partum day; Repro = reproductive; TG = teratogenicity; UR = urinalysis; WI = water intake
MIREX AND CHLORDECONE 71

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Figure 2-4. Levels of Significant Exposure to Chlordecone – Oral

Acute (≤14 days)
MIREX AND CHLORDECONE 72

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Figure 2-4. Levels of Significant Exposure to Chlordecone – Oral

Acute (≤14 days)
MIREX AND CHLORDECONE 73

2. HEALTH EFFECTS

Figure 2-4. Levels of Significant Exposure to Chlordecone – Oral

Intermediate (15–364 days)
MIREX AND CHLORDECONE 74

2. HEALTH EFFECTS

Figure 2-4. Levels of Significant Exposure to Chlordecone – Oral

Intermediate (15–364 days)
MIREX AND CHLORDECONE 75

2. HEALTH EFFECTS

Figure 2-4. Levels of Significant Exposure to Chlordecone – Oral

Chronic (≥365 days)
MIREX AND CHLORDECONE 76

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Table 2-5. Levels of Significant Exposure to Mirex – Dermal

Species 

(strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

ACUTE EXPOSURE

Rat

(Sherman)

10 M,10 F

NS NS LE Death >2,000 LD50

Gaines 1969

INTERMEDIATE EXPOSURE

Mouse

(CD-1)

30 F

4 weeks

3 times/week

(paint)

0, 3.6 BI, HP Cancer 3.6 F Skin tumor promotion 

Meyer et al. 1993

Mouse

(CD-1)

30 F

20 weeks

2 times/week

(paint)

0, 3.6 BI, HP Cancer 3.6 F Skin tumor promotion

Meyer et al. 1994

Mouse

(CD-1)

30 F

4 weeks

3 times/week

(paint)

0, 3.6 HP Cancer 3.6 F Mild epidermal hyperplasia

Moser et al. 1992

Mouse

(CD-1)

30 F

20 or 

34 weeks

3 times/week

(paint)

0, 0.45, 0.9, 

1.8, 3.6

BI, HP Cancer 0.45 F Skin tumor promotion

Moser et al. 1992

Mouse

(CD-1)

30 M, 30 F

20 weeks

3 times/week

(paint)

0, 3.6 CS, GN, HP Cancer 0.45 F Skin tumor promotion

Moser et al. 1993

BI = biochemical changes; CS = clinical signs; F = female(s); GN = gross necropsy; HP = histopathology; LD50 = lethal dose, 50% kill; LE = lethality; 

LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level; NS = not specified; M = male(s)
MIREX AND CHLORDECONE 77

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Table 2-6. Levels of Significant Exposure to Chlordecone – Dermal

Species (strain)

No./group

Exposure 

parameters

Doses

(mg/kg/day)

Parameters 

monitored Endpoint

NOAEL 

(mg/kg/day)

Less 

serious 

LOAEL 

(mg/kg/day)

Serious 

LOAEL 

(mg/kg/day) Effect

ACUTE EXPOSURE

Rat

(Sherman)

10 M,10 F

NS NS LE Death >2,000 LD50

Gaines 1969

Rabbit

(NS)

10 M

NS 20 LE Death 410 M LD50

Larson et al. 1979b

F = female(s); LD50 = lethal dose, 50% kill; LE = lethality; LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level; NS = not 

specified; M = male(s)
MIREX AND CHLORDECONE 78

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2.2 DEATH

Mirex. Oral LD50 values for mirex obtained in rats have been somewhat variable. In one study, 

administration of mirex in corn oil resulted in an LD50 value in females of 365 mg/kg (Gaines and 

Kimbrough 1970), whereas in another study, the LD50 values in male and female rats were 740 and 

600 mg/kg, respectively, after administration of mirex in corn oil, but in excess of 3,000 mg/kg after 

administration in peanut oil (Gaines 1969). Mehendale et al. (1973) reported death of 2/5 female rats 

during a 5-day period of mirex gavage dosing at 50 mg/kg/day. Pregnant rats appear to be somewhat 

more sensitive to the lethal effect of mirex. Although a single oral dose of mirex at 25 mg/kg resulted in 

no mortality in nonpregnant females (Mehendale et al. 1973), 16–25% mortality in pregnant rats occurred 

at doses ranging from 6 to 10 mg/kg/day over a 10–11-day period during gestation (Byrd et al. 1981; 

Chernoff et al. 1979a; Khera et al. 1976) and mortality rates of 32–36% were observed in rat and mouse 

pups exposed through the milk during the first 4 days of lactation at these doses (Chernoff et al. 1979a). 

Four of 20 maternal rats died during oral exposure to mirex at 6 mg/kg/day on gestation days 6–15 (Khera 

et al. 1976). Twelve of 15 mice died during a 14-day study that employed oral dosing with mirex at

10 mg/kg/day (Fujimori et al. 1983). In male dogs, a single oral dose of mirex at 1,250 mg/kg was lethal 

to three of five treated animals; there were no deaths among five dogs similarly treated at 1,000 mg/kg 

(Larson et al. 1979a).

Several studies evaluated mortality in laboratory animals orally exposed to mirex for intermediate 

durations. Mortality was increased in adult male rats at doses as low as 5 mg/kg/day for 30 days 

(Mehendale 1981), in adult female rats at doses as low as 5.7 mg/kg/day for 90 days (Gaines and 

Kimbrough 1970; Larson et al. 1979a), and in rat pups at 1.8–2.8 mg/kg/day for the duration of lactation 

(Gaines and Kimbrough 1970). In mice, 100% mortality occurred following 1.3 mg/kg/day for 60 days 

and 0–25% mortality occurred at 0.65 mg/kg/day for 120 days (Ware and Good 1967). Death occurred in 

one of two dogs treated orally with mirex at 4.8 mg/kg/day for 13 weeks (Larson et al. 1979a). In a 

2-year study in rats, males exhibited mirex treatment-related increased mortality at 1.8 mg/kg/day 

(63 versus 15% in controls), but females exhibited no mirex-related decrease in survival at as much as 

7.7 mg/kg/day (NTP 1990). In an 18-month oral study of mice, unscheduled death was observed among 

all mice at 4.8 mg mirex/kg/day (Innes et al. 1969). In a 15-month study, Wolfe et al. (1979) reported 

20 and 92% mortality among mice ingesting mirex at 0.24 and 2.4 mg/kg/day, respectively.

The dermal LD50 value for mirex in rats was reported to be in excess of 2,000 mg/kg (Gaines 1969).
MIREX AND CHLORDECONE 79

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Chlordecone. Single-dose oral LD50 values in rats for chlordecone were reported to be 126 mg/kg in 

females (Larson et al. 1979b) and 91.3 mg/kg (Pryor et al. 1983) and 132 mg/kg (Larson et al. 1979b) in 

males. An oral LD50 for male and female rats was 125 mg/kg (Gaines 1969). LD50 values for male 

rabbits and dogs (sex not specified) were 71 and 250 mg/kg, respectively (Larson et al. 1979b). A single 

oral dose of 110 mg/kg resulted in the death of 5/20 pregnant mice; at 125 mg/kg, death occurred in 

17/40 pregnant mice (Kavlock et al. 1985). No mortality was observed in male rats dosed with 

chlordecone at approximately 10 mg/kg/day for 10 days (Simmons et al. 1987), but 8/42 pregnant mice

died during oral treatment with chlordecone at 10 mg/kg/day on gestation days 7–16 (Chernoff and 

Rogers 1976). Gavage dosing of 24 mg chlordecone/kg/day during gestation days 8–12 resulted in the 

death of 5/27 pregnant mice (Seidenberg et al. 1986). Ingestion of milk from dams given 18 mg

chlordecone/kg/day during the first 4 days of lactation resulted in 64% mortality in mouse pups (Chernoff 

et al. 1979a). Daily oral administration of chlordecone to male mice at 25 or 50 mg/kg/day resulted in 

100% mortality by treatment days 12 and 6, respectively (Desaiah et al. 1980b).

In intermediate-duration studies of male rats, 2/5 rats died during 5 weeks of oral exposure to chlordecone 

at 8.6 mg/kg/day (Mehendale 1981) and 6/10 rats died during 15 weeks of treatment at 4.1 mg/kg/day 

(Pryor et al. 1983). In mice of both sexes, at a dose of 11 mg/kg/day for up to 12 months, only 12% 

mortality was observed among adult mice, whereas all four treated juvenile mice died, indicating a greater 

sensitivity in immature mice (Huber 1965). All 15 male mice exposed orally with chlordecone at

10 mg/kg/day died during a scheduled 33-day dosing period (Fujimori et al. 1983). Survival was 

decreased in female rats receiving chlordecone from the diet at 2.2 mg/kg/day for up to 2 years (Larson et 

al. 1979b), both male and female rats receiving chlordecone from the diet at 1.7–2.0 mg/kg/day for up to 

80 weeks (NCI 1976), and male mice receiving chlordecone from the diet at 3.4 mg/kg/day for up to 80 

weeks (NCI 1976).

The dermal LD50 value for chlordecone in rats was reported to be in excess of 2,000 mg/kg (Gaines 

1969). In male rabbits exposed dermally to chlordecone in corn oil, an LD50 value of 410 mg/kg was 

reported (Larson et al. 1979b).

2.3 BODY WEIGHT

Mirex. No studies were located regarding body weight effects in humans exposed to mirex. Decreases 

>10% in body weight or body weight gain have been observed in studies of laboratory animals following 

acute-, intermediate-, and chronic-duration oral exposure to mirex (Buelke-Sam et al. 1983; Byrd et al. 
MIREX AND CHLORDECONE 80

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1981; Chadwick et al. 1977; Chernoff et al. 1979a, 1979b; Chu et al. 1981b; Curtis and Hoyt 1984; 

Davison et al. 1976; Elgin et al. 1990; Fujimori et al. 1983; Jovanovich et al. 1987; Khera et al. 1976; 

Larson et al. 1979a; Mehendale et al. 1973; NTP 1990; Ritchie and Ho 1982; Rogers and Grabowski 

1984; Villeneuve et al. 1977).

Chlordecone. Weight loss was reported among 27 of 133 workers examined as a result of intermediateor chronic-duration occupational exposures to chlordecone (Cannon et al. 1978). Weight loss (up to 

60 pounds in 4 months) was reported in 10 of 23 workers with blood chlordecone levels in excess of 

2 μg/L (Taylor et al. 1978). Decreases >10% in body weight or body weight gain have also been 

observed in studies of laboratory animals following acute-, intermediate-, and chronic-duration oral 

exposure to chlordecone (Albertson et al. 1985; Cannon and Kimbrough 1979; Chernoff and Kavlock 

1982; Chernoff and Rogers 1976; Curtis and Hoyt 1984; Curtis and Mehendale 1979; EPA 1986a; 

Fabacher and Hodgson 1976; Huang et al. 1980; Kavlock et al. 1987a; Klingensmith and Mehendale 

1982a; Larson et al. 1979b; Mehendale et al. 1977, 1978b; Pryor et al. 1983; Seidenberg et al. 1986; 

Simmons et al. 1987; Smialowicz et al. 1985; Swanson and Wooley 1982). In the report by Larson et al. 

(1979b), the decreases in body weight were observed in the presence of increases in food consumption, 

indicating a decrease in food utilization efficiency and/or increased stress to the animals.

2.4 RESPIRATORY

Mirex. No studies were located regarding respiratory effects in humans or animals exposed to mirex.

Chlordecone. Pleuritic chest pains were reported by 32 of 133 workers examined for toxicity following 

intermediate- or chronic-duration occupational exposure at a chlordecone-manufacturing facility (Cannon 

et al. 1978); pleuritic chest pains were reported by 18 of 23 workers with blood levels in excess of 2 μg/L. 

Further examination of these workers did not reveal any dyspnea, and chest x-rays revealed no lung 

pathology (Taylor 1982, 1985). Extremely limited information was located regarding respiratory effects 

in animals following oral exposure to chlordecone. Routine histopathological examination of the lungs of 

rats in both 90-day and 2-year feeding studies with doses as high as 4 mg/kg/day showed no adverse 

effects. Also, routine histopathological examination of the lungs of dogs exposed to doses as high as 

0.625 mg/kg/day in a 2-year feeding study showed no effects (Larson et al. 1979b). It is unclear how 

many lung tissue samples were actually examined; the dog study used only two animals/sex/dose.
MIREX AND CHLORDECONE 81

2. HEALTH EFFECTS

2.5 CARDIOVASCULAR

Mirex. No studies were located regarding cardiovascular effects in humans exposed to mirex. Limited 

information was located regarding cardiovascular effects of mirex in animals. Changes in blood flow 

patterns were seen in pregnant rats given gavage doses of mirex at 10 mg/kg/day for varying periods 

during pregnancy (Buelke-Sam et al. 1983). In this study, a single oral dose resulted in a decrease in 

blood flow to the stomach, while 5 and 10 daily doses resulted in decreased blood flow to other essential 

internal organs (lungs, liver, spleen, or kidneys). Five days of exposure also resulted in decreased cardiac 

output, but this effect had disappeared by day 10 of exposure. There was also a significant decrease in the 

heart weight of the maternal rats. Another study showed that rats given mirex at 100 mg/kg/day by 

gavage for 3 days experienced a slight inhibition of Na+K+ATPase in myocardial membranes (Desaiah 

1980). The biological significance of this effect is unknown. There was no gross or histopathological 

evidence of mirex-related adverse cardiac effects among rats ingesting mirex for 13 weeks at doses as 

high as 64 mg/kg/day (Larson et al. 1979a).

Chlordecone. Symptoms associated with the cardiovascular system were not commonly reported by 

133 workers exposed for intermediate or chronic durations to unspecified levels of chlordecone at a 

chlordecone-manufacturing facility (Cannon et al. 1978; Taylor 1982, 1985; Taylor et al. 1978). 

Furthermore, results from electrocardiography of 23 workers with active symptoms of chlordecone 

intoxication were normal (Taylor 1982, 1985). Maternal serum chlordecone was not associated with 

hypertensive disorders or preeclampsia in pregnant women (Saunders et al. 2014). See Error! Reference 

source not found. for additional study details.

Available information regarding the cardiovascular effects of chlordecone in animals is also limited. 

Acute-duration studies have primarily examined biochemical parameters. For example, gavage dosing of 

rats with chlordecone (≥10 mg/kg/day for 3 days) resulted in inhibition of myocardial Na+K+ATPase 

(Desaiah 1980). At ≥25 mg/kg/day, inhibition of mitochondrial Mg2+ATPase occurred; decreased 

norepinephrine and dopamine binding to myocardial membranes was observed at 50 mg/kg/day. 

Similarly, inhibition of calcium uptake, Ca2+ATPase activity, and protein phosphorylation was observed 

in rat cardiac sarcoplasmic reticulum following gavage doses of chlordecone at 8.3 mg/kg/day for 3 days 

(Kodavanti et al. 1990a). Because of the importance of calcium regulation in all phases of the cardiac 

cycle, this might indicate a decrease in cardiac effectiveness.
MIREX AND CHLORDECONE 82

2. HEALTH EFFECTS

Vasodilation of tail vessels has been observed in rats following oral administration of chlordecone for 

90 days at 4 mg/kg/day (Larson et al. 1979b). The cause of the vasodilation was not investigated, but was 

suggested to have been associated with altered thermoregulatory mechanism.

Routine histopathological analyses of heart samples have not shown significant changes following oral 

exposure of rats to chlordecone for 2 years at 2.2 mg/kg/day or dogs for 124–128 weeks at 

0.625 mg/kg/day (Larson et al. 1979b). However, these studies are limited in that it is unclear how many 

heart samples were actually examined, and the dog study employed only two animals/sex/dose.

2.6 GASTROINTESTINAL

Mirex. No studies were located regarding gastrointestinal effects in humans exposed to mirex. Limited 

information was located regarding gastrointestinal effects in animals following oral exposure to mirex; 

however, the available data indicate that diarrhea is a relatively common result of high-dose mirex 

exposure. Several acute- and intermediate-duration studies have identified diarrhea in treated animals, 

but few of these studies presented sufficient information to assign a LOAEL for this effect. Diarrhea was 

identified as a predominant sign in female rats that died during a l0-day gavage study, but the mirex doses 

at which this was observed were not specified (6 or 12.5 mg/kg/day) (Khera et al. 1976). Similarly, 

diarrhea was noted as one of the clinical signs seen in rats after a single gavage dose, but it was unclear 

whether this effect occurred at the lowest dose (100 mg/kg) at which clinical signs were observed (Gaines 

and Kimbrough 1970). Diarrhea was observed in rats fed a total of 365 mg/kg over 12 days, but the daily 

dose was not specified (Kendall 1974). Mild diarrhea was observed in treated rats (10 mg/kg/day) 

starting on the 8th day of exposure and continuing over the duration of a 30-day dietary study (Mehendale 

1981). Diarrhea was also observed in a 90-day gavage study of rats, but the dose (5, 12.5, or 

25 mg/kg/day) at which it was observed was not reported (Dietz and McMillan 1979). Severe diarrhea 

was reported in mice following gastric intubation with mirex for up to 15 days, but the report did not state 

which of the doses (10, 25, or 50 mg/kg/day) caused this effect (Fujimori et al. 1983). Necropsy showed 

hemorrhagic intestines, indicating a gastrointestinal origin for the diarrhea rather than a neurally mediated 

response.

Chlordecone. No studies were located regarding gastrointestinal effects in humans exposed to 

chlordecone. Mild diarrhea has also been observed in a 33-day gavage study of mice receiving 

chlordecone at 10 mg/kg/day; however, necropsy revealed no evidence of treatment-related effects on 

stomach or intestines (Fujimori et al. 1983). Likewise, routine histopathological analyses of 
MIREX AND CHLORDECONE 83

2. HEALTH EFFECTS

gastrointestinal tissues showed no compound-related effects in rats after 2 years of oral exposure to 

chlordecone at 1.25 mg/kg/day or in dogs after 124–128 weeks of exposure at 0.625 mg/kg/day (Larson et 

al. 1979b). Both of these studies are limited in that it is unclear whether tissues from all exposed animals 

were examined and only two animals/sex/group were included in the dog study.

2.7 HEMATOLOGICAL

Mirex. No studies were located regarding hematological effects in humans exposed to mirex. Adverse 

hematological effects have not been reported to be a prominent feature of mirex toxicity in animals. No 

effects on standard hematological parameters were observed in male rats after 14 days of gavage 

administration to mirex at 10 mg/kg/day (Villeneuve et al. 1977). However, a single oral dose of 

100 mg/kg mirex to rats resulted in a 12% increase in hematocrit (Ervin and Yarbrough 1983). The 

hematocrit was increased 26–27% in adrenalectomized rats. The significance of this effect is unclear. 

Most intermediate-duration studies have shown no effect of mirex on hematological parameters. No 

effect on routine hematological parameters occurred in rats treated for 28 days at oral doses as high as 

6.5 mg/kg/day (Chu et al. 1980b; Yarbrough et al. 1981). In addition, no effects were observed among

rats receiving mirex from the food for 148 days at 3 mg/kg/day (Chu et al. 1981a). In contrast, oral 

exposure of rats to mirex for 13 weeks resulted in decreased hemoglobin at 28 mg/kg/day and increased 

leukocytes at 64 mg/kg/day (Larson et al. 1979a). Increased hematocrit was reported for a male dog that 

died during a 13-week study in which the dog received mirex from the food at 4.8 mg/kg/day (Larson et 

al. 1979a). There was no evidence of mirex treatment-related hematological effects among rabbits 

following repeated dermal application (unspecified amount) of mirex for 9 weeks (Larson et al. 1979a).

Chlordecone. No studies were located regarding hematological effects in humans exposed to 

chlordecone. Studies examining the hematological effects of chlordecone in experimental animals have 

also given predominantly negative results. In intermediate-duration studies in rats, no effect on any 

hematological parameters occurred following 28 days of dietary exposure to chlordecone at 

0.086 mg/kg/day (Chu et al. 1980b) or 90 days of dietary exposure at doses up to 7.8 or 6.7 mg/kg/day for 

males and females, respectively (Larson et al. 1979b). Similarly, in chronic-duration studies, no effects 

were seen during routine hematology in rats receiving chlordecone from the food for 2 years at up to 

2.2 mg/kg/day or in dogs receiving chlordecone from the food for 124–128 weeks at doses up to 

0.625 mg/kg/day (Larson et al. 1979b).
MIREX AND CHLORDECONE 84

2. HEALTH EFFECTS

2.8 MUSCULOSKELETAL

Mirex. No studies were located regarding musculoskeletal effects in humans or animals exposed to 

mirex.

Chlordecone. Skeletal muscle biopsies obtained from six workers who had experienced tremors, muscle 

weakness, gait ataxia, and incoordination as a result of intermediate- or chronic-duration occupational 

exposure to high concentrations of chlordecone revealed a predominance of fiber grouping characteristic 

of myopathic conditions, and a slight increase in lipochrome content (Martinez et al. 1978); the biological 

significance of this effect is unknown. It is unclear whether the myopathy was a direct toxic effect of 

chlordecone on the muscle or whether the myopathy was a consequence of neuronal dysfunction. 

Arthralgia in the proximal joints was reported by 4 of 23 workers with active symptoms of chlordecone 

intoxication (Taylor 1982, 1985); no cause for the joint pain could be determined.

Studies examining the effects of acute-duration oral exposure to large amounts of chlordecone suggest 

that direct toxic effects of chlordecone on muscle occur. A single gavage dose of chlordecone to rats at 

between 72 and 98 mg/kg resulted in increasing muscle weakness (Egle et al. 1979). Weakness was 

observed on the first day of treatment and continued to increase throughout a 49-day observation period. 

Following 2–3 days of oral exposure to chlordecone (25 and 50 mg/kg/day), inhibition of Mg2+ATPase 

was observed in sarcoplasmic reticulum of treated rats (Mishra et al. 1980). There was no histopathologic 

evidence of chlordecone-related effects on skeletal muscle among laboratory animals treated for longer 

durations at lower dose levels. For example, no compound-related effects were reported among rats 

receiving chlordecone from the diet for 90 days at up to 7.37 and 8.21 mg/kg/day (males and females, 

respectively), other rats treated for or 2 years at up to 1.25 mg/kg/day, or dogs treated for 124–128 weeks 

at up to 0.625 mg/kg/day (Larson et al. 1979b).

2.9 HEPATIC

Mirex. The hepatotoxicity of mirex in humans has not been demonstrated. One study of human subjects 

(sex and number not specified) from a chronically-exposed cohort in southeast Ohio assessed the potential 

for mirex to induce cytochrome P4501A2 (CYP1A2) using a breath test that measures caffeine 

metabolism. The mirex-exposed subjects had elevated caffeine metabolism as compared to negative 

control individuals (subjects with no known exposure to mirex or polyhalogenated biphenyls or other 

related chemicals) in which the metabolism did not increase (Lambert et al. 1992). However, the study 

did not assess liver function.
MIREX AND CHLORDECONE 85

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Mirex-related hepatic effects have been well characterized in experimental animals. The changes 

observed in livers include both adaptive and toxic effects. The adaptive effects observed are those 

generally produced by halogenated hydrocarbons and include the following:

• Increased liver weight or size (Abston and Yarbrough 1976; Byard et al. 1975; Chadwick et al. 

1977; Chambers and Trevethan 1983; Chu et al. 1980a, 1981a, 1981b; Curtis and Hoyt 1984; Dai 

et al. 2001; Davison et al. 1976; Elgin et al. 1990; Ervin and Yarbrough 1983; Fujimori et al. 

1983; Fulfs et al. 1977; Gaines and Kimbrough 1970; Hewitt et al. 1979; Jovanovich et al. 1987; 

Karl and Yarbrough 1984; Larson et al. 1979a; Mehendale 1981; Mehendale et al. 1973; Pittz et 

al. 1979; Plaa et al. 1987; Purushotham et al. 1988; Ritchie and Ho 1982; Robacker et al. 1981; 

Robinson and Yarbrough 1978a, 1978b; Teo and Vore 1991; Thottassery and Yarbrough 1991; 

Villeneuve et al. 1977; Warren et al. 1978; Williams and Yarbrough 1983; Wilson and Yarbrough 

1988; Yarbrough et al. 1981, 1984, 1986a, 1986b, 1992)

• Hepatocellular hypertrophy (Davison et al. 1976; Fulfs et al. 1977; Gaines and Kimbrough 1970; 

Ulland et al. 1977; Yarbrough et al. 1981)

• Cytoplasmic eosinophilia with migration of basophilic granules (Chu et al. 1981a; NTP 1990; 

Yarbrough et al. 1981)

• Increased smooth endoplasmic reticulum content (Baker et al. 1972; Curtis et al. 1981; Davison 

et al. 1976; Fulfs et al. 1977; Gaines and Kimbrough 1970; Mehendale et al. 1989)

• Increased microsomal protein content (Chambers and Trevethan 1983; Davison et al. 1976; Elgin 

et al. 1990; Karl and Yarbrough 1984; Klingensmith and Mehendale 1983a; Pittz et al. 1979; 

Villeneuve et al. 1977; Yarbrough et al. 1981, 1986a)

• Increased CYP450 content (Baker et al. 1972; Chambers and Trevethan 1983; Cianflone et al. 

1980; Curtis et al. 1981; Davison et al. 1976; Fujimori et al. 1983; Iverson 1976; Klingensmith 

and Mehendale 1983a; Kocarek et al. 1991; Peppriell 1981; Robacker et al. 1981; Robinson and 

Yarbrough 1978a; Yarbrough et al. 1981, 1986a)

• Increased NADPH2-cytochrome c reductase (Chambers and Trevethan 1983; Fujimori et al. 

1983; Robacker et al. 1981; Yarbrough et al. 1986a), accompanied or unaccompanied by an 

increase in microsomal enzyme activity (Byard et al. 1975; Chadwick et al. 1977; Chambers and 

Trevethan 1983; Chu et al. 1981a, 1981b; Cianflone et al. 1980; Curtis et al. 1981; Fabacher and 

Hodgson 1976; Iverson 1976; Mehendale et al. 1973; Robacker et al. 1981; Stevens et al. 1979; 

Villeneuve et al. 1977; Warren et al. 1978; Yarbrough et al. 1981, 1986a)

Marked hepatic toxicity has been observed in laboratory animals orally exposed to mirex. The primary 

form of hepatotoxicity observed in rats is hepatobiliary toxicity, typically expressed as decreased 

hepatobiliary excretion of selected substances often in the presence of increased bile flow (e.g., Bell and 

Mehendale 1985; Berman et al. 1986; Curtis and Mehendale 1979; Dahlstrom-King et al. 1992; Hewitt et 

al. 1986a; Larson et al. 1979a; Mehendale 1976, 1977a, 1979; Teo and Vore 1991). Decreased uptake of 
MIREX AND CHLORDECONE 86

2. HEALTH EFFECTS

substances into rat hepatocytes was observed after gavage dosing, suggesting that transport of substances 

into hepatocytes may contribute to the decrease in their biliary excretion (Teo and Vore 1990).

Other evidence of generalized mirex-related hepatic toxicity in orally-exposed laboratory animals 

includes:

• Increases in serum ALT and/or AST (Fouse and Hodgson 1987; Mitra et al. 1990)

• Periportal liposis and degeneration of the endoplasmic reticulum (Kendall 1979)

• Increased hepatic lipids or decreased hepatic glutathione or glucocorticoid receptors (Ervin and 

Yarbrough 1983; Sunahara and Chiesa 1992; Thottassery and Yarbrough 1991)

• Swollen hepatocytes or megalocytosis (NTP 1990; Plaa et al. 1987; Ulland et al. 1977)

• Increased hepatic lipid (Fulfs et al. 1977)

• Increased serum triglycerides (Jovanovich et al. 1987)

• Hepatic glycogen depletion in rats (Elgin et al. 1990; Ervin and Yarbrough 1983; Jovanovich et 

al. 1987; Kendall 1974, 1979) and mice (Fujimori et al. 1983)

• Vacuolation, necrosis, and/or degeneration (Chu et al. 1981b; Davison et al. 1976; Gaines and 

Kimbrough 1970; Hewitt et al. 1979; Larson et al. 1979a; NTP 1990)

Chlordecone. Mild hepatomegaly (occasionally with splenomegaly) was noted in 9 of 23 workers with 

chlordecone blood levels in excess of 2 μg/L, but there were no observed changes in organ function and 

only slight increases in serum alkaline phosphatase in several of the men (Taylor 1982, 1985; Taylor et al. 

1978). When liver function and structure were evaluated in 32 men exposed to high concentrations of 

chlordecone while employed for 1–22 months (5.6 months average) in the production of chlordecone,

hepatomegaly was reported in 20 of the workers, 10 of whom exhibited minimal splenomegaly as well 

(Guzelian et al. 1980). In the exposed workers, urinary excretion of glucaric acid was significantly 

increased and the half-life of orally administered antipyrine in the blood was significantly decreased, 

indicating increased microsomal enzyme activity. Needle biopsies of hepatic tissue from 12 of the 32 

workers showed marked proliferation of smooth endoplasmic reticulum in several samples. All of these 

are considered to be adaptive changes. Limited evidence of hepatic toxicity in these workers included 

small increases in serum alkaline phosphatase in 7 of the 32 workers. In addition, liver biopsies showed 

lipofuscin accumulation in 11 of 12, mild inflammatory changes in 5 of 12, vacuolization of nuclei in 3 of 

12, mild portal fibrosis in 3 of 12, fatty infiltration in 3 of 12, and paracrystalline mitochondrial inclusions 

in 4 of 12 individuals tested. Retention of sulfobromophthalein (intravenously administered to evaluate 
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liver function) was normal; serum levels of bilirubin, albumin, globulin, ALT and AST activity, and γglutamyl transferase activity were also normal (Guzelian et al. 1980).

Chlordecone causes both adaptive and toxic changes in the livers of experimental animals. Adaptive 

responses of the liver seen after oral exposure of rats, mice, or gerbils to chlordecone include the 

following:

• Increased liver size or weight (Cannon and Kimbrough 1979; Chernoff and Rogers 1976; Curtis 

and Mehendale 1979; EPA 1986a; Fabacher and Hodgson 1976; Fujimori et al. 1983; Huber 

1965; Larson et al. 1979b; Mehendale 1981; Mehendale et al. 1977, 1978; Purushotham et al. 

1988; Simmons et al. 1987; Swartz and Schutzmann 1986, 1987)

• Hepatocellular hypertrophy (Cannon and Kimbrough 1979)

• Increased smooth endoplasmic reticulum content (Curtis et al. 1981; Lockard et al. 1983a, 

1983b; Mehendale et al. 1989)

• Increased microsomal protein content (Chambers and Trevethan 1983; Klingensmith and 

Mehendale 1982b, 1983b; Mehendale et al. 1977, 1978)

• Increased CYP450 content (Agarwal and Mehendale 1984b; Britton et al. 1987; Cai and 

Mehendale 1990; Chambers and Trevethan 1983; Chaudhury and Mehendale 1991; Fabacher and 

Hodgson 1976; Fujimori et al. 1983; Kitchin and Brown 1989; Klingensmith and Mehendale 

1982b, 1983b; Kocarek et al. 1991; Mehendale et al. 1977, 1978)

• Increased NADPH2-cytochrome c reductase (Chambers and Trevethan 1983; Fujimori et al. 

1983; Mehendale et al. 1977, 1978); and/or microsomal enzyme activity (Chaudhury and 

Mehendale 1991; Cianflone et al. 1980; Curtis et al. 1981; Fabacher and Hodgson 1976; 

Klingensmith and Mehendale 1982b; Mehendale et al. 1977, 1978)

Indicators of chlordecone-induced liver toxicity in orally-exposed laboratory animals include:

• Decreased bile acid concentration, decreased bile acid secretion, and increased bile flow (Teo and 

Vore 1991)

• Decreased serum triglycerides and LDL cholesterol (Chetty et al. 1993a, 1993b)

• Increased serum alkaline phosphatase and ALT (EPA 1986a)

• Increased mannitol recovery (indicates decreased permeability of the canalicular membrane) or 

increased lysosomal fragility (Hewitt et al. 1986a, 1990)

• Decreased hepatic glycogen (Fujimori et al. 1983)
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• Vacuolation, necrosis, and/or degeneration (Cannon and Kimbrough 1979; Hewitt et al. 1979; 

Huber 1965; NCI 1976)

• Hepatocellular hyperplasia (NCI 1976)

Several studies reported decreased biliary excretion of selected xenobiotics following repeated oral 

exposure to chlordecone (e.g., Curtis and Hoyt 1984; Curtis and Mehendale 1979; Curtis et al. 1979, 

1981; Faroon and Mehendale 1990; Faroon et al. 1991; Mehendale 1977b). These effects were observed 

in the absence of biochemical or histopathological evidence of chlordecone treatment-related adverse 

liver effects. The altered biliary excretion of selected xenobiotics is not considered of itself representative 

of an adverse liver effect; therefore, the results are not summarized in Table 2-4 or plotted in Figure 2-4.

Ultrastructural changes in livers from rats receiving chlordecone from the diet for 15 days at 

0.86 mg/kg/day included fragmentation of, and/or a decrease in rough endoplasmic reticulum, minute 

vacuolation of the cytoplasm, and/or tortuous bile canaliculi and deformed and swollen microvilli (Curtis 

et al. 1981; Faroon and Mehendale 1990; Faroon et al. 1991). These ultrastructural changes were 

observed in the absence of light microscopic evidence of histopathological liver effects. Furthermore, 

similar ultrastructural effects were not observed in another study that employed similar exposure of the 

same strain of rats (Lockard et al. 1983a, 1983b). Therefore, these ultrastructural changes are not 

considered evidence of chlordecone treatment-related adverse liver effects and are not summarized in 

Table 2-4 or plotted in Figure 2-4.

2.10 RENAL

Mirex. No data were located regarding renal effects in humans exposed to mirex. No effect on rat kidney 

weight or blood urea nitrogen and no adverse histopathological findings were reported following a single 

oral dose at 50 mg/kg or three daily doses at 10 mg/kg/day (Plaa et al. 1987). No effect on kidney weight, 

blood urea nitrogen, or ion exchange in the kidneys and no adverse histopathological findings were 

reported in mice following a single oral dose at 50 mg/kg (Hewitt et al. 1979). No treatment-related 

histopathological renal effects or changes in urinalysis parameters were observed in 13-week oral studies 

of rats receiving mirex from the diet at doses as high as 110 mg/kg/day or dogs receiving mirex from the 

diet at doses as high as 2.5 mg/kg/day (Larson et al. 1979a). Chu et al. (1980b) reported moderate focal 

lymphoid aggregates and multiple focal interstitial mononuclear infiltrates in the kidneys of 2/10 rats 

following dietary exposure to mirex for 28 days at 0.086 mg/kg/day. However, the significance of these 

findings is limited by the low number of animals with these findings and the use of only a single dose, 

precluding determination of the presence or absence of a dose-response relationship. Nephropathy 
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increased in severity in rats following 2 years of dietary exposure to mirex at 20.7 mg/kg/day among 

males and ≥2 mg/kg/day among females (NTP 1990). 

Chlordecone. No data were located regarding renal effects in humans exposed to chlordecone. Increases 

in blood urea nitrogen and kidney weight were observed following a 10-day oral exposure of rats to 

chlordecone at 10 mg/kg/day (EPA 1986a). An increase in eosinophilic inclusions in the proximal 

tubules was observed in 2 of 10 rats examined following oral exposure to chlordecone for 28 days at 

0.05 mg/kg/day (Chu et al. 1980b). However, the biological significance of this finding is unknown 

based on the small number of animals with this lesion and the use of only one dose, precluding the 

determination of a dose-response relationship. Renal pathology was observed in rats following 

intermediate- and chronic-duration exposures to relatively small oral doses of chlordecone. At 9 months 

of a 2-year oral study of rats receiving chlordecone from the diet, higher concentrations of urinary protein 

were reported in all groups of chlordecone-treated males and in females treated ≥0.48 mg/kg/day 

compared to controls (Larson et al. 1979b). At most time points ≥1 year, higher concentrations of urinary 

protein were observed in males and females at all treatment levels. However, statistical comparisons 

were not performed and only 5 males and 5 females per group were evaluated, thus precluding 

meaningful conclusions regarding adverse effect levels. At 12- and 24-month sacrifices, relative kidney 

weights among chlordecone-treated groups were not significantly different from those of controls. At 

12-month sacrifice, there was no evidence of treatment-related kidney lesions. At 2-year terminal 

sacrifice, the severity of observed glomerulosclerosis was increased in both males and females at doses 

≥0.45 mg/kg/day. No increases in urinary protein or adverse histopathological changes were seen in the 

kidneys of dogs receiving chlordecone from the diet for 124–128 weeks at 0.625 mg/kg/day (Larson et al. 

1979b).

2.11 DERMAL

Mirex. No data were located regarding dermal effects in humans exposed to mirex. Hair loss in the very 

young is the primary dermal effect observed in animals as a result of oral exposure to mirex. Hair loss 

was reported in an acute-duration exposure study in which rats were given a total of 365 mg/kg in the diet 

over a 12-day period (Kendall 1974), but a LOAEL could not be determined because the daily dose was 

not reported. Hair loss was also reported in a 90-day gavage study in rats (5, 12.5, and 25 mg/kg/day) 

(Dietz and McMillan 1979), but the specific dose associated with this effect was not specified, precluding 

determination of LOAEL for this effect. Mild epidermal proliferation was reported among mice 

administered dermal application of mirex at 3.6 mg/kg, 3 times/week for 4 weeks (Moser et al. 1992). 
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Application of an unspecified amount of mirex to the skin of rabbits for 6–7 hours/day, 5 days/week for 

9 weeks, resulted in slight erythema and scaling after day 5 (Larson et al. 1979a). This effect was 

reversible after 2 days without treatment.

Chlordecone. Eighty-nine of 133 workers interviewed as a result of intermediate- or chronic-duration 

occupational exposure to high concentrations of chlordecone during its manufacture reported skin rashes 

of an erythematous, macropapular nature at some time during occupational exposure to high 

concentrations of chlordecone during its manufacture (Cannon et al. 1978). Among 23 of these workers 

with blood chlordecone levels in excess of 2 μg/L, 6 men reported rashes following exposure (Taylor et 

al. 1978). It is likely that these rashes were the direct result of dermal exposure. However, insufficient 

information was given to eliminate a systemic effect resulting from inhalation and/or oral exposure.

No signs of dermal irritation were observed in rabbits following dermal application of a 20% solution of 

chlordecone in corn oil of chlordecone (Larson et al. 1979b). No effects on the skin were observed during 

routine histopathological analyses of the skin of rats receiving chlordecone from the diet for 90 days at 

doses as high as 7.37–8.21 mg/kg/day or for 2 years at doses as high as 4 mg/kg/day, or in dogs exposed 

for 124–128 weeks at doses as high as 0.625 mg/kg/day (Larson et al. 1979b). Increased dermatitis was 

reported in an 80-week dietary cancer bioassay of rats receiving chlordecone from the diet at doses as low 

as 0.56 mg/kg/day (NCI 1976).

2.12 OCULAR

Mirex. No data were located regarding ocular effects in humans exposed to mirex.

Production of cataracts in the very young was observed in rats receiving mirex orally during 12 days at a 

total dose of 365 mg/kg (Kendall 1974); a LOAEL could not be determined because the daily dose was 

not reported. Cataracts were produced in other newborn rats and mice following early postnatal oral 

exposure (Chernoff et al. 1979a; Rogers and Grabowski 1984; Scotti et al. 1981). Cataracts were 

characterized as diffuse anterior corneal opacities, and lenses were found to have increased water and 

sodium content relative to potassium content (Rogers and Grabowski 1984). Histopathological analyses 

showed increased vacuoles, pyknotic nuclei, swollen fibers, and/or degeneration. Cataracts were 

produced in newborn rodents that received mirex indirectly through the mother’s milk (Chernoff et al. 

1979a; Rogers and Grabowski 1984). Administration of mirex directly to the newborn by gavage at 

5 mg/kg/day starting on postpartum day 1 resulted in swelling of the lens fibers as early as postpartum 
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day 7, with degeneration and necrosis of the lenses apparent with increasing duration of exposure (Scotti 

et al. 1981). Dietary exposure of maternal animals to mirex at doses as low as 1.25 mg/kg/day during 

postpartum days 1–4 or to doses as low as 1.8–2.8 mg/kg/day throughout the period of lactation (Gaines 

and Kimbrough 1970) also resulted in cataracts in rat pups. Exposure during the first few days of life 

appears to be critical to the development of cataracts. A single oral dose resulted in cataracts only if 

administered on or before postpartum day 6 and resulted in outlined lenses if administered on or before 

postpartum day 8 (Chernoff et al. 1979a). Eye irritation was also reported in a 90-day gavage study of 

rats (5, 12.5, and 25 mg/kg/day), but the specific dose associated with this effect was not specified, thus 

precluding determination of a LOAEL (Dietz and McMillan 1979).

Chlordecone. Vision was blurred in 15 of 23 workers with chlordecone blood levels in excess of 2 μg/L; 

the workers were occupationally exposed during the manufacture of chlordecone (Taylor 1982, 1985). 

Other effects on vision are discussed in Section 2.15 (Neurological). 

There was no indication of treatment-related ocular effects on the offspring of maternal rats or mice orally 

exposed to chlordecone during the first 4 days of lactation at doses as high as 10 and 24 mg/kg/day, 

respectively (Chernoff et al. 1979b).

2.13 ENDOCRINE

Thyroid

Limited information was located regarding mirex or chlordecone and thyroid status in humans. Han et al. 

(2019) reported an inverse association between serum mirex/chlordecone levels and incidence of thyroid 

disease in a case-control study in eastern China (see Tables 2-1 and 2-2 for additional information).

Mirex. Studies in rats indicate that mirex is toxic to the thyroid (Chu et al. 1981a, 1981b; NTP 1990; 

Singh et al. 1982, 1985). Doses of 0.49 mg/kg/day mirex in the diet for 28 days resulted in a reversible 

reduction in colloid, a thickening of follicular epithelium, and angular collapse of the follicles, but no 

effect on serum levels of T3 or T4 (Chu et al. 1980a, 1981a, 1981b). Ultrastructural analyses of thyroids 

from rats treated for 28 days showed dilation of the rough endoplasmic reticulum at 0.67 mg/kg/day and 

increased columnar cells with irregularly shaped lysosomal bodies, dilation of cisternae, and increased 

vacuolization at 6.7 mg/kg/day (Singh et al. 1982, 1985). Similar effects were observed following dietary 

exposure to 0.25 mg/kg/day for 148 days (Chu et al. 1981a) and for 28 days (Chu et al. 1981b). Dietary 
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exposure to 0.7 mg/kg/day and above for 2 years also resulted in an increase in cystic follicles in male rats 

(NTP 1990). 

Chlordecone. No studies were located regarding thyroid effects in animals exposed to chlordecone.

Adrenal

Mirex. No studies were located regarding adrenal gland effects in humans exposed to mirex. Studies in 

animals indicate that the adrenal gland hypertrophies and releases increased levels of corticosterone in 

response to mirex exposure (Ervin and Yarbrough 1985; Jovanovich et al. 1987; Williams and Yarbrough 

1983). Single gavage doses of 20 mg/kg resulted in an increased level of serum corticosterone in rats 

(Williams and Yarbrough 1983); 100 mg/kg resulted in increases of adrenal weight, cholesterol, lipid, and 

protein content (Williams and Yarbrough 1983) and increased serum adrenocorticotropic hormone (Ervin 

and Yarbrough 1985). Seven days of exposure at 2,100 mg/kg/day also increased adrenal weight in rats 

(Jovanovich et al. 1987). Consistent with the ability of corticosterone to mobilize fatty acids for energy, a 

decrease in body fats was observed in this study. No effects on the adrenal medulla were observed 

following 8-day dietary exposure of rats to mirex at 17 mg/kg/day (Baggett et al. 1980).

Chlordecone. Emeville et al. (2013) found no association between serum chlordecone and blood levels 

of steroid hormones in a population-based cross-sectional study; see Error! Reference source not found.

for additional study details.

Limited information is available regarding the effects of chlordecone on the adrenal glands of animals. 

Increased relative adrenal weight was observed in rats following a single oral dose of 35 mg/kg (Swanson 

and Wooley 1982) and following 10 days of gavage dosing at 10 mg/kg/day (EPA 1986a). An enlarged 

adrenal gland with hyperplasia and hypertrophy of the cortical cells was observed in rats receiving 

chlordecone from the diet for 3 months at 1.17 mg/kg/day (Cannon and Kimbrough 1979). Decreased 

adrenal lipid was reported for rats receiving chlordecone from the diet for 90 days at 2.4 mg/kg/day 

(Larson et al. 1979b). Consistent with a corticosterone-induced increase in lipid utilization, decreased 

body fat was observed in rats receiving chlordecone from the diet for 16 days at 2.5 or 5 mg/kg/day

(Mehendale et al. 1977, 1978), 15 or 20 days at 9.7 mg/kg/day (Klingensmith and Mehendale 1982a), or 

in mice treated for 33 days at 10 mg/kg/day (Fujimori et al. 1983). In contrast to the absence of mirexrelated noncancer effects on the adrenal medulla, chlordecone induced a decrease in the medullary 

content of epinephrine of rats orally treated for 8 days at 17 mg/kg/day (Baggett et al. 1980).
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2.14 IMMUNOLOGICAL

Mirex. No studies were located regarding immunological effects in humans exposed to mirex. Available 

information regarding potential for mirex-induced immunological effects in animals is limited to a single 

account of 32% decreased spleen weight among maternal rats gavaged with mirex at 10 mg/kg/day for up 

to 10 days during gestation (Buelke-Sam et al. 1983). Oral administration of chlordecone in corn oil to 

male Fischer 344 rats did not cause dose-related changes in lymphoproliferative responses of splenic 

lymphocytes to the T-cell mitogens, phytohemagglutinin or pokeweed mitogen; it did cause decreases in 

the proliferative response to the T-cell mitogen, concanavalin A, and the B-cell mitogen, Salmonella 

typhimurium mitogen, but only at a dose (10 mg/kg/day for 10 days) that also resulted in impaired overall 

health of the rats (EPA 1986a; Smialowicz et al. 1985). Statistically significant reductions in spleen and 

thymus weights, and in natural killer cell activity of splenocytes against allogeneic (W/Fu-Gl rat 

lymphoma) and xenogeneic (YAK-1 mouse lymphoma) tumor cell lines (EPA 1986a; Smialowicz et al. 

1985), were observed in rats only at a dose (10 mg/kg/day) producing generalized toxicity. Also, a slight 

decrease in total leukocyte count (EPA 1986a) and a 49% decrease in neutrophils (Smialowicz et al. 

1985) were observed at toxic doses. The authors suggested that these effects were associated with the 

compromised health status of the animals and were not due to selective toxicity toward the immune 

system. The limitations of these studies include lack of information on cell-mediated functions, such as 

alloantigen reactivity and cytotoxicity, and on humoral immunity in the treated animals. However, as part 

of a study evaluating the effects of calcium deficiency on the toxicity of chlordecone in male rats, an 

increase in plaque-forming cells was observed at the lowest chlordecone dose tested (0.86 mg/kg/day) 

(Chetty et al. 1993c).

Chlordecone. No studies were located regarding immunological effects in humans exposed to 

chlordecone. A significant reduction of thymus weight was observed in rats 3 weeks after a single oral 

dose of chlordecone at 75 mg/kg (Swanson and Wooley 1982). It is likely that this effect may have been 

associated with generalized toxicity in the experimental animals.

2.15 NEUROLOGICAL

Mirex. No studies were located regarding neurological effects in humans exposed to mirex. Clinical 

signs indicative of neurotoxicity have not been widely reported in animals treated with mirex. However, 

a number of studies did note some abnormal behavior following oral administration of mirex. Following 

acute-duration exposures of rats to large doses (12.5–>365 mg/kg) of mirex, lethargy, weakness, 
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hyperexcitability, and/or tremors have been observed (Gaines and Kimbrough 1970; Kendall 1974). 

Although the precise doses associated with specific neurotoxic effects were not specified in these studies, 

single oral doses at ≥100 mg/kg were necessary. Juvenile rats showed a high sensitivity to acute exposure 

to mirex immediately after birth. Lactational exposure via dams treated with mirex at 2.5 mg/kg/day on 

lactation days 1–4 caused no behavioral abnormalities at the time of exposure, but resulted in increased 

activity when the offspring reached adulthood (Reiter 1977).

Intermediate-duration exposures to mirex generally resulted in lethargy as the predominant clinical sign at 

lower exposures and hyperexcitability at higher doses. Lethargy was observed at a mirex dose level of 

8.2–10 mg/kg/day during both 15- and 30-day dietary studies in rats (Curtis and Hoyt 1984; Mehendale 

1981). Decreased operant responding was also observed in rats gavaged for 90 days at 5 mg/kg/day 

(Dietz and McMillan 1979). Mirex had no effect on motor coordination of mice gavaged for 15 days at 

10 mg/kg/day, but some mice were observed to become too weak to balance on a glass rod during the 

15-day treatment period (Fujimori et al. 1983). In a 13-week dietary study of rats, mirex treatment at 

28 mg/kg/day did not affect behavior, but at 110 mg/kg/day, rats became hyperexcitable and developed

tremors and convulsions (Larson et al. 1979a). Longer-duration exposures also resulted in increased 

excitability. Hypoactivity, irritability, and tremors were observed in rats receiving mirex from the diet for 

up to 148 days at 3 mg/kg/day (Chu et al. 1981a).

Chlordecone. Examinations of 133 workers occupationally exposed to chlordecone during its production 

revealed 61 cases of tremors, 58 cases of nervousness or unfounded anxiety, and 42 cases of visual 

difficulties (Cannon et al. 1978). Tremors were observed in all 23 workers with blood chlordecone levels 

in excess of 2 μg/L (Taylor et al. 1978). The tremors were characterized as intention tremors or as 

occurring with a fixed posture against gravity (Taylor 1982, 1985). The tremors were most apparent in 

the upper extremities, but were also detectable in the lower extremities. In the more severe cases, gait 

was affected. Mental disturbances consisting of irritability and poor recent memory were reported by 

13 of the 23 workers. Standard tests of memory and intelligence showed clear evidence of an 

encephalopathy in 1 of the 13 workers (Taylor 1982, 1985). The worker with encephalopathy reported 

auditory and visual hallucinations and demonstrated whole-body myoclonic jerks in response to loud 

noises. In 15 of the 23 workers, vision was blurred (Taylor 1982, 1985). Other effects on vision were 

characterized by a disruption of ocular motility by a brief series of rapid multidirectional eye movements 

at the end of a saccade (a quick, simultaneous movement of both eyes between two or more phases of 

fixation in the same direction). Visual acuity and smooth pursuit eye movements were unaffected. The 

rapid eye movements were considered to conform to the usual description of opsoclonus (a saccadic 
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oscillation without intersaccadic intervals, consisting of conjugate multidirectional saccades occurring in 

random directions with varying amplitudes). Headaches of mild-to-moderate severity were reported by 

9 of the 23 workers. Three of these nine workers had increased cerebrospinal fluid pressure and 

papilledema (Sanborn et al. 1979; Taylor 1982, 1985). Nerve conduction velocity tests, 

electroencephalography, radioisotope brain scans, computerized tomography, and analyses of cerebral 

spinal fluid content were normal. Sural nerve biopsies obtained from five workers with detectable tremor, 

mental disturbances consisting of irritability and poor recent memory, rapid random eye movements, 

muscle weakness, gait ataxia, incoordination, or slurred speech revealed a greatly decreased number of 

small myelinated and unmyelinated axons (Martinez et al. 1978). Ultrastructural analyses of the nerves 

showed increased interstitial collagen, redundant folds in the Schwann cell cytoplasm, and the presence of 

occasional crystalloid inclusions suggesting that chlordecone exerted a direct toxic effect on the Schwann 

cell. Examination of 16 of the 23 affected individuals from 5 to 7 years after cessation of exposure and 

after body levels of chlordecone had been substantially reduced showed that 9 were asymptomatic, 5 had 

persistent tremor or nervousness, and 3 had emotional problems (Taylor 1982, 1985).

The neurotoxicity of chlordecone, which includes tremoring and/or a time-dependent exaggerated startle 

response, has been widely studied in experimental animals. Single oral doses of chlordecone resulted in 

increased tremoring and/or an exaggerated response to audio or tactile stimuli (Albertson et al. 1985; 

Aldous et al. 1984; Egle et al. 1979; End et al. 1981; Huang et al. 1980; Hwang and van Woert 1979; 

Maier and Costa 1990; Swanson and Wooley 1982). Following single oral doses as low as 3.5 mg/kg in 

rats, increased tremoring during handling was observed for up to 1 week (Swanson and Wooley 1982). In 

mice, tremors, decreased motor coordination, and hyperexcitability were observed following a single oral 

dose of chlordecone at 10 mg/kg (Huang et al. 1980). In these studies, the tremors were apparent at 

earlier times when higher doses were used than when lower doses were used. Abnormal gait was also 

apparent after single oral doses of 72–98 mg/kg (Egle et al. 1979). Slightly lower multiple oral doses 

given over several days produced increased tremors, exaggerated startle responses, and/or abnormal gait 

(Aldous et al. 1984; Baggett et al. 1980; Chang-Tsui and Ho 1979; Desaiah et al. 1980b; Fujimori et al. 

1982a; Hoskins and Ho 1982; Huang et al. 1980; Jordan et al. 1981; Klingensmith and Mehendale 1982b; 

Mishra et al. 1980; Smialowicz et al. 1985). In rats, tremors and an exaggerated startle response were 

observed at oral doses as low as 9.7 mg/kg/day over 5 days (Klingensmith and Mehendale 1982b). An 

increased startle response without visible tremoring was observed at doses as low as 2.5 mg/kg/day over 

10 days (EPA 1986a). This study was part of a toxicity screen performed at EPA in which male Fischer344 rats received gavage doses of chlordecone at 0.625–10 mg/kg/day for 10 consecutive days. At a dose 

of 2.5 mg/kg/day, the amplitude of the acoustic startle response was significantly increased with the 
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highest decibel stimulus (80 decibels). At 5 and 10 mg/kg/day, the amplitude of the acoustic startle 

response was significantly increased with all intensities of stimulus (50, 65, and 80 decibels). Motor 

activity in a figure-8 maze was decreased at 10 mg/kg/day. 

Tremoring, accompanied or unaccompanied by increased responsiveness to touch and noise, have also 

been observed in a number of intermediate-duration studies of chlordecone (Agarwal and Mehendale 

1984a; Cannon and Kimbrough 1979; Curtis and Hoyt 1984; Curtis and Mehendale 1979; Dietz and 

McMillan 1979; Fujimori et al. 1983; Huber 1965; Klingensmith and Mehendale 1982a; Larson et al. 

1979b; Linder et al. 1983; Mehendale 1981; Mehendale et al. 1978; Pryor et al. 1983; Squibb and Tilson 

1982a; Swartz and Schutzmann 1986, 1987). Mild tremors were observed in rats receiving chlordecone 

from the diet for up to 90 days at doses as low as 0.83 mg/kg/day (Linder et al. 1983). Squibb and Tilson 

(1982a) reported increased startle response among rats receiving chlordecone from the diet at an 

estimated dose of 1.0 mg/kg/day, but no tremoring or effects on reflexes such as the tail flick response or 

the negative geotaxis test were observed, indicating that the startle response may be a sensitive indicator 

of chlordecone-induced neuronal dysfunction (Squibb and Tilson 1982a). Chronic-duration studies in rats 

have also demonstrated increased tremoring. Tremoring was observed at 2.2 mg/kg/day but not at 

0.89 mg/kg/day in a 2-year rat dietary study (Larson et al. 1979b). Tremoring was also observed in rats 

and mice receiving chlordecone from the diet for up to 80 weeks at doses as low as 0.56 and 

3.4 mg/kg/day, respectively (NCI 1976). No tremors or other behavioral abnormalities were observed in 

dogs receiving chlordecone from the diet for up to 2 years at 1.2 mg/kg/day (Larson et al. 1979b).

Several acute-duration studies have attempted to correlate the tremoring with underlying neurochemical 

changes. However, in many cases, it has been difficult to determine whether the effects observed were 

causative or the result of other underlying effects. Inhibition of brain Na+K+

ATPase and Mg2+ATPases 

has been correlated with the onset and diminution of tremoring in both rats and mice (Bansal and Desaiah 

1985; Desaiah et al. 1980b; Jordan et al. 1981). However, other studies have not produced similar results 

(Maier and Costa 1990; Mishra et al. 1980). In rats, mixed results have been obtained regarding changes 

in norepinephrine and dopamine levels in brains from treated animals. Some studies have reported that 

norepinephrine uptake and dopamine uptake and binding were decreased (Chang-Tsui and Ho 1980;

Desaiah 1985) and striatal dopamine synthesis, uptake, and release were inhibited (Fujimori et al. 1986) at 

tremorgenic doses; other studies have found no effect on norepinephrine or on dopamine content (Aldous 

et al. 1984; End et al. 1981) or synthesis (End et al. 1981) at equally tremorgenic doses. Effects on 

calcium have also been observed in treated rats and mice. Decreased calcium uptake occurred in rats 

following a single oral dose of 40 mg/kg (End et al. 1981), and decreased brain calcium content was 
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2. HEALTH EFFECTS

observed in adult mice following a single oral dose of 25 mg/kg (Hoskins and Ho 1982). Decreased brain 

calmodulin was observed in rats at 2.5 mg/kg/day for 10 days (Desaiah et al. 1985).

2.16 REPRODUCTIVE

Mirex. Possible associations between serum mirex and selected reproductive health outcomes were 

evaluated in three studies. In a cross-sectional study of women, 45–55 years of age, participating in the 

National Health and Nutrition Examination Survey (NHANES), serum mirex was associated with being 

menopausal (Grindler et al. 2015). In a case-control study, there was no significant difference in 

geometric mean mirex level (lipid-standardized) between endometriosis cases controls (Lebel et al. 

1998). A borderline association was reported for mirex serum level and risk of endometriosis in a 

population-based case-control study; however, no association was found when cases were limited to 

ovarian endometriosis (Upson et al. 2013). See Error! Reference source not found. for additional study 

details.

Studies in animals suggest that both male and female reproductive systems are adversely affected by 

mirex. Gavage treatment of male rats to 6 mg/kg/day mirex daily for 10 days decreased their fertility 

significantly. Although residues of mirex were found in the testes, this did not affect reproduction 

parameters in subsequent mating trials. The authors attributed the observed decrease in the incidence of 

pregnancy in females mated with males in this dose group in the first trial to a subclinical toxic effect as 

suggested by reduction in body weight gain in the dosed males (Khera et al. 1976). Gestational exposure 

of female rats with higher dosages (12.5 mg/kg/day; gestation days 6–15) of mirex resulted in increased 

resorptions and failure of pregnancy in 45% of dams (Grabowski and Payne 1980; Khera et al. 1976). 

Gestational gavage treatment of female rats at 10 mg/kg/day for 5 days resulted in decreased ovarian and 

uterine weights and reduced blood flow to the ovaries, uterus, and fetuses (Buelke-Sam et al. 1983). This 

effect was not observed if the duration of exposure during gestation was shortened to 1 day or lengthened 

to 10 days; thus, the significance of this effect is unknown.

Gavage administration of mirex to adult male CD-1 mice at 5 mg/kg/day for 21 days resulted in 

approximately 27% decreased mean absolute seminal vesicle weight; the mean body weight of mirextreated mice was not significantly different from controls (Dai et al. 2001). In a 28-day dietary study, 

decreased sperm count was noted in male rats at dosages as low as 0.043 mg/kg/day (Yarbrough et al. 

1981); the significance of this finding is unclear because the decreases were not dose-related and was not 

observed at the highest dose (6.5 mg/kg/day) tested. The study also reported testicular degeneration at
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6.5 mg/kg/day. However, there was no evidence of treatment-related effects on fertility when mirex was 

fed to male rats at 1.3–3.1 mg/kg/day for 2 generations (Gaines and Kimbrough 1970). In contrast, 

females given 1.8–2.8 mg/kg/day for 2 generations produced decreased numbers of litters (Gaines and 

Kimbrough 1970). Administration of 0.49 mg/kg/day to male and female rats for 91 days prior to mating 

and then through lactation resulted in decreases in mating and litter size (Chu et al. 1981b). Male and 

female mice treated at 0.94 mg/kg/day for 30 days prior to mating, and then for an additional 90 days, 

experienced reduced fecundity and reduced litter size and number of offspring (Ware and Good 1967); 

however, only one dosage level was tested. Dietary exposure of wild mice to 2.4 mg/kg/day mirex for 

15 months inhibited reproduction (Wolfe et al. 1979). However, this study was limited in that few 

reproductive parameters were measured and mice of unknown genetic background were used.

Chlordecone. The available human data on chlordecone provide qualitative evidence to support the 

conclusion that intermediate- or chronic-duration exposures to high concentrations of chlordecone in the 

workplace causes oligospermia and decreases sperm motility among male workers (Guzelian 1982a, 

1982b; Taylor 1982, 1985; Taylor et al. 1978). The threshold for abnormally low sperm counts was 

considered to be approximately 1 μg chlordecone per liter of serum, and the number of motile sperm cells 

increased as the serum chlordecone concentration decreased (Guzelian 1982a). Despite loss of sperm 

motility in some of the workers, there were no reported difficulties with fertility (Taylor 1982, 1985). 

These studies, however, can only be used as suggestive evidence of chlordecone-induced male 

reproductive toxicity because the airborne concentrations of chlordecone and the frequency of exposure 

were not quantified and effects on sperm morphology were not examined.

Chlordecone produced reproductive toxicity in both male and female animals. Gavage dosing of male 

rats at 0.625, 1.25, or 5 mg/kg/day for 10 days resulted in decreased sperm count; however, increased 

sperm count was observed at 2.5 and 10 mg/kg/day and increased relative testes weight was noted at 

10 mg/kg/day (EPA 1986a). In a dominant lethality study, male rats were administered chlordecone by 

gavage for 5 days at 11.4 mg/kg/day, followed 2 days later by a 14-week mating period whereby the 

males were mated with naive, nulliparous females each week for 14 consecutive weeks (Simon et al. 

1986). There was no effect on male fertility under the conditions of the study. Persistent vaginal estrus 

was reported in female mice administered chlordecone by gavage for 2 weeks at 2 mg/kg/day (Swartz et 

al. 1988).

Effects observed after intermediate-duration exposure of male and female mice to chlordecone include 

decreases in numbers of litters, litter size, and frequency of litter production (Good et al. 1965; Huber 
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1965). These effects were observed at dietary doses as low as 1.87 mg/kg/day for 130 days (Huber 1965) 

and 0.94 mg/kg/day for 6 months (Good et al. 1965).

Dietary exposure of male rats to ≥0.83 mg/kg/day of chlordecone for 90 days resulted in decreased sperm 

motility and viability; at ≥1.67 mg/kg/day, decreases in seminal vesicle and prostate weights were 

observed (Linder et al. 1983). Despite these effects, the fertility, litter size, sperm morphology, sperm 

count, and histopathology of male gonads were unaffected. In a reproductive toxicity study, Cannon and 

Kimbrough (1979) evaluated the effects of chlordecone on fertility of male and female rats receiving 

chlordecone from the diet for 3 months at 0 or 1.17–1.58 mg/kg/day (males) and 0 or 1.62–

1.71 mg/kg/day (females). During a 4.5-month recovery period, mating of untreated females to 

chlordecone-treated males, chlordecone-treated females to untreated males, chlordecone-treated males to 

chlordecone-treated females, and untreated males to untreated females were performed twice. There were 

no apparent effects on fertility in pairings of control females with chlordecone-treated males; however, no 

litters were produced from matings of chlordecone-treated females to untreated males. In mice treated at 

higher doses (5.2 mg/kg/day chlordecone for 160 days), no effect on spermatogenesis occurred, but a 

decrease in litter size was observed when treated males were mated with control females (Huber 1965). 

Testicular atrophy was reported for adolescent rats receiving chlordecone from the diet for 90 days at 

2.1 mg/kg/day as part of a 2-year study (Larson et al. 1979b).

Intermediate-duration oral exposure of female animals indicates that chlordecone may cause effects such 

as persistent vaginal estrus, decreased ovulation, and reproductive failure. Persistent vaginal estrus was 

observed in female mice receiving chlordecone for 3–6 weeks at doses as low as 1.87–2 mg/kg/day 

(Huber 1965; Swartz and Mall 1989; Swartz et al. 1988). Increased atresia of follicles (Swartz and Mall 

1989), decreased ovulation (Swartz et al. 1988), and small- and medium-sized follicles (Swartz and Mall 

1989) were observed in mice after 4 weeks of exposure to 8 mg/kg/day of chlordecone. Similarly, 

decreased numbers of corpora lutea were observed in mice receiving chlordecone from the diet for 

130 days at 1.87 mg/kg/day (Huber 1965). Decreased numbers of litters or complete reproductive failure 

were observed among female rats receiving chlordecone from the diet for 3 months at 1.62 mg/kg/day 

(Cannon and Kimbrough 1979) and female mice receiving chlordecone from the diet for 160 days at

7.5 mg/kg/day for 160 days (Huber 1965).

The only animal study that referred to reproductive effects following dermal exposure to chlordecone was 

conducted in rabbits by Allied Chemical. This study was not available for review. A published review of 

the study (Epstein 1978) indicated that chlordecone applied to shaved skin for 8 hours/day, 5 days/week, 
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for 3 weeks induced testicular atrophy in two of six rabbits following application at 5 mg/kg and in one of 

six rabbits following application at 10 mg/kg. No other toxic effects were noted. This study is limited by 

the lack of dose response and lack of a NOAEL for the effect observed.

2.17 DEVELOPMENTAL

Mirex. Several epidemiological studies have evaluated potential associations between maternal mirex 

exposure and alterations in birth outcome and development of the reproductive and neurological systems; 

a summary of these studies is presented in Table 2-1. No associations between maternal blood or cord 

blood mirex levels and birth weight (Fenster et al. 2006; Guo et al. 2014; Hjermitslev et al. 2020), crownheel length (Fenster et al. 2006), gestation age at birth (Hjermitslev et al. 2020), or gestation length 

(Fenster et al. 2006) were observed. A birth cohort study reported inverse associations between maternal 

serum mirex levels and cord blood levels of testosterone, prolactin, cortisol, cortisone, androstenedione/

dehydroepiandrosterone, and testosterone/androstenedione in male infants (Araki et al. 2018). The study 

also found associations between maternal serum mirex and male cord blood dehydroepiandrosterone, 

follicle-stimulating hormone (FSH), adrenal androgen/glucocorticoid, and FSH/inhibin B. Additionally, a 

case-control study found an association between the presence of mirex in the placenta and the risk of 

urogenital malformations in male infants (Fernandez et al. 2007). However, the mean concentration of 

mirex in placentas from the control group was 3.7±3.37 ng/g of lipid, compared to only 1.4±1.1 ng/g of 

lipid in placentas from the group with urogenital malformations, a finding that underscores the fact that 

this association could not be attributed to mirex per se, but only to a combination of mirex and other 

mirex-like compounds. No association was found between serum mirex and menarcheal status in a 

population-based cohort of girls 10–16.9 years of age (Denham et al. 2005). A cross-sectional study 

found an inverse association between the presence of mirex in placental tissues and cognitive 

development in boys at 4 years of age, specifically reductions in working memory and quantitative 

function compared to unexposed children of the same age and sex (Puertas et al. 2010). 

Exposure of maternal rats and mice to mirex during gestation resulted in increases in resorptions and 

stillbirths and decreases in postnatal viability at doses as low as 6–10 mg/kg/day when administered 

during periods of gestation (Buelke-Sam et al. 1983; Byrd et al. 1981; Grabowski 1983; Grabowski and 

Payne 1980, 1983a, 1983b; Gray et al. 1983; Rogers and Grabowski 1983). Examination of fetuses at the 

end of gestation showed increases in the incidence of edematous fetuses and fetuses with cardiac 

arrhythmias (primarily first-degree heart block) (Buelke-Sam et al. 1983; Byrd et al. 1981; Chernoff et al. 

1979b; Grabowski 1981, 1983; Grabowski and Payne 1980, 1983a, 1983b; Kavlock et al. 1982; Khera et 
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al. 1976). The final trimester appeared to be the most sensitive period for induction of cardiac 

dysrhythmias; the incidence was slightly increased at doses as low as 0.1 mg/kg/day during gestation 

days 15.5–21.5 (Grabowski 1983). These effects were generally seen at lower doses than the increases in 

mortality. Other visceral anomalies were not widely reported, but instances of anomalies such as 

enlarged cerebral ventricles, undescended testes, ectopic gonads, hydrocephaly, scoliosis, cleft palate, 

fleshy heart, enlarged atrium, or short tail were reported in a few studies (Chernoff et al. 1979b; Kavlock 

et al. 1982; Khera et al. 1976). Additional effects observed in fetuses included decreased skeletal 

ossification (Chernoff et al. 1979b), decreased fetal weight (Buelke-Sam et al. 1983; Byrd et al. 1981; 

Chernoff and Kavlock 1982; Gray and Kavlock 1984; Gray et al. 1983; Kavlock et al. 1982; Khera et al. 

1976), decreased serum glucose and hematocrit (Rogers et al. 1984), decreased serum plasma proteins 

(Grabowski 1981), decreased fetal liver weight and glycogen content (Kavlock et al. 1982), decreased 

renal protein and alkaline phosphatase (Kavlock et al. 1982), decreased kidney weights at postpartum 

day 250 (Gray and Kavlock 1984; Gray et al. 1983), increased dyspnea (Grabowski and Payne 1983a),

and increased liver and thyroid lesions (Chu et al. 1981a). Cataracts were also observed in offspring in 

several studies (Chernoff et al. 1979b; Chu et al. 1981a; Gaines and Kimbrough 1970; Rogers and 

Grabowski 1983; Rogers et al. 1984); however, cataracts also resulted from early postnatal exposure 

(Chernoff et al. 1979a; Rogers and Grabowski 1984; Scotti et al. 1981).

Chlordecone. Several human studies were designed to evaluate possible associations between cord blood 

chlordecone levels and risk of developmental effects in participants in the TIMOUN prospective motherchild cohort study in Guadeloupe, French West Indies, where pesticides (including chlordecone) were 

extensively used on banana plantations. Kadhel et al. (2014) reported that maternal blood chlordecone 

levels were inversely associated with gestation length and associated with risk of preterm birth. Hervé et 

al. (2016) found no association between cord blood chlordecone level and gestational weight. No 

associations were observed between maternal blood chlordecone or cord blood chlordecone levels and 

risk of malformations or undescended testes (Rouget et al. 2019). Another study found that cord blood 

chlordecone level was positively associated with increased thyroid-stimulating hormone (TSH) level in 

male infants evaluated at 3 months of age and with free thyroxine levels in female infants at 3 months of 

age (Cordier et al. 2015). Cord blood chlordecone level was positively associated with increased body 

mass index in boys evaluated at 3 months of age and in girls at 8 months of age (Costet et al. 2015). Four 

studies evaluated possible associations between maternal chlordecone levels and neurodevelopment. 

Cord blood chlordecone level was associated with signs of neurodevelopmental delay in 7-month-old 

infants (Dallaire et al. 2012). Boucher et al. (2013) and Cordier et al. (2015) reported inverse associations

between cord blood chlordecone level and fine motor function among 18-month-old boys; no association 
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was found in girls. Among 7-year-old children, no association was observed between chlordecone in cord 

blood samples (taken at birth) or blood samples (taken at 7 years of age) and sex-typed toy preference 

(Cordier et al. 2019). 

Although impaired spermatogenesis among male workers occupationally exposed to chlordecone did not 

appear to affect their fertility (Guzelian 1982a, 1982b; Taylor 1982, 1985; Taylor et al. 1978), it is unclear 

whether abnormalities in their sperm may have resulted in developmental effects in offspring.

Gestational exposure of rats and mice to chlordecone resulted in increased stillbirths and decreased 

postnatal viability (Chernoff and Kavlock 1982; Chernoff and Rogers 1976; EPA 1986a; Gray and 

Kavlock 1984; Gray et al. 1983; Huber 1965; Kavlock et al. 1985; Seidenberg and Becker 1987; 

Seidenberg et al. 1986). The increase in fetal/pup mortality was observed at doses as low as 

10 mg/kg/day when administered to rats during gestation days 7–16 (EPA 1986a) and at doses as low as 

12 mg/kg/day when administered to mice during gestation days 7–16 (Chernoff and Rogers 1976). 

Edema was reported in rat fetuses at doses of 10 mg/kg/day during gestation days 7–16 (Chernoff and 

Rogers 1976), but this effect was not noted in other developmental toxicity studies with chlordecone. 

Other indicators of developmental toxicity included decreased fetal or neonatal weight and/or skeletal 

ossification (Chernoff and Kavlock 1982; Chernoff and Rogers 1976; EPA 1986a; Gray and Kavlock 

1984; Kavlock et al. 1985, 1987b; Seidenberg et al. 1986) and a few instances of anomalies and 

malformations such as enlarged renal pelvis, undescended testes, enlarged cerebral ventricles, clubfoot, 

fused vertebrae or ribs, and encephalocele (Chernoff and Rogers 1976; Kavlock et al. 1985). Anovulation 

and persistent vaginal estrus were observed in female offspring of maternal rats given 15 mg/kg/day of 

chlordecone on gestation days 14–20 (Gellert and Wilson 1979). However, no effects on vaginal patency 

or fertility were observed in female offspring of maternal mice gavaged at 20 mg/kg/day during gestation 

days 8–12 or 14–18 (Gray and Kavlock 1984).

Exposure of female rats to chlordecone for 60 days prior to mating through lactation day 12 showed 

subtle neurological changes in the offspring later in life (Rosecrans et al. 1982; Seth et al. 1981; Squibb 

and Tilson 1982b). Although major reflexes were unaltered, the offspring of dams exposed to 

0.3 mg/kg/day showed increased serotonin turnover and decreased dopamine in response to stress 

(Rosecrans et al. 1982). Offspring of mice exposed to 0.075 mg/kg/day in this exposure paradigm 

showed an increased reactivity to apomorphine (a dopamine agonist) (Squibb and Tilson 1982b). These 

studies suggest that perinatal exposure to low doses of chlordecone may affect dopaminergic function in 
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adult offspring; however, none of these studies demonstrated a treatment-related effect on neurological 

function. Therefore, the results are not summarized in Table 2-4 or plotted in Figure 2-4.

Squibb and Tilson (1982b) also noted significantly depressed mean body weight in the male and female 

offspring at postpartum day 100 from mothers receiving chlordecone from the diet at 0.45 and 

≥0.075 mg/kg/day, respectively. However, the toxicological significance of this finding is uncertain 

because there was no effect on offspring body weight at postpartum day 30. Therefore this result is not 

summarized in Table 2-4 or plotted in Figure 2-4.

Laessig et al. (2007) administered chlordecone (5 mg/kg) in a single intraperitoneal dose to pregnant 

Sprague-Dawley rats on gestation day 16 and assessed its effect on sexually-differentiated behavior of the 

adult offspring. The offspring were gonadectomized on postnatal day (PND) 50 to eliminate effects of 

circulating hormones and were sequentially tested for sex-typic spontaneous behaviors in open field 

(PND 60) and elevated plus maze (PND 61–63) tests to assess the effects of prenatal exposure to 

chlordecone on sexually differentiated behavior in Sprague-Dawley rats. Gonadectomized male and 

female offspring were also assessed for reproductive behavior following sex-specific steroid treatment. 

On PND 68 or 69, male and female offspring were treated with a chemical paradigm that induces lordosis 

(a female sexual behavior). On PND 70, male offspring received a testosterone implant; these males were 

assessed 6 weeks later for mounting behavior with a sexually-responsive female. On PND 120, blood 

was collected from male and female offspring for assessment of serum testosterone levels. There were no 

apparent chlordecone treatment-related effects on time to parturition, litter size, sex ratio, or growth 

indices of offspring compared to controls. Chlordecone-exposed (in utero) gonadectomized female 

offspring exhibited significantly increased ratio of inner to total crossings in the open field; significant 

increases in lordosis response with steroid priming and mounting with prolonged testosterone 

administration were observed in both male and female offspring. These results suggest that chlordecone 

may interfere with estrogen-dependent events during sexual differentiation of the brain that impact later 

activation of hormone-dependent behavior.

Gely-Pernot et al. (2018) administered chlordecone to pregnant female mice by daily gavage at 

0.1 mg/kg/day during gestation days 6.5–15.5. The study authors reported decreased numbers of 

spermatogonia and spermatozoa among F1 and/or F3 progeny; meiotic defects in spermatocytes; and 

altered expression of genes associated with chromosome segregation, cell division, and DNA repair (note 

only the parental [F0] dams were administered chlordecone). In a similarly-designed study (Legoff et al. 

2019), increased numbers of meiotic double-strand breaks were reported in oocytes from mouse fetuses. 
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Adult progeny of the chlordecone-treated maternal mice exhibited delayed puberty, decreased numbers of 

primordial follicles, and increased numbers of atretic follicles; these changes were associated with altered 

epigenetic features. Both studies only tested a single dose; thus, dose-response relationships cannot be 

evaluated. Study weaknesses include the lack of examination for potential maternal toxicity, although the 

study authors stated that the selected dose level (0.1 mg/kg/day) “has no effect on murine health;” lack of 

information regarding numbers of pregnant mice/group, numbers of litters produced, numbers of litters 

contributing to the quantitative data reported; and use of only four progeny/group in some of the analyses.

Based on these limitations, the reported results from these studies are not included in Table 2-4 or

Figure 2-4.

2.18 OTHER NONCANCER

Diabetes

Mirex. Possible associations between mirex serum levels and risk of diabetes were evaluated in several 

population-based human studies (Aminov et al. 2016; Codru et al. 2007; Everett and Matheson 2010; Son 

et al. 2010). There was no convincing evidence of mirex-related increased risk of diabetes. Refer to 

Error! Reference source not found. for individual study details. Serum glucose levels were decreased 

uniformly in all studies that examined this parameter following oral exposure of animals to high doses of 

mirex (Chu et al. 1981b; Ervin and Yarbrough 1983; Fujimori et al. 1983; Jovanovich et al. 1987; 

Robinson and Yarbrough 1978a; Williams and Yarbrough 1983; Yarbrough et al. 1981). Decreases were 

observed following single oral doses as low as 8 mg/kg in rats (Robinson and Yarbrough 1978a) and 

dietary doses as low as 0.25 mg/kg/day for 28 days in rats (Chu et al. 1981b).

Chlordecone. No association was found between maternal serum chlordecone and risk of diabetes 

mellitus in pregnant women participating in a prospective mother-child cohort study (Saunders et al. 

2014). Reports of chlordecone-induced effects on serum glucose in animals were limited to a single 

report of decreased serum glucose in mice exposed for 4 days at doses as low as 25 mg/kg/day or for 

33 days at doses as low as 10 mg/kg/day (Fujimori et al. 1983).

Thermoregulation

Mirex. No studies were located regarding thermoregulatory effects in humans or animals exposed to 

mirex.
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Chlordecone. No data were located regarding thermoregulatory effects in humans exposed to 

chlordecone. Chlordecone was shown to cause a decrease in core temperature following ingestion of a 

single dose of 55 or 75 mg/kg in rats (Swanson and Wooley 1982). The core temperatures were 

depressed for up to 12 days after administration of 75 mg/kg of chlordecone. Slight hyperthermia 

occurred after the body temperature recovered. Slight hyperthermia was also observed in rats after 

12 weeks of exposure at 7.1 mg/kg/day (Pryor et al. 1983).

Metabolic Syndrome

Mirex. Rosenbaum et al. (2017) found no association between serum mirex level and occurrence of 

metabolic syndrome in a cross-sectional study. See Error! Reference source not found. for additional 

study details.

2.19 CANCER

Mirex. Six epidemiological studies evaluated possible associations between mirex and cancer outcomes 

in the general population; additional information on these studies is presented in Table 2-1. Mixed results 

were found in three case-control studies evaluating breast cancer. One study reported an inverse

association between lipid-adjusted median serum mirex concentration and risk of breast cancer (Itoh et al. 

2009), a second study found no association between blood mirex level and risk of postmenopausal breast 

cancer (Moysich et al. 1998), and the third study reported an association between serum mirex level and 

risk of breast cancer (Wielsoe et al. 2017). Two case-control studies found no evidence of a positive 

association between lipid-adjusted serum mirex concentration and risk of prostate cancer (Koutros et al. 

2105a, 2015b; Sawada et al. 2010). A positive association between mirex blood level and risk of nonHodgkin lymphoma (NHL) was reported in a population-based, case-control study (Spinelli et al. 2007).

The carcinogenicity of mirex has been demonstrated in animal studies. An increase in the incidence of 

neoplastic liver nodules (described as nonencapsulated, circumscribed areas of parenchyma usually 

occupying the space of several lobules) was observed in male CD rats receiving mirex from the diet for 

18 months at 7.2 mg/kg/day (Ulland et al. 1977). NTP (1990) fed mirex in the diet to F344/N rats 

(52/sex) for 2 years at 0, 0.1, 1.0, 10, 25, or 50 ppm. Based on absence of observable toxic effects in 

female rats, other groups of females were similarly treated at 0, 50, or 100 ppm mirex in the diet. 

Estimated average mirex doses to the males and females (combined) in the initial portion of the study 
MIREX AND CHLORDECONE 106

2. HEALTH EFFECTS

were 0, 0.007, 0.075, 0.75, 1.95, and 3.85 mg/kg/day, respectively. In the second portion of the study, 

estimated doses to the 0, 50, and 100 ppm females were 0, 3.9, and 7.7 mg/kg/day, respectively. 

Significantly increased incidences of neoplastic liver nodules (usually consisting of enlarged hepatocytes 

with eosinophilic or clear cytoplasm arranged in irregular distorted cords one or two cell layers thick, but 

some consisting of cells with basophilic cytoplasm) were observed among male rats at doses 

≥0.75 mg/kg/day (incidences of 14/52, 15/52, and 26/52 for 0.75, 1.95, and 3.85 mg/kg/day dose groups, 

respectively, versus 3/52 among controls) and among female rats in the second portion of the study at 

3.9 and 7.7 mg/kg/day (incidences of 23/52 and 30/52, respectively, versus 2/52 among controls). 

Incidences of hepatocellular carcinoma among mirex-treated male and female rats were not significantly 

different from that of controls. Incidences of benign or malignant pheochromocytoma (combined) in the 

adrenal gland of male rats occurred with a significant positive dose-related trend; incidences at 

1.95 mg/kg/day (18/51) and 3.85 mg/kg/day (20/51) were significantly higher than that of controls

(10/51). Most adrenal gland pheochromocytomas were benign. Transitional cell papillomas of the renal 

pelvis of male rats occurred with a significant positive dose-related trend, although the tumor was only

observed in 1/51 and 3/52 males at the dose levels of 1.95 and 3.85 mg/kg/day, respectively. Female rats 

exhibited significantly increased incidence of mononuclear cell leukemia at doses ≥0.075 mg/kg/day

(14/52, 18/52, 27/104, and 14/52 at 0.075, 0.75, 1.95, 3.85–3.9, and 7.7 mg/kg/day, respectively, versus 

14/104 among controls; incidences from the two portions of the study combined). NTP concluded that 

under the conditions of the study, there was clear evidence of carcinogenic activity among the high-dose 

male and female F344/N rats. An audit summary of this report states that because of an apparent 

disproportionate number of liver tissue samples taken from the high-dose groups, additional and 

comparative liver sections were made for control groups of both sexes and the high-dose male group after 

the initial Pathology Working Group (PWG) review of this study. A second PWG, convened to review 

the liver sections, concluded that any discrepancies noted during the review of the pathology materials 

were minor in nature and not clustered in any one group of study animals. Consequently, the NTP 

considered the data produced from this study supportive of the conclusion of clear evidence of 

carcinogenic activity for mirex in F344/N rats.

Both male and female mice (18/sex/dose) of the (C57BL/6 x C3H/Anf)F1 or (C57BL/6 x AKR)F1 strains 

showed a significant increase in the incidence of hepatomas in a screening study in which mirex was 

administered first by gavage from 7 until 28 days of age at 10 mg/kg/day and then in the diet at 28 ppm

(estimated dose of 4.5 mg/kg/day) until terminal sacrifice at weeks 59–70 (estimated time-weighted 

average dose of 4.8 mg/kg/day) (Innes et al. 1969).
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Chlordecone. Plasma chlordecone level was positively associated with risk of prostate cancer in a 

population-based, case-control study (Multigner et al. 2010). The positive association appeared to be 

strongest among subjects with family history of prostate cancer and among subjects with past residence in 

western countries. See Error! Reference source not found. for additional study details.

Liver biopsy samples taken from 12 workers with hepatomegaly resulting from intermediate or chronicduration exposures to unspecified high levels of chlordecone showed no evidence of cancer (Guzelian et 

al. 1980). However, conclusions from this study are limited by the very small number of workers 

sampled, the relatively brief duration of exposures, and the absence of a sufficient latent period for tumor 

development. The average exposure of the subjects was 5–6 months and they were examined 

immediately after exposure.

Chlordecone was shown to be carcinogenic in rats and mice. The results of NCI (1976) bioassays in mice 

and rats clearly suggest that chlordecone induces hepatocellular carcinomas in both sexes of rats and 

mice. Administration of chlordecone to Osborne-Mendel rats via the diet for 80 weeks resulted in a 

significant increase in the incidence of hepatocellular carcinomas over pooled controls in both males and 

females at time-weighted average doses of 1.7 mg/kg/day in males and 2.0 mg/kg/day in females (NCI 

1976). In the NCI (1976) bioassay of rats, the incidence of hepatocellular carcinomas was significantly 

increased (p<0.05) in both sexes with a dose-related trend. The incidence of hepatocellular carcinomas in 

high-dose males and females were 7 and 22% for males and females, respectively. Nevertheless, this 

study had several limitations. Initial doses were not well tolerated because the Maximum Tolerated Dose 

(MTD) was exceeded, as indicated by excessive deaths. Doses were reduced 17–33% from initial doses 

once or twice during the experiment. During the final 75 days of treatment, high-dose males received 

chlordecone on alternative weeks only. Doses above the MTD were used for 42–386 days. An unusually 

high mortality rate occurred in control animals, and only pooled controls were used in this bioassay.

Administration of chlordecone to B6C3F1 mice for 80 weeks also resulted in significantly increased 

incidences of hepatocellular carcinomas in both males and females at doses as low as 3.4-3.5 mg/kg/day 

(NCI 1976). In the NCI (1976) bioassay in mice, the incidence of hepatocellular carcinomas was 

significantly increased (p<0.05) in both males and females with a dose-related trend. The incidences of 

hepatocellular carcinomas were 81 and 88% in low- and high-dose males, respectively, and 52 and 47% 

in low-and high-dose females, respectively. In addition, a decrease of latency time of tumor appearance 

was observed in treated mice, as compared to controls. Nevertheless, this study had several limitations. 

An abnormally high incidence (32%) of hepatocellular carcinomas was found in the matched control 
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group of male mice. In addition, initial doses were not well tolerated because of exceedance of the MTD,

as indicated by excessive deaths. Doses were reduced 25–50% from initial doses once or twice during the 

experiment. Doses above the MTD were used for 90–134 days. An unusually high mortality rate 

occurred in control animals as well.

In its evaluations, the Department of Health and Human Services (DHHS) has determined that both mirex 

and chlordecone may reasonably be anticipated to be carcinogenic on the basis of sufficient evidence of 

carcinogenicity in animals (NTP 2016a, 2016b). The Integrated Risk Information System (IRIS) of EPA

does not include a carcinogenicity evaluation for mirex (see IRIS 1992). EPA (IRIS 2009) evaluated 

available human and animal data for chlordecone and determined that chlordecone is likely to be 

carcinogenic to humans, based on increased incidence of hepatocellular carcinomas in both sexes of rats 

and mice (NCI 1976).

Mirex has been shown to be a nonmutagenic hepatocarcinogen in animals. Mirex was tested at a dermal 

dose of 3.6 mg/kg for 4 weeks in female CD-1 mice to evaluate tumor promoter activity and evidence of 

epidermal hyperplasia after initiation with 7,12-dimethyl-benz[a]anthracene (DMBA) at 200 nmol/day for 

1 week (Meyer et al. 1993; Moser et al. 1992, 1993). Positive control mice were treated with 2 nmol/day 

of the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), following initiation 

with DMBA. A third group of mice was treated with both 3.6 mg/kg mirex and 2 nmol/day TPA for 

4 weeks following initiation with DMBA. Multiple applications of mirex for 4 weeks to the DMBAinitiated mice resulted only in minimal increases in the number of nucleated epidermal cell layers. In 

contrast, a definitive hyperplastic response of 6–7 cell layers was observed after repeated application with 

TPA to the DMBA-initiated mice. Mice that were promoted with mirex or TPA without DMBA initiation 

did not develop tumors. At 20 weeks, DMBA-initiated mice promoted with 3.6 mg/kg mirex developed 

an average of 14.2 tumors. Mice promoted with 2 nmol/day TPA bore 4.7 tumors per mouse. Mice copromoted with 3.6 mg/kg mirex and 2 nmol TPA gave a greater-than-additive response (35.4 tumors per 

mouse). The tumor incidence was also greater than additive in mice co-promoted with 3.6 mg/kg mirex 

and 2 nmol/day TPA. The tumors consisted mainly of papillomas with some squamous cell carcinomas. 

The study also found a 90% incidence (activation) of the c-Ha-ras tumor gene in these co-promoted 

tumors. Under conditions where both 3.6 mg/kg/day mirex and 2 nmol/day gave a similar tumor yield, 

only the TPA response was associated with biochemical markers of enhanced cell proliferation, induction 

of epidermal ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. On the 

basis of the data, the authors concluded that there is evidence for a dual effect of mirex during co-
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promotion: first, as an independent tumor promoter with a mechanism different than that of phorbol esters 

and, second, as a compound that also potentiates skin tumor promotion by TPA.

A second study examined the effects of DMBA initiated mirex-promoted tumors in female mice on 

ovarian hormones. This study found that the loss of ovary (OVX) protected the female mice (40%) from 

mirex tumor promotion. Tumor promotion was unaffected in DMBA-initiated OVX mice promoted with 

TPA. Based on the data, the authors concluded that there is a structural specificity in the tumorpromoting ability of mirex in mouse skin and that mirex is a much more effective skin tumor promoter in 

female CD-1 mice than in male CD-1 mice or OVX mice (Meyer et al. 1994).

2.20 GENOTOXICITY

Available data suggest that neither mirex nor chlordecone are genotoxic.

Limited information is available regarding the potential for mirex- or chlordecone-induced genotoxicity in 

vivo (Table 2-7). Mirex did not induce dominant lethal mutations following gavage treatment of male rats 

at 1.5–6.0 mg/kg/day for 10 consecutive days (Khera et al. 1976). Single gavage dosing of female 

Sprague-Dawley rats with mirex at 90 or 120 mg/kg resulted in no evidence of significant damage to 

DNA as measured by alkaline elution (Mitra et al. 1990). Oral administration of mirex to male mice at 

86.8 mg/kg/day for 5 days did not induce DNA strand breaks in hepatocytes (Umegaki et al. 1993). 

Miyagawa et al. (1995) reported 4–9.5-fold increases in replicative DNA synthesis within hepatocytes of 

8-week-old male B6C3F1 mice at 24–39 hours following gavage administration of mirex at 60 mg/kg. 

Marked disturbances in the distribution of ploidy (diploid and tetraploid nuclei) were observed in livers 

from male Sprague-Dawley rats fed 100 ppm mirex (equivalent to ≈5 mg/kg/day) for 13 months 

(Abraham et al. 1983). Mirex selectively reduced the number of tetraploids with the most significant 

reduction noted in hepatocellular carcinomas; however, nuclei in the areas adjacent to these tumors were 

also primarily composed of diploids. These data should be interpreted with caution since isolation of 

nuclei from tumors is difficult and because “of the fantastic variety of forms that tumor nuclei assume” 

(Smuckler et al. 1976). Additionally, the relevance to humans is not clear since human liver is mainly 

composed of diploid cells (99%) and contains few tetraploids (Adler et al. 1981).
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Table 2-7. In Vivo Genotoxicity of Mirex and Chlordecone in Orally-Exposed 

Animals

Species Endpoint Results Reference

Mirex

Male rat germinal cells Dominant lethal mutations – Khera et al. 1976

Rat hepatocytes DNA damage (alkaline elution) – Mitra et al. 1990

Mouse hepatocytes DNA strand breaks – Umegaki et al. 1993

Mouse hepatocytes DNA synthesis + Miyagawa et al. 1995

Rat hepatocytes Selective reduction of polyploid cells + Abraham et al. 1983

Chlordecone

Male rat germinal cells Dominant lethal mutations – Simon et al. 1986

Rat hepatocytes DNA damage (alkaline elution) – Kitchin and Brown 1989

Rat hepatocytes Unscheduled DNA synthesis/DNA 

strand breaks

+/– Ikegwuonu and Mehendale 

1991

DNA = deoxyribonucleic acid; – = negative result; + = positive result; +/– = inconclusive results

Chlordecone did not induce dominant lethal mutations following gavage treatment of male rats for 5 days 

at 3.6 or 11.4 mg /kg/day (Simon et al. 1986). There was no evidence of chlordecone-induced DNA 

damage following gavage treatment of female Sprague-Dawley rats at 19 or 57 mg/kg both 21 and 

4 hours prior to sacrifice (Kitchin and Brown 1989). Chlordecone induced a low level of unscheduled 

DNA synthesis in hepatocytes from male Sprague-Dawley rats gavaged at 10 mg/kg (Ikegwuonu and 

Mehendale 1991). However, the response (≈1.2-fold over control) was too marginal to conclude a 

positive effect. The comparative evaluation of chlordecone effects on adenosine diphosphateribosyltransferase (ADPRT) activity and DNA strand breaks provided inconsistent results. Although the 

data suggest that chlordecone treatment increased DNA strand breaks, ADPRT activity was suppressed 

rather than stimulated; stimulation would be expected when DNA strand breaks occur.

Results from genotoxicity testing of mirex and chlordecone in vitro are summarized in Table 2-8. Mirex 

was not mutagenic to Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 either with or 

without exogenous metabolic activation (Mortelmans et al. 1986; Probst et al. 1981; Schoeny et al. 1979). 

Probst et al. (1981) found no evidence of a mutagenic response in S. typhimurium strains TA1538, C3076, 

D3052, or G46 or Escherichia coli strains WP2 or WP2 uvrA either with or without exogenous metabolic 

activation. Mirex was also negative for the induction of prophage in E. coli either with or without 

exogenous metabolic activation (Houk and DeMarini 1987). Mirex was not mutagenic to human foreskin 

fibroblasts (Detroit-550) either with or without exogenous metabolic activation (Tong et al. 1981). 
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Table 2-8. Genotoxicity of Mirex and Chlordecone In Vitro

Species (test system) Endpoint

Results

Reference

Activation

With Without

Mirex

Salmonella typhimurium TA98, 

TA100, TA1535, TA1537

Gene mutation – – Mortelmans et al. 1986

S. typhimurium TA98, TA100, 

TA1535, TA1537

Gene mutation – – Schoeny et al. 1979

S. typhimurium TA98, TA100, 

TA1535, TA1537, TA1538, 

C3076, D3052, G46

Gene mutation – – Probst et al. 1981

Escherichia coli WP2, 

WP2uvrA

Gene mutation – – Probst et al. 1981

E. coli WP2s (λ), SR714 λ Prophage induction – – Houk and DeMarini 1987

Human foreskin fibroblasts 

(Detroit-550 cells)

Gene mutation – – Tong et al. 1981

Mouse hepatocytes Preferential binding to 

polyploid cells

NA + Rosenbaum and Charles 

1986

Rat, mouse, and/or hamster 

hepatocytes

Unscheduled DNA 

synthesis

NA – Maslansky and Williams 

1981; Probst et al. 1981; 

Williams 1980

Chinese hamster lung 

fibroblasts (V79)

Inhibition of metabolic 

cooperation

NA + Tsushimoto et al. 1982

Chlordecone

S. typhimurium TA98, TA100, 

TA1535, TA1537

Gene mutation – – Mortelmans et al. 1986

S. typhimurium TA98, TA100, 

TA1535, TA1537

Gene mutation – – Schoeny et al. 1979

S. typhimurium TA98, TA100, 

TA1535, TA1537, TA1538, 

C3076, D3052, G46

Gene mutation – – Probst et al. 1981

E. coli WP2, WP2uvrA Gene mutation – – Probst et al. 1981

Rat liver epithelial cells Gene mutation – – Williams 1980

Testicular cells from human 

organ transplant donors

Single-stranded DNA 

breaks

NA + Bjorge et al. 1996

Rat testicular cells Single-stranded DNA 

breaks

NA + Bjorge et al. 1996

Chinese hamster ovary cells Structural chromosome 

aberrations

– – Galloway et al. 1987

Chinese hamster ovary cells Sister chromatid 

exchange

– + Galloway et al. 1987

Chinese hamster M3-1 cells Structural chromosome 

aberrations

NR +/– Bale 1983

Rat, mouse, and/or hamster 

hepatocytes

Unscheduled DNA 

synthesis

NA – Maslansky and Williams 

1981; Probst et al. 1981
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Table 2-8. Genotoxicity of Mirex and Chlordecone In Vitro

Species (test system) Endpoint

Results

Reference

Activation

With Without

Chinese hamster lung 

fibroblasts (V79)

Inhibition of metabolic 

cooperation

NA + Tsushimoto et al. 1982

DNA = deoxyribonucleic acid; NA = not applicable; NR= not reported; – = negative result; + = positive result; 

+/– = inconclusive results

Rosenbaum and Charles (1986) provided evidence that mirex preferentially binds to freshly prepared 

polyploid mouse hepatocytes; the response was partially Na+ dependent and completely Ca2+ dependent. 

Subcytotoxic doses of mirex did not induce unscheduled DNA synthesis in primary hepatocytes 

recovered from rats, mice, or hamsters (Maslansky and Williams 1981; Williams 1980). Similar results 

were obtained by Probst et al. (1981) using primary rat hepatocytes exposed to 1,000 μmol/L mirex. 

Metabolic cooperation between 6-thioguanine-resistant (6-TGr) mutants (HGPRT-

) and 

6-thioguanineinsensitive (6-TGs) wild-type (HGPRT+) Chinese hamster lung fibroblasts (V79) was 

inhibited by mirex (Tsushimoto et al. 1982).

In agreement with the findings from microbial gene mutation studies with mirex, there is no evidence that 

chlordecone is a mutagen for S. typhimurium or E. coli (Mortelmans et al. 1986; Probst et al. 1981; 

Schoeny et al. 1979). Williams (1980) found no evidence of mutagenicity in chlordecone-treated rat liver 

epithelial cells either with or without exogenous metabolic activation. Chlordecone (≥300 μM) induced 

significantly increased frequencies of single-stranded DNA (ssDNA) breaks in testicular cells from 

human organ transplant donors and from Wistar rats (Bjorge et al. 1996). Chlordecone did not increase 

the frequency of Chinese hamster ovary cells with abnormal chromosome morphology over a 

nonactivated concentration range of 10–20 mg/L or an activated concentration range of 5–15 mg/L 

(Galloway et al. 1987). Chlordecone (1.67–10.00 mg/L) did increase the frequency of sister chromatid 

exchange in Chinese hamster ovary cells, but only without exogenous metabolic activation and only in the 

presence of cell-cycle delay (Galloway et al. 1987). Evidence of a clastogenic effect reported by Bale 

(1983) for Chinese hamster M3-1 cells exposed to 2, 4, or 6 mg/L chlordecone was inconclusive. The 

significant (p<0.05) increase in the aberration yield at 6 mg/L could not be fully assessed because 

chromatid and chromosome gaps (the predominant type of aberration) were included in the statistical 

analysis and there was a high background frequency of cells treated with solvent (dimethyl sulfoxide) that 

had abnormal values. Subcytotoxic doses of chlordecone did not induce unscheduled DNA synthesis in 
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primary hepatocytes recovered from rats, mice, or hamsters (Maslansky and Williams 1981; Williams 

1980). Similar results were obtained by Probst et al. (1981) using primary rat hepatocytes exposed to 

1,000 μmol/L chlordecone. Metabolic cooperation between 6-thioguanine-resistant (6-TGr) mutants 

(HGPRT-

) and 6-thioguanineinsensitive (6-TGs) wild-type (HGPRT+) Chinese hamster lung fibroblasts 

(V79) was inhibited by chlordecone (Tsushimoto et al. 1982).

2.21 MECHANISMS OF ACTION

Pharmacokinetic Mechanisms. The specific mechanism by which mirex is transferred from the gut, 

lungs, or skin to the blood is not known. However, mirex is a highly stable, lipophilic compound that is 

resistant to metabolism. It has a high lipid:water partition coefficient, so it partitions readily to fat and 

demonstrates a very high potential for accumulation in tissues (Chambers et al. 1982; Ivie et al. 1974a).

The specific mechanism by which chlordecone is transferred from the gut, lungs, or skin to the blood is 

not known. However, the preferential distribution of chlordecone to the liver rather than the fat tissues 

suggests that it may be transported in the plasma differently from other organochlorine compounds (Soine 

et al. 1982). In vitro and in vivo studies of human, rat, and pig plasma showed that chlordecone is 

preferentially bound by albumin and high-density lipoproteins (HDL), which may explain its tissue 

distribution. Other organochlorine pesticides such as aldrin and dieldrin bind to very-low-density 

lipoproteins (VLDL) and LDL and distribute preferentially to fat (Soine et al. 1982).

Hepatotoxicity. Several studies have attempted to define the mechanism by which mirex and chlordecone 

inhibit hepatobiliary excretion. At very high levels, both mirex (Chetty et al. 1983a; Desaiah 1980) and 

chlordecone (Bansal and Desaiah 1985; Chetty et al. 1983a; Curtis and Mehendale 1979; Desaiah et al. 

1980b, 1991; Jinna et al. 1989; Jordan et al. 1981; Kodavanti et al. 1990a; Mehendale 1979) depress 

ATPase activity or cellular energy utilization at moderate to relatively high doses (2.5–100 and 50–

100 mg/kg/day, respectively), thereby inhibiting the biliary excretion of substances. The inhibition does 

not appear to be due to inhibition of metabolism of the substance to be excreted in the bile or to decreased 

bile flow (Mehendale 1977a). Possible explanations for the decreased excretion of metabolites in the bile 

include decreased uptake of substances by the hepatocyte (Teo and Vore 1990), a decreased transfer of 

chemicals from the hepatocyte to the bile (Berman et al. 1986), and leaking of metabolites from the bile 

duct via a paracellular pathway (Curtis and Hoyt 1984). The decrease in transfer may be due to decreased 

permeability of the canalicular membrane (Hewitt et al. 1986a) resulting from inhibition of the 

Mg2+ATPase activity of the bile canaliculi (Bansal and Desaiah 1985; Curtis 1988; Curtis and Mehendale 
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1981) or perturbations of plasma membrane (Rochelle et al. 1990). Although the precise mechanism for 

the hypothermia induced by chlordecone is unknown, data suggest a role of central nervous system 

dopaminergic or α-noradrenergic activity in expression of hypothermia. The decrease in body 

temperature produced by chlordecone was mimicked by intracisternal norepinephrine (Cook et al. 1988a, 

1988b) and was blocked by administration of α-noradrenergic antagonists and by 6-hydroxydopamine, a 

treatment that depletes noradrenergic neurons in the brain (Cook et al. 1988b). Pretreatment with the 

dopamine antagonist, haloperidol, was also capable of blocking the hypothermia (Hsu et al. 1986). It has 

been suggested that the decrease in body temperature is the result of centrally mediated vasodilation 

(Cook et al. 1988a, 1988b), but direct evidence for this has not yet been obtained.

Mitochondrial oligomycin-sensitive Mg2+ATPase is thought to play a major role in oxidative 

phosphorylation (Boyer et al. 1977). It has been suggested that impairment of mitochondrial energy 

metabolism by chlordecone may contribute to the decreases in body weight observed following exposure 

to this chemical (Desaiah 1981).

Carpenter et al. (1996) examined ultrastructural, protein, and lipid profiles in the livers of chlordeconetreated mice. Male C57BL/6N mice were administered chlordecone intraperitoneally, followed 3 days 

later by intraperitoneal injection of radiolabeled chlordecone. Livers and kidneys were subsequently 

removed for assessment of radioactivity. Livers were examined for histological and ultrastructural 

changes and total lipid content and fatty acid profiles in livers and kidneys were determined. 

Pretreatment with unlabeled chlordecone resulted in dose-dependent decreased accumulation of 

chlordecone in the liver; renal accumulation was not affected. Chlordecone induced marked hepatic 

mitochondrial swelling, decreased the number of cytoplasmic lipid droplets in hepatocytes, induced 

proliferation and vesiculation of smooth endoplasmic reticulum, and increased the number of intracellular 

peroxisome-like structures. Chlordecone did not alter the total lipid content of the liver or kidney. The 

changes in the liver suggest that chlordecone caused alterations in hepatocellular transport, storage, and 

metabolism pathways via increased hepatocyte secretory activity.

Neurotoxicity. Several studies have been undertaken in an attempt to define the mechanism of the 

neurotoxic effects of chlordecone. No single mechanism has been identified that readily explains the 

neurotoxic effects of chlordecone. However, studies have revealed substantial information regarding the 

effects of chlordecone on the nervous system. Chlordecone does not appear to act through a mechanism 

similar to other chlorinated hydrocarbon insecticides such as dieldrin or lindane. Chlordecone has a 

different profile of neurotoxicity in that it primarily causes hyperexcitability and tremors, but no 
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convulsions, and appears to lack activity at the γ-aminobutyric acid (GABA) receptor in mammals 

(Bloomquist et al. 1986; Chang-Tsui and Ho 1979; Lawrence and Casida 1984; Seth et al. 1981). 

Chlordecone has been shown to be a potent antagonist of the picrotoxinin binding site on the GABA 

receptor in cockroaches (Matsumura 1985). However, this finding is difficult to interpret based on the 

poor binding at a comparable site in mammalian tissues.

The hyperexcitability and tremor induced by chlordecone are similar to that produced by dichlorodiphenyldichloroethane (DDT). However, it has been suggested that the mechanism of these tremors is 

different; diphenylhydantoin exacerbates chlordecone-induced tremor but suppresses tremor induced by 

DDT (Hong et al. 1986; Tilson et al. 1985, 1986). The tremors induced by chlordecone appear to be 

initiated in the central nervous system above the level of the spinal cord, since transection of the spinal 

cord resulted in elimination of the tremors below the level of transection (Hwang and van Woert 1979).

Several pharmacological studies indicate that α-noradrenergic and serotonergic transmitter systems in the 

central nervous system are the primary neurotransmitter systems involved in the expression of the tremor 

and enhanced startle response produced by chlordecone (Gerhart et al. 1982, 1983, 1985; Herr et al. 1987; 

Hong et al. 1984; Hwang and van Woert 1979). These conclusions are supported by a number of studies 

examining brain neurochemistry following administration of tremorgenic doses of chlordecone (Brown et 

al. 1991; Chen et al. 1985; Hong et al. 1984; Tilson et al. 1986; Uphouse and Eckols 1986). However, 

dopamine (Desaiah 1985; Fujimori et al. 1982a) and acetylcholine (Aronstam and Hong 1986; Gerhart et 

al. 1983, 1985) have also been implicated.

At the cellular level, chlordecone causes spontaneous neurotransmitter release (End et al. 1981) and 

increases in free intracellular calcium in synaptosomes (Bondy and Halsall 1988; Bondy and McKee 

1990; Bondy et al. 1989; Komulainen and Bondy 1987). This appears to be due, at least in part, to 

increased permeability of the plasma membrane (Bondy and Halsall 1988; Bondy and McKee 1990; 

Bondy et al. 1989; Komulainen and Bondy 1987), activation of voltage-dependent calcium channels 

(Komulainen and Bondy 1987), and inhibition of brain mitochondrial calcium uptake (End et al. 1979, 

1981).

Chlordecone also decreased the activity of calmodulin-stimulated enzymes (Kodavanti et al. 1988, 1989a; 

Vig et al. 1990, 1991) and of enzymes integral to maintenance of neuronal energy and ionic gradients; 

Na+

K+ATPase (Bansal and Desaiah 1982; Chetty et al. 1983b; Desaiah 1981; Desaiah et al. 1980b; 

Folmar 1978; Jinna et al. 1989; Singh et al. 1984), oligomycin-sensitive Mg2+ATPase (Chetty et al. 
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2. HEALTH EFFECTS

1983b; Desaiah et al. 1980b; Jinna et al. 1989; Mishra et al. 1980), and Ca2+ATPase (Desaiah et al. 1991; 

Jinna et al. 1989; Mishra et al. 1980) activities in brain tissues have been shown to be decreased by 

exposure to chlordecone both in vivo and in vitro. It is unclear whether inhibition of these enzymes is 

directly responsible for the effects of chlordecone on intracellular calcium or whether these changes are 

coincidental with the changes in intracellular calcium.

Reproductive Toxicity. Mechanisms underlying many of the adverse effects of chlordecone on 

reproductive function may be related to the estrogenic properties of chlordecone. Following both in vitro

(Bulger et al. 1979; Hammond et al. 1979) and parenteral administration (Williams et al. 1989a), 

chlordecone was shown to bind to estrogen receptors and to cause translocation of the receptor from the 

cytoplasm to the nuclear fraction. When the activity of chlordecone was compared in uterine and brain 

tissues, the effect was greater in the uterine tissue (Williams et al. 1989a). Chlordecone caused the 

translocation of estrogen receptors from the cytosolic to the nuclear fraction in both isolated rat uteri and 

ovariectomized immature rats (Bulger et al. 1979; Williams et al. 1989a). These results indicate that 

chlordecone may act directly on the uterus. Johnson (1996) found that chlordecone-induced uterine 

effects (hypertrophy, hyperplasia) observed in ovariectomized immature rats were enhanced by 

coadministration of estradiol. These results suggest that both the estrogen and xenoestrogen are 

influencing uterine hypertrophy and hyperplasia by a single mechanism. Chlordecone demonstrated 

fairly high affinity for recombinant human estrogen receptors (Bolger et al. 1998; Scippo et al. 2004). 

Chlordecone exhibited approximately equal affinity for both subtypes of human estrogen receptors (ERα

and ERβ) (Kuiper et al. 1998); the binding affinity was on the order of 1,000-fold less than that of 

estradiol. In a study by Johnson et al. (1995), uterine levels of adenosine 3'5'-cyclic monophosphate 

(cAMP) decreased with increasing uterine weight following repeated exposure to chlordecone in 

ovariectomized immature rats. Levels of cAMP were not decreased in similarly treated rats that were also

given the antiestrogen (ICI-182,780), indicating that the chlordecone-induced effect on cAMP is estrogen 

receptor-dependent.

The affinity of chlordecone for estrogen appears to be tissue-dependent. Although competition between 

[

3

H]estradiol and chlordecone was comparable in magnitude within estrogen receptor preparations from 

brain or uterine tissues of rats, in vivo binding of chlordecone in the brain of ovariectomized rats was 

much less than that observed in the uterus (Williams et al. 1989b). The basis for this may result, at least 

in part, from a greater time requirement for chlordecone to reach a concentration in the brain that could 

result in a significant estrogenic effect. Although chlordecone may mimic the effect of estrogen in uterine 
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tissue, chlordecone appears to function as an estrogen antagonist in central nervous tissue (Huang and 

Nelson 1986; Uphouse et al. 1986).

Chlordecone has been evaluated for its potential to bind to receptors other than the estrogen receptor and 

was found to have relatively high affinity for recombinant human progesterone receptors (Scippo et al. 

2004). In ovariectomized (NBZ x NZW) F1 mice, both estradiol (an estrogen) and chlordecone were 

shown to accelerate development of the autoimmune disorder, systemic lupus erythematosus (Wang et al. 

2007a). However, it was found that chlordecone was not simply mimicking estrogen, based on 

contrasting effects on splenic B-cells populations. In a follow-up a study, also in ovariectomized (NBZ x 

NZW) F1 mice, Wang et al. (2007b) compared the effects of chlordecone and estradiol treatment on 

serum levels of the autoimmune-accelerating hormone, prolactin. In chlordecone-treated mice, they 

found a dose-dependent decrease in prolactin levels (compared to controls). However, in estradiol-treated 

mice, prolactin levels were 10–20 fold higher than controls. In a related study, chlordecone exhibited 

characteristics of a partial androgen antagonist, based on reduced inhibition of 5α-dihydroxytestosteronemediated activation of luciferase activity by 6.9 μM chlordecone in the human PC-3 prostate carcinoma 

cell line (Schrader and Cooke 2000).

Results from a study by Das et al. (1997) indicate that chlordecone-induced uterine effects may also be 

induced via a pathway other than that which includes the estrogen receptor. Chlordecone upregulated 

uterine expression of an estrogen-responsive gene, lactoferrin, in ERα knockout mice, whereas these 

effects were not elicited by 17β-estradiol. Neither the estrogen receptor antagonist ICI-182,780 nor 

17β-estradiol inhibited the chlordecone-induced uterine expression of lactoferrin in these mice. 

Substantially less is known about the mechanism by which mirex causes reproductive toxicity. Mirex 

does not, however, appear to produce its reproductive toxicity by mimicking estrogen (Gellert 1978; 

Hammond et al. 1979). Dai et al. (2001) hypothesized that modulation of testosterone metabolism via 

induction of specific CYP isoforms may be a contributing factor in mirex-induced antiandrogenic effects. 

Evidence includes significantly increased (3.1-fold greater than controls) total CYP contents in 

homogenated livers of adult male CD-1 mice administered mirex by gavage at 5 mg/kg/day for 21 days 

(Dai et al. 2001). Western blot analysis indicated that CYP2E1 and CYP3A were the isoforms induced to 

the greatest extent. Incubation of testosterone with microsomes from the treated mice resulted in an 

approximately 2.5-fold increase in testosterone hydrolase activity.
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Developmental Toxicity. No information was located regarding possible mechanisms of mirex 

developmental toxicity. Laessig et al. (2007) administered chlordecone (5 mg/kg) in a single 

intraperitoneal dose to pregnant Sprague-Dawley rats on gestation day 16 and assessed its effect on 

sexually-differentiated behavior of the adult offspring. The offspring were gonadectomized on PND 50 to 

eliminate effects of circulating hormones and were sequentially evaluated for sex-typic spontaneous 

behaviors in open field (PND 60) and elevated plus maze (PND 61–63) performance. Gonadectomized 

male and female offspring were also assessed for reproductive behavior following sex-specific steroid 

treatment. On PND 68 or 69, male and female offspring were treated with a chemical paradigm that 

induces lordosis (a female sexual behavior). On PND 70, male offspring received a testosterone implant; 

these males were assessed 6 weeks later for mounting behavior with a sexually-responsive female. On 

PND 120, blood was collected from male and female offspring for assessment of serum testosterone 

levels. There were no apparent chlordecone treatment-related effects on time to parturition, litter size, sex 

ratio, or growth indices of offspring compared to controls. Chlordecone-exposed (in utero) 

gonadectomized female offspring exhibited a significantly increased ratio of inner to total crossings in the 

open field; significant increases in lordosis response with steroid priming and mounting with prolonged 

testosterone administration were observed in both male and female offspring. These results suggest that 

chlordecone may interfere with estrogen-dependent events during sexual differentiation of the brain that 

impact later activation of hormone-dependent behavior.

Tumor Promotion. There is convincing evidence that mirex and chlordecone interfere with cell-to-cell 

communication. Tsushimoto et al. (1982) demonstrated that metabolic cooperation between 

6-thioguanine-resistant (6-TGr

) mutants (HGPRT-) and 6-TGr wild-type (HGPRT+) Chinese hamster lung

fibroblasts (V79) was inhibited by both mirex and chlordecone. In this assay system, the ability of 

HGPRT+ cells to transport a lethal substrate (formed from the metabolism of 6-thioguanine) to HGPRT 

cells (6-TGr

) is evaluated. Transport of the mononucleotide of thioguanine from the HGPRT+ to the 

HGPRT- cells occurs presumably through gap junctions and results in the killing of heretofore 6-TGr

cells. Therefore, increased survival of the HGPRT- cells in the presence of a test material indicates an 

interference with metabolic cooperation. Mirex doses ranging from 3 to 12 mg/L induced a dose-related 

increase in the recovery of 6-TGr colonies. The maximum percentage recovery of 6-TGr cells (≈70%)

was noted at 12 mg/L. Chlordecone also inhibited metabolic cooperation at concentrations well below the 

cytotoxic level. However, in contrast to the mirex data, chlordecone produced a much steeper doseresponse between 1 and 4 mg/L with the maximum percentage of 6-TGr cell recovery (70%) occurring at 

4 mg/L. While it is tempting to speculate that chlordecone is a more potent inhibitor of metabolic 

cooperation, the differences observed may be explained by differences in solubility. Chlordecone also 
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reversibly disrupted gap junctional communication in human embryonic palatal mesenchyme cells when 

tested by assessing Lucifer yellow dye transfer (Caldwell and Loch-Caruso 1992).

Starcevic et al. (2001) designed an experiment to test whether chlordecone disrupts adherens junctions in 

human breast epithelial cells cultured on Matrigel. When exposed to chlordecone, MCF-10ATG3B 

human breast epithelial cells exhibited significantly decreased E-cadherin and beta-catenin protein levels; 

desmoglein and α- and γ-catenin levels did not vary significantly from control levels. Chlordecone also 

caused disruption in E-cadherin-γ-catenin association. These results indicate that chlordecone disrupts 

cellular architecture, which may ultimately play a role in development of neoplastic lesions. Chlordecone 

in combination with other xenobiotic chemicals such as carbon tetrachloride and ether reduced the 

threshold values of toxicity by several fold for those chemicals and decreased the aromatase activity by 

50% in some cases. Prolonged exposures to low doses of xenobiotics amplified aromatase inhibition by 

50 times. Because chlordecone is known to bioaccumulate, chronic, low-level exposures may result in 

body burden levels that could also affect cell signaling mechanisms (Benachour et al. 2007).

Collectively, results from several studies provide evidence that mirex acts as a tumor promoter with a 

mechanism different from that of phorbol esters and that mirex potentiates skin tumor promotion by TPA 

in DMBA-initiated mice (Meyer et al. 1993, 1994; Moser et al. 1992, 1993). Twenty weeks of thrice 

weekly dermal application of mirex (200 nmole) to DMBA-initiated mice resulted in 96% skin tumor 

incidence with an average of 4 tumors/mouse; similar treatment of other mice with TPA (2 nmole) 

resulted in 78% tumor incidence with 14 tumors/mouse. TPA-treated (but not mirex-treated) mice 

exhibited a hyperplastic response; this result indicates that mechanisms of mirex tumor promotion differ 

from those of TPA. Co-application of 200 nmole mirex and 2 nmole TPA on DMBA-initiated mouse 

skin yielded 28 tumors/mouse (compared to 14 tumors/mouse after mirex treatment separately and 

4 tumors/mouse after TPA treatment separately). In addition, co-treatment with mirex and TPA resulted 

in earlier tumor development; after 8 weeks of promotion, 90% of cotreated mice bore tumors compared 

to 47% of mice treated with mirex separately and 17% of mice treated with TPA separately. Mirexpromoted skin tumors in DMBA-initiated mice were 3 times more prevalent in female than male mice and 

3 times less prevalent in ovariectomized mice, suggesting that ovarian hormones may influence mirextumor promotion sensitivity.

Kim and coworkers (Kim and Smart 1995; Kim et al. 1997) reported that mirex promoted the 

development of papillomas involving a Ha-ras mutation in DMBA-initiated mice. The ovarian hormone 

17β-estradiol may be involved in mirex skin tumor promotion in mice. Porter et al. (2002) assessed the 
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role of 17β-estradiol in mirex skin tumor promotion by applying topical mirex to ovariectomized mice 

that had subcutaneous implants either with or without the hormone. Ovariectomized mice with implanted 

17β-estradiol exhibited normal physiological levels of serum 17β-estradiol throughout the treatment 

period. The 17β-estradiol implants restored approximately 80% of the mirex tumor promoting response 

of intact mice. 17β-Estradiol implants in male mice increased sensitivity to mirex tumor promotion as 

well, but not to the level of response seen in intact female mice.

There are convincing data from a metabolic cooperation assay (Tsushimoto et al. 1982) and a dye transfer 

assay (Caldwell and Loch-Caruso 1992) indicating that mirex and chlordecone interfere with intracellular 

communication. Inhibition of cell-to-cell communication is a property exhibited by numerous promoters 

(Williams 1980). Similarly, the data indicating that both agents probably induce liver tumors in rodents 

through epigenetic/promoter mechanisms are supported by the striking similarities that these test 

materials share with many established promoters: (1) tumors induced by mirex or chlordecone are found 

predominantly in rat or mouse livers; (2) neither agent is genotoxic; (3) both agents induce ornithine 

decarboxylase activity; (4) there is no evidence of covalent binding to DNA; and (5) both agents lack 

reactive functional groups. Mirex has not been evaluated for promoter activity in vivo; however, 

chlordecone was shown to be a tumor promotor in a two-stage assay in which the initiator, 

diethylnitrosamine, was given orally to partially hepatectomized Sprague-Dawley rats followed by 

subcutaneous doses of chlordecone. The treatment resulted in hyperplastic liver nodules in seven of eight 

initiated males and hepatocellular carcinomas in five of six initiated females.

The weight of evidence from in vivo and in vitro genetic toxicology tests, in vivo liver function studies, 

and the two-stage tumor promotion assay is adequate to conclude that chlordecone is a promotor rather 

than an initiator of carcinogenesis. While the evaluation of mirex in an in vivo tumor promoter assay is 

desirable, it is, nevertheless, concluded that there is sufficient evidence to consider mirex a probable 

promoter.
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BIOMARKERS, CHEMICAL INTERACTIONS

3.1 TOXICOKINETICS 

Mirex. Mirex is absorbed from the digestive tract of animals. Following exposure to mirex, an initial 

rapid excretion of the majority of the ingested mirex occurs via the feces within the first 48 hours 

postdosing. This fecal mirex represents unabsorbed compound. Once absorbed, mirex is widely 

distributed throughout the body, but is sequestered in the fat. It has a long retention time in the body. 

Mirex is not metabolized in humans, rodents, cows, or minipigs. The parent compound is the only 

radiolabeled compound that has been found in the plasma, fat, and feces. In animals, mirex is excreted 

unchanged mainly in the feces; urinary excretion is negligible. Mirex is also excreted in human milk. 

Only a very limited number of studies were located regarding the toxicokinetics of mirex via inhalation or

dermal routes. Limited data indicate that mirex is absorbed by rats following exposure to the compound 

in cigarette smoke.

Chlordecone. Occupational studies indicate that chlordecone is absorbed via the inhalation and oral 

routes. Chlordecone is readily absorbed from the gastrointestinal tract of humans and animals. 

Chlordecone is widely distributed throughout the body and concentrates in the liver of humans and 

animals. It has a long retention time in the body. Chlordecone is metabolized to chlordecone alcohol in 

humans, gerbils, and pigs. Rats, guinea pigs, and hamsters cannot convert chlordecone to chlordecone 

alcohol. Chlordecone, chlordecone alcohol, and their glucuronide conjugates are slowly excreted in the 

bile and eliminated in the feces. However, a substantial enterohepatic recirculation of chlordecone exists 

that curtails its excretion in the feces. Chlordecone is also excreted in saliva and mother’s milk. Only a 

very limited number of studies were located regarding the toxicokinetics of chlordecone via inhalation or

dermal routes. Occupational studies indicate that chlordecone can be absorbed via inhalation and oral 

routes. Limited animal data indicate that dermal absorption of chlordecone is low.

3.1.1 Absorption 

Mirex. Very limited data show that inhaled mirex can be rapidly absorbed into the blood of rats (Atallah 

and Dorough 1975; Dorough and Atallah 1975). The fate of [14C] mirex in cigarette smoke was assessed 

in rats with the aid of a smoking device (Atallah and Dorough 1975; Dorough and Atallah 1975). Eight 

5-mL puffs were administered to the trachea of rats at 15-second intervals. At 2–4 minutes after 
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inhalation, 47% of the radiolabel was exhaled, 36% was found in the lung, 11% was found in the blood, 

and 1% was found in the heart.

Several studies in rats indicate that mirex is absorbed from the digestive tract following gavage 

administration with a corn oil vehicle (Byrd et al. 1982; Gibson et al. 1972; Mehendale et al. 1972). 

Experiments with rats given single oral doses of mirex ranging from 0.2 to 10 mg/kg showed that an 

initial rapid excretion of mirex occurs in the feces within the first 48 hours post-dosing (Byrd et al. 1982; 

Gibson et al. 1972; Mehendale et al. 1972). The excretion of mirex in the feces within this time period is 

attributed to unabsorbed mirex. A majority (85–94%) of the total quantity excreted after 7 days is 

eliminated in this first rapid excretion phase (Gibson et al. 1972; Mehendale et al. 1972). Other data 

provided an absorption estimate of 69%, which occurred with female rats given a single oral dose of 

10 mg/kg (Byrd et al. 1982). Similarly, most of the fecal mirex was recovered within the first 48 hours. 

This was attributed to the elimination of unabsorbed mirex (Byrd et al. 1982). Intestinal absorption of 

mirex was slightly decreased by the presence of an existing body burden (Gibson et al. 1972). For 

example, rats fed 12.5 mg/kg of unlabeled mirex before administration of a single dose (0.2 mg/kg) of 

mirex excreted 25% of the administered dose in the feces, as compared with 18% excretion for the 

animals given only a single dose (Gibson et al. 1972).

Orally administered mirex is rapidly absorbed by rats and monkeys. Peak plasma concentrations of 

14C-mirex occurred within 4–7 hours after female rats were given a single gavage dose of 10 mg/kg mirex 

in corn oil (Byrd et al. 1982) and within 2 hours after male rats were administered a single oral dose of 

100 mg/kg (Brown and Yarbrough 1988). 14C-Mirex levels in plasma peaked 5 hours after oral 

administration of 1 mg/kg mirex administered via a capsule to a female rhesus monkey (Wiener et al. 

1976). Thereafter, the decline in plasma 14C concentration continued at a much slower rate and paralleled 

that in the intravenously-dosed monkeys (Wiener et al. 1976).

Mirex rapidly entered the maternal bloodstream of pregnant rats following gavage administration of 

5 mg/kg mirex in corn oil on gestation days 15, 18, or 20 (Kavlock et al. 1980). Four hours after oral 

dosing on gestation day 15, the plasma concentration of mirex was 13 ppm. Mirex plasma concentrations 

were significantly affected by both the time of administration and the hour of observation. Higher plasma 

concentrations were found at older gestation ages (13 ppm on gestation day 15, compared to 23 ppm on 

gestation day 20; measured 4 hours after administration). Plasma concentrations declined with time after 

dosing (Kavlock et al. 1980).
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Mirex concentrations in plasma of pregnant goats receiving daily doses of 1 mg/kg, administered via 

capsule, for 61 weeks stabilized after 15 weeks (Smrek et al. 1977). An increase in the dose from 1 to 

10 mg/kg at the end of the study resulted in an increase in the plasma level of mirex. Females dosed for 

18 weeks starting at the first day postpartum had plasma levels that were similar to females that were 

started on mirex in early pregnancy (Smrek et al. 1977).

Chlordecone. Chlordecone is absorbed after occupational exposure; however, due to extremely poor 

workplace hygiene in available sources of human data, relative contributions from inhalation, oral, and 

dermal exposure routes are not available (Cannon et al. 1978; Cohn et al. 1978; Taylor 1982, 1985). 

Mean blood levels of workers exposed to chlordecone at a manufacturing plant in Hopewell, Virginia 

were 2.53 ppm for workers manifesting illness (nervousness or unfounded anxiety; pleuritic chest pain; 

weight loss of up to 60 pounds in 4 months; visual difficulties; skin rashes of an erythematous, 

macropapular nature) and 0.6 ppm for workers with no illness (Cannon et al. 1978). Two months 

following cessation of exposure, blood levels in workers were in excess of 2 ppm (Taylor 1982, 1985). 

Following exposure in humans, mean half-lives of 96 days (range of 63–148 days) (Adir et al. 1978) and 

165 days (Cohn et al. 1978) in blood have been reported for chlordecone. This relatively long half-life 

may be due to the high degree of lipid solubility and limited metabolism of chlordecone.

Chlordecone is readily absorbed (90%) from the gastrointestinal tract of rodents and has a long half-life 

(Egle et al. 1978). In rats exposed to a single gavage dose of 40 mg/kg chlordecone in corn oil, the blood 

half-lives at 4, 8, and 14 weeks posttreatment were 8.5, 24, and 45 days, respectively (Egle et al. 1978). 

Chlordecone is also rapidly absorbed by pregnant rats (Kavlock et al. 1980). Four hours after gavage 

dosing (5 mg/kg mirex in corn oil) on gestation day 15, the plasma concentration of chlordecone was 

6 ppm.

Chlordecone in acetone is absorbed to a limited extent following dermal exposure in rats (Hall et al. 1988; 

Shah et al. 1987). The percent of dose absorbed was determined by dividing the radioactivity in the body 

(carcass) and in the excreta by the total radioactivity recovered (in carcass, excreta, treated skin, and 

washes of the application materials). The results showed that fractional absorption decreased as the dose

of chlordecone increased. At 72 hours after exposure to 0.29, 0.54, or 2.68 μmol 14C-chlordecone/cm2

, 

skin penetration of chlordecone in young rats was 10.17, 7.23, and 1.93%, respectively, of the applied 

dose. Skin penetration of chlordecone in adult rats at 72 hours was 9.2, 5.96, and 1.03% for the low-, 

middle-, and high-dose groups, respectively. The area of application when expressed as the percentage of 

the total surface area (≈2.3%) was the same in both young and adult rats. The actual amount of
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chlordecone absorbed (0.03 pmol/cm2) was similar for all dose groups, suggesting that saturation 

occurred at the low dose. No significant age-dependent differences in dermal absorption were seen.

3.1.2 Distribution 

Mirex. Mirex has been detected in a variety of human samples. Mirex levels of 0.16–5.94 and 0.3–

1.13 ppm (males and females, respectively) were found in adipose tissue samples taken either from 

postmortem examinations or during surgery (Kutz et al. 1974). The adipose tissue samples came from 

individuals who lived in areas in which mirex was used extensively in a program to control fire ants. 

Adipose tissue levels of mirex ranging from 0.03 to 3.72 ppm have been found in residents living near a 

dump site in Tennessee (Burse et al. 1989). Mirex has also been detected in human serum samples (e.g., 

Butler Walker et al. 2003; Fenster et al. 2006; Greizerstein et al. 1999; Schell et al. 2003; van Oostdam et 

al. 2004), milk samples from lactating women (Fitzgerald et al. 2001; Greizerstein et al. 1999; Mes et al. 

1978; Newsome and Ryan 1999; Newsome et al. 1995), and placental tissue and umbilical cord blood 

(Butler Walker et al. 2003; Lopez-Espinosa et al. 2007). 

Only very limited animal data were located regarding the distribution of absorbed mirex following 

inhalation exposure. Mirex was found in the lungs (36%), blood (11%), and hearts (1%) of rats exposed 

to mirex in cigarette smoke (Atallah and Dorough 1975; Dorough and Atallah 1975).

Following oral dosing in animals, mirex is distributed to various tissues and sequestered in fat. Females 

generally accumulated greater amounts than males. Mirex demonstrated an affinity for lipids in male and 

female rats given a single oral dose of mirex (0.2 mg/kg); highest concentrations were found in fat

(Chambers et al. 1982; Gibson et al. 1972). The levels in fat of females were approximately 2 times 

higher than levels in fat of males (Chambers et al. 1982). For females, mirex levels in the fat ranged from 

338 to 944 ng/g at 7 days and increased to 483–1,043 ng/g at 14 days. For males, mirex levels in fat 

ranged from 161 to 479 ng/g at 7 days and from 419 to 530 ng/g at 14 days. Mirex also accumulated in 

nervous tissue, with females accumulating higher amounts than males (Chambers et al. 1982). Mirex 

concentrations in the nervous tissue in males and females at 7 days posttreatment were 13.228 ng/g and 

40–59 ng/g, respectively; concentrations declined during posttreatment days 7–14. Mirex accumulated in 

various other tissues of both males and females, including gastrointestinal tract, liver, lung, heart, kidney, 

adrenals, brain, skeletal muscle, spleen, and thymus (Chambers et al. 1982; Gibson et al. 1972).
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Seven days after a single administration of mirex (6 mg/kg) to rats, 34% of the total dose was retained in 

the tissues and organs; 27.8% was stored in the fat, 3.2% was stored in the muscle, and 1.75% was stored 

in the liver (Mehendale et al. 1972). The remaining tissues each retained <1% of the total dose. No 

metabolite of mirex was detected in the tissues. The repetitive administration of 10 mg/kg mirex to rats 

resulted in an accumulation of mirex in several tissues (plasma, liver, kidney, fat), with more 

accumulating in fat tissue (Plaa et al. 1987). Following oral administration of 1 mg/kg 14C-mirex to a 

female rhesus monkey, the highest tissue levels of radioactivity were found in fat, followed by large 

intestine, adrenal glands, liver, ovaries, and peripheral nerves (Wiener et al. 1976). The administered 

dose of radioactivity was distributed as follows: 55.3% was recovered in fat and ≤2% was recovered in 

the remaining tissues. Mirex was the only labeled compound identified in fat. Mirex fed to minipigs for 

7 consecutive days (3–4.5 mg/kg/day) was distributed to backfat (41.5 ppm), liver (1.24 ppm), kidney 

(0.44 ppm), plasma (0.04 ppm), and red blood cells (0.01 ppm) at 9 days after dosing (Morgan et al. 

1979).

Mirex was detected in brains from male rats within 0.5–2 hours after a single oral dose of 100 mg/kg 

mirex (Brown and Yarbrough 1988). By 96 hours, the following concentrations (in μmol 14C-mirex/g) 

were measured in the brain regions: cerebral cortex (0.47), cerebellum (0.50), brain stem (0.73), and 

spinal cord (0.75). Mirex was also distributed to the liver, kidneys, testes, and omental fat. Peak tissue 

concentrations of mirex in the kidneys, testes, liver, and omental fat occurred 12, 48, 48, and 96 hours 

postdosing, respectively. Following a single oral dose of 50 mg/kg mirex to mice, mirex was distributed 

to the brain; mirex levels in the striatum and medulla/pons were significantly higher than in the cortex, 

midbrain, or cerebellum at 48 hours postdosing (Fujimori et al. 1982b). However, at 6, 12, and 96 hours

postdosing, discrete brain area levels of mirex did not differ significantly. Mirex levels in whole brain 

and plasma were 3–40 times lower than levels found in chlordecone-treated mice, and mirex showed lessspecific distribution in discrete areas of the brain than did chlordecone (Fujimori et al. 1982b). Samples 

of brain tissue from rats fed 0, 0.089, or 0.89 mg mirex/kg/day for 34–49 days showed that mirex

accumulates in rat brain tissue in a dose-dependent manner; mirex levels in brain tissue were 7–8 times 

higher in the high-dose group than in the low-dose group (Thorne et al. 1978).

Mirex accumulates in maternal tissues, readily crosses the placenta of animals, and accumulates in fetal 

tissues. Maximum concentrations of mirex found in the placenta of rats ranged from 3.5 to 4 ppm at 

4 hours postdosing (Kavlock et al. 1980). Mirex levels in the placenta at 48 hours postdosing were <50% 

of the 4-hour level. The uptake of mirex by fetal organs was in the order of liver > brain = heart > kidney 

in a ratio of 3:2:2:1. Fetal mirex concentrations remained low at 4 hours postdosing, increased slightly at 
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24 hours, and decreased thereafter. The decline noted in the second 24-hour period was due to both organ 

growth and mirex elimination. Mirex accumulated in maternal and fetal tissues at all dose levels (1.5, 3, 

6, 12.5 mg/kg given on gestation days 6–15) (Khera et al. 1976). At the 12.5 mg/kg/day dose level, fetal 

brain levels were >3 times higher (31.5 ppm) than mean maternal brain levels (8.87 ppm). All other mean 

fetal tissue values were lower than mean maternal values. The highest maternal levels of mirex were 

found in the fat, indicating the potential for long-term sequestering of the compound.

In a study in which dams were dosed with 1 or 10 mg/kg of mirex on days 2–5 postpartum, mirex was 

found in the stomach milk of pups (Kavlock et al. 1980). Mirex appeared in the milk in direct proportion 

to the dose. Mirex was also distributed to the liver, brain, and eyes of the pups in the approximate ratio of 

40:4:1. Mirex tissue levels paralleled milk levels.

Mirex concentrations in adipose tissues of goats fed daily doses of 1 mg/kg did not reach a steady state,

but continued to increase throughout a 61-week exposure period and did not seem to be affected by 

pregnancy or lactation (Smrek et al. 1977). When the dose was increased from 1 to 10 mg/kg, the adipose 

tissue levels did not increase dramatically. Twenty-eight days postdosing, the following residue levels 

were found in tissues of lactating cows given daily doses of 0.005 mg/kg/day for 28 days: 0.21 ppm in fat, 

0.03 ppm in liver, and 0.02 ppm in kidney (Dorough and Ivie 1974). Muscle and brain contained no 

detectable residues. Mirex was the only compound identified in the fat. Analyses of the composition of 

residues in liver and kidney were not performed.

There was a dose-related increase in the levels of mirex in fat of rats fed 0.02, 0.2, or 1.5 mg/kg/day for 

16 months (Ivie et al. 1974a). Mirex levels in fat were 120-fold higher than corresponding dietary 

intakes. Mirex levels increased in tissues throughout the exposure period, with fat accumulating the 

highest amounts of mirex. No plateau of residue accumulation occurred in any tissue during the feeding 

period. Removal of animals from treatment after 6 months resulted in a decline of residue levels in all 

tissues.

Mirex is rapidly absorbed and distributes to plasma and liver after intraperitoneal injection. Peak 

concentrations were seen at 3 hours postdosing in plasma and 6 hours postdosing in the liver following 

single or multiple doses of mirex (4 mg/kg) injected into mice (Charles et al. 1985). Significant amounts 

were rapidly taken up by the liver (21–29%) within the first 3–6 hours postdosing. Plasma-to-liver ratios 

were low (<1), indicating an increased influx of the chemical into tissue. Mirex decay curves for plasma 

and liver during 72 hours postdosing showed a biphasic pattern that consisted of a rapid phase (up to 
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24 hours) and a slow phase (24–72 hours). For plasma, the half-lives were 9.2 and 62.8 hours for the 

rapid and slow phases, respectively. For liver, the half-lives for the rapid and slow phases were 12.1 and 

62.4 hours, respectively (Charles et al. 1985).

Mirex was rapidly cleared from the blood of rats following intravenous injection of 10 mg/kg (Byrd et al. 

1982). Mirex blood levels at 8 hours postinjection were <4% of the levels seen 2 minutes postinjection. 

Pharmacokinetic modeling predicted that intravenously administered mirex was quickly cleared from the 

blood into a rapidly equilibrating compartment. Over the next several weeks, mirex was redistributed to a 

slowly equilibrating compartment, which acted as a depot for mirex storage (Byrd et al. 1982). The 

biological half-life of mirex was estimated to be 435 days (Byrd et al. 1982).

Following a single intravenous dose of 1 mg/kg to female rhesus monkeys, 86–87% of the administered 

dose was recovered in fat, 3.7–10% in skin, 0.6–1.7% in skeletal muscle, and <0.5% in other tissues 

(Wiener et al. 1976). Mirex was the only compound identified in fat.

Chlordecone. In humans, chlordecone is absorbed and distributed to various tissues and has a long 

retention time in the body (Cannon et al. 1978; Cohn et al. 1978; Taylor 1982, 1985). Chlordecone was 

eliminated slowly from the blood (half-life of 165 days) and fat (half-life of 125 days) of industrial 

workers (Cohn et al. 1978). Tissue-to-blood ratios for liver, fat, muscle, and gallbladder bile were 15, 

6.7, 2.9, and 2.5, respectively (Guzelian et al. 1981). The relatively higher partition of chlordecone to

blood (fat-to-blood concentration ratio of 1:7) compared to that of other organochlorine pesticides (e.g., 

DDT with a fat-to-blood concentration ratio of 300:1) may be explained by the fact that chlordecone is 

bound specifically by the proteins in plasma, particularly high-density lipoproteins (HDLs), unlike most 

organochlorine pesticides, which distribute among tissues in direct proportion to the concentration of 

tissue fat (Guzelian et al. 1981).

In rats, chlordecone was absorbed and distributed to various tissues, with the highest concentrations in 

liver (Egle et al. 1978; Hewitt et al. 1986b; Plaa et al. 1987). Chlordecone was detected in liver

(125.8 mg/kg), adipose tissue (27.3 mg/kg), kidney (25.2 mg/kg), and plasma (4.9 mg/L) of rats 8 days 

following a single oral dose of 50 mg/kg (Hewitt et al. 1986b). Chlordecone was detected in liver, 

kidney, and fat of rats following single or repetitive dosing (0.5, 1, 2, 2.5, 5, 10, or 25 mg/kg) (Plaa et al. 

1987). For all dose groups, the liver contained the highest concentration, followed by kidney, then fat. 

The ratios of tissue levels in animals that received multiple doses to levels in animals that received single 

doses were as follows: 4.27 (plasma), 3.27 (liver), 3.74 (kidney), and 3.42 (fat). These ratios show an 
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even accumulation of chlordecone in the tissues. Rats given four daily doses of 10 mg/kg chlordecone 

had tissue-to-blood distribution ratios for fat, liver, muscle, and skin of 15, 55, 5, and 6, respectively 

(Bungay et al. 1981).

Studies show that pretreatment with an inducer (phenobarbital) or inhibitor (SKF-525A) of CYP450 

causes an alteration in the distribution of chlordecone in rats (Aldous et al. 1983). Following a single oral 

dose of chlordecone alone, the liver had the highest chlordecone level, followed by adrenal gland, lung, 

kidney, and spinal cord (Aldous et al. 1983). Pretreatment with phenobarbital (particularly with multiple 

phenobarbital doses) caused an increase in the accumulation of chlordecone in the liver compared to 

animals given no pretreatment. This hepatic increase resulted in a significant decrease of chlordecone 

levels in other tissue (e.g., brain, kidney, muscle) as well as significantly reduced excretion. Pretreatment 

with SKF-525A caused a nonsignificant reduction in chlordecone levels in the liver and significant 

increases in digestive system tissues. The results of the chlordecone distribution following SKF-525A 

pre-dosing must be interpreted with caution, since the effects may have resulted partly from SKF-525Amediated decreases in absorption of chlordecone (Aldous et al. 1983).

Following a single oral dose of 50 mg/kg chlordecone to male mice, chlordecone was distributed to the 

brain (Fujimori et al. 1982b; Wang et al. 1981). The results showed that the striatum and medulla/pons 

had significantly higher levels of chlordecone than the cortex, midbrain, or cerebellum (Fujimori et al. 

1982b). Mice similarly treated with mirex did not exhibit marked differences in distribution among these 

brain areas. Chlordecone levels were 3–40 times higher than mirex levels in plasma and brain. 

Following repeated oral doses of chlordecone (10 mg/kg/day) for 12 days, the compound was rapidly 

absorbed and distributed to the brain (Wang et al. 1981). Plasma levels of chlordecone increased during 

the 12-day treatment period. Brain levels of chlordecone increased linearly for the first 8 days and 

reached a plateau of 90 μg/g on the 10th day (Wang et al. 1981).

Chlordecone is well distributed throughout the reproductive tract of male rats and appears in the ejaculate. 

In rats given a single oral dose of 40 mg/kg chlordecone, the descending order of concentration was vas 

deferens (81.6) > seminal vesicular fluid (19.7) > unwashed sperm (14.6) > prostate (11.3) > seminal 

vesicle (6.2) > washed sperm (1.97). This relationship persisted as levels declined over the 21-day 

observation period (Simon et al. 1986).

Chlordecone accumulates in maternal tissues, readily crosses the placenta of rats, and accumulates in fetal 

tissues (Chernoff et al. 1979b; Kavlock et al. 1980). Four hours following a single oral dose of 5 mg/kg, 
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maximal concentrations of chlordecone in the placenta ranged from 3.5 to 4 ppm (Kavlock et al. 1980). 

Concentrations of chlordecone in the placenta remained steady for up to 48 hours postdosing. 

Chlordecone levels in the fetus were generally highest in the liver, followed by the brain, heart, and 

kidney. Concentrations increased during the first 24 hours after dosing and declined in the second 

24-hour period, regardless of gestation age at the time of dosing (Kavlock et al. 1980). Chlordecone 

levels found in maternal and fetal tissues were slightly higher than the levels of mirex following 

administration of equal doses (Kavlock et al. 1980). The livers of weanling rats fed diets of 0.05 mg/kg 

chlordecone or mirex for 28 days accumulated higher levels of chlordecone (6.1 ppm) than mirex 

(0.89 ppm) (Chu et al. 1980b). Possible explanations for this are that mirex is more poorly absorbed from 

the feed than is chlordecone or that the absorbed dose of mirex accumulates in the liver to a lesser extent 

than absorbed chlordecone (Chu et al. 1980b).

In a study in which lactating rat dams were dosed with 1 or 10 mg/kg chlordecone on days 2–

5 postpartum, chlordecone was found in the stomach milk of pups (Kavlock et al. 1980). Chlordecone 

appeared in the milk in direct proportion to the dose. Chlordecone was distributed to the liver, brain, and 

eyes of the pups in the approximate ratio of 16:4:1 (Kavlock et al. 1980).

3.1.3 Metabolism 

Mirex. Radiolabeling experiments showed that mirex is not metabolized in humans, rodents, cows, or 

minipigs; the parent compound was the only radiolabeled compound present in the plasma, fat, and feces 

(Dorough and Ivie 1974; Gibson et al. 1972; Kutz et al. 1974; Mehendale et al. 1972; Morgan et al. 

1979). However, a monohydro derivative of mirex was identified in the feces, but not the fat or plasma, 

of rhesus monkeys given an oral or intravenous dose of mirex (Pittman et al. 1976; Stein et al. 1976; 

Wiener et al. 1976). It is believed that the suspected metabolite may have arisen as a result of bacterial 

action in the lower gut or feces (Stein et al. 1976).

The potential for in vivo conversion of mirex to chlordecone was also examined (Morgan et al. 1979). 

Mirex was found in a variety of tissues from minipigs administered mirex in the feed for 7 days; however, 

chlordecone was not detected in any tissues (Morgan et al. 1979). This result indicates that significant in 

vivo conversion of absorbed mirex to chlordecone is not likely.

Chlordecone. The fate of chlordecone in humans involves uptake by the liver, enzymatic reduction to 

chlordecone alcohol, conjugation with glucuronic acid, partial conversion to unidentified polar forms, and 
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excretion of these metabolites mainly as glucuronide conjugates into bile (Fariss et al. 1980; Guzelian et 

al. 1981) (see Figure 3-1). Of the total chlordecone measured in bile of occupationally exposed workers, 

the predominant portion (72%) was unconjugated, with only a small portion conjugated with glucuronic 

acid or sulfate (9%) (Fariss et al. 1980). The remaining fraction (19%) of total chlordecone measured in 

the bile was stable polar metabolites, which were resistant to β-glucuronidase. Following treatment of 

bile with β-glucuronidase plus sulfatase, the ratio of total chlordecone to total chlordecone alcohol was 

1:3 in human bile (Fariss et al. 1980). Bioreduction of chlordecone to chlordecone alcohol is speciesspecific since rats treated orally or intraperitoneally with chlordecone produced no chlordecone alcohol in 

the feces, bile, or liver (Fariss et al. 1980; Guzelian et al. 1981; Houston et al. 1981). Following treatment 

of bile with β-glucuronidase plus sulfatase, the ratio of total chlordecone to total chlordecone alcohol in 

rat bile was in excess of 150:1 for orally exposed rats (Fariss et al. 1980; Guzelian et al. 1981). Guinea 

pigs and hamsters given an intraperitoneal dose of 20 mg/kg chlordecone also did not convert 

chlordecone to chlordecone alcohol, as indicated by the fact that no chlordecone alcohol was detected in 

the feces, bile, or liver (Houston et al. 1981). Therefore, rats, guinea pigs, and hamsters are not good 

animal models for predicting chlordecone metabolism in humans because they do not convert 

chlordecone to chlordecone alcohol. Gerbils were found to be the most suitable animal model of 

chlordecone metabolism in humans because only gerbils converted chlordecone to its alcohol (Houston et 

al. 1981). Reduction of chlordecone is catalyzed in gerbil liver by a species-specific reductase, 

chlordecone reductase. This chlordecone reductase was characterized in gerbil liver cytosol in vitro and 

determined to be of the “aldo-keto reductase” family (Molowa et al. 1986). It is specific to gerbils and 

humans (Molowa et al. 1986). Like humans, chlordecone-treated gerbils excreted chlordecone alcohol 

exclusively in the stool and not in the urine (Houston et al. 1981). Following intraperitoneal dosing of 

20 mg/kg 14C-chlordecone, the ratio of chlordecone to chlordecone alcohol in the bile of gerbils was 

approximately 2.5:1. No quantitative estimate of the extent to which chlordecone was metabolized was 

given. Following treatment of bile with β-glucuronidase plus acid hydrolysis, the ratio of chlordecone to 

chlordecone alcohol in the bile was 1:2, indicating that chlordecone is present in the bile largely in the 

form of its glucuronide conjugate (Houston et al. 1981). Incubation of chlordecone with the cytosolic 

fraction of gerbil liver homogenate in the presence of NADPH produced chlordecone alcohol (Houston et 

al. 1981). Intraperitoneally-injected chlordecone was biotransformed in pigs to conjugated chlordecone, 

chlordecone alcohol, and conjugated chlordecone alcohol, which were excreted in the bile and eliminated 

in the feces (Soine et al. 1983). Relatively high levels of chlordecone alcohol and conjugated chlordecone 

alcohol in the bile and the absence of these metabolites in the plasma and liver suggest that chlordecone 

alcohol is formed and conjugated in the liver and excreted into the bile (Soine et al. 1983).
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Figure 3-1. Proposed Metabolic Pathways for Chlordecone

O

Cl

10

O

O

OH

OH

HO

COOH

H

Cl

10

OH

HO

Cl

10

OH

H

Cl

10

O

O

OH

OH

HO

COOH

Cl

10

Chlordecone

Chlordecone

hydrate

Chlordecone

alcohol

UDP

alpha-Dglucuronic

acid

HOH [H]

Chlordecone

glucuronide

(mono or di)?

Chlordecone

alcohol

glucuronide

UDP

alpha-Dglucuronic

acid

 

Source: Fariss et al. 1980

3.1.4 Excretion 

Mirex. Available information regarding mirex-related excretion in humans is limited. Mirex was 

detected in milk samples from lactating women (Fitzgerald et al. 2001; Greizerstein et al. 1999; Mes et al. 

1978; Newsome and Ryan 1999; Newsome et al. 1995).

In animals, mirex is excreted unchanged mainly in the feces; urinary excretion is negligible (Byrd et al. 

1982; Chambers et al. 1982; Gibson et al. 1972; Ivie et al. 1974a). Female rats receiving a single oral 

dose of 14C-mirex (0.2 mg/kg) excreted 18% of the total administered dose in the feces during a 7-day 

posttreatment period; very little was excreted in the urine (0.3% of the total dose) (Gibson et al. 1972). 

Of the total quantity eliminated, 85% was excreted in the feces within the first 48 hours. This percentage 

represents unabsorbed material. The virtual lack of urinary excretion and the fact that fecal excretion was 
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only about 3% of the administered dose after the initial 48 hours suggest that mirex is not metabolized in 

rats and that the absorbed portion is only slowly excreted. In female rats administered a single oral dose 

of 10 mg/kg mirex, cumulative fecal excretion of mirex during 21 days posttreatment was 18–45% (Byrd 

et al. 1982). Most of the fecal mirex was excreted within 48 hours and represented unabsorbed mirex. A 

biological half-life of mirex was estimated to be 460 days by a model developed to simulate mirex 

pharmacokinetics after oral administration (Byrd et al. 1982). Male rats receiving a single oral dose of 

mirex at 6 mg/kg excreted 58.5% of the administered dose in the feces during 7 days posttreatment

(Mehendale et al. 1972). Fifty-five percent of the administered dose was excreted in the feces within the 

first 48 hours post-dosing and probably represented unabsorbed dose from the gut. Only 0.69% of the 

administered dose was excreted in the urine. Mirex was the only treatment-related compound identified 

in the urine or feces. A half-life of 38 hours was estimated based on the first rapid elimination. A second 

half-life was projected to be >l00 days, indicating a very slow rate of elimination from the body.

Following oral administration of 1 mg/kg 14C-mirex to a female rhesus monkey, 25% of the radioactivity

was recovered in the feces within 48 hours, with a cumulative excretion of 26.5% over 23 days. Less than 

1% was recovered in the urine over 23 days (Wiener et al. 1976). A monohydro derivative of mirex was 

identified in the feces of rhesus monkeys given daily doses of 1 mg/kg mirex; the exact duration of dosing 

was not specified (Stein and Pittman 1977).

The secretion of mirex in milk was a major route of elimination for nursing rat dams given either 1 or 

10 mg/kg/day of mirex via gavage on postpartum days 2–5 (Kavlock et al. 1980). Mirex entered the milk 

supply more quickly than chlordecone. Greater amounts of mirex were excreted via the milk as compared 

with chlordecone because of the octanol-water partition coefficient. Mirex was also excreted in the milk 

of lactating goats given daily doses of 1 mg/kg for 18 or 61 weeks followed by daily doses of 10 mg/kg 

for 4 weeks (Smrek et al. 1977). The concentration of mirex in colostrum fat ranged from 16 to 20 ppm. 

Colostrum, which is fluid secreted for the first few days after parturition, is characterized by high protein 

and antibody content. Over 8 weeks, the levels of mirex in milk fat decreased to less than half the amount 

excreted in colostrum immediately after birth of the kids. The goats eliminated more mirex in colostrum 

than in regular milk. A lactating Jersey cow given a daily dose equivalent to 0.005 mg/kg/day in the diet 

for 28 days, excreted 50% of the administered dose in the feces during the 28-day exposure period 

(Dorough and Ivie 1974). Only approximately 3% of the administered dose of mirex was excreted in the 

feces in the 28 days after treatment ended. These results show that the radioactivity in the feces 

represents unabsorbed mirex, and that the turnover rate of mirex stored in the tissues is very low. In this 

study, mirex was also found in cow’s milk. About 10% of the administered dose was excreted in the milk 
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10 days after treatment began. Cumulative excretion in the milk was 13% after 28 days of exposure. 

Only 2% of the administered dose was excreted in the milk during the entire 28-day post-treatment 

period. The levels of mirex in milk equilibrated after 1 week of treatment, with the concentration in 

whole milk being 0.058 ppm. One week after treatment ended, the residues in the milk dropped to 

0.006 ppm and then declined to 0.002 ppm after 28 days (Dorough and Ivie 1974). Mirex was the only 

treatment-related compound identified in the feces and cow’s milk.

Mirex has a long retention time in the body and is excreted slowly. Cumulative fecal excretion was 7% of 

the administered dose 21 days following intravenous dosing of 10 mg/kg in rats (Byrd et al. 1982). 

Cumulative urinary excretion was <1% of the administered dose (Byrd et al. 1982). The biological halflife of mirex was estimated to be 435 days (Byrd et al. 1982). Cumulative fecal excretion was 4.69 and 

6.91% of the dose after 106 and 388 days, respectively, following a single intravenous dose of 1 mg/kg to 

female monkeys (Wiener et al. 1976). Cumulative urinary excretion accounted for 0.18–0.37% of the 

administered dose by the end of 1 week. Mirex was the only labeled compound identified in the feces. 

An unidentified substance found in the feces was thought to be a decomposition product of mirex, not a 

metabolite (Wiener et al. 1976). Mirex and an unidentified metabolite, a nonpolar derivative, were found 

in the feces of rhesus monkeys given an intravenous dose of 1 mg/kg of mirex (Stein et al. 1976). It is 

believed that the suspected metabolite may have arisen as a result of bacterial action in the lower gut or 

feces (Stein et al. 1976).

Chlordecone. Chlordecone, chlordecone alcohol, and their glucuronide conjugates were excreted in the 

bile and eliminated via the feces of humans occupationally exposed to chlordecone (Blanke et al. 1978; 

Boylan et al. 1979; Cohn et al. 1978; Guzelian et al. 1981). In the study of Guzelian et al. (1981), most of 

the total chlordecone measured in bile was unconjugated (72%), a small amount (9%) was conjugated 

with glucuronic acid, and the final portion (19%) was present as an uncharacterized “acid releasable” 

form. Only a minor amount of chlordecone alcohol (<10%) was present in bile as the free metabolite; the 

remainder was conjugated with glucuronide. A substantial enterohepatic recirculation of chlordecone 

exists that curtails its excretion (Boylan et al. 1979; Cohn et al. 1978; Guzelian et al. 1981). Only 5–10% 

of the biliary chlordecone entering the lumen of the duodenum appeared in the feces (Cohn et al. 1978; 

Guzelian et al. 1981). Similarly, the rate of chlordecone excretion in the bile was, on average, 19 times 

greater than the rate of elimination of chlordecone in the stool (Cohn et al. 1978). Chlordecone was not 

detected in the sweat and was detected in only minor quantities in urine, saliva, and gastric juice (Cohn et 

al. 1978). Similarly, stool contained 11–34% of the quantities excreted in bile for workers exposed for 

6 months (Boylan et al. 1979). When biliary contents were diverted, fecal excretion of chlordecone 
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alcohol fell to low or undetectable levels; however, chlordecone excretion in feces persisted, suggesting a 

nonbiliary mechanism for the excretion of chlordecone into the intestine and feces (Boylan et al. 1979). 

Analogous experiments with rats gave similar results (Boylan et al. 1979). With no bile in the gut, the 

average amount of chlordecone in the human stool in two 72-hour collections was eight times as great as 

with the biliary circuit intact (Boylan et al. 1979). This suggests that bile may suppress nonbiliary 

excretion of chlordecone. When bile was completely diverted from the intestines of rats, however, fecal 

excretion of radiolabel was unchanged (Boylan et al. 1979).

In rats, chlordecone is slowly eliminated in the feces (Egle et al. 1978). Rats given a single oral dose of 

40 mg/kg 14C-chlordecone excreted 65.5% of the administered dose in the feces and 1.6% of the dose in 

the urine by 84 days (Egle et al. 1978). Less than 1% of the administered dose was expired as 

radiolabeled carbon dioxide (14C-CO2) (Egle et al. 1978). Rats fed 14C-chlordecone (0.2 mg/kg/day for 

3 days) excreted 52.16% of the radioactivity in the feces and 0.52% in the urine 25 days postdosing 

(Richter et al. 1979).

Chlordecone was excreted in the saliva of rats following administration of 50 mg/kg (Borzelleca and 

Skalsky 1980; Skalsky et al. 1980). Peak levels of chlordecone in saliva were reached 6–24 hours 

postdosing (Borzelleca and Skalsky 1980; Skalsky et al. 1980). The saliva-to-plasma ratios were 

<1 throughout the study period, indicating that chlordecone is not actively concentrated by the salivary 

glands (Borzelleca and Skalsky 1980). Thus, chlordecone enters the salivary tissue (submaxillary, 

parotid, and sublingual tissues) and saliva by passive diffusion (Borzelleca and Skalsky 1980; Skalsky et 

al. 1980).

Chlordecone is also excreted in the milk of nursing rats (Kavlock et al. 1980). When compared with 

mirex-treated rats, chlordecone entered the milk supply more slowly than mirex. More mirex was 

excreted via the milk than chlordecone because of a higher octanol-water partition coefficient.

Chlordecone was detected in the bile and feces of rats, guinea pigs, hamsters, gerbils, and pigs given 

intraperitoneal doses of 20 mg/kg chlordecone (Houston et al. 1981; Soine et al. 1983). Rats given 

intraperitoneal injections of chlordecone had a fecal excretion half-life of 40 days (Pore 1984). 

Chlordecone alcohol was detected in the bile and feces of gerbils and pigs only (Houston et al. 1981; 

Soine et al. 1983).
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Chlordecone appeared in the bile within 1–3 hours after intravenous dosing of rats (0.1, 1, or 10 mg/kg) 

(Bungay et al. 1981). The average concentration of chlordecone in the bile varied linearly with dose: 

0.051, 0.50, and 5 μg/g in the low-, middle-, and high-dose groups, respectively (Bungay et al. 1981). 

Rats given a single intravenous dose of 1 mg/kg had a chlordecone excretion rate in the bile of 0.22% of 

the dose per hour (Bungay et al. 1981).

3.1.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

PBPK models use mathematical descriptions of the uptake and disposition of chemical substances to 

quantitatively describe the relationships among critical biological processes (Krishnan et al. 1994). PBPK 

models are also called biologically based tissue dosimetry models. PBPK models are increasingly used in 

risk assessments, primarily to predict the concentration of potentially toxic moieties of a chemical that 

will be delivered to any given target tissue following various combinations of route, dose level, and test 

species (Clewell and Andersen 1985). Physiologically based pharmacodynamic (PBPD) models use 

mathematical descriptions of the dose-response function to quantitatively describe the relationship 

between target tissue dose and toxic endpoints. 

PBPK models for mirex have not been developed. Several models were developed for chlordecone. 

Bungay et al. (1979) developed a model to predict the kinetics of chlordecone in the gastrointestinal tract 

by comparing excretion following oral administration to intact rats and intravenous administration to bilecannulated rats. Heatherington et al. (1998) used experimental data from chlordecone-treated young and 

adult rats to predict percutaneous absorption and disposition. El-Masri et al. (1995) evaluated interactions 

between chlordecone and carbon tetrachloride in the rat liver using pharmacokinetic and 

pharmacodynamic modeling. Belfiore et al. (2007) developed a model to describe sequestration of 

chlordecone in the rat liver. None of the models are useful for predicting the toxicokinetic behavior or 

target concentrations of chlordecone in humans.

3.1.6 Animal-to-Human Extrapolations 

The toxicokinetics of mirex has been widely studied in experimental animals (Atallah and Dorough 1975; 

Brown and Yarbrough 1988; Byrd et al. 1982; Chambers et al. 1982; Dorough and Atallah 1975; Gibson 

et al. 1972; Ivie et al. 1974a; Kavlock et al. 1980; Mehendale et al. 1972; Morgan et al. 1979; Plaa et al. 

1987; Smrek et al. 1977; Wiener et al. 1976). Available data demonstrate that mirex accumulates in 

tissues (particularly fat), is not metabolized, and is slowly excreted in feces. Most animal studies were 

conducted using rats. A few studies using monkeys, goats, or cows yielded results generally similar to 
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those reported for rats. Limited human data have not identified or quantified the toxicokinetics of mirex 

(Burse et al. 1989; Kutz et al. 1974; Mes et al. 1978). No information was located to indicate that the 

toxicokinetics of mirex in humans would be significantly different from that observed in experimental 

animals.

Toxicokinetic studies have been performed using multiple animal species; the data indicate that rats, 

guinea pigs, and hamsters may not represent appropriate models for extrapolation to humans because 

these animal species do not convert chlordecone to chlordecone alcohol (Fariss et al. 1980; Guzelian et al. 

1981; Houston et al. 1981). Gerbils and pigs may be more appropriate species to study animal-to-human 

extrapolation because these species convert chlordecone to chlordecone alcohol (Houston et al. 1981; 

Soine et al. 1983). Limited human toxicokinetic data are available for chlordecone (Adir et al. 1978; 

Blanke et al. 1978; Boylan et al. 1978; Cannon et al. 1978; Cohn et al. 1978; Guzelian et al. 1981; Taylor 

1982, 1985). It does not appear that sufficient data exist to provide meaningful extrapolation from 

animals to humans with respect to chlordecone toxicokinetics.

3.2 CHILDREN AND OTHER POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans. Potential effects on offspring resulting from exposures of parental 

germ cells are considered, as well as any indirect effects on the fetus and neonate resulting from maternal 

exposure during gestation and lactation. Children may be more or less susceptible than adults to health 

effects from exposure to hazardous substances and the relationship may change with developmental age. 

This section also discusses unusually susceptible populations. A susceptible population may exhibit 

different or enhanced responses to certain chemicals than most persons exposed to the same level of these 

chemicals in the environment. Factors involved with increased susceptibility may include genetic 

makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). 

These parameters can reduce detoxification or excretion or compromise organ function. 

Populations at greater exposure risk to unusually high exposure levels to mirex or chlordecone are 

discussed in Section 5.7, Populations with Potentially High Exposures.

Review of the literature regarding toxic effects of mirex and chlordecone did not reveal any human 

populations that are known to be unusually sensitive to mirex or chlordecone. However, based on 
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knowledge of the toxicities of mirex and chlordecone, some populations can be identified that may 

demonstrate unusual sensitivity to these chemicals. Those with potentially high sensitivity to mirex 

include the very young. Those with potentially high sensitivity to chlordecone include juvenile and 

elderly persons as well as persons being treated with some antidepressants or the anticonvulsant, 

diphenylhydantoin.

In experimental animals, mirex administered within the week after birth causes a high incidence of 

cataracts and other lesions of the lens (Chernoff et al. 1979a; Gaines and Kimbrough 1970; Rogers and 

Grabowski 1984; Scotti et al. 1981). These effects were observed whether the neonatal animals received 

mirex through the milk of lactating dams or directly by gavage. Although it is unclear whether the lens of 

humans also undergoes a similar period of susceptibility, the possibility exists that newborn children may 

also develop cataracts if exposed to mirex shortly after birth.

Studies in rats have demonstrated that certain treatments exacerbate the tremors associated with 

chlordecone exposure. These include pretreatment with the anticonvulsant, diphenylhydantoin (Hong et 

al. 1986; Tilson et al. 1985, 1986), and treatment with the non-selective serotonergic receptor agonist, 

quipazine (Gerhart et al. 1983). Therefore, persons being treated with diphenylhydantoin for epilepsy or 

quipazine for depression may be likely to experience more severe tremors upon exposure to high levels of 

chlordecone. Extrapolating from the effects seen in animals with quipazine, it might be likely that 

persons taking the prescription drug Prozac®, a selective serotonin reuptake inhibitor (SSRI) used to treat 

depression, may also experience more severe tremors. Furthermore, the elderly may be a susceptible 

population because serotonin metabolism is increased during aging (Walker and Fishman 1991).

Studies in animals have also shown that juvenile animals experience a higher death rate than adults 

following exposure to chlordecone at equivalent mg/kg doses (Huber 1965). No explanation was given 

for these findings, but similar sensitivities may exist in children. Furthermore, although inhibition of 

Na+

K+ATPase, Mg2+ATPase, and Ca2+ATPase activities have not been definitively shown to be the 

mechanism underlying chlordecone toxicity, sufficient evidence exists to suggest that their inhibition may 

be involved in a number of adverse effects. Neonatal rats have shown a greater inhibition of these 

enzymes than adult rats (Jinna et al. 1989). This provides additional support for the suggestion that 

infants and young children may represent a susceptible population to the toxic effects of chlordecone.

In contrast, a recent study of developing postnatal rats has shown that the young may be less susceptible 

to at least one of the toxic effects of chlordecone. Young and adolescent rats show less potentiation of 
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carbon tetrachloride toxicity than adult rats (Cai and Mehendale 1993). This may be due to a combination 

of incomplete development of the microsomal enzyme systems and a higher level of hepatic regenerating 

activity in the very young rats. In adolescent rats (35 and 45 days old), the microsomal enzyme activity is 

comparable to adult levels, but the level of damage is still less than in adult rats (60 days old). This may 

be due to that fact that hepatic regenerating activity remained higher in the adolescents than in the adults.

Several studies (Dalu and Mehendale 1996; Dalu et al. 1995, 1998; Murali et al. 2004) provide additional 

insight to earlier findings of age-related differences in the lethality and hepatotoxicity induced by 

exposure of rats to nontoxic levels of chlordecone and subsequent exposure to otherwise nonlethal levels 

of carbon tetrachloride. Results of Blain et al. (1999) indicate both sex- and age-dependent influences on 

chlordecone-carbon-tetrachloride-induced hepatotoxicity in rats.

In studies performed by Sobel and coworkers (Sobel et al. 2005, 2006; Wang et al. 2008), chronic 

exposure of systemic lupus erythematosus-prone female (NZB x NZW) F1 mice to chlordecone via 

subcutaneously-implanted pellets significantly shortened the time to onset of elevated autoantibody titers 

and renal disease in a dose-related manner. These effects were not seen in nonlupus-prone BALB/c mice. 

These results indicate that humans with lupus may be particularly sensitive to chlordecone toxicity.

3.3 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as biomarkers of exposure, biomarkers of effect, and biomarkers of susceptibility 

(NAS/NRC 1989).

A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the product of an interaction 

between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment 

of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally the substance 

itself, substance-specific metabolites in readily obtainable body fluid(s), or excreta. Biomarkers of 

exposure to mirex or chlordecone are discussed in Section 3.3.1. The National Report on Human 

Exposure to Environmental Chemicals provides an ongoing assessment of the exposure of a generalizable 

sample of the U.S. population to environmental chemicals using biomonitoring (see 

http://www.cdc.gov/exposurereport/). If available, biomonitoring data for mirex or chlordecone from this 

report are discussed in Section 5.6, General Population Exposure. 
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Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that (depending on magnitude) can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effect caused 

by mirex or chlordecone are discussed in Section 3.3.2.

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.2, Children and Other Populations that are Unusually Susceptible.

3.3.1 Biomarkers of Exposure

The primary biomarkers of exposure to mirex include mirex concentrations in blood (Butler Walker et al. 

2003; Byrd et al. 1982; Fenster et al. 2006; Greizerstein et al. 1999; Kavlock et al. 1980; Schell et al. 

2003; Smrek et al. 1977; van Oostdam et al. 2004; Wiener et al. 1976), fat (Burse et al. 1989; Kutz et al. 

1974), feces (Byrd et al. 1982; Chambers et al. 1982; Gibson et al. 1972; Ivie et al. 1974a), or breast milk 

(Dorough and Ivie 1974; Fitzgerald et al. 2001; Greizerstein et al. 1999; Kavlock et al. 1980; Mes et al. 

1978; Newsome and Ryan 1999; Newsome et al. 1995; Smrek et al. 1977). Since mirex is not 

metabolized, it is the only biomarker to be measured in these biological media. Since mirex is retained in 

the body for long periods of time and only slowly excreted, its measurement is useful as a biomarker of 

acute-, intermediate-, or chronic-duration exposures to both low and high levels. Biomonitoring levels for 

mirex are presented in Section 5.6.

The biomarkers of exposure to chlordecone include blood or saliva concentrations of chlordecone, and 

fecal or bile concentrations of chlordecone, chlordecone alcohol, and/or their glucuronide conjugates. 

Blood samples are the most useful tool for epidemiological studies of exposure to chlordecone (Guzelian 

et al. 1981). The unusually high concentration of chlordecone in blood compared with its concentration 

in fat (1:7 in humans), which is due to chlordecone’s association with plasma proteins, and its long halflife, make chlordecone in blood (a readily sampled tissue) a good biomarker of exposure. The blood 
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concentration of chlordecone serves as an accurate reflection of total body content of chlordecone. Blood 

is the best biological material to monitor and to use for determining acute, intermediate, and chronic 

exposures to both low and high levels of chlordecone.

Blood is a better indicator of exposure to chlordecone than saliva (Borzelleca and Skalsky 1980; Skalsky 

et al. 1980). Chlordecone has been detected in saliva of humans only in trace amounts and in rats at 

concentrations 3–4 times lower than in blood (Guzelian et al. 1981; Skalsky et al. 1980). Peak 

chlordecone concentrations occurred within the first 24 hours of exposure; therefore, the period of utility 

of saliva as a biomarker is limited. The movement of chlordecone from blood into saliva is one of passive 

diffusion and is not concentration dependent (Borzelleca and Skalsky 1980; Skalsky et al. 1980). Thus, 

blood is a better biological material than saliva for monitoring chlordecone exposure.

Other biomarkers of exposure include tissue concentrations of chlordecone (Bungay et al. 1981; Cannon 

et al. 1978; Cohn et al. 1978; Egle et al. 1978; Hewitt et al. 1986b; Plaa et al. 1987; Taylor 1982, 1985) 

and fecal or bile concentrations of chlordecone, chlordecone alcohol, and their glucuronide conjugates 

(Blanke et al. 1978; Boylan et al. 1979; Cohn et al. 1978; Guzelian et al. 1981). These can be measured 

and are reliable indicators of exposure to chlordecone.

3.3.2 Biomarkers of Effect

Microsomal enzyme induction has been shown to be increased by both mirex and chlordecone in humans 

and/or experimental animals. Serum levels of chlordecone associated with enzyme induction in exposed 

workers were estimated to range from 100 to 500 μg/L (Guzelian 1985). Urinary D-glucaric acid levels 

have been shown to be a sensitive indicator of microsomal enzyme induction in workers exposed to 

chlordecone (Guzelian 1985). However, other substances such as barbiturates, phenytoin, chlorbutanol, 

aminopyrine, phenylbutazone, and contraceptive steroids as well as other organochlorinated pesticides 

also cause microsomal enzyme induction and cause changes in urinary D-glucaric acid (Morgan and Roan 

1974).

Studies in experimental animals suggest that biliary excretion of chemicals from the liver may be 

impaired by mirex or chlordecone (Berman et al. 1986; Curtis and Hoyt 1984; Curtis and Mehendale 

1979; Curtis et al. 1979, 1981; Davison et al. 1976; Mehendale 1976, 1977a, 1977b, 1981; Teo and Vore 

1991). Measurement of serum bile acid levels may provide information regarding biliary excretory 

function.
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Studies in experimental animals have also shown increased urinary protein accompanied or 

unaccompanied by histopathological changes of the kidneys following exposure to mirex (NTP 1990) or 

chlordecone (Larson et al. 1979b). Although these changes are not specific for mirex or chlordecone, 

measurement of these parameters may provide information about renal damage in exposed populations.

Chlordecone causes a number of neurotoxic responses in humans and animals exposed to sufficiently high 

levels. Tremor accentuated by intentional acts, sustained postural movement, anxiety, and/or fatigue have

been observed in workers exposed to high levels of chlordecone. Tremorograms have been used to 

objectively assess tremors associated with chlordecone exposure in humans (Taylor et al. 1978). An 

infrared reflection technique and oculography have been used to assess oculomotor disturbances caused 

by chlordecone (Taylor et al. 1978). Standard tests for memory and intelligence can be used to determine 

the presence of encephalopathy, but in the absence of baseline preexposure levels for individuals, subtle 

changes may be difficult to detect.

Decreased sperm count has been observed following exposure to mirex or chlordecone in humans and/or 

experimental animals. Clinically, the most straightforward biomarker would be examination of sperm in 

the ejaculate. However, testicular biopsies may also be helpful. Both procedures have been used to 

assess the male reproductive toxicity of chlordecone in exposed persons (Taylor et al. 1978).

3.4 INTERACTIONS WITH OTHER CHEMICALS 

Limited data are available regarding interactions with other chemicals that affect the toxicity of mirex or 

chlordecone. Selected agents have been shown to exacerbate or suppress chlordecone-induced tremors in 

laboratory animals. Pretreatment of rats with diphenylhydantoin resulted in exacerbation of chlordeconeinduced tremors (Hong et al. 1986; Tilson et al. 1985, 1986). The mechanism for the exacerbation of the 

tremors is unknown. Therefore, if persons receiving diphenylhydantoin treatment for epilepsy were 

exposed to sufficiently high concentrations of chlordecone, increased tremor severity may be likely to 

occur. Treatment with quipazine (a nonselective serotonergic receptor agonist) was shown to potentiate 

chlordecone-induced tremors in rats (Gerhart et al. 1983). Therefore, it is possible that persons being 

treated for depression with quipazine or with SSRIs such as Prozac® may experience enhanced tremors.

A number of pharmacological agents have been shown to decrease the tremors produced by chlordecone 

in rats (Gerhart et al. 1983, 1985; Herr et al. 1987). Agents shown to be effective in at least one study 
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include yohimbe or phenoxybenzamine (α-noradrenergic antagonists), mecamylamine (a nicotinic 

antagonist), chlordiazepoxide (α benzodiazepine), muscimol (a GABA agonist), and mephenesin (a 

centrally acting muscle relaxant). Persons being treated therapeutically with any of these drugs are likely 

to experience diminished tremors following exposure to chlordecone.

Pretreatment of rats with difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, prior 

to exposure to a tremorgenic dose of chlordecone, also resulted in inhibition of the tremor (Tilson et al. 

1986). DFMO was more effective if given 5 hours prior to the chlordecone than if given 24 hours prior to 

exposure. The DFMO was ineffective if given 19 hours after chlordecone exposure. These results 

suggest an interaction of the polyamine synthetic pathway with tremors produced by chlordecone. The 

mechanism of the interaction is unclear, but may involve effects of polyamines on intracellular calcium 

homeostasis. Persons being treated with DFMO for cancer or protozoal infections would be likely to 

have reduced tremor severity after exposure to chlordecone.

Cholestyramine, a chelating agent, binds chlordecone present in the gastrointestinal tract and limits its 

enterohepatic recirculation (Boylan et al. 1978; Cohn et al. 1978). This interaction leads to increased 

excretion of chlordecone and decreased toxicity. Thus, persons being treated with cholestyramine to 

lower plasma cholesterol may experience increased excretion of chlordecone and decreased toxicity.

A number of animal studies have focused on effects of chlordecone on toxicity produced by other agents. 

Although these studies do not address the issue of interactions that affect chlordecone toxicity, results are 

summarized below.

By far, the most extensively studied interaction of mirex or chlordecone is the ability of chlordecone to 

markedly potentiate the hepatotoxicity of halomethanes such as carbon tetrachloride (Agarwal and 

Mehendale 1983a; Bell and Mehendale 1985; Chaudhury and Mehendale 1991; Curtis et al. 1979, 1981; 

Davis and Mehendale 1980; Klingensmith and Mehendale 1981, 1982b, 1983a, 1983b; Klingensmith et 

al. 1983; Kodavanti et al. 1989b, 1990a, 1991; Lockard et al. 1983a, 1983b; Mehendale and Klingensmith 

1988; Soni and Mehendale 1993; Tabet et al. 2016), bromotrichloromethane (Agarwal and Mehendale 

1982; Faroon and Mehendale 1990; Faroon et al. 1991; Klingensmith and Mehendale 1981), and 

chloroform (Cianflone et al. 1980; Hewitt et al. 1979, 1983, 1986a, 1986b, 1990; Iijima et al. 1983; 

Mehendale et al. 1989; Purushotham et al. 1988). For example, pretreatment of rats with 5 mg/kg 

chlordecone resulted in a 67-fold increase in carbon tetrachloride-induced lethality due to liver failure 

(Klingensmith and Mehendale 1982b). The increase in hepatotoxicity is characterized by increased serum 
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enzymes, extensive necrosis, increased destruction of CYP450 isozymes, and decreased biliary function. 

The potentiation of hepatotoxicity does not appear to be due solely to increased metabolism of the 

haloalkanes to toxic intermediates (CCl3, free radical and phosgene) and, as such, is distinct from the 

potentiation of halomethane toxicity by phenobarbital (Agarwal and Mehendale 1984a, 1984d; Bell and 

Mehendale 1987; Klingensmith and Mehendale 1983b; Mehendale and Klingensmith 1988; Mehendale 

1990) or mirex (Bell and Mehendale 1985; Cianflone et al. 1980; Hewitt et al. 1979, 1986a; Mehendale 

and Klingensmith 1988; Mehendale et al. 1989; Purushotham et al. 1988).

Several studies (Dalu and Mehendale 1996; Dalu et al. 1995, 1998; Murali et al. 2004) provide additional 

insight to findings of age-related differences in the lethality and hepatotoxicity induced by exposure of 

rats to nontoxic levels of chlordecone and subsequent exposure to otherwise nonlethal levels of carbon 

tetrachloride (Cai and Mehendale 1993). Results of Blain et al. (1999) indicate both sex- and agedependent influences on chlordecone-carbon tetrachloride induced hepatotoxicity in rats.

The primary mechanism for potentiation of hepatotoxicity may be the suppression of the early tissue 

regenerative response normally seen in livers of rats and mice exposed to low doses of halomethanes 

(Mehendale 1992, 1994). The dramatic increase in mitotic activity that normally occurs soon after 

halomethane exposure does not occur in chlordecone-pretreated animals (Faroon and Mehendale 1990; 

Lockard et al. 1983b). Gerbils, which do not exhibit early hepatocellular regeneration following 

halomethane exposure (and thus are more susceptible to the toxic and lethal effects of halomethanes), do 

not exhibit potentiation following chlordecone pretreatment (Cai and Mehendale 1990, 1991a). 

Experiments performed with partially hepatectomized animals provide further evidence for the role of 

suppressed regeneration following carbon tetrachloride exposure (Cai and Mehendale 1991b). Partial 

hepatectomy, which stimulates tissue regeneration, afforded partial protection from the potentiating 

effects of chlordecone in rats (Bell et al. 1988; Rao et al. 1989; Young and Mehendale 1989). Similarly, 

Cai and Mehendale (1993) have shown that young rats with greater hepatocellular regenerative activity 

than adult rats also experience less hepatocellular damage following exposure to both chlordecone and 

carbon tetrachloride. Cellular changes that may facilitate the chlordecone-induced suppression of 

regeneration include marked depletion of hepatocellular glycogen (Bell and Mehendale 1987; Faroon et 

al. 1991; Lockard et al. 1983a, 1983b), depletion of ATP (Faroon et al. 1991; Kodavanti et al. 1990b), and 

disruptions in the regulation of intracellular calcium (Agarwal and Mehendale 1984a, 1984c, 1984d, 

1986; Hegarty et al. 1986; Kodavanti et al. 1991). It has been demonstrated that suppression of cell 

division due to glycogen depletion results in decreased ATP availability and, consequently, suppressed 

cellular regeneration (Soni and Mehendale 1993, 1994).
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Both mirex and chlordecone are microsomal enzyme inducers, and as such, enhance the metabolism of 

compounds oxidized or reduced by the mixed function oxygenase system. For example, the metabolism 

of lindane was enhanced in rats previously exposed to chlordecone (Chadwick et al. 1979). For chemicals 

that undergo a loss of activity with metabolism, a decrease in effectiveness would be likely in mirex- or 

chlordecone-exposed persons. For example, pretreatment of rats with chlordecone reduced the 

cholinesterase inhibition produced by a subsequent dose of methyl parathion (Tvede et al. 1989). In this 

study, methyl parathion was apparently metabolized to its active metabolite, methyl paraoxon, and the 

methyl paraoxon was further metabolized to an inactive metabolite. For chemicals that undergo a 

transformation to an active or toxic metabolite, enhanced activity/toxicity would be likely in mirex- or 

chlordecone-exposed persons. An example of this type of interaction was shown in the enhancement of 

acetaminophen toxicity by 30 mg/kg of mirex or chlordecone (Fouse and Hodgson 1987). 

Acetaminophen causes hepatic necrosis as the result of the binding of the reactive intermediate, 

postulated to be N-acetylquinoneimine, formed by the microsomal CYP450 dependent monooxygenase 

system. Mirex and chlordecone increased the activity of this system, and as a result, the toxicity of the 

acetaminophen was increased.
MIREX AND CHLORDECONE 145

CHAPTER 4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY

Information regarding the chemical identity of mirex and chlordecone is located in Table 4-1. 

Table 4-1. Chemical Identity of Mirex and Chlordeconea

Characteristic

Information

Mirex Chlordecone

Chemical name 1,1a,2,2,3,3a,4,5,5,5a,5b,6-Dodecachlorooctahydro-1,3,4-metheno1H-cyclobuta[cd]- pentalene1,1a,3,3a,4,5,5,5a,5b,6-Decachlorooctahydro-1,3,4- metheno2H-cyclobuta[cd] pentalen-2-one

Synonym(s) and registered 

trade name(s)

1,2,3,4,5,5-Hexachloro1,3-cyclopentadiene dimerb; 

dodecachlorooctahydro1,3,4-metheno-1H-cyclobuta[cd] 

pentaleneb 

CG-1283; Dechlorane; ENT 25719d

Decachloroketonec; decachlorooctahydro-1,3,4-metheno2H-cyclobuta[cd]pentalen-2-onec

GC 1189; Kepone; Merexc

Chemical formula C10Cl12 C10Cl10O

Chemical structure

CAS Registry Number 2385-85-5 143-50-0

aAll information obtained from Budavari et al. 1989, except where noted. bIARC 1979. cIARC 1979. dNLM 2020. 

CAS = Chemical Abstracts Service 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of mirex and chlordecone is located in 

Table 4-2. 
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4. CHEMICAL AND PHYSICAL INFORMATION

Table 4-2. Physical and Chemical Properties of Mirex and Chlordecone

Property

Information

Mirex Chlordecone

Molecular weight 545.59 490.68

Color Snow-white Tan-whiteb

Physical state Crystalline solid Crystalline solid

Melting point 485°C (decomposes) 350°C (decomposes)b

Boiling point No data No data

Density at 25°C No data No data

Odor Odorless Odorlessc

Odor threshold 5.0667 mg/m3 d

Solubility:

Water Practically insoluble

0.60 mg/Le

insolublef

0.2 mg/L at 24°C (practical grade)f

Slightly soluble

3.0 mg/Le

practically insolubleb

Organic solvents Dioxane (15.3%); xylene (14.3%); 

benzene (12.2%); CCl4 (7.2%); 

methyl ethyl ketone (5.6%)

Soluble in hydrocarbon solvents, 

alcohols, ketones

Partition coefficients:

Log Kow 5.28g 4.50h

Log Koc 3.763f 3.38–3.415h

Vapor pressure at 25°C 3x10-7 mm Hgf <3x10-7 mm Hgb

Henry's law constant:

at 20°C 839.37 Pa m3/molei 2.50x10-8 atm

At 22°C 5.16x10-4 atm m3/molej m3/moleh

Autoignition temperature Nonflammableb Nonflammable

Flashpoint No data No data

Flammability limits Nonflammabled

Supports combustion

Nonflammable

Conversion factors 1 ppm=0.041 mg/m3 1 ppm=0.046 mg/m3

Explosive limits No data No data

aAll information obtained from Budavari et al. 1989, except where noted. bIARC 1979. cVerschueren 1983.

dNLM 2020. eKenaga 1980. f

IARC 1979. gNiimi 1991. hHoward 1991. i

Domine et al. 1992. j

Yin and Hassett 1986.

CCl4 = carbon tetrachloride
MIREX AND CHLORDECONE 147

CHAPTER 5. POTENTIAL FOR HUMAN EXPOSURE

5.1 OVERVIEW 

Mirex has been identified in at least 9 of the 1,867 hazardous waste sites that have been proposed for 

inclusion on the EPA National Priorities List (NPL) (ATSDR 2019). However, the number of sites in 

which mirex has been evaluated is not known. The number of sites in each state is shown in Figure 5-1. 

Figure 5-1. Number of NPL Sites with Mirex Contamination

Chlordecone has been identified in at least 4 of the 1,867 hazardous waste sites that have been proposed 

for inclusion on the EPA National Priorities List (NPL) (ATSDR 2019). However, the number of sites in 

which chlordecone has been evaluated is not known. The number of sites in each state is shown in

Figure 5-2.
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5. POTENTIAL FOR HUMAN EXPOSURE

Figure 5-2. Number of NPL Sites with Chlordecone Contamination

• The most likely source of potential exposure of the general population to mirex or chlordecone is 

from consumption of contaminated food sources, particularly in the eastern portion of the United 

States where mirex and chlordecone were most frequently used.

• People who live or work near hazardous waste sites where mirex and/or chlordecone may be 

stored could most likely be exposed from contaminated sediment or soil.

• Both mirex and chlordecone bind strongly to organic matter in water, sediment, and soil where 

they may persist for long periods of time.

• Both mirex and chlordecone are lipophilic and bioaccumulate and biomagnify in aquatic and 

terrestrial food chains.

As a result of human health concerns, production of mirex ceased in 1976, at which time industrial 

releases of this chemical to surface waters were also curtailed. However, releases from waste disposal 

sites continue to add mirex to the environment. Virtually all industrial releases of mirex were to surface 

waters, principally Lake Ontario via contamination of the Niagara and Oswego Rivers. About 75% of the 

mirex produced was used as a fire retardant additive, while 25% was used as a pesticide. As a pesticide, 

mirex was widely dispersed throughout the southern United States where it was used in the fire ant 

eradication program for over 10 years.

Adsorption and volatilization are the more important environmental fate processes for mirex, which 

strongly binds to organic matter in water, sediment, and soil. When bound to organic-rich soil, mirex is 

highly immobile; however, when adsorbed to particulate matter in water, it can be transported great 
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5. POTENTIAL FOR HUMAN EXPOSURE

distances before partitioning out to sediment. Atmospheric transport of mirex has been reported based on 

its detection in remote areas without anthropogenic sources, although this is not a major source of mirex 

in the environment. Given the lipophilic nature of this compound (high octanol-water partition 

coefficient), mirex is both bioaccumulated and biomagnified in aquatic and terrestrial food chains.

Mirex is a very persistent compound in the environment and is highly resistant to both chemical and 

biological degradation. The primary process for the degradation of mirex is photolysis in water or on soil 

surfaces; photomirex is the major transformation product of photolysis. In soil or sediments, anaerobic 

biodegradation is also a major removal mechanism whereby mirex is slowly dechlorinated to the 

10-monohydro derivative. Aerobic biodegradation in soil is a very slow and minor degradation process. 

Twelve years after the application of mirex to soil, 50% of the mirex and mirex-related compounds 

remained on the soil. Between 65 and 73% of the residues recovered were mirex and 3–6% were 

chlordecone, a transformation product (Carlson et al. 1976).

Mirex has been detected at low concentrations in ambient air (mean 0.35 pg/m3

) and rainfall samples 

(<0.5 ng/L) from polluted areas of the Great Lakes region. In addition, the compound has been detected 

in drinking water samples from the Great Lakes area of Ontario, Canada. Mirex has also been detected in 

groundwater samples from agricultural areas of New Jersey and South Carolina.

Mirex has been monitored in surface waters, particularly during the period that it was still being 

produced. Concentrations of mirex in Lake Ontario, the Niagara River, and the St. Lawrence River were 

in the ng/L (ppt) range. The highest concentrations of mirex, 1,700 μg/kg (ppb), were found in sediments 

in Lake Ontario where they accumulated after the deposition of particulate matter to which the mirex was 

bound. A dynamic mass balance for mirex in Lake Ontario and the Gulf of St. Lawrence estimated that 

approximately 2,700 kg (6,000 pounds) of mirex have entered Lake Ontario over the past 40 years, of 

which 550 kg (1,200 pounds) have been removed (exclusive of sedimentation and burial) mainly by 

transport on sediment particles via outflowing water and migrating biota contaminated with mirex.

The high bioconcentration factor (BCF) values (up to 15,000 for rainbow trout) observed for mirex 

indicate that this compound will be found in high concentrations in aquatic organisms that inhabit areas 

where the water and sediments are contaminated with mirex. Fish taken from Lake Ontario, the St. 

Lawrence River, and the southeastern United States (areas where mirex was manufactured or used as a 

pesticide) had the highest mirex levels. There were fish consumption advisories in effect in three states 

(New York, Pennsylvania, and Ohio) that were triggered by mirex contamination in fish. Waterfowl and 
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5. POTENTIAL FOR HUMAN EXPOSURE

game animals have also been found to accumulate mirex in their tissues. Data on mirex residues in foods 

do not show a consistent trend with regard to contaminant levels or frequency of detection. Mirex was 

irregularly detected in Food and Drug Administration (FDA) Pesticide Residue Monitoring Studies since 

1978, but has not been detected in the most recent FDA survey. Little information on the specific foods 

in which residues were found or levels detected was located.

General population exposure to mirex has been determined as a result of several monitoring studies (CDC 

2019; EPA 1986b; Kutz et al. 1979; Stehr-Green 1989). Levels of mirex in most tissues are very low (at 

or near the detection limit). Examination of the 1982 National Adipose Tissue Survey failed to detect 

mirex in the adipose tissues of children <14 years old, although mirex residues were detected in adults. 

People who live in areas where mirex was manufactured or used have higher levels in their tissues. 

Women who live in these areas were found to have detectable levels of mirex in their milk that could be 

passed on to their infants. Since mirex is no longer manufactured, occupational exposure currently is 

limited to workers at waste disposal sites or those involved in remediation activities involving the cleanup and removal of contaminated soils or sediments.

Production of chlordecone ceased in 1975 as a result of human health concerns; at that time industrial 

releases of this chemical to surface waters via a municipal sewage system were curtailed. However, 

releases from waste disposal sites may continue to add chlordecone to the environment. Major releases of 

chlordecone occurred to the air, surface waters, and soil surrounding a major manufacturing site in 

Hopewell, Virginia. Releases from this plant ultimately contaminated the water, sediment, and biota of 

the James River, a tributary to the Chesapeake Bay.

Atmospheric transport of chlordecone particles was reported during production years based on results 

from high volume air samplers installed at the site and up to 15.6 miles away. Chlordecone is not 

expected to be subject to direct photodegradation in the atmosphere. Chlordecone is very persistent in the 

environment. Chlordecone, like mirex, will strongly bind to organic matter in water, sediment, and soil. 

When bound to organic-rich soil, chlordecone is highly immobile; however, when adsorbed to particulate 

matter in surface water, chlordecone can be transported great distances before partitioning out to 

sediment. Sediment in extensive areas of the James River served as a sink or reservoir for this compound. 

The primary process for the degradation of chlordecone in soil or sediments is anaerobic biodegradation. 

Based on the lipophilic nature of this compound (high octanol-water partition coefficient), chlordecone 

has a tendency to both bioaccumulate and biomagnify in aquatic food chains. BCF values >60,000 have 

been measured in Atlantic silversides, an estuarine fish species.
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No information was found on atmospheric concentrations of chlordecone other than historic monitoring 

data from samples collected in the vicinity of the manufacturing site. Chlordecone has been monitored in 

surface waters, particularly during the period shortly before and after production was terminated. In 

1977, chlordecone was detected in surface water samples from the James River at low concentrations 

(<10 ng/L [ppt]), although it was not detected in more recent monitoring studies. The highest 

concentrations of this compound are found in sediments, principally in the James River where it had 

accumulated after the deposition of particulate matter to which the chlordecone was bound. In 1978, 

chlordecone was detected in sediments from the James River below its production site at concentrations 

in the mg/kg (ppm) range.

The high BCF values observed for chlordecone (>60,000) indicate that the compound will be found in 

high concentrations in aquatic organisms that dwell in waters or sediments contaminated with 

chlordecone. Chlordecone has been detected in fish and shellfish from the James River, which empties 

into the Chesapeake Bay, at levels in the μg/g (ppm) range. There was a fish consumption advisory in 

effect for the lower 113 miles of the James River. Chlordecone residues were detected in foods analyzed 

in 1978–1982 and 1982–1986 as part of the FDA Pesticide Residue Monitoring Studies. Chlordecone 

was detected in one of 27,065 food samples analyzed by 10 state laboratories, but was not detected in the 

FDA Pesticide Residue Monitoring Studies in 1986–1991 or in the most recent (2017) study. No 

information on the specific foods in which residues were found or levels detected was located.

General population exposure to chlordecone has not been determined because this compound has not been 

monitored in any national program (CDC 2019; EPA 1986b; Kutz et al. 1979; Phillips and Birchard 1991; 

Stehr-Green 1989). Levels of chlordecone were detected in 9 of 298 samples of human milk collected 

from women in the southern United States. Residues were detected only in residents of areas that had 

been extensively treated with the pesticide mirex for fire ant control. People who lived in the area where 

chlordecone was manufactured had higher levels in their blood during production years. Women who 

lived in these areas could pass chlordecone in their milk to their nursing infants. Workers who 

manufactured chlordecone developed an occupationally-related illness. However, chlordecone is no 

longer manufactured, so occupational exposure is limited to workers at waste disposal sites or those 

involved in remediation activities involving the clean-up and removal of contaminated soils or sediments.
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5. POTENTIAL FOR HUMAN EXPOSURE

5.2 PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

5.2.1 Production

No information is available in the TRI database on facilities that manufacture or process mirex and 

chlordecone because these chemicals are not required to be reported under Section 313 of the Emergency 

Planning and Community Right-to-Know Act (Title III of the Superfund Amendments and 

Reauthorization Act of 1986) (EPA 2005).

Mirex is not known to occur in the environment as a natural product (IARC 1979; Waters et al. 1977a). 

Although it was originally synthesized in 1946, mirex was not commercially introduced in the United 

States until 1959, when it was produced by the Allied Chemical Company under the name GC-1283 for 

use in pesticide formulations and as an industrial fire retardant under the trade name Dechlorane® (EPA 

1978a; IARC 1979; Waters et al. 1977a). Mirex was produced as a result of the dimerization of 

hexachlorocyclopentadiene in the presence of an aluminum chloride catalyst (IARC 1979; Sittig 1980).

The technical grade of mirex consisted of a white crystalline solid in two particle size ranges, 5–10 and 

40–70 microns (IARC 1979). Technical-grade preparations of mirex contained 95.18% mirex, with 

2.58 mg/kg chlordecone as a contaminant (EPA 1978b; WHO 1984). Several formulations of mirex have 

been prepared in the past for various pesticide uses. Some of the more commonly used formulations of 

mirex used as baits were made from corn cob grit impregnated with vegetable oil and various 

concentrations of mirex. Insect bait formulations for aerial or ground applications contained 0.3–0.5% 

mirex, and fire ant formulations contained 0.075–0.3% mirex (IARC 1979).

Mirex is no longer produced commercially in the United States. Hooker Chemical Company (Niagara 

Falls, New York) manufactured and processed mirex from 1957 to 1976 (Lewis and Makarewicz 1988). 

An estimated 3.3 million pounds (1.5x106 kg) of mirex were produced by Hooker Chemical Company 

between 1959 and 1975, with peak production occurring between 1963 and 1968 (EPA 1978b). About 

25% of the mirex produced was used as a pesticide and the remaining 75% was used as an industrial fire 

retardant additive (EPA 1978b). Hooker Chemical Company reported purchasing 1.5 million pounds of 

mirex (680,400 kg) from Nease Chemical Company during this period. The Nease Chemical Company of 

State College, Pennsylvania, manufactured mirex from 1966 to 1974 (EPA 1978b). Allied Chemical 

Company also manufactured technical-grade mirex and mirex bait in Aberdeen, Mississippi (EPA 1978b), 

but Allied Chemical formally transferred all registrations on mirex, along with the right to manufacture 
MIREX AND CHLORDECONE 153

5. POTENTIAL FOR HUMAN EXPOSURE

and sell mirex bait, to the Mississippi Department of Agriculture on May 7, 1976 (IARC 1979; Waters et 

al. 1977a, 1977b).

Chlordecone is not known to occur in the environment as a natural product (IARC 1979). Chlordecone 

has been produced by reacting hexachlorocyclopentadiene and sulfur trioxide under heat and pressure in 

the presence of antimony pentachloride as a catalyst. The reaction product is hydrolyzed with aqueous 

alkali, neutralized with acid; chlordecone is recovered via centrifugation or filtration and hot air drying 

(Epstein 1978). Chlordecone was produced in 1951, patented in 1952, and introduced commercially in 

the United States by Allied Chemical in 1958 under the trade names Kepone® and GC-1189 (Epstein 

1978; Huff and Gerstner 1978). The technical grade of chlordecone, which typically contained 94.5% 

chlordecone, was available in the United States until 1976 (IARC 1979). Chlordecone was also found to 

be present in technical-grade mirex at concentrations of up to 2.58 mg/kg and in mirex bait formulations 

at concentrations of up to 0.25 mg/kg (EPA 1978b; IARC 1979). Approximately 55 different commercial 

formulations of chlordecone have been prepared since its introduction in 1958 (Epstein 1978). The major 

form of chlordecone, which was used as a pesticide on food products, was a wettable powder (50% 

chlordecone) (Epstein 1978). Formulations of chlordecone commonly used for nonfood products were in 

the form of granules and dusts containing 5 or 10% active ingredient (Epstein 1978). Other formulations 

of chlordecone contained the following percentages of active ingredient: 0.125% (used in the United 

States in ant and roach traps), 5% (exported for banana and potato dusting), 25% (used in the United 

States in ant and roach bait), 50% (used to control mole crickets in Florida), and 90% (exported to Europe 

for conversion to kelevan for use on Colorado potato beetles in eastern European countries) (Epstein 

1978).

Chlordecone is no longer produced commercially in the United States. Between 1951 and 1975, 

approximately 3.6 million pounds (1.6 million kg) of chlordecone were produced in the United States 

(Epstein 1978). During this period, Allied Chemical Company produced approximately 1.8 million 

pounds (816,500 kg) of chlordecone at plants in Claymont, Delaware; Marcus Hook, Pennsylvania; and 

Hopewell, Virginia. In 1974, because of increasing demand for chlordecone and a need to use their 

facility in Hopewell, Virginia, for other purposes, Allied Chemical transferred its chlordecone 

manufacturing to Life Sciences Products Company (EPA 1978b). Life Sciences Products produced an 

estimated 1.7 million pounds (771,000 kg) of chlordecone from November 1974 through July 1975 in 

Hopewell, Virginia (Epstein 1978). Hooker Chemical Company also produced approximately 

49,680 (22,500 kg) pounds of chlordecone in the period from 1965 to 1967 at a plant at Niagara Falls, 
MIREX AND CHLORDECONE 154

5. POTENTIAL FOR HUMAN EXPOSURE

New York. Nease Chemical Company produced approximately 65,780 pounds (30,000 kg) of 

chlordecone between 1959 and 1966 at a plant in State College, Pennsylvania (Epstein 1978).

5.2.2 Import/Export

No current data are available regarding import volumes of mirex. Mirex has reportedly been imported to 

the United States from Brazil, but data on the amounts of mirex imported are not available (DHHS 1991; 

IARC 1979).

No current data are available regarding import volumes of chlordecone.

Technical mirex and technical chlordecone are not exported since these substances are no longer 

produced in the United States.

Over 90% of the mirex produced from the 1950s until 1975 was exported to Latin America, Europe, and 

Africa (Sterret and Boss 1977). No other historic data regarding the export of mirex were located.

Diluted technical-grade chlordecone (80% active ingredient) was exported to Europe, particularly 

Germany, in great quantities from 1951 to 1975 by the Allied Chemical Company (Epstein 1978) where 

the diluted technical product was converted to an adduct, kelevan. Approximately 90–99% of the total 

volume of chlordecone produced during this time was exported to Europe, Asia, Latin America, and 

Africa (DHHS 1991; EPA 1978a).

5.2.3 Use

Because it is nonflammable, mirex was marketed primarily as a flame retardant additive in the United 

States from 1959 to 1972 under the trade name Dechlorane® for use in various coatings, plastics, rubber, 

paint, paper, and electrical goods (Budavari et al. 1989; EPA 1978b; IARC 1979; Kutz et al. 1985; 

Verschueren 1983). Mirex was most commonly used in the 1960s as an insecticide to control the 

imported fire ants (Solenopsis invicta and S. richteri) in Alabama, Arkansas, Florida, Georgia, Louisiana, 

Mississippi, North Carolina, South Carolina, and Texas (Carlson et al. 1976; EPA 1978b; IARC 1979; 

Waters et al. 1977a, 1977b). From 1962 to 1976, approximately 132 million acres (53.4 million hectares) 

in nine states were treated with approximately 485,000 pounds (226,000 kg) of mirex at a rate of 4.2 

g/hectare (later reduced to 1.16 g/hectare) (IARC 1979). Mirex was chosen for fire ant eradication 
MIREX AND CHLORDECONE 155

5. POTENTIAL FOR HUMAN EXPOSURE

programs because of its effectiveness and selectiveness for ants (Carlson et al. 1976; Waters et al. 1977a, 

1977b). It was originally applied aerially at concentrations of 0.3–0.5%.

However, aerial application of mirex was replaced by mound application because of suspected toxicity to 

estuarine species and because the goal of the fire ant program was changed from eradication to selective 

control. Mirex was also used successfully in controlling populations of leaf cutter ants in South America, 

harvester termites in South Africa, Western harvester ants in the United States, mealybugs in pineapples 

in Hawaii, and yellowjacket wasps in the United States (EPA 1978b; IARC 1979; Waters et al. 1977a). 

All registered products containing mirex were effectively canceled on December 1, 1977 (Sittig 1980). 

However, selected ground application was allowed until June 30 1978, at which time the product was 

banned in the United States with the exception of continued use in Hawaii on pineapples until stocks on 

hand were exhausted (EPA 1976; Holden 1976; Sittig 1980; Waters et al. 1977b).

Until August 1, 1976, chlordecone was registered in the United States for use on banana root borer (in the 

U.S. territory of Puerto Rico); this was its only registered food use. Additional registered formulations 

included nonfood use on nonfruit-bearing citrus trees to control rust mites; on tobacco to control tobacco 

and potato wireworms; and for control of the grass mole cricket, and various slugs, snails, and fire ants in 

buildings, lawns, and on ornamental shrubs (EPA 1978b; Epstein 1978; IARC 1979). The highest 

reported concentration of chlordecone in a commercial product was 50%, which was used to control the 

grass mole cricket in Florida (Epstein 1978). Chlordecone has also been used in household products such 

as ant and roach traps at concentrations of approximately 0.125% (IARC 1979). The concentration used 

in ant and roach bait was approximately 25% (Epstein 1978). All registered products containing 

chlordecone were effectively canceled as of May 1, 1978 (Sittig 1980).

5.2.4 Disposal

Since mirex and chlordecone are not flammable and are very stable in the environment, many disposal 

methods investigated for these chemicals have proven unsuccessful (Sullivan and Krieger 1992; Tabaei et 

al. 1991; Waters et al. 1977a).

Mirex is unaffected by hydrochloric, sulfuric, and nitric acids, and would be expected to be extremely 

resistant to oxidation except at the high temperatures of an efficient incinerator (EPA 1978b; Sittig 1980; 

WHO 1984). A recommended method of disposal for mirex is incineration or long-term storage 

(Holloman et al. 1975; IARC 1979). Polyethylene glycol or tetraethylene glycol and potassium 
MIREX AND CHLORDECONE 156

5. POTENTIAL FOR HUMAN EXPOSURE

hydroxide when used in combination with sodium borohydride or alkoxyborohydrides, produce a 

powerful reducing media which quantitatively destroys mirex at 70°C. The reduction rate is further 

increased by using tetrahydrofuran and catalytic quantities of Bu3SnH/AiBN, which produce 100% 

destruction of mirex to hexahydromirex within 1 hour at 58°C (Tabaei et al. 1991).

Chlordecone is considered an EPA hazardous waste and must be disposed of according to EPA 

regulations (EPA 1980). Degradation of chlordecone has been evaluated in the presence of molten 

sodium (Greer and Griwatz 1980). Addition of chlordecone to molten sodium at a temperature of 250°C 

resulted in significant degradation of chlordecone with small quantities of <12 ppm observed in the 

reaction products. Microwave plasma has also been investigated as a potential disposal mechanism for 

chlordecone (DeZearn and Oberacker 1980). An estimated 99% decomposition was observed in a 5-kw 

microwave plasma system for 80% chlordecone solution, slurry, or solid. Another recommended disposal 

method for chlordecone is destruction in an incinerator at approximately 850°C followed by off-gas

scrubbing to absorb hydrogen chloride (IRPTC 1985).

Activated carbon adsorption has been investigated for the treatment of waste waters contaminated with 

chlordecone (EPA 1982). The discharge of chlordecone in sewage disposal systems is not recommended,

as it may destroy the bacteriological system (IRPTC 1985). Chlordecone as a waste product in water may 

be dehalogenated by a process involving ultraviolet light and hydrogen as a reductant. The reaction is pH 

dependent, and degradation is best when the system contains 5% sodium hydroxide. Using this method, 

95–99% of chlordecone is removed within 90 minutes. The degradation products are the mono-, di-, tri-, 

tetra-, and pentahydro derivatives of chlordecone. This degradation method is applicable to chlordecone 

in hazardous wastes at concentrations in the ppm (mg/L) range and lower (Reimers et al. 1989; Sittig 

1980).

5.3 RELEASES TO THE ENVIRONMENT 

Mirex has been detected in air, surface water, soil and sediment, aquatic organisms, and foodstuffs. 

Historically, mirex was released to the environment primarily during its production or formulation for use 

as a fire retardant and as a pesticide. There are no known natural sources of mirex and production of the 

compound was terminated in 1976. Hazardous waste disposal sites and contaminated sediment sinks in 

Lake Ontario were the major sources for mirex releases to the environment (Brower and Ramkrishnadas 

1982; Comba et al. 1993).
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5. POTENTIAL FOR HUMAN EXPOSURE

Chlordecone has been detected in the air, surface water, soil and sediment, aquatic organisms and 

foodstuffs. Historically chlordecone was released to the environment primarily during its production at a 

manufacturing facility in Hopewell, Virginia. There are no known natural sources of chlordecone and 

production of the compound was terminated in 1975. Hazardous waste disposal sites and contaminated 

sediment sinks in the James River were the major sources for chlordecone release to the environment 

(EPA 1978a; Huggett and Bender 1980; Lunsford et al. 1987).

5.3.1 Air

There is no information on releases of mirex and chlordecone to the atmosphere from manufacturing and 

processing facilities because these releases are not required to be reported (EPA 2005).

Little information on historic releases of mirex to the air was located. Some atmospheric contamination 

may have occurred due to releases from manufacturing facilities, which were primarily located near 

Niagara Falls, New York, and State College, Pennsylvania; however, no quantitative sampling data were 

located (EPA 1978a). Atmospheric releases of mirex could result from airborne dust from the production 

and processing of mirex or Dechlorane®, combustion of products containing Dechlorane®, or 

volatilization of mirex applied as a pesticide (WHO 1984). Because mirex was principally dispersed as a 

pesticide in a bait form associated with corn cob grit particles that settle rapidly, the amount of mirex 

remaining airborne should have been insignificant. Furthermore, volatilization of mirex after application 

should also have been insignificant because of the high melting point and low vapor pressure of the bait 

(EPA 1978a).

Although release of mirex to the atmosphere was probably small in comparison to amounts released to 

surface water, soil, and sediment, infrequent detections of minute concentrations of mirex in air (mean 

concentration 0.35 pg/m3

) and rainfall (<0.5 ng/L [ppt]) samples have been reported many years after 

production ceased (Hoff et al. 1992; Strachan 1990; Wania and MacKay 1993). Arimoto (1989) 

estimated that 5% of the total input of mirex to Lake Ontario was attributed to atmospheric deposition.

Large amounts of chlordecone were released into the air from a chemical manufacturing plant in 

Hopewell, Virginia, from April 1974 through June 1975. Throughout the manufacturing period, 

extensive areas of the environment were contaminated with chlordecone because of improper 

manufacturing and disposal processes (Lewis and Lee 1976). Concentrations of chlordecone in the air 

surrounding the plant ranged from 0.18 ng/m3 to a maximum of 54.8 μg/m3 which was found in a sample 
MIREX AND CHLORDECONE 158

5. POTENTIAL FOR HUMAN EXPOSURE

collected 200 m from the plant (Epstein 1978). High-volume air samplers in operation 200 m from the 

plant were found to contain this chlordecone level, which constituted over 50% of the total particulate 

loading. Chlordecone concentrations at more distant sites (up to 15.6 miles away) ranged from 1.4 to 

20.7 ng/m3 (Epstein 1978). The long-range transport properties of chlordecone indicate that at least a 

small portion of the chlordecone emissions were of a fine particle size having a relatively long residence 

time in the atmosphere (Lewis and Lee 1976).

5.3.2 Water 

There is no information on releases of mirex and chlordecone to water from manufacturing and 

processing facilities because these releases are not required to be reported (EPA 2005).

Mirex has been released to surface waters via waste waters discharged from manufacturing and 

formulation plants, in activities associated with the disposition of residual pesticides, and as a result of its 

direct use as a pesticide, particularly in the fire ant eradication program conducted in several southern 

states.

Releases of mirex in industrial wastes were greatest during the manufacture of this chemical between 

1957 and 1976 by the Hooker Chemical and Plastics Corporation in Niagara Falls, New York. Releases 

to the Niagara River peaked between 1960 and 1962 at 200 kg/year (440 pounds/year), but subsequently 

declined to 13.3 kg/year (29 pounds/year) in 1979, and 8 kg/year (18 pounds/year) in 1981 (Durham and 

Oliver 1983; Lewis and Makarewicz 1988). Releases to the Oswego River occurred as a result of 

discharges from Armstrong World Industries Inc. in Volney, New York (Lum et al. 1987; Mudambi et al. 

1992). Since production of mirex was discontinued in 1976 (Kaiser 1978), releases after 1976 were the 

result of leaching from dump sites adjacent to the Niagara and Oswego Rivers, both of which feed into 

Lake Ontario (Kaminsky et al. 1983) and releases of mirex from sediment sinks in Lake Ontario. Total 

loading of mirex to Lake Ontario has been estimated to be 688 kg (1,517 pounds), with half of this 

incorporated into the sediments (Van Hove Holdrinet et al. 1978; Lewis and Makarewicz 1988). A study 

by Comba et al. (1993), however, estimated total loading of mirex to Lake Ontario to be 2,700 kg (6,000 

pounds) over 40 years, of which 550 kg (1,200 pounds) has been removed mainly by transport via 

outflowing water into the St. Lawrence River.

In addition to direct releases of mirex to surface waters that occurred at the manufacturing plant in 

Niagara Falls, New York, an estimated 226,000 kg (498,000 pounds) of mirex were used as a pesticide to 
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5. POTENTIAL FOR HUMAN EXPOSURE

treat 132 million acres (53.4 million hectares) in nine southern states from 1962 to 1976 as part of the fire 

ant eradication program conducted by the Department of Agriculture (IARC 1979). Mirex insecticide 

baits were dispersed by aerial applications, and mirex could be released into surface water directly or 

could reach surface waters via runoff. Because mirex binds tightly to organic-rich soils, leaching is not 

generally expected to occur. However, mirex residues have been detected (concentration unspecified) in 

groundwater well samples collected in proximity to agricultural land in New Jersey (Greenburg et al. 

1982). In a South Carolina study, mirex was also detected in potable water supplies in two rural counties. 

Mirex was detected in 12.5% of water samples at a mean concentration of 2 ng/L (ppt) (range from not 

detectable to 30 ng/L) in Chesterfield County and was detected in 72.7% of the water samples at a mean 

concentration of 83 ng/L (range of not detectable to 437 ng/L) in rural Hampton County. The authors 

attributed the higher mirex residues in the potable water of Hampton County to the extensive use of mirex 

in this county for fire ant control (Sandhu et al. 1978).

Chlordecone has been primarily released to surface waters in waste waters from a manufacturing plant in 

Hopewell, Virginia, and may be released in activities associated with the disposal of residual pesticide 

stocks, and as a result of the direct use of mirex. Chlordecone has been released directly as a contaminant 

of mirex and indirectly from the degradation of mirex.

Production of chlordecone at a manufacturing plant in Hopewell, Virginia, from 1966 to 1975, resulted in 

the release of the compound, primarily through industrial discharge of waste water into the Hopewell 

municipal sewage system, which discharged into Baileys Creek, and ultimately flowed into the James 

River. Leaching and erosion of contaminated soils from the plant site and direct discharge of solid wastes 

also contributed to the chlordecone content in the James River estuary (Colwell et al. 1981; Nichols 

1990). Effluent from the manufacturing plant contained 0.1–1.0 mg/L (ppm) chlordecone, and water 

from the plant’s holding ponds contained 2 to 3 mg/L (ppm) chlordecone (Epstein 1978). It has been 

estimated that 7,500–45,000 kg (16,500–100,000 pounds) of the 1,500,000 kg (3.3 million pounds) of 

chlordecone produced at the plant entered the estuary in industrial effluent or runoff (Colwell et al. 1981; 

Nichols 1990).

Another source of chlordecone release to water may result from the application of mirex containing 

chlordecone as a contaminant and by the degradation of mirex, which was used extensively in several 

southern states. Carlson et al. (1976) reported that dechlorinated products including chlordecone were 

formed when mirex bait, or mirex deposited on soil after leaching from the bait, was exposed to sunlight, 
MIREX AND CHLORDECONE 160

5. POTENTIAL FOR HUMAN EXPOSURE

other forms of weathering, and microbial degradation over a period of 12 years. Chlordecone residues in 

the soil could find their way to surface waters via runoff.

5.3.3 Soil 

There is no information on releases of mirex and chlordecone to soil from manufacturing and processing 

facilities because these releases are not required to be reported (EPA 2005).

Mirex is not currently registered for use in the United States, so release of mirex to soil from pesticide 

applications is no longer of concern. However, use of mirex as a pesticide for fire ant control required the 

spraying of this chemical on soils of an estimated 132 million acres in the southern United States (IARC 

1979). An estimated 226,000 kg (498,000 pounds) of mirex were used in nine states from 1962 to 1976 

as part of the fire ant eradication program conducted by the Department of Agriculture (IARC 1979).

Releases of mirex to sediment as a result of industrial waste water discharges were noted in Lake Ontario 

near the mouth of the Niagara River. Lake Ontario sediment concentrations were correlated with the 

years of peak production and use, and were found to decrease in the upper sediments as use was restricted 

in the late 1970s (Durham and Oliver 1983). Total loading of mirex to Lake Ontario has been estimated 

to be 688 kg (1,517 pounds), with half of this amount incorporated into the sediments (Van Hove 

Holdrinet et al. 1978; Lewis and Makarewicz 1988). However, a study by Comba et al. (1993) involving 

development of a mass balance model for mirex in Lake Ontario and the Gulf of St. Lawrence estimated 

that over 40 years, approximately 2,700 kg (6,000 pounds) of mirex entered Lake Ontario, of which 

550 kg (1,200 pounds) has been removed via transport to the St. Lawrence estuary. Removal of mirex 

from Lake Ontario has resulted primarily by outflowing water containing suspended sediment.

Chlordecone is not currently registered for use in the United States. However, use of chlordecone as a 

pesticide to control banana borers on bananas, tobacco wireworms on tobacco, mole crickets on turf, and 

various slugs, snails, and ants in buildings, lawns, and ornamental shrubs, required the application of this 

chemical to soils (Epstein 1978; IARC 1979). No estimate of the amount of chlordecone released from 

these uses was found. Chlordecone releases to soils may also occur as a result of the application of mirex 

containing chlordecone as a contaminant and by the degradation of mirex which was used extensively in a 

regional fire ant eradication program. As stated in Section 5.2.2, Carlson et al. (1976) reported that 

dechlorinated products, including chlordecone, were formed when mirex bait, or mirex deposited on soil 

after leaching from the bait, was exposed to sunlight, other forms of weathering, and microbial 
MIREX AND CHLORDECONE 161

5. POTENTIAL FOR HUMAN EXPOSURE

degradation over a period of 12 years. No estimates of the amount of chlordecone released from the 

application and degradation of mirex are available.

Chlordecone releases to soil occurred at a production facility in Hopewell, Virginia. Soil samples 

adjacent to the site contained 1–2% chlordecone (l0,000–20,000 mg/kg [ppm]), and surface soils up to 

3,000 feet from the site contained concentrations of 2–6 mg/kg (ppm) (Epstein 1978).

The major release of chlordecone to sediments, however, occurred indirectly as a result of waste water 

discharges, runoff of contaminated soil, and direct disposal of solid wastes at a production facility in 

Hopewell, Virginia. An estimated l0,000–30,000 kg (22,000–66,100 pounds) of chlordecone are

associated with bottom sediment in the James River estuary (Huggett and Bender 1980; Nichols 1990). 

This sediment serves as a reservoir for future release of chlordecone via resuspension of sediments 

resulting from storms or dredging activities (Lunsford et al. 1987).

5.4 ENVIRONMENTAL FATE 

5.4.1 Transport and Partitioning 

Mirex. Because mirex is a very hydrophobic compound with a low vapor pressure, atmospheric transport 

is unlikely (Hoff et al. 1992). These authors reported detecting mirex in only 5 of 143 samples at a 

maximum and mean concentration of 22 pg/m3 and 0.35 pg/m3

, respectively. Based on a vapor pressure 

of <3x10-7 mm Hg at 25°C, mirex is expected to exist mainly in the particulate phase with a small 

proportion existing in the vapor phase in the ambient atmosphere (IARC 1979). A mass balance approach 

to the movement of mirex within Lake Ontario indicates that 5% of the total input of mirex to the lake can 

be attributed to atmospheric deposition compared with 72% of benzo(a)pyrene (Arimoto 1989).

Based on a calculated soil sorption coefficient (Koc) of 1,200 (5,800 experimental) for mirex, this 

compound will tightly bind to organic matter in soil and, therefore, will be highly immobile. Thus, mirex 

is most likely to enter surface waters as a result of soil runoff (Kenaga 1980). In addition, most land 

applications of mirex to soils containing high organic content would result in very little leaching through 

soil to groundwater. However, leaching of mirex from some agricultural soils can occur as mirex has 

been detected in groundwater wells near agricultural areas (Greenburg et al. 1982; Sandhu et al. 1978).

When released to surface waters, mirex will bind primarily (80–90%) to the dissolved organic matter in 

the water with a small amount (10–20%) remaining in the dissolved fraction, because mirex is a highly 
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5. POTENTIAL FOR HUMAN EXPOSURE

hydrophobic compound (Yin and Hassett 1989). Mean mirex concentrations in sediments, collected at 

four basins in Lake Ontario between 1982 and 1986, ranged from 30 to 38 μg/kg in three of the basins 

within the water circulation pattern of the lake. A fourth basin outside the pattern showed much lower 

concentrations (6.4 μg/kg), indicating that mirex was being transported with the lake water (Oliver et al. 

1989). The residence time for mirex in Lake Ontario water was estimated to be 0.3 years. This indicated 

that mirex was either scavenged by particles or was chemically reactive and, therefore, was rapidly 

removed from the water column (Arimoto 1989).

Since the only sources of mirex in Lake Ontario are contaminated sediments, mirex in the water column is 

assumed to have come from resuspended sediments (Oliver et al. 1989). The source of the mirex in Lake 

Ontario surficial sediments was determined to be suspended sediments from the Niagara River, which 

were found to contain 8–15 and 55 μg/g (ppm) mirex in the upper and lower river sections, respectively. 

The surficial sediments contained 3 μg/g in the upper river (above the manufacturing and dump sites), 

86 μg/g in the lower river (below the sites), and 10 μg/g in the western basin of Lake Ontario, indicating 

that mirex-containing sediments were being carried down the river with the current and deposited in Lake 

Ontario (Mudroch and Williams 1989). Kaminsky et al. (1983), reported a range of 8.2–62 ppb (μg/kg) 

in sediment from the eastern and central basins of Lake Ontario. Over 94% of the suspended particulate 

matter entering the lake is eventually deposited in lake sediments (Lum et al. 1987). Mirex 

concentrations in sediments of Lake Ontario show a strong correlation with peak production years 

(Durham and Oliver 1983; Eisenreich et al. 1989). Although there was evidence of sediment bioturbation 

by deposit-feeding worms and burrowing organisms, the sediment profiles for mirex and other chlorinated 

hydrocarbons were not destroyed (Eisenreich et al. 1989). Between the 1960s when mirex production 

began, and the early 1980s after production ceased, levels of mirex in bottom sediments increased in Lake 

Ontario, with the Niagara River being the major source of this compound (Allan and Ball 1990).

Mirex may be removed from Lake Ontario by several mechanisms, including the transport of 

contaminated suspended particulate material via water outflow into the St. Lawrence River, biomass 

removal through fishing and migration (e.g., migrating eels contaminated with mirex), volatilization, and 

photolysis (Comba et al. 1993; Lum et al. 1987). Transport of mirex accumulated in body tissues by eels 

has been estimated to be 2,270 grams annually or twice the amount of mirex removed by transport of 

suspended particulates (1,370 grams annually) (Lum et al. 1987).

The transport of mirex out of Lake Ontario, (a known reservoir), to its tributaries is also possible as a 

result of migrating fish, which move from the lake into the tributary streams to spawn. Fish, such as 
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5. POTENTIAL FOR HUMAN EXPOSURE

Pacific salmon, become contaminated with mirex while in the lake. These fish then swim upstream in the 

tributaries to their spawning grounds, spawn, and die. A direct transfer of mirex may then occur when 

resident stream fish feed on the decomposing carcasses and/or eggs, both of which contain mirex 

residues. Indirect transfer can occur as a result of the release of mirex from the salmon into the water or 

sediments and subsequent movement up the food chain. Movement of mirex back into Lake Ontario is 

also possible when the contaminated eggs hatch and surviving juvenile salmon return to the lake (Lewis 

and Makarewicz 1988).

Algae are known to bioaccumulate mirex, with BCFs in the range of 3,200–7,300, while bacteria have a 

BCF of 40,000 with an octanol-water partition coefficient of 7.8 million (Baughman and Paris 1981). 

Based on a water solubility of 0.6 mg/L, a BCF of 820 was calculated for mirex (Kenaga 1980). 

Bioaccumulation of mirex also occurred in invertebrates exposed to 0.001–2.0 μg/g mirex in water; tissue 

residues ranged from 1.06 to 92.2 μg/g (de la Cruz and Naqvi 1973). After 28 days of exposure, the BCF 

values for the amphipod (Hyallelu azteca) and crayfish (Orconectes mississippiensis) were 2,530 and 

1,060 respectively. Fathead minnows exposed to 33 μg/L (ppb) mirex for 56 days accumulated 122 μg/g 

(ppm) mirex tissue residues (BCF of 3,700), with no other evident metabolic products. Residues 

decreased to 88.6 μg/g 28 days after mirex was removed from the water (Huckins et al. 1982). The halflife of mirex in rainbow trout was >1,000 days in fish exposed for 96 days to a mean concentration of 

4.1 ng/L, although equilibrium was not reached during the test period. A subsequent analysis comparing 

a laboratory BCF for mirex in rainbow trout (1,200) with an actual BCF found in rainbow trout in Lake 

Ontario (15,000), indicated that ingestion of contaminated food (as would occur in the lake), rather than 

absorption across the gills, is the primary exposure route for trout (Oliver and Niimi 1985).

Biomagnification of mirex is supported by a study of various aquatic organisms that comprise an aquatic 

food chain in Lake Ontario (Oliver and Niimi 1988) (see Table 5-1).

Table 5-1. Concentrations of Mirex in Aquatic Organisms

Sample Mirex concentration (μg/kg wet weight unless otherwise noted)

Water 31±12 pg/L wet weight

Bottom sediment 3.9±1.9 μg/kg dry weight

Suspended sediment 15±4.4 μg/kg dry weight

Plankton 1.3±0.1

Mysids 8±2.8

Amphipods 12±6.7

Oligochaetes 6.9±2.9
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5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-1. Concentrations of Mirex in Aquatic Organisms

Sample Mirex concentration (μg/kg wet weight unless otherwise noted)

Sculpins 57

Alewives 45

Small smelts 26±3.6

Large smelts 53

Average fish 180±150

Source: Oliver and Niimi 1988

In these food chains, alewives feed primarily on mysids and to a lesser extent on amphipods; sculpins 

feed on amphipods, then mysids; smelt feed on mysids. Mysids feed on zooplankton, with amphipods 

and oligochaetes consuming detrital matter. The alewives and smelt are preyed upon by salmonids, such 

as trout (Oliver and Niimi 1988). A comparison of concentrations of mirex in lake trout, a predator 

species, with those in smelt, a prey species, gives a ratio of 1.26, indicating that biomagnification occurs 

up the food chain (Thomann 1989).

Mirex can also bioaccumulate in terrestrial plants. Azalea leaves, exposed to 0.023 μg/kg of mirex in 

greenhouse air, had significant uptake of the pesticide resulting in a BCF of 1.18x107 (log BCF=7.07) 

(Bacci et al. 1990). Mirex residues ranging from 10 to 1,710 μg/kg (ppb) were detected in soybeans, 

garden beans, sorghum, and wheat seedlings grown on substrates containing 0.3–3.5 mg/kg (ppm) mirex 

(de la Cruz and Rajanna 1975). Based on these data and known soil concentrations, it has been estimated 

that plants grown on contaminated soil could contain 0.0002–2 μg/kg (ppb) mirex (EPA 1978a). No 

information on the uptake of mirex by plants under field conditions was located.

In a 1972 residue study conducted in Mississippi during the time when mirex was being used extensively 

in fire ant control programs, Naqvi and de la Cruz (1973) reported mirex accumulation in grassland 

invertebrates (e.g., spiders and grasshoppers) ranging from 100 to 700 μg/kg (ppb) (mean 280 μg/kg). 

Hebert et al. (1994) studied organochlorine pesticides in a terrestrial food web on the Niagara Peninsula 

in Ontario, Canada, from 1987 to 1989. These authors reported mirex concentrations in the various food 

web compartments as follows: soil (not detectable), plants (not detectable), earthworms (not detectable to 

0.4 μg/kg), mammals (not detectable to 0.5 μg/kg), starlings (0.9–1.6 μg/kg), robins (4.7–18.9 μg/kg), and 

kestrels (4.7–22.2 μg/kg), which suggests that biomagnification of mirex is occurring. The earthworm 

appeared to be a particularly important species for organochlorine transfer from the soil to organisms 

occupying higher trophic levels. Connell and Markwell (1990) reported transfer of lipophilic compounds 
MIREX AND CHLORDECONE 165

5. POTENTIAL FOR HUMAN EXPOSURE

(such as mirex) through a three-phase system involving soil to soil water to earthworm partitioning. The 

transfer is a passive process and is principally dependent on the lipid content of the worms and the 

organic content of the soil.

Chlordecone. The fate and transport of chlordecone is very similar to mirex. Based on its low vapor 

pressure and high Koc, chlordecone in the air may be expected to be associated primarily with particulate 

matter (Kenaga 1980). However, only small amounts of chlordecone may volatilize into the air. 

Chlordecone volatilizes more slowly from water (0.024% applied amount/mL of evaporated water) than 

from sand, loam, or humus soil (0.036, 0.035, and 0.032%, respectively) (Kilzer et al. 1979).

Atmospheric transport of chlordecone particles was reported as a result of emissions from a production 

facility in Virginia. Chlordecone concentrations at up to 15.6 miles away ranged from 1.4 to 20.7 ng/m3

(Epstein 1978). The long-range transport properties of chlordecone indicate that at least a portion of the 

emissions were of a fine particle size having a relatively long residence time in the atmosphere (Lewis 

and Lee 1976).

The major industrial release of chlordecone occurred to surface waters of the James River. Chlordecone, 

because of its relatively low solubility in water and lipophilic nature, is readily absorbed to particulate 

matter in water and is ultimately deposited in sediments (EPA 1978a; Lunsford et al. 1987). Once 

adsorbed to sediments, chlordecone remains relatively immobile in the normal range of pH (7–8) and 

salinity (0.06–19.5 %) encountered in an estuary. While chlordecone is associated mainly with the 

organic portion of bottom sediments, sediment areas with high percentages of inorganic mineral grains 

are relatively free of contamination. The greatest mass of chlordecone (an estimated 6,260 pounds 

[2,840 kg]) was found in a sink where the sedimentation was relatively rapid. Transport is primarily 

through adsorption of chlordecone to fine organic particles in the water column. Its movement and 

deposition follow estuarine circulation, which is seaward from the freshwater reaches and upper estuarine 

water layer, and reflux downward for suspended materials (Nichols 1990).

While much of the chlordecone that was present in contaminated sediments in 1976 is still in the 

sediment, it is continuously being buried under several centimeters of new sediment each year (Huggett 

and Bender 1980). Storm activities and dredging are of concern because they would result in 

reenrichment of the surface sediments in areas with chlordecone contaminated sediment previously buried 

by natural ongoing sedimentation processes in the estuary (Huggett and Bender 1980; Lunsford et al. 

1987).
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Chlordecone has been found to have a very high bioaccumulation potential in fish and other aquatic 

organisms. Atlantic menhaden (Brevoortia lyrunnus) and Atlantic silver-sides (Menidia menidiu) had 

28-day BCFs of 2,300–9,750 and 21,700–60,200, respectively (Roberts and Fisher 1985). Based on a 

water solubility of 3 mg/L, a BCF of 333 was estimated for chlordecone. However, the measured value 

was 8,400 (Kenaga 1980). Using a log octanol-water partition coefficient for chlordecone of 6.08, a BCF 

of 6,918 was estimated for the oyster (Hawker and Connell 1986). However, an oyster BCF of 

10,000 has been reported with tissue concentrations at equilibrium within 8–17 days (Bahner et al. 1977). 

For estuarine organisms such as mysids, grass shrimp, sheepshead minnows, and spot, BCFs were 

measured to be 13,000, 11,000, 7,000, and 3,000, respectively (Bahner et al. 1977). Shad roe taken from 

the James River contained chlordecone levels that were 140% higher than muscle tissue residues, 

indicating a partitioning of the chemical into the lipid-rich eggs (Bender and Huggett 1984).

The accumulation of chlordecone was studied in a terrestrial/aquatic laboratory model ecosystem by 

Francis and Metcalf (1984). Radiolabeled chlordecone was applied to sorghum seedlings grown on the 

terrestrial portion of the aquarium. The treated seedlings were eaten by salt marsh caterpillars. In the 

aquatic portion, chlordecone was transferred through several species-an algae, snail, water flea mosquito 

larvae, and mosquito fish. After 33 days, the BCFs were 0.35 for the algae, 637.4 for the snails, 506.9 for 

the mosquito larvae, and 117.9 for the mosquito fish. A BCF for chlordecone of approximately 2.1 was 

determined for a water-algae-oyster food chain; however, a biomagnification factor >10.5 was measured 

for a water-brine shrimp-mysid-spot food chain with a water concentration of 0.1 mg/L (ppm) 

chlordecone (Bahner et al. 1977).

Plant uptake of chlordecone from the soil via the roots, and volatilization of chlordecone from soil with 

plant uptake via the leaves were found to be negligible in a closed laboratory system using barley 

seedlings. This indicates that bioaccumulation of chlordecone by plants (lowest on the terrestrial food 

chain) is very unlikely based on its log soil adsorption coefficient of almost 4.0 (Topp et al. 1986). No 

information on the uptake of chlordecone by plants under field conditions was located.
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5.4.2 Transformation and Degradation 

Air

Mirex. Little information was found on the degradation of mirex in the atmosphere. Mirex is expected to 

be stable against photogenerated hydroxyl radicals in the atmosphere (Eisenreich et al. 1981).

Chlordecone. Photolysis of chlordecone in the atmosphere does not appear to be an important 

degradation pathway for this compound. While nonvolatile products of photolysis were not monitored, 

only 1.8% of the chlordecone adsorbed on silica gel and exposed to ultraviolet light (wavelength 

>290 nm) was photolyzed to carbon dioxide or other volatile compounds (Freitag et al. 1985).

Water

Mirex. The degradation of mirex in water occurs primarily by photolysis. During the photodecomposition of mirex, the chlorine atoms are replaced by hydrogen atoms. The primary photoreduction 

product of mirex in water is photomirex (Andrade et al. 1975); the rate of this reaction can be increased 

by the presence of dissolved organic matter (such as humic acids) and was greatest at 265 nm in Lake 

Ontario water (Mudambi and Hassett 1988). In Lake Ontario, Mudambi et al. (1992) reported that the 

ratio of photomirex to mirex (P/M) increased in the stratified surface layer of the lake from spring until 

autumn and in water from Oswego Harbor. P/M ratios in the mirex source sediments (the Niagara and 

Oswego Rivers) were very low (<0.07), whereas higher P/M ratios were seen in the lake bottom 

sediments (>0.10) and surface waters (>0.30). These findings suggest that photomirex in Lake Ontario is 

produced by photolysis of mirex present in the surface waters and it is then partitioned between water, 

sediment, and biota.

Chlordecone. Degradation of chlordecone to an unidentified compound was studied in water in a 

terrestrial/aquatic laboratory model ecosystem. Degradation occurred to some extent during the 33-day

exposure period, and unidentified metabolites were detected in all organisms in the system-algae, snail, 

mosquito, and mosquito fish (Francis and Metcalf 1984). An earlier laboratory study in which fathead 

minnows were exposed to chlordecone in a flow-through diluter system for 56 days found that 

chlordecone was bioconcentrated 16,600 times by the minnows; however, only 1–5% of these residues 

were chlordecone (Huckins et al. 1982). Several observations suggested that some of the chlordecone 

residues present in the minnows were chemically bound to biogenic compounds.
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5. POTENTIAL FOR HUMAN EXPOSURE

Pseudomonas aeruginosa strain K03 and a mixed aerobic enrichment culture isolated from sewage sludge 

lagoon water were found to aerobically transform chlordecone to monohydrochlordecone in 8 weeks. 

Monohydrochlordecone constituted 14.2 and 14.5% of the chlordecone transformation products for the 

P. aeruginosa and mixed aerobic enrichment culture, respectively. The P. aeruginosa K03 strain and the 

mixed culture also produced 15.6 and 4.2% dihydrochlordecone, respectively (Orndorff and Colwell 

1980). None of the bacterial strains were able to use chlordecone as a sole carbon source; therefore, cometabolism appeared to be the only degradation process. Complete mineralization of chlordecone by 

bacteria is unlikely (Orndorff and Colwell 1980). Degradation of chlordecone can occur via microbial 

action, but the rate and extent of transformation are such that microbial action will not cause rapid 

removal of chlordecone from the environment except under highly enriched and selected conditions. 

Aerobic degradation of chlordecone by activated sludge from a municipal sewage plant showed that 

<0.1% of the applied chlordecone was degraded in 5 days, and the sludge showed a bioaccumulation 

factor of 9,900 compared with the concentration in the water (Freitag et al. 1985).

Sediment and Soil

Mirex. Degradation of mirex in soil may occur by photolysis or anaerobic biodegradation, both of which 

are very slow removal processes. Mirex is highly resistant to aerobic biodegradation and, as such, is 

extremely persistent in soils (estimated half-life of 10 years) (Carlson et al. 1976; Lal and Saxena 1982). 

Mirex appears to have no adverse effect on resident microbial communities (Jones and Hodges 1974). 

Upon exposure to ultraviolet light, mirex is known to degrade to chlordecone, photomirex, and/or 

dihydromirex (Francis and Metcalf 1984). Detectable levels of mirex photodegradation products 

(monohydro derivative and chlordecone hydrate) occur within 3 days after exposure of mirex to sunlight, 

although after 28 days of exposure, approximately 90% of the mirex was unchanged (Ivie et al. 1974b). 

Anaerobic degradation relies on iron(II) porphyrin as the reductant for the dehalogenation reaction (Kuhn 

and Suflita 1989).

Under anaerobic conditions, mirex was slowly dechlorinated to the 10-monohydro derivative by 

incubation with sewage sludge bacteria for 2 months (Andrade and Wheeler 1974; Andrade et al. 1975; 

Williams 1977). The primary removal mechanism for mirex was anaerobic degradation as demonstrated 

by the 6-month stability of the compound in nine aerobic soils and lake sediments (Jones and Hodges 

1974).
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5. POTENTIAL FOR HUMAN EXPOSURE

Aerobic degradation of mirex is a very slow and minor degradation process. Twelve years after the 

application of mirex to soil at 1 pound/acre, 50% of the mirex and mirex-related organochlorine 

compounds remained in the soil; 65–73% of the residues consisted of mirex and 3–6% consisted of 

chlordecone. Although concentrations were slightly higher, similar ratios of mirex (76–81%) and 

chlordecone (1–6%) residues were seen 5 years after an accidental spill of mirex bait on soil. Mirex 

underwent photolysis to form four dechlorination products: two monohydro and two dihydro compounds 

(Carlson et al. 1976). Two soil microbes, Bacillus sphaericus and Streptomyces albus, isolated from a 

field previously treated with mirex, were able to utilize 1% mirex as a sole carbon source. However, the 

rate of degradation, as demonstrated by carbon dioxide evolution, was slow and only about 10–20% 

greater than the controls after 20 hours (Aslanzadeh and Hedrick 1985).

No evidence of microbial degradation was detected for mirex exposed to hydrosoils (soils formed under 

conditions of saturation, flooding, or ponding long enough during the growing season to develop 

anaerobic conditions in the upper part) from a reservoir (not previously contaminated with chlordecone) 

and from chlordecone-contaminated hydrosoils from the James River area of Virginia under either 

anaerobic or aerobic conditions for 56 days (Huckins et al. 1982). The concentrations of chlordecone in 

the anaerobic and aerobic hydrosoils averaged 0.38 and 0.54 μg/g, respectively. Some photodegradation 

of mirex to photomirex was seen in an artificial salt marsh ecosystem; the photomirex was subsequently 

photodegraded to the 2,8- or 3,8-dihydro derivative. Most mirex loss occurred during the first 7 days 

after application (from 2.65 to 2.13 mg/g) with a steady accumulation of photomirex (610 ppb/day 

[μg/kg/day]) through day 21, accumulation of 17 μg/kg/day of 2,8- or 3,8-dihydro derivative through day 

35, and an accumulation rate of 206 μg/kg/day for the 10-monohydro photoproduct that is formed in the 

presence of amines. The 8-monohydro derivative (photomirex) was found to accumulate in the salt marsh 

organisms and sediment (Cripe and Livingston 1977).

Application of radiolabeled mirex to plants grown in a terrestrial/aquatic laboratory model ecosystem 

indicated that when the plant leaves were eaten by caterpillars, the aquatic system became contaminated. 

Mirex was detected in all segments of two aquatic food chains (alga > snail and plankton > daphnia > 

mosquito > fish) within 33 days. Undegraded mirex contributed to over 98.6, 99.4, 99.6, and 97.9% of 

the radiolabel in fish, snails, mosquitoes, and algae, respectively. No metabolites of mirex were found in 

any of the organisms (Francis and Metcalf 1984; Metcalf et al. 1973).

Chlordecone. Chlordecone is similar to mirex in structure and is also highly persistent in soils and 

sediments (half-life expected to be analogous to 10 years duration for mirex) because of its resistance to 
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5. POTENTIAL FOR HUMAN EXPOSURE

biodegradation, although some microbial metabolism of chlordecone has been reported (Lal and Saxena 

1982; Orndorff and Colwell 1980). No evidence of microbial degradation was detected for chlordecone 

exposed to hydrosoils from a reservoir (not previously contaminated with chlordecone) and from Bailey 

Creek (contaminated with chlordecone) under either anaerobic or aerobic conditions for 56 days (Huckins 

et al. 1982).

Three Pseudomonas species extracted from soil samples to which chlordecone was added (1 mg/mL) 

were found to utilize chlordecone, as a sole carbon source, with quantifiable degradation (67–84%) in 

14 days. Among the degradation products of chlordecone, only hydrochlordecone and 

dihydrochlordecone were identified (George and Claxton 1988; George et al. 1986). Sewage sludge 

bacteria and sediment bacteria, primarily P. aeruginosa strain KO3, were able to aerobically degrade 

chlordecone by 10–14% to monohydrochlordecone and, to a lesser extent, dihydrochlordecone in 

8 weeks. None of the bacterial strains was able to use chlordecone as a sole carbon source; therefore, cometabolism appeared to be the only degradation process. Complete mineralization of chlordecone by 

bacteria is unlikely (Orndorff and Colwell 1980). Concentrations of chlordecone >0.2 mg/L are likely to 

inhibit microbial activity, whereas concentrations <0.01 mg/L had no effects on cell count or uptake of 

amino acids. Bacteria in James River sediment did not produce significant concentrations of chlordecone 

metabolites (Colwell et al. 1981).

Degradation of chlordecone in a terrestrial ecosystem was studied by applying the compound to soil, 

growing plants on the soil; and then determining the amount of chlordecone in each compartment after 

1 week. During this time, only 0.1% of the applied chlordecone (2 mg/kg) was decomposed to carbon 

dioxide from the soil, and 0.3 mg/kg (approximately 15% of the applied concentration) was accumulated 

by the barley plants. Less than 10% of the applied chlordecone was degraded in the soil or converted by 

the barley plants, and there was no volatilization of the compound from the soil to the air (Kloskowski et 

al. 1981). A laboratory soil-plant system showed that degradation of chlordecone, as determined by soil 

residues remaining after volatilization and mineralization, was 1–3% after 1 week; this compared 

favorably with the residues remaining in soil in the field after one growing season (Scheunert et al. 1983). 

Analysis of soil contaminated with chlordecone collected in the vicinity of the chlordecone production 

facility showed some photolytic degradation of the compound with the production of small amounts of

monohydro isomers of chlordecone (Borsetti and Roach 1978).
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5. POTENTIAL FOR HUMAN EXPOSURE

5.5 LEVELS IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to mirex and chlordecone depends, in part, on the 

reliability of supporting analytical data from environmental samples and biological specimens. 

Concentrations of mirex and chlordecone in unpolluted atmospheres and in pristine surface waters are 

often so low as to be near the limits of current analytical methods. In reviewing data on mirex and 

chlordecone levels monitored or estimated in the environment, it should also be noted that the amount of 

chemical identified analytically is not necessarily equivalent to the amount that is bioavailable.

The lowest limit of detections that are achieved by analytical analysis in environmental media are 

summarized in Table 5-2 for mirex and Table 5-3 for chlordecone.

Table 5-2. Lowest Limit of Detection for Mirex Based on Standardsa

Media Detection limit Reference

Air 0.1 ng/m3 Lewis et al. 1977

Drinking water 10 ng/L Sandhu et al. 1978

Surface water and groundwater 10 ng/L Sandhu et al. 1978

Soil 1 ppb Seidel and Lindner 1993

Sediment 0.002 ppb Sergeant et al. 1993

Whole blood 0.04 ng/g Mes 1992

aDetection limits based on using appropriate preparation and analytics. These limits may not be possible in all 

situations.

Table 5-3. Lowest Limit of Detection for Chlordecone Based on Standardsa

Media Detection limit Reference

Air 10 ng/sample NIOSH 1984

Water 20 ng/L Saleh and Lee 1978

Soil 10–20 ppb Saleh and Lee 1978

Sediment 10–20 ppb Saleh and Lee 1978

Whole blood 10 μg/L Caplan et al. 1979

aDetection limits based on using appropriate preparation and analytics. These limits may not be possible in all 

situations.

No data are available on levels of mirex or chlordecone in air, water, and soil at NPL sites (ATSDR 

2019).
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5. POTENTIAL FOR HUMAN EXPOSURE

5.5.1 Air 

Mirex. Mirex has been detected in wet precipitation over rural areas at concentrations <1 ng/L (ppt) 

(EPA 1981). Rain fall samples collected at several sites in 1985–1986 as part of the Great Lakes 

Organics Rain Sampling Network contained from >0.2 to <0.5 ng/L (ppt) of mirex. Mirex was not 

detected consistently at many stations throughout the sampling period; therefore, quantitative results for 

mirex were not presented (Strachan 1990). Air samples taken over southern Ontario in 1988 showed 

mirex in 5 of 143 samples, at an annual mean concentration of 0.35 pg/m3 (range, 0.1–22 pg/m3

), with all 

of the positive samples detected in polluted environments (Hoff et al. 1992).

Chlordecone. Information on atmospheric concentrations of chlordecone is limited to air sampling 

results obtained at the Life Sciences Products Company production site in Hopewell, Virginia. High 

volume air filter samples collected 200 m from the plant in March 1974 prior to initiation of production at 

the site contained only 0.18 to 0.35 ng/m3 of chlordecone. Subsequent air sampling after production was

initiated ranged from 3 to 55 μg/m3

. During production years 1974 and 1975, air concentrations at more 

distant sites up to 15.6 miles from Hopewell, Virginia, ranged from 1.4 to 20.7 ng/m3 (Epstein 1978).

5.5.2 Water 

Mirex. Mirex was detected in rural drinking water samples at concentrations ranging from not detectable 

to 437 ng/L (ppt) (Sandhu et al. 1978). In a survey in 1987, mirex was detected in only 5 of 1,147 

drinking water samples from Ontario, Canada (maximum concentration of 5 ng/L [ppt]) (Environment

Canada 1992).

The pollution of the Niagara River from chemical manufacturing effluents and leachates from chemical 

manufacturing waste dumps has been well documented. Between 1975 and 1982, mirex was detected in 

the aqueous phase of 6 of 22 samples in the Niagara River at levels between 0.0005 and 0.0075 ng/L (ppt) 

(Allan and Ball 1990). Twelve percent of 104 whole water samples, collected from the Niagara River 

between 1981 and 1983, had mirex concentrations that ranged from below the detection limit 

(0.06 ng/L[ppt]) to 2.6 ng/L, with a median concentration of 0.06 ng/L (Oliver and Nicol 1984). Mirex 

was detected in the suspended particulate phase of 42 Niagara River water samples taken at the mouth of 

the river in 1986–1987; 17% of the samples had a mean mirex concentration of 0.022 ng/L (ppt) (Allan 

and Ball 1990).
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5. POTENTIAL FOR HUMAN EXPOSURE

In 1982, Mudambi et al. (1992) reported the mean mirex concentrations in the Lake Ontario system 

ranging from 1.85 to 30 pg/L. An intralake comparison of chemicals found in the Great Lakes during the 

1986 spring turnover did not detect mirex in any of the lakes (Stevens and Neilson 1989), nor in the 

dissolved or particulate fractions of water from the St. Lawrence River between 1981 and 1987 (Germain 

and Langlois 1988). In 1986, low levels of mirex were found in 8 of 14 water samples taken at various 

locations along the St. Lawrence River (Kaiser et al. 1990). The highest concentration observed was 

0.013 ng/L (ppt). Sergeant et al. (1993) reported mirex concentrations in Lake Ontario water samples 

declined from 0.0015 μg/L (1.5 ng/L) in 1986 to <0.0004 μg/L (0.4 ng/L) in 1988.

Mirex was detected in water samples taken in 1972 from areas in Mississippi that had been aerially 

treated with mirex to control the imported red fire ant (Spence and Markin 1974). Water samples taken 

from the bottom of a pond showed residue values that remained higher and more constant than those 

taken from the surface of the pond. Water showed the highest residues immediately after treatment 

(bottom, 0.53 μg/L [ppb]; surface, 0.02 μg/L [ppb]), and detectable levels were still present as long as 

3 months after treatment (bottom, 0.005 μg/L [ppb]; surface, 0.003 μg/L [ppb]) (Spence and Markin 

1974).

Chlordecone. The solubility of chlordecone in water is low (1–3 mg/L) and as with mirex, contamination 

is more likely to be associated with the particulate matter in the water rather than the water itself. 

Chlordecone was detected primarily in water samples collected in and around the production facility site 

in Hopewell, Virginia, and in adjacent waters of the James River estuary. Effluent from the Life Sciences 

Products Company facility contained 0.1–1.0 mg/L (ppm) chlordecone, while water in holding ponds at 

the site contained 2–3 mg/L (ppm) chlordecone (Epstein 1978). Levels of chlordecone in river water in 

August 1975 ranged from not detectable (<50 ng/L [ppt]) in the York River and Swift Creek areas, to 

levels of 1–4 μg/L (ppb) in Baileys Creek which received direct effluent discharges from the Hopewell 

Sewage Treatment Plant. Water concentrations of up to 0.3 μg/L (ppb) were detected in the James River 

at the mouth of Bailey Creek and in the Appomattox River (upstream from Hopewell) at 0.1 μg/L (ppb) 

(Epstein 1978). Hopewell drinking water drawn from the James River contained no detectable 

chlordecone levels (EPA 1978a; Epstein 1978). In 1977, 12 years after production of chlordecone began 

and 2 years after production ceased, average concentrations of chlordecone in estuarine water (dissolved) 

were <10 ng/L (ppt) (Nichols 1990). In October 1981, 6 years after production at the plant ceased, 

chlordecone water concentrations ranged from not detectable to 0.02 μg/L (ppb) (Lunsford et al. 1987).
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5. POTENTIAL FOR HUMAN EXPOSURE

5.5.3 Sediment and Soil 

Mirex. Mirex was identified in sediment samples collected in 1979 from Bloody Run Creek, which is a 

drainage ditch for the Hyde Park landfill in Niagara Falls, New York. Mirex levels in the sediment 

ranged from 0.5 to 2 mg/kg (ppm) (detection limit, 0.5 mg/kg [ppm]) (Elder et al. 1981).

Between 1979 and 1981, mean mirex concentrations in suspended sediments of the Niagara River 

declined from 12 to 1 ng/L (ppt); concentrations in bottom sediments were generally low, ranging from 

<1 μg/kg (ppb) to a maximum value of 890 μg/kg (ppb), at a site believed to be the source of mirex to the 

river (Allan and Ball 1990). In 1981, mirex was detected in sediments of Lake Ontario near the mouth of 

the Niagara River at increasing concentrations to a maximum of 1,700 μg/kg (ppb) at a sediment depth of 

9 cm. Concentrations decreased between 9 and 13 cm and were not detected in sediments below a depth 

of 13 cm. Concentrations were chronologically correlated with mirex production and peak sales periods 

and were reduced when its use was restricted (Durham and Oliver 1983). In 1982, mirex was detected in 

settling particulates from sediment traps in the Niagara River (average, 7 μg/kg [ppb]; range, 3.9–

18 μg/kg [ppb]), resuspended bottom sediments from the Niagara Basin of Lake Ontario (average, 

9.45 μg/kg [ppb], range 5.2−16 μg/kg [ppb]), and bottom sediments from Lake Ontario (average, 

48 μg/kg [ppb]) (Oliver and Charlton 1984).

An analysis of urban runoff and sediment runoff collected between 1979 and 1983 from 12 urban areas in 

the Canadian Great Lakes Basin showed that mirex was not detected in any runoff waters, although it was 

found in 10% of 129 runoff sediment samples at a mean concentration of 1.3 μg/kg (ppb) (Marsalek and 

Schroeter 1988). Sediment samples collected from the St. Lawrence River between 1979 and 1981 

contained low concentrations of mirex (median, <0.1 μg/kg; range, <0.1–3.3 μg/kg), indicating that Lake 

Ontario is the source of the contamination to the river (Sloterdijk 1991). Low levels of mirex were found 

in bottom sediment core samples taken from the riverine lakes in the St. Lawrence River in October 1985; 

the average concentration of mirex was 0.43 μg/kg (range, <0.01–0.95 μg/kg) (Kaiser et al. 1990). In 

1987, mirex was detected in suspended sediments throughout the St. Lawrence River. At the St. 

Lawrence River stations near Kingston, the mirex concentration was approximately 5 μg/kg (ppb), but 

declined to about 1 μg/kg (ppb) near Quebec City (Kaiser et al. 1990).

In 1971 and 1972, mirex was detected in soil and sediment samples taken from areas in Louisiana and 

Mississippi that had been aerially treated with mirex to control the imported red fire ant (Spence and 

Markin 1974). In Louisiana, samples were collected throughout the first year after spraying. Soil and 
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5. POTENTIAL FOR HUMAN EXPOSURE

sediment residues in the Louisiana study peaked after 1 month (soil, 2.5 μg/kg [ppb]; sediment, 0.7 μg/kg 

[ppb]) and gradually declined over the remainder of the year. In Mississippi, samples were collected for 

4 months following spraying. Sediment residues in Mississippi also peaked about 1 month after spraying 

(1.1 μg/kg [ppb]) and gradually declined over the next couple of months. The residue levels found in soil 

in Mississippi were much more variable and showed no distinctive pattern (Spence and Markin 1974).

Less than 10% of the sediment samples taken from the San Joaquin River and its tributaries in California 

(an area of heavy organochloride pesticide use) in 1985 contained mirex residues; all samples contained 

<0.1 μg/kg (ppb) (Gilliom and Clifton 1990).

Studies of sediment from seven sampling stations in the Upper Rockaway River, New Jersey, showed that 

sediment quality corresponded to the land-use data for the area (Smith et al. 1987). The two upstream 

stations, which drain primarily forested areas of the Upper Rockaway Basin, had low mirex 

concentrations in the sediments (<0.1 μg/kg). The remaining stations, which drained an area consisting of 

residential, commercial, and industrial land including six EPA Superfund sites, had mirex concentrations 

ranging from 8.2 to 80 μg/kg (ppb) (Smith et al. 1987).

Sediment samples taken from 51 sampling locations in the Gulf of Mexico for the National Oceanic and 

Atmospheric Administration (NOAA) Status and Trends Mussel Watch Program were analyzed for mirex 

contamination (Sericano et al. 1990; Wade et al. 1988). Average mirex concentrations of 0.07 μg/kg 

(ppb) (range, <0.01–0.67) and 0.18 μg/kg (ppb) (range, <0.02–3.58) were found in sediments in 1986 and 

1987, respectively. The sampling sites represent the contaminant loading for the Gulf of Mexico estuaries 

removed from known point-sources of contamination (Sericano et al. 1990; Wade et al. 1988).

Chlordecone. With the exception of the James River area of Virginia, very little information is available 

on chlordecone residues in soil and sediment. Chlordecone was detected in soil immediately surrounding 

the Life Sciences Products Company in Hopewell, Virginia, at levels of 1–2% (10,000–20,000 mg/kg) 

and contamination extended to 1,000 m at concentrations of 2–6 mg/kg (ppm) (Huggett and Bender 

1980).

Assessment of sediment cores taken from the James River below Hopewell, Virginia, indicated that 

chlordecone concentrations were greatest nearest the release site. Sediment concentrations of 

chlordecone in Baileys Creek, the waterbody into which effluent from the Hopewell municipal sewage 

treatment facility was discharged, were 2.2 mg/kg (ppm) (Orndorff and Colwell 1980). Chlordecone 
MIREX AND CHLORDECONE 176

5. POTENTIAL FOR HUMAN EXPOSURE

concentrations of 0.44–0.74 mg/kg were found at sediment depths of 55–58 cm in the main channel of the 

James River. This area had the highest sedimentation rate (>19 cm/year). Further downriver, (80 km 

from Hopewell) in the James River estuary, chlordecone concentrations decreased and maximum 

concentrations were found closer to the sediment surface. The highest chlordecone concentration of 

0.18 mg/kg (ppm) was from a sediment depth of 46–48 cm in an area with a sedimentation rate of 

10 cm/year (Cutshall et al. 1981).

5.5.4 Other Media 

Mirex. In general, because releases of mirex from its production and use as a pesticide were terminated 

in the late 1970s, mirex residues in various biological organisms are much lower than those reported 

during or shortly after its peak years of production and use. This trend is supported by both regional and 

national studies.

In areas where mirex was historically used for fire ant control, it has been detected in fish and other 

aquatic biota from contaminated rivers. An analysis of mirex residues in primary, secondary, and tertiary 

consumers in oxbow lakes in Louisiana in 1980 indicated that although mirex was not detected in any 

water or sediment samples, or in the tissues of primary consumers (some fish), it was detected in the 

tissues of secondary consumers (fish and birds that consume invertebrates and insects), and in all tertiary 

consumers (fish-eating fish, birds, and snakes). The highest mean mirex concentrations were found in 

cottonmouth snakes (0.11 mg/kg [ppm]) (Niethammer et al. 1984). Fish taken from the lower Savannah 

River during 1985 had mirex residues in their tissues that ranged from nondetectable to 1 mg/kg (ppm) 

wet weight, although most residues were near 0.02 mg/kg (Winger et al. 1990).

Of all the Coho salmon collected from all of the Great Lakes in 1980, only fish taken from Lake Ontario 

contained detectable mirex residues at an average concentration of 0.14 μg/g (ppm) (Clark et al. 1984). 

The mean concentration of mirex residues in rainbow trout taken from Lake Ontario was 0.11 μg/g (ppm), 

while the mean water concentration in the lake was 0.008 ng/L (ppt) (Oliver and Niimi 1985). Borgmann 

and Whittle (1991) studied the contaminant concentration trends in Lake Ontario lake trout from 1977 to 

1988. Mirex concentrations generally declined from 0.38 μg/g (ppm) in 1977 to 0.17 μg/g (ppm) in 1988, 

although there was considerable variability in the mirex residue data. The concentrations of mirex also 

showed a distinct east-west gradient across the lake. The highest mirex residues were detected in fish 

collected at the western side of the basin and were 70% above those detected in fish collected at the 

eastern portion of the basin. Suns et al. (1993) conducted a similar study of spatial and temporal trends of 
MIREX AND CHLORDECONE 177

5. POTENTIAL FOR HUMAN EXPOSURE

organochlorine contaminants in spottail shiners from selected sites in the Great Lakes. These authors 

reported that mirex was only detected in fish from the Niagara River, the Credit River in western Lake 

Ontario, and in the St. Lawrence River at Cornwall. Mirex concentrations in spottail shiners collected 

during the late 1980s were generally lower than mirex residues found in spottail shiner samples collected 

during the 1970s. Considerable fluctuation in mirex residues in spottail shiners was observed, which 

precluded proper trend assessment. Based on the fish data, mirex inputs to Lake Ontario appeared to be 

continuing on an intermittent basis. Newsome and Andrews (1993) analyzed mirex in fillet samples of 

11 commercial fish species from the Great Lakes. The highest mirex concentrations were found in carp 

from a closed fishery area (120 μg/kg [ppb]), eel (56.8 μg/kg), carp from an open fishery area 

(5.24 μg/kg), bullhead (3.63 μg/kg), and trout (2.38 μg/kg).

Burbot, a bottom-feeding fish, taken from remote lakes in Canada in 1985–1986, contained liver 

concentrations of mirex ranging between 3.7 and 17.4 μg/kg (ppb) lipid weight (detection limit, 

0.5 μg/kg), while photomirex was not detected. The lowest mirex values were seen in fish from the most 

remote locations, suggesting that atmospheric transport of this compound was occurring (Muir et al. 

1990).

Ninety percent of the mussels collected in 1985 at various points along the St. Lawrence River contained 

mirex at levels up to 1.6 μg/kg (ppb). The only source of mirex was contaminated particles entering the 

river from Lake Ontario; mussels collected from the Ottawa River, which does not receive its water from 

Lake Ontario, did not contain any mirex. The mirex concentrations in the mussels decreased with 

distance from the lake (Metcalfe and Charlton 1990).

Mirex concentrations were measured in 78 snapping turtles collected from 16 sites in southern Ontario, 

Canada, during 1988–1989 to evaluate the risk to human health (Hebert et al. 1993). Mean 

concentrations of mirex in the muscle tissue were below fish consumption guidelines for mirex 

(100 μg/kg [ppb]) and ranged from not detectable to 3.95 μg/kg (ppb). However, mirex concentrations in 

older turtles from some sites were as high as 9.3 μg/kg (ppb).

Freshwater fish sampled (as part of the U.S. Fish and Wildlife Service National Contaminant 

Biomonitoring Program) between 1980 and 1984 contained detectable concentrations of mirex. Mirex 

was detected in 18% of the 1980 samples (maximum concentration, 210 μg/kg [ppb]; mean concentration, 

0.01 μg/g) and in 13% of the 1984 samples (maximum concentration, 440 μg/kg [ppb]; mean 

concentration, 10 μg/kg). The highest mirex concentrations were detected in whole fish taken from Lake 
MIREX AND CHLORDECONE 178

5. POTENTIAL FOR HUMAN EXPOSURE

Ontario, the St. Lawrence River, and the southeastern United States, all areas where mirex had been 

manufactured or used (Schmitt et al. 1990). In the EPA National Study of Chemical Contaminants in 

Fish, mirex was detected at 38% of 362 sites sampled. The mean mirex concentration was 3.86 μg/kg 

(ppb) and the maximum concentration was 225 μg/kg (ppb). The highest concentrations of mirex were 

detected in fish collected in the Lake Ontario area of New York State (EPA 1992). In the EPA National 

Study of Chemical Contaminants in Lake Fish (EPA 2009a), mirex was detected in 2% of the 486 fish 

sampling locations for predator fish, with a maximum concentration of 9 ppb, and in 4.8% of the 

395 sample locations for bottom dwelling fish, with a maximum concentration of 29 ppb.

Of oysters (Crassostrea virginica) sampled throughout the United States between 1965 and 1972 for the 

National Pesticide Monitoring Program, only those from South Carolina locations had detectable mirex 

residues (maximum concentration, 540 μg/kg [ppb]) with most residues being <38 μg/kg (ppb) (Butler 

1973). Oysters taken from 49 sampling locations in the Gulf of Mexico for the NOAA Status and Trends 

Mussel Watch Program 1986–1987 were analyzed for mirex contamination (Sericano et al. 1990; Wade et 

al. 1988). Average mirex concentrations of 1.40 μg/kg (ppb) (range, <0.25–15.8 μg/kg) and 1.38 μg/kg 

(ppb) (range, <0.25–16.1) were found in oysters in 1986 and 1987, respectively (Sericano et al. 1990). 

The sampling sites represent the contaminant loading for the Gulf of Mexico estuaries removed from 

known point-sources of contamination (Wade et al. 1988).

Mirex was also detected in the muscle and liver tissues of seven species of aquatic and terrestrial 

mammals collected in areas of Alabama and Georgia that had been repeatedly treated with mirex to 

suppress fire ant populations from March 1973 through July 1976. At 6 months post-treatment, skunk 

and opossum muscle tissue contained the highest mean mirex concentrations of 3.50 and 1.5 1 μg/g 

(ppm), respectively (Hill and Dent 1985). Two years post-treatment, muscle residues declined in all 

species except the mink, which increased from 0.14 μg/g at 6 months post-treatment to a mean muscle 

residue of 0.28 μg/g at 1 year post-treatment and 0.53 μg/g at 2 years post-treatment.

Mirex was detected in the subcutaneous fat and breast muscle of 55 waterfowl collected in New York 

State during 1981 and 1982. Average mirex levels were 280 μg/kg (ppb) in fat and 2.0 μg/kg in breast 

muscle (Kim et al. 1985). Mirex was detected at a concentration of >500 μg/kg (ppb) in 24 of 

164 samples of subcutaneous fat of six species of waterfowl (mallard, black duck, scaup, wood duck, 

bufflehead, and Canada goose) harvested by hunters in 1983–1984 (Foley 1992). Mirex was detected in 

fat samples from 5 of 26 goldeneyes shot by hunters in December 1988 in New York State; however, no 

quantitative information on mirex residues was provided (Swift et al. 1995). Gebauer and Weseloh 
MIREX AND CHLORDECONE 179

5. POTENTIAL FOR HUMAN EXPOSURE

(1993) used farm-raised mallards as sentinels for accumulation of pollutants at three sites in southern 

Ontario, Canada. The sites included the Hamilton Harbor Confined Disposal Facility designated as an 

“Area of Concern” because of high pollutant concentrations of sediment; the Winona Sewage Lagoons, 

which contained high concentrations of metals; and Big Creek Marsh, which served as a reference area. 

The geometric mean concentrations of mirex detected in muscle tissue at each site were 7.1 μg/kg (ppb) at 

the Hamilton Harbor site after 115 days; 0.07 μg/kg at the sewage lagoon site after 112 days; and 

0.14 μg/kg at the reference site after 30 days.

Mirex residues were detected in food samples analyzed as part of the FDA Pesticide Residue Monitoring 

Studies conducted from 1978 to 1982 of 49,877 food samples and from 1982 to 1986 of 49,055 food 

samples; however, the frequency of detection was unspecified but was <1 and 2% respectively (Yess 

1988; Yess et al. 1991). Mirex was not detected in 27,065 samples of food collected in 10 state food 

laboratories from 1988 and 1989 (Minyard and Roberts 1991). Mirex was also not detected in 

domestically produced or imported foods sampled as part of the FDA Pesticide Residue Monitoring Study 

during 1989 (FDA 1990), was detected (at <1% occurrence) in foods sampled in 1990 (FDA 1991), and 

was not detected in foods sampled in 1991 (FDA 1992) and 1992 (FDA 1993) or in the most recent 

(2017) survey (FDA 2019). 

Chlordecone. Because releases of chlordecone from its production and use ceased in the late 1970s, 

current chlordecone residues in various biological organisms are generally lower than those reported 

during its peak production years (1974–1975). Releases of chlordecone from the manufacturing plant in 

Hopewell, Virginia, severely contaminated the James River estuary in Virginia from 1966 through 1975. 

In 1977, 12 years after production of chlordecone began and 2 years after it ceased, average chlordecone 

concentrations in various biological organisms in the estuary were as follows (Nichols 1990): 

phytoplankton, 1.30 μg/g; zooplankton, 4.80 μg/g; freshwater fish, 2.50 μg/g; migratory fish, 0.40 μg/g; 

and benthic fauna (molluscs), 1.50 μg/g. Considerable variations in chlordecone concentrations detected 

in fish species in the James River were in part associated with different life histories and residence times 

of each species in the estuary (Huggett and Bender 1980). Freshwater species that were permanent 

residents in the upper estuary exhibited the highest range in tissue residues varying from <0.1 μg/g (ppm) 

for channel catfish to >2 μg/g for largemouth bass. Residues in marine fish increased with length of 

exposure time in the James River. American shad that inhabited the estuary only briefly showed average 

chlordecone residues of <0.1 μg/g. Longer-term residents that spent 6–9 months in the estuary, such as 

spot and croaker, contained 1 μg/g. Concentrations in resident estuarine species ranged from 0.7 μg/g for 

the bay anchovy to 2.7 μg/g for white perch.
MIREX AND CHLORDECONE 180

5. POTENTIAL FOR HUMAN EXPOSURE

Dredging of the James River in Virginia increased the chlordecone levels in resident clams (Rangia 

cuneata). The river has contaminated sediments containing up to 3.5 μg/g (ppm) chlordecone. Prior to 

the 2-week dredging period, chlordecone concentrations in the water column ranged from nondetectable 

to 0.02 μg/L (ppb); background concentrations in the clams ranged from 0.06 to 0.14 μg/g. During the 

dredging, body burdens of chlordecone in clams increased by 0.01–0.04 μg/g (ppm). Two weeks after the 

dredging was completed, residues in the clams had not returned to predredging levels (Lunsford et al. 

1987).

In addition to the James River area, chlordecone residues of 0.025 and 0.23 mg/kg (ppm) were detected in 

trout and suckers, respectively, collected from Spring Creek 18 miles downstream of the Nease Chemical 

Plant in Pennsylvania (EPA 1978a). This plant produced small quantities of chlordecone from 1966 to 

1974 (Epstein 1978).

Because chlordecone contamination of the James River in Virginia and Spring Creek in Pennsylvania 

represented relatively isolated incidents resulting from industrial negligence and because the compound 

was not used extensively on agricultural crops in the United States, monitoring for this compound has not 

been included as part of the U.S. Fish and Wildlife Service National Contaminant Biomonitoring Program 

(Schmitt et al. 1990), the EPA National Study of Chemical Residues in Fish (EPA 1992), EPA National 

Study of Chemical Contaminants in Lake Fish (EPA 2009a).

Chlordecone residues were detected in the FDA Pesticide Residue Monitoring Studies of 49,877 food 

samples from 1978 to 1982 and of 49,055 food samples from 1982 to 1986; however, the frequency of 

detection was unspecified but was less than 1 and 2%, respectively (Yess 1988; Yess et al. 1991). 

Chlordecone was also detected in 1 of 27,065 samples of food collected from 10 state laboratories during 

1988 and 1989 (Minyard and Roberts 1991). Chlordecone was not detected in any domestically produced 

or imported foods analyzed as part of the FDA Pesticide Residue Monitoring Studies during 1988–1989, 

1989–1990, 1990–1991, and 1991–1992 (FDA 1990, 1991, 1992, 1993) or in the most recent (2017) 

survey of imported foods (FDA 2019).

5.6 GENERAL POPULATION EXPOSURE 

Mirex. Mirex has not been produced since 1976 and has not been used in the United States since 1977, 

when all registered uses of the product were canceled. The potential for exposure of the general 
MIREX AND CHLORDECONE 181

5. POTENTIAL FOR HUMAN EXPOSURE

population, therefore, is relatively small and should continue to diminish over time. Members of the 

general population may be exposed to low concentrations of mirex primarily through consumption of 

contaminated food stuffs, in particular contaminated fish and shellfish from Lake Ontario, the St. 

Lawrence River, and Spring Creek in Pennsylvania, which were all contaminated by industrial discharges, 

and areas of the southern United States that were extensively treated with mirex for fire ant control. No 

dietary intake estimates are available (FDA 1990, 1991, 1992) since mirex has been so infrequently found 

in foodstuffs in recent years. Mirex exposure from drinking water has not been found to constitute 

significant human exposure since mirex is relatively insoluble in water and rapidly adsorbs to sediment 

(EPA 1978a).

Mirex has been detected in the general U.S. population. The National Human Monitoring Program for 

Pesticides detected mirex at low frequencies in human adipose tissue collected nationwide. In 1972, 

mirex was detected in 0.05% of all samples and in 1973, mirex was detected in 0.09% of all samples; 

however, by 1974, the percentage of positive samples had increased to 0.11% (Kutz et al. 1979). Mirex 

was detected in 13% of samples collected as part of the 1982 National Adipose Tissue Survey (EPA 

1986b). Concentrations of mirex ranged from 0.008 to 0.39 μg/g (ppm) (mean concentration 0.025 μg/g). 

Further analysis of adipose tissue samples collected as part of the 1982 National Adipose Tissue Survey 

failed to detect mirex in any tissues from children (newborn infants to 14-year-olds); however, tissue 

samples from adults 15–44 and ≥45 years old were found to contain mirex residues. The greatest 

concentrations (values not provided) for 15–44-year-old adults were found in the Northeast and South 

Atlantic States, while the greatest concentrations for >45-year-old adults were found in the West South 

Central States and Northeast States (Phillips and Birchard 1991).

In a survey of human adipose tissue from residents of southwestern Ontario between 1976 and 1979, 

mirex was detected in 32.8% of the samples at mean concentrations of <0.01 mg/kg (ppm). In 1980–

1981, it was detected in more samples (64.8%) at greater concentrations (mean concentration, 

0.04 mg/kg); however, in 1983–1984, it was detected in only 6.2% of the samples at an average 

concentration of 0.06 mg/kg. Adipose tissue collected from 13 infants during this time contained 

<0.01 mg/kg mirex, except for one sample that contained 0.02 mg/kg. Mirex was not detected in any 

blood or human milk samples collected for this survey (Frank et al. 1988). A 1985 nationwide study of 

chlorinated hydrocarbons in the adipose tissue of Canadians found mirex to be present in all 108 samples 

collected nationwide at a mean concentration of 7 ng/g (ppb) (maximum concentration, 72 ng/g). The 

high rate of detection was a result of improved analytical procedures and lower limits of detection than 

those used in earlier studies. Residues were evenly distributed throughout the country and did not differ 
MIREX AND CHLORDECONE 182

5. POTENTIAL FOR HUMAN EXPOSURE

significantly between the sexes or by age (Mes et al. 1990). In a 1990–1991 survey of human adipose 

tissue from residents of British Columbia, Canada, mirex was detected at a minimum, mean, and 

maximum concentration of 1.15, 6.10, and 33.3 ng/g (ppb) lipid, respectively (Teschke et al. 1993).

Mirex residues in human blood serum were measured as part of the National Report on Human Exposure 

to Environmental Chemicals. In the Second National Health and Nutrition Examination Survey 

(NHANES II), conducted between 1976 and 1980. Of the 4,038 samples analyzed, mirex concentrations 

ranged from not detectable to detected but below quantifiable levels (10 μg/L [ppb]) (Stehr-Green 1989). 

In the Fourth National Report on Human Exposures to Environmental Chemicals (CDC 2019), mirex 

levels in serum (lipid adjusted) were reported according to various age groups, gender, and race/ethnicity. 

The results are presented in Tables 5-4, 5-5, 5-6, and 5-7.

Mirex was detected (mean detection limit 3 pg/g [ppt]) in 62% of 412 breast milk samples collected from 

women in all Canadian provinces (Mes et al. 1993). The mean, median, and maximum mirex 

concentrations were 0.14, 0.08, and 6.56 ng/g (ppb), respectively, in whole milk and 4.2, 2.3, and 

124.5 ng/g, respectively, in milk fat. In previous studies, mirex residues were not detected. None of the 

1,436 human milk samples collected in the United States in the late 1970s as part of the National Human 

Milk Study contained identifiable levels of mirex (Savage et al. 1981). A similar national study of 

nursing mothers in Canada (Mes et al. 1986) also failed to detect mirex in any human milk samples. The 

high rate of detection in the Mes et al. (1993) study was a result of improved analytical procedures and 

lower limits of detection.

An analysis of potential human exposure to contaminants in drinking water and foods was conducted in 

Ontario, Canada, in 1980. Mirex was detected only in edible fish taken from Toronto Harbor on Lake 

Ontario. The average mirex concentrations were 0.001 mg/kg (ppm) wet weight for white sucker, 

0.01 mg/kg wet weight for rainbow trout, and 0.033 mg/kg wet weight for northern pike. Estimated 

human exposure levels, based on an average fish consumption of 0.53 kg/year for each fish species, were 

0.0005 for white sucker, 0.005 for rainbow trout, and 0.017 mg/year for northern pike, respectively 

(Davies 1990).

Mirex is no longer manufactured, formulated, or used in the United States. Therefore, there is currently 

no occupational exposure to this chemical associated with its production or application as a pesticide. 

Current occupational exposure is most likely to occur for workers employed at waste disposal sites or 

those engaged in remediation activities including removal of soils and sediments contaminated with 
MIREX AND CHLORDECONE 183

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-4. Geometric Mean and Selected Percentiles of Mirex (Lipid Adjusted) 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 (NHANES) 1999–2004

Survey yearsa

Geometric mean 

(95% CI)

Selected percentiles (95% CI) Sample 

50 size th 75th 90th 95th

Total 1999–2000

2001–2002

2003–2004

*b

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

15.8 (<LOD–73.7)

8.40 (<LOD–13.0)

<LOD

57.1 (13.2–230)

13.2 (7.90–29.6)

1,853

2,257

1,951

Age group

12–19 years 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

659

728

592

≥20 years 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

19.6 (<LOD–108)

9.10 (<LOD–15.6)

<LOD

71.0 (14.6–305)

15.4 (8.10–37.1)

1,194

1,529

1,359

Gender

Males 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

16.1 (<LOD–65.6)

9.70 (<LOD–15.4)

<LOD

50.8 (12.3–225)

15.5 (9.70–24.4)

887

1,052

949

Females 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

15.0 (<LOD–108)

<LOD

<LOD

63.0 (12.0–374)

11.6 (<LOD–31.3)

966

1,205

1,002

Race/ethnicity

Mexican 

Americans

1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

617

548

459

NonHispanic 

blacks

1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

13.7 (<LOD–47.3)

<LOD

15.5 (<LOD-42.2)

51.3 (15.4–230)

18.1 (8.70–40.8)

39.5 (<LOD–115)

153 (30.5–425)

40.3 (15.5–82.7)

398

500

484
MIREX AND CHLORDECONE 184

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-4. Geometric Mean and Selected Percentiles of Mirex (Lipid Adjusted) 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 (NHANES) 1999–2004

Survey yearsa

Geometric mean 

(95% CI)

Selected percentiles (95% CI) Sample 

50 size th 75th 90th 95th

NonHispanic 

whites

1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

15.1 (<LOD–104)

<LOD

<LOD

66.7 (12.5–291)

11.6 (<LOD–23.4)

688

1,049

884

aThe limit of detection for survey years 1999–2000, 2001–2002, and 2003–2004 were 14.6, 10.5, and 7.8 ng/g, respectively. bNot calculated: proportion of results below limit of detection was too high to provide a valid result.

CI = confidence interval; LOD = limit of detection

Source: CDC 2019
MIREX AND CHLORDECONE 185

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-5. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex 

(Lipid Adjusted) Pooled 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 (NHANES) 2005–2010

Category

Age 

(years)

Survey 

yearsa

Weighted arithmetic 

meanb

Unadjusted standard 

errorc Number of poolsd

NonHispanic 

white male

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*e

*

*

3.88f

*

*

6.39f

4.25

5.25

5.32

6.36

4.89

*

*

*

2.18

*

*

2.15

0.31

1.32

0.61

1.34

0.44

9

6

10

12

15

17

12

16

17

15

23

21

NonHispanic 

white 

female

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

*

*

*

2.42

2.05

3.32

3.51

3.90

4.42

*

*

*

*

*

*

0.14

0.28

0.33

0.24

0.39

0.4

10

7

8

16

13

19

13

17

17

17

21

22

NonHispanic 

black 

male

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

2.68

*

*

5.90

16.8f

6.44

27.2f

13.9

14.2

*

*

*

0.59

*

*

0.49

6.1

1.04

10.1

2.1

4.1

13

6

6

6

6

7

5

6

7

5

8

9
MIREX AND CHLORDECONE 186

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-5. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex 

(Lipid Adjusted) Pooled 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 (NHANES) 2005–2010

Category

Age 

(years)

Survey 

yearsa

Weighted arithmetic 

meanb

Unadjusted standard 

errorc Number of poolsd

NonHispanic 

black 

female

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

1.62

*

*

5.92

5.42

5.03

10.3

24.0f

7.49

*

*

*

0.32

*

*

0.65

1.21

0.84

2.7

9.3

1.68

14

5

6

7

8

7

7

8

7

5

7

7

Mexican 

American 

male

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

*

*

*

2.66

4.37f

3.08

2.89

11.0f

5.1

*

*

*

*

*

*

0.74

1.38

0.83

0.78

8.0

1.27

11

6

8

9

9

8

4

6

8

4

5

5
MIREX AND CHLORDECONE 187

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-5. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex 

(Lipid Adjusted) Pooled 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 (NHANES) 2005–2010

Category

Age 

(years)

Survey 

yearsa

Weighted arithmetic 

meanb

Unadjusted standard 

errorc Number of poolsd

Mexican 

American 

female

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

*

*

*

1.84

3.76f

*

2.84

2.59

4.04

*

*

*

*

*

*

0.34

1.3

*

0.37

0.49

0.97

16

5

7

9

8

10

6

6

9

3

5

6

All 

Hispanic 

male

12–19

20–39

40–59

≥60

2009–2010

2009–2010

2009–2010

2009–2010

*

*

4.58

5.18

*

*

1.27

0.82

11

13

13

8

All 

Hispanic 

female

12–19

20–39

40–59

≥60

2009–2010

2009–2010

2009–2010

2009–2010

*

*

*

4.13

*

*

*

0.55

10

14

14

11

aThe limits of detection for survey years 2005–2006, 2007–2008, and 2009–2010 were 1.46, 1.4, and 2.19 ng/g, 

respectively.

bWeighted arithmetic means are not comparable to weighted geometric means.

cUnadjusted standard errors do not incorporate survey design effects.

dEach pool was composed of serum from eight persons. eNot calculated: proportion of results below limit of detection was too high to provide a valid result.

f

Standard error of the mean estimate is >30%.

CI = confidence interval; LOD = limit of detection

Source: CDC 2019
MIREX AND CHLORDECONE 188

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-6. Geometric Mean and Selected Percentiles of Mirex (Whole Weight) Serum Concentrations (in ng/g of 

Serum or Parts per Billion) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES) 1999–2004

Survey yearsa

Geometric mean 

(95% CI)

Selected percentiles (95% CI) Sample 

50 size th 75th 90th 95th

Total 1999–2000

2001–2002

2003–2004

*b

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

0.100 (<LOD–0.470)

0.54 (<LOD–0.084)

<LOD

0.410 (0.080–1.73)

0.093 (0.052–0.170)

1,853

2,257

1,951

Age group

12–19 years 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

659

728

592

≥20 years 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

0.140 (<LOD–0.690)

0.059 (<LOD–0.102)

<LOD

0.470 (0.090–1.92)

0.106 (0.053–0.215)

1,194

1,529

1,359

Gender

Males 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

0.110 (<LOD–0.470)

0.064 (<LOD–0.106)

<LOD

0.370 (0.090–1.37)

0.108 (0.062–0.170)

887

1,052

949

Females 1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

0.090 (<LOD–0.510)

<LOD

<LOD

0.430 (0.070–1.79)

0.077 (<LOD–0.170)

966

1,205

1,002

Race/ethnicity

Mexican 

Americans

1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

617

548

459

NonHispanic 

blacks

1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

0.090 (<LOD–0.240)

<LOD

0.090 (<LOD–0.220)

0.310 (0.090–1.41)

0.112 (0.055–0.268)

0.220 (<LOD–0.450)

1.08 (0.170–3.02)

0.256 (0.089–0.635)

398

500

484
MIREX AND CHLORDECONE 189

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-6. Geometric Mean and Selected Percentiles of Mirex (Whole Weight) Serum Concentrations (in ng/g of 

Serum or Parts per Billion) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES) 1999–2004

Survey yearsa

Geometric mean 

(95% CI)

Selected percentiles (95% CI) Sample 

50 size th 75th 90th 95th

NonHispanic 

whites

1999–2000

2001–2002

2003–2004

*

*

*

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

<LOD

0.100 (<LOD–0.610)

<LOD

<LOD

0.450 (0.080–1.79)

0.079 (<LOD–0.174)

688

1,049

884

aThe limit of detection for survey years 1999–2000, 2001–2002, and 2003–2004 were 14.6, 10.5, and 7.8 ng/g, respectively. bNot calculated: proportion of results below limit of detection was too high to provide a valid result.

CI = confidence interval; LOD = limit of detection

Source: CDC 2019
MIREX AND CHLORDECONE 190

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-7. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex 

(Whole Weight) Pooled Serum Concentrations (in ng/g of Serum or Parts per 

Billion) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES) 2005–2010

Category

Age 

(years)

Survey 

yearsa

Weighted arithmetic 

meanb

Unadjusted standard 

errorc Number of poolsd

NonHispanic 

white male

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*e

*

*

0.027f

*

*

0.048f

0.031

0.034

0.036

0.040

0.030

*

*

*

0.014

*

*

0.016

0.003

0.008

0.004

0.008

0.003

9

6

10

12

15

17

12

16

17

15

23

21

NonHispanic 

white 

female

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

*

*

*

0.018

0.014

0.021

0.026

0.026

0.027

*

*

*

*

*

*

0.002

0.002

0.002

0.002

0.003

0.002

10

7

8

16

13

19

13

17

17

17

21

22

NonHispanic 

black 

male

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

0.016

*

*

0.038

0.109f

0.041

0.168f

0.084

0.076

*

*

*

0.004

*

*

0.003

0.04

0.008

0.062

0.012

0.023

13

6

6

6

6

7

5

6

7

5

8

9
MIREX AND CHLORDECONE 191

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-7. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex 

(Whole Weight) Pooled Serum Concentrations (in ng/g of Serum or Parts per 

Billion) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES) 2005–2010

Category

Age 

(years)

Survey 

yearsa

Weighted arithmetic 

meanb

Unadjusted standard 

errorc Number of poolsd

NonHispanic 

black 

female

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

0.009

*

*

0.038

0.032

0.028

0.067

0.146f

0.043

*

*

*

0.002

*

*

0.004

0.008

0.005

0.016

0.057

0.01

14

5

6

7

8

7

7

8

7

5

7

7

Mexican 

American 

male

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

*

*

*

0.022f

0.031f

0.020

0.022f

0.074f

0.031

*

*

*

*

*

*

0.007

0.01

0.005

0.008

0.052

0.008

11

6

8

9

9

8

4

6

8

4

5

5

Mexican 

American 

female

12–19

20–39

40–59

≥60

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

2005–2006

2007–2008

2009–2010

*

*

*

*

*

*

0.014

0.024f

*

0.022

0.018

0.023

*

*

*

*

*

*

0.003

0.008

*

0.005

0.003

0.005

16

5

7

9

8

10

6

6

9

3

5

6

All 

Hispanic 

male

12–19

20–39

40–59

≥60

2009–2010

2009–2010

2009–2010

2009–2010

*

*

0.031

0.032

*

*

0.008

0.005

11

13

13

8
MIREX AND CHLORDECONE 192

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-7. Weighted Arithmetic Mean and Unadjusted Standard Error of Mirex 

(Whole Weight) Pooled Serum Concentrations (in ng/g of Serum or Parts per 

Billion) for the U.S. Population from the National Health and Nutrition 

Examination Survey (NHANES) 2005–2010

Category

Age 

(years)

Survey 

yearsa

Weighted arithmetic 

meanb

Unadjusted standard 

errorc Number of poolsd

All 

Hispanic 

female

12–19

20–39

40–59

≥60

2009–2010

2009–2010

2009–2010

2009–2010

*

*

*

0.027

*

*

*

0.003

10

14

14

11

aThe limits of detection for survey years 2005–2006 and 2007–2008 were 1.46 and 1.4 ng/g, respectively. bWeighted arithmetic means are not comparable to weighted geometric means.

cUnadjusted standard errors do not incorporate survey design effects.

dEach pool was composed of serum from eight persons. eNot calculated: proportion of results below limit of detection was too high to provide a valid result.

f

Standard error of the mean estimate is >30%.

CI = confidence interval; LOD = limit of detection

Source: CDC 2019

mirex. There is a slight possibility of exposure for workers involved in dredging activities (e.g., sediment 

remediation work performed by the Corps of Engineers).

Chlordecone. Chlordecone has not been produced since 1975 or used in the United States since 1978 

when all registered uses of the product were canceled. The potential for exposure of the general 

population, therefore, is relatively small and should continue to diminish over time. Members of the 

general population may be exposed to low concentrations of chlordecone primarily through consumption 

of contaminated foodstuffs, in particular contaminated fish and shellfish from the James River in Virginia. 

No dietary intake estimates are available (FDA 1990, 1991, 1992) since chlordecone has been so 

infrequently found in foodstuffs in recent years. Chlordecone exposure from drinking water has not been 

found to constitute significant human exposure since chlordecone is relatively insoluble in water and 

rapidly adsorbs to sediment (EPA 1978a).

No information was located for the general population on chlordecone concentrations in human adipose 

tissue or blood as this compound was not included in any major national study (e.g., National Human 

Adipose Study). Chlordecone was detected in 9 of 298 samples of human milk collected in the southern 

United States; however, the detection limit was relatively high (1 μg/kg) (EPA 1978a).
MIREX AND CHLORDECONE 193

5. POTENTIAL FOR HUMAN EXPOSURE

With regard to occupational exposures, chlordecone was detected in blood samples from workers at the 

Life Sciences Products Company in Hopewell, Virginia. Chlordecone levels in the blood of 32 workers 

at the manufacturing plant ranged from 0.165 to 26.0 μg/mL (ppm) (Epstein 1978). The mean blood level 

of workers exhibiting symptoms of nervousness and tremors was 8.48 μg/mL, compared to a mean of 

1.57 μg/mL in workers exhibiting no symptoms (Epstein 1978). In another occupational study, Cannon 

et al. (1978) reported maximum chlordecone blood levels in workers at the Hopewell facility of 

11.8 μg/mL. Chlordecone blood levels of workers who reported illness averaged 2.53 μg/mL, while 

blood levels for workers reporting no illness averaged 0.6 μg/mL.

In 1975, when chlordecone was still being produced, over half of the workers at a manufacturing plant 

developed clinical illness characterized by nervousness, tremor, weight loss, opsoclonus, pleuritic and 

joint pain, and oligospermia (Cannon et al. 1978). During the years of production, chlordecone was also 

detected in family members of the plant workers at the Life Sciences Products Company in Hopewell, 

Virginia. Although half of the workers at the plant had clinical signs of chlordecone poisoning, such 

signs were detected in only two family members who washed contaminated clothes (Cannon et al. 1978). 

Another study also found higher chlordecone levels in members of chlordecone workers’ families 

compared with families of workers at other local industries or other community residents (Taylor et al. 

1978). Such illness could have been mitigated by appropriate occupational health measures that would 

prevent the transport of contaminated materials from the workplace, such as not bringing work clothes 

home (Knishkowy and Baker 1986).

Current occupational exposure is most likely to occur for workers employed at waste disposal sites or 

those engaged in remediation activities associated with the clean-up or removal of soils or sediments that 

are contaminated with chlordecone.

5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

A susceptible population will exhibit a different or enhanced response to mirex and chlordecone than will 

most persons exposed to the same level of mirex or chlordecone in the environment. Reasons include 

genetic make-up, developmental stage, age, health and nutritional status (including dietary habits that may 

increase susceptibility, such as inconsistent diets or nutritional deficiencies), and substance exposure 

history (including smoking). These parameters result in decreased function of the detoxification and 

excretory processes (mainly hepatic, renal, and respiratory) or the pre-existing compromised function of 

target organs (including effects or clearance rates and any resulting endproduct metabolites). For these 
MIREX AND CHLORDECONE 194

5. POTENTIAL FOR HUMAN EXPOSURE

reasons, the elderly with declining organ function and the youngest of the population with immature and 

developing organs are generally expected be more vulnerable to toxic substances than healthy adults.

Review of the literature regarding toxic effects of mirex and chlordecone did not reveal any human 

populations that are known to be unusually sensitive to mirex or chlordecone. However, based on 

knowledge of the toxicities of mirex and chlordecone, some populations can be identified that may 

demonstrate unusual sensitivity to these chemicals. Those with potentially high sensitivity to mirex 

include the very young. Those with potentially high sensitivity to chlordecone include juvenile and 

elderly person and persons being treated with some classes of antidepressants that affect serotonin or the 

anticonvulsant, diphenylhydantoin.

In experimental animals, mirex administered within the week after birth causes a high incidence of 

cataracts and other lesions of the lens (Chernoff et al. 1979a; Gaines and Kimbrough 1970; Rogers and 

Grabowski 1984; Scotti et al. 1981). These effects were observed whether the neonatal animals received 

mirex through the milk of lactating dams or directly by gavage. Although it is unclear whether the lens of 

humans also undergoes a similar period of susceptibility, the possibility exists that newborn children may 

also develop cataracts if exposed to mirex shortly after birth.

Studies in rats have demonstrated that certain treatments exacerbate the tremors associated with 

chlordecone exposure. These include pretreatment with the anticonvulsant, diphenylhydantoin (Hong et 

al. 1986; Tilson et al. 1985, 1986), and treatment with the nonselective serotonergic receptor agonist, 

quipazine (Gerhart et al. 1983). Therefore, persons being treated with diphenylhydantoin for epilepsy or 

quipazine for depression may be likely to experience more severe tremors upon exposure to high levels of 

chlordecone. Extrapolating from the effects seen in animals with quipazine, it might be likely that 

persons taking the prescription drug Prozac®, a SSRI used to treat depression, will also experience more 

severe tremors. Furthermore, the elderly may be a susceptible population because serotonin metabolism 

is increased during aging (Walker and Fishman 1991).

Studies in animals have also shown that juvenile animals experience a higher death rate than adults 

following exposure to chlordecone at equivalent mg/kg doses (Huber 1965). No explanation was given 

for these findings, but similar sensitivities may exist in children. Furthermore, although inhibition of 

Na+-K+ATPase, Mg2+ATPase, and Ca2+ATPase activities have not been definitively shown to be the 

mechanism underlying chlordecone toxicity, sufficient evidence exists to suggest that their inhibition may 

be involved in a number of adverse effects. Neonatal rats have shown a greater inhibition of these 
MIREX AND CHLORDECONE 195

5. POTENTIAL FOR HUMAN EXPOSURE

enzymes than adult rats (Jinna et al. 1989). This provides additional support for the suggestion that 

infants and young children may represent a susceptible population to the toxic effects of chlordecone.

In contrast, a study of developing postnatal rats has shown that the young may be less susceptible to at 

least one of the toxic effects of chlordecone. Young and adolescent rats show less potentiation of carbon 

tetrachloride toxicity than adult rats (Cai and Mehendale 1993). This may be due to a combination of 

incomplete development of the microsomal enzyme systems and a higher level of hepatic regenerating 

activity in the very young rats. In adolescent rats (35 and 45 days old), the microsomal enzyme activity is 

comparable to adult levels, but the level of damage is still less than in adult rats (60 days old). This may 

be due to that fact that hepatic regenerating activity remained higher in the adolescents than in the adults.

In studies performed by Sobel and coworkers (Sobel et al. 2005, 2006; Wang et al. 2008), chronic 

exposure of systemic lupus erythematosus-prone female (NZB x NZW) F1 mice to chlordecone via 

subcutaneously-implanted pellets significantly shortened the time to onset of elevated autoantibody titers 

and renal disease in a dose-related manner. These effects were not seen in nonlupus-prone BALB/c mice.

These results indicate that humans with lupus may be particularly sensitive to chlordecone toxicity.

Members of the general population who currently have potentially high exposures to mirex include 

recreational and subsistence fishers who may consume large quantities of fish and shellfish from 

waterbodies with mirex contamination, hunters who consume game species that may be contaminated 

with mirex, populations living near sites where mirex was manufactured or waste disposal sites 

contaminated with mirex, or populations living in areas where mirex was used extensively for fire ant 

control.

Mirex contamination has triggered the issuance of several human health advisories nationwide. In 1993, 

mirex was identified as the causative pollutant in eight fish consumption advisories in three different 

states (Ohio, New York, and Pennsylvania) (EPA 1993). In 2019, New York still had mirex fish 

advisories in six waterbodies (Lake Ontario, Niagara River downstream of Niagara Falls, Irondequoit 

Bay, Oswego River, Salmon River, and St. Lawrence River) (NYS 2019). 

Persons living in areas where mirex has been used for fire ant control or near where it was manufactured 

may be at increased risk of exposure. Human tissue samples (unspecified) taken from 186 people at sites 

treated with mirex over the previous 10 years had mirex residues in the range of <1–1.32 μg/g (ppm) 

(mean concentration, 0.38 μg/g) (EPA 1980). A 1975–1976 survey of 624 human adipose tissue samples 
MIREX AND CHLORDECONE 196

5. POTENTIAL FOR HUMAN EXPOSURE

from subjects living in eight southern states where mirex had been used for fire ant control indicated that 

10.2% of the population in the area had detectable levels of mirex at a geometric mean concentration of 

0.286 μg/g (ppm). Populations living in two states, Texas and North Carolina, had no detectable mirex 

residues in their tissues, whereas 51.1% of the samples from populations in Mississippi had detectable 

levels (mean concentration, 0.290 μg/g) (Kutz et al. 1985). Mirex was detected in human adipose tissue 

samples from residents of northeast Louisiana during the late 1970s (Greer et al. 1980). Concentrations 

of mirex in adipose tissue collected during surgery and during postmortem examinations ranged from 

0.01 to 0.60 μg/g (ppm) with a mean mirex concentration of 0.14 μg/g. Human adipose tissue samples 

from northeastern Louisiana, an agricultural area, contained detectable amounts of mirex in 20 of 

22 samples in 1977 at a mean concentration of approximately 0.15 μg/g (ppm), 10 of 10 samples in 1980 

at a mean concentration of 0.25 μg/g, and only 2 of 10 samples in 1984 at a mean concentration of 

0.15 μg/g (Holt et al. 1986).

A comparison of mirex residues in adipose tissue samples collected between 1979 and 1981 from 

residents of Kingston, Ontario (a city located on Lake Ontario), and residents of Ottawa, Ontario, 

indicated that persons living in Kingston had significantly higher mirex and photomirex residues than 

those in Ottawa (27 and 9 ng/g [ppb], respectively, in Kingston versus 11 and 6 ng/g, respectively, in 

Ottawa). Males from Kingston had significantly higher levels of mirex (38 ng/g) than females from the 

area (12 ng/g); this gender difference was not explained or seen in the Ottawa samples (Williams et al. 

1984). A subsequent 1984 study examined mirex levels in six additional cities on the Canadian portion of 

Lake Ontario. The overall mean mirex residue in human adipose tissue was 11±13 ng/g (ppb) (males, 

12±15 ng/g; females, 9.6±10 ng/g) (Williams et al. 1988).

Mirex levels in the blood of pregnant women in Jackson, Mississippi, and the Mississippi Delta area 

where mirex was extensively used were correlated with the health of the infants they bore. The mean 

mirex level in maternal blood was 0.54 μg/L (ppb) for 106 samples; however, mirex levels in the blood of 

the infants were not correlated with differences in gestation times, Apgar score, or other problems at birth. 

Only three children with neurological problems had mothers with pesticide levels, including mirex, above 

the mean levels (Lloyd et al. 1974).

In 1977, mirex was detected in human milk and colostrum samples of women living in upstate New York. 

Milk from women in Oswego and Rochester, areas adjacent to Lake Ontario (known to be contaminated 

with mirex), was compared with milk from women in Albany (considered to be free from mirex 

contamination). Mean mirex concentrations from women in each area were as follows: 0.057 ng/g in 
MIREX AND CHLORDECONE 197

5. POTENTIAL FOR HUMAN EXPOSURE

colostrum (n=24) and 0.07 ng/g in milk (n=6), Albany; 0.51 ng/g in colostrum (n=18) and 0.120 ng/g in 

milk (n=16), Oswego; and 0.035 ng/g in colostrum (n=4) and 0.162 ng/g in milk (n=6), Rochester. Only 

2 of the 28 milk samples (both from Oswego) were below the detection limit of 0.01 ng/g (ppb), while 

16 of 24 colostrum samples in Albany, 10 of 18 colostrum samples from Oswego, and 2 of 4 colostrum 

samples from Rochester were below the detection limit. None of the women reported eating freshwater 

fish, a possible source of the mirex contamination (Bush et al. 1983).

Members of the general population currently having potentially higher exposure to chlordecone include 

recreational and subsistence fishers who may consume large quantities of fish and shellfish from 

waterbodies with chlordecone contamination, populations living near sites where chlordecone was 

manufactured, or waste disposal sites contaminated with chlordecone.

Chlordecone contamination has triggered the issuance of one human health advisory. As of September 

1993, chlordecone was identified as the causative pollutant in an advisory issued by the State of Virginia 

for the 113 miles of the James River Estuary. The advisory extends from Richmond, Virginia, 

downstream to the Hampton-Norfolk Bridge Tunnel including all tributaries to the James River (EPA

1993).

The only data on chlordecone residues in populations living near a production site are historic and were 

collected several decades ago. The EPA initiated a community survey in August 1975 shortly after 

production of chlordecone was halted to determine chlordecone levels in blood of persons living in the 

vicinity of the Hopewell manufacturing plant. Two hundred nine community residents, none of whom 

had ever been employed at the Allied Chemical plant or Life Sciences Products Company (LSPC) were 

surveyed. Chlordecone blood levels were <5 ppb in 39% of residents living 0.25 miles south of the LSPC 

plant, in 7.7% of residents living 0.25 miles north of the LSPC plant, in 5.9% of residents living 0.5 miles 

from the site, in 2.6% of residents living 0.75 miles from the site, and in 3.3% of residents living 1 mile 

from the site. Chlordecone blood levels were approximately linear as a function of proximity to the LSPC 

site (Epstein 1978). No additional information was located on current chlordecone levels in residents of 

the Hopewell, Virginia, area.
MIREX AND CHLORDECONE 198

CHAPTER 6. ADEQUACY OF THE DATABASE

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of mirex and chlordecone is available. Where adequate 

information is not available, ATSDR, in conjunction with NTP, is required to assure the initiation of a 

program of research designed to determine the adverse health effects (and techniques for developing 

methods to determine such health effects) of mirex and chlordecone.

Data needs are defined as substance-specific informational needs that, if met, would reduce the 

uncertainties of human health risk assessment. This definition should not be interpreted to mean that all 

data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.1 Information on Health Effects

Studies evaluating the health effects of inhalation, oral, and dermal exposure of humans and animals to 

mirex and chlordecone that are discussed in Chapter 2 are summarized in Figures 6-1 and 6-2, 

respectively. The purpose of these figures is to illustrate the information concerning the health effects of 

mirex and chlordecone. The number of human and animal studies examining each endpoint is indicated 

regardless of whether an effect was found and the quality of the study or studies. 

Epidemiological data regarding potential health effects in humans exposed to mirex are essentially limited 

to investigations using mirex levels in blood samples (one study included placental mirex) as the basis for 

exposure data. Human data for chlordecone come from reports of an occupational cohort of workers 

exposed during the manufacture of chlordecone and from investigations using chlordecone levels in blood 

samples or cord blood as the basis for exposure data. In the occupational cohort, exposure was classified 

as intermediate-to-chronic; no precise duration or level of exposure to chlordecone could be quantified 

from these reports. A single route of exposure could not be established for this worker population; poor 

hygiene in the plant made inhalation, oral, and dermal exposure routes likely to occur. The information 

on human exposure in this study is extremely limited because of the possible contamination with the 

precursor used to manufacture chlordecone, hexachloropentadiene.
MIREX AND CHLORDECONE 199

6. ADEQUACY OF THE DATABASE

Figure 6-1. Summary of Existing Health Effects Studies on Mirex By Route and 

Endpoint* 

Potential body weight, liver, and developmental effects were the most studied endpoints 

The majority of the studies examined oral exposure in animals (versus humans) 

*Includes studies discussed in Chapter 2; the number of studies include those 

finding no effect and those examining multiple endpoints. No inhalation studies 

were located.
MIREX AND CHLORDECONE 200

5. POTENTIAL FOR HUMAN EXPOSURE

Figure 6-2. Summary of Existing Health Effects Studies on Chlordecone By Route 

and Endpoint* 

Potential body weight, liver, and neurological effects were the most studied endpoints 

The majority of the studies examined oral exposure in animals (versus humans) 

*Includes studies discussed in Chapter 2; the number of studies include those 

finding no effect and those examining multiple endpoints. No inhalation or 

dermal studies in humans or animals were located.
MIREX AND CHLORDECONE 201

6. ADEQUACY OF THE DATABASE

The database for the health effects of mirex and chlordecone following oral administration in 

experimental animals is more substantial. However, no information is available on the health effects of 

inhalation exposure to mirex or chlordecone in animals.

People living near hazardous waste sites may be exposed to mirex or chlordecone primarily via dermal 

contact with or ingestion of contaminated soils since mirex and chlordecone are bound to soil particles. 

Another possible mechanism for oral exposure to mirex and chlordecone is the ingestion of pesticideladen dust carried by the wind from a waste site or treated field and deposited on garden crops. Ingestion 

of contaminated water is not likely to be a significant route of exposure since mirex and chlordecone have 

very limited water solubility and are generally not found in groundwater. Likewise, inhalation exposure 

to mirex and chlordecone via volatilization from contaminated media is not a likely major route of 

exposure since mirex and chlordecone are essentially nonvolatile. For the general population, the primary 

route of exposure to mirex and chlordecone is via ingestion of residues on contaminated foods. 

Therefore, information on the toxicity following ingestion and dermal exposure is most relevant for 

individuals living in the vicinity of hazardous waste sites.

6.2 Identification of Data Needs 

Missing information in Figures 6-1 and 6-2 should not be interpreted as a “data need”. A data need, as 

defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data Needs Related to 

Toxicological Profiles (ATSDR 1989), is substance-specific information necessary to conduct 

comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly as any 

substance-specific information missing from the scientific literature.

Acute-Duration MRLs. No acute-duration inhalation MRLs were derived for mirex or chlordecone 

because no exposure-response inhalation data were located. No acute-duration oral MRL was derived for 

mirex because the lowest LOAEL from available acute-duration oral studies was for serious effects (heart 

block and arrhythmias in fetuses from dams exposed during gestation) and the effects were observed at 

the lowest dose tested (Grabowski 1983). An acute-duration oral MRL was derived for chlordecone 

based on neurological effects in an animal study. Human data for mirex are essentially limited to 

evaluations of health outcomes associated with mirex blood levels for which exposure-response data and 

information regarding duration of exposure are not available. Human data for chlordecone are limited as 

well. Data are available from one cohort of workers involved in the production of chlordecone (Cannon 

et al. 1978; Guzelian et al. 1980; Martinez et al. 1978; Sanborn et al. 1979; Taylor 1982, 1985; Taylor et 
MIREX AND CHLORDECONE 202

6. ADEQUACY OF THE DATABASE

al. 1978). No particular exposure route or exposure duration could be established and the workers were 

likely exposed to other toxic substances as well. Other available human studies consist of evaluations of 

health outcomes associated with chlordecone blood levels for which exposure-response data are not 

available. Oral exposure to mirex or chlordecone from food sources grown in mirex- or chlordeconecontaminated soil is the most likely source of mirex or chlordecone blood levels at present because mirex 

and chlordecone have not been used as pesticides for decades, although they persist in soil. Additional 

animal studies could be designed to determine an appropriate basis for deriving acute-duration inhalation 

MRLs for mirex and chlordecone and an acute-duration oral MRL for mirex. Inhalation data do not 

appear to be particularly necessary because significant inhalation exposure is not likely since neither 

mirex nor chlordecone readily enter the air from other media where they may be present.

Intermediate-Duration MRLs. Limited human data are not suitable for MRL derivation. No 

intermediate-duration inhalation MRLs were derived for mirex or chlordecone because no exposureresponse inhalation data were located. No intermediate-duration oral MRL was derived for mirex 

because the most suitable point of departure based on available data is a LOAEL for endocrine effects in 

weanling rats in the absence of a NOAEL. Application of a total uncertainty factor of 1,000 (10 for 

extrapolation from a LOAEL to a NOAEL, 10 for extrapolation from animals to humans, and 10 for 

human variability) would result in an intermediate-duration oral MRL that is lower than the chronicduration oral MRL derived for mirex. An intermediate-duration oral MRL was derived for chlordecone 

based on neurological effects reported in a rat study (Linder et al. 1983). Additional animal studies could 

be designed to determine an appropriate basis for deriving intermediate-duration inhalation MRLs for 

mirex and chlordecone and an intermediate-duration oral MRL for mirex. Inhalation data do not appear 

to be particularly necessary because significant inhalation exposure is not likely since neither mirex nor 

chlordecone readily enter the air from other media where they may be present.

Chronic-Duration MRLs. Limited human data are not suitable for MRL derivation. No chronicduration inhalation MRLs were derived for mirex or chlordecone because no exposure-response 

inhalation data were located. A chronic-duration oral MRL was derived for mirex based on 

histopathologic liver effects in a 2-year rat study (NTP 1990). A chronic-duration oral MRL was derived 

for chlordecone based on renal effects in a 2-year rat study (Larson et al. 1979b). Additional animal 

studies could be designed to determine an appropriate basis for deriving chronic-duration inhalation 

MRLs for mirex and chlordecone. However, inhalation data do not appear to be particularly necessary 

because significant inhalation exposure is not likely since neither mirex nor chlordecone readily enter the 

air from other media where they may be present.
MIREX AND CHLORDECONE 203

6. ADEQUACY OF THE DATABASE

Health Effects. 

Hepatic Effects. There is some evidence of hepatic effects associated with occupational 

exposure to chlordecone when it was being produced (Guzelian 1982a, 1982b; Taylor 1982, 

1985; Taylor et al. 1978). There is limited evidence of mirex-related effects on CYP-induced 

metabolism (Lambert et al. 1992). A variety of oral studies in animals identify the liver as a 

target of mirex and chlordecone toxicity. Additional animal data do not appear necessary. 

However, human populations with potential for exposure to mirex or chlordecone should be 

monitored for possible exposure-related hepatic effects.

Neurological Effects. Examinations of workers occupationally exposed to chlordecone during 

its production revealed some signs of neurotoxicity (e.g., tremors, anxiety, visual difficulties, 

irritability, poor recent memory, blurred vision, headaches) (Cannon et al. 1978; Taylor 1982, 

1985; Taylor et al. 1978). Sural nerve biopsies from workers with the most notable signs of 

neurotoxicity revealed decreased numbers of small myelinated and unmyelinated axons (Martinez 

et al. 1978). Neurological effects have been widely reported in animal studies that employed oral 

exposure to mirex or chlordecone. Additional animal studies to not appear necessary. However, 

human populations with potential for exposure to mirex or chlordecone should be monitored for 

possible exposure-related neurological effects.

Renal Effects. No information was located regarding mirex- or chlordecone-induced renal 

effects in humans. However, the kidney was identified as a target of mirex and chlordecone 

toxicity in 2-year rat studies (Larson et al. 1979b; NTP 1990). Additional animal studies do not 

appear necessary. However, human populations with potential for exposure to mirex or 

chlordecone should be monitored for possible exposure-related renal effects.

Reproductive Effects. There is some evidence of adverse effects on the male reproductive 

system associated with occupational exposure to chlordecone when it was being produced 

(Guzelian 1982a, 1982b; Taylor 1982, 1985; Taylor et al. 1978). Results from two human studies 

provide evidence that mirex in the blood may be associated with female reproductive effects 

(Grindler et al. 2015; Upson et al. 2013). A variety of oral studies in animals identify the 

reproductive system as a target of mirex and chlordecone toxicity. Additional animal data do not 

appear necessary. However, human populations with potential for exposure to mirex or 

chlordecone should be monitored for possible exposure-related reproductive effects.
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6. ADEQUACY OF THE DATABASE

Developmental Effects. Limited results from human studies provide suggestive evidence that 

blood levels of mirex (Araki et al. 2018; Puertas et al. 2010) or chlordecone (Boucher et al. 2013; 

Cordier et al. 2015; Dallaire et al. 2012; Kadhel et al. 2014) may be associated with 

developmental effects. A variety of oral studies in animals identify developmental endpoints as 

targets of mirex and chlordecone toxicity. Additional animal data do not appear necessary. 

However, human populations with potential for exposure to mirex or chlordecone should be 

monitored for possible exposure-related developmental effects.

Cancer. Limited human data provide little evidence for mirex- or chlordecone-induced 

carcinogenicity. In population-based, case-control studies, lipid-adjusted serum mirex was 

associated with risk of non-Hodgkin’s lymphoma (Spinelli et al. 2007) and plasma chlordecone 

was associated with risk of prostate cancer (Multigner et al. 2010). Other human studies that 

evaluated potential associations between blood mirex and selected cancer endpoints found no 

evidence for an association (Itoh et al. 2009; Koutros et al. 2015a, 2015b; Moysich et al. 1998; 

Sawada et al. 2010). The carcinogenicity of mirex and chlordecone has been demonstrated in rats 

and mice (NCI 1976; NTP 1990). Additional animal carcinogenicity studies do not appear 

necessary. However, human populations with potential for exposure to mirex or chlordecone 

should be monitored for possible exposure-related carcinogenic effects.

Epidemiology and Human Dosimetry Studies. A single epidemiological cohort was located for 

occupational exposure to chlordecone (Cannon et al. 1978; Guzelian et al. 1980; Sanborn et al. 1979; 

Taylor 1982, 1985). The routes of exposure in this study were probably mixed because of the poor 

hygiene in the chlordecone manufacturing plant (Taylor 1982, 1985). The most likely identifiable 

subpopulations exposed to mirex or chlordecone would be individuals who live in areas where these 

pesticides may persist in environmental media or have become bioconcentrated in food sources. Welldesigned epidemiological studies of these subpopulations specifically examining a wide range of health 

endpoints would be useful to evaluate possible human health outcomes similar to those observed in 

animal studies.

Biomarkers of Exposure and Effect. The biomarkers of exposure to mirex and chlordecone are 

well established and specific to each compound. The known biomarkers of exposure to mirex are its 

concentrations in blood, fat, feces, and milk. The known biomarkers of exposure for chlordecone include 

its concentrations in blood, saliva, and tissues, and concentrations of chlordecone or its metabolite in 
MIREX AND CHLORDECONE 205

6. ADEQUACY OF THE DATABASE

feces or bile. Of the biomarkers of exposure listed for chlordecone, the blood is the most useful 

biological material to monitor in order to determine exposure to chlordecone.

Several potential biomarkers for the effects of mirex and chlordecone have been identified. These include 

levels of urinary D-glucaric acid to measure hepatic enzyme induction, elevated urinary protein and renal 

histopathology to assess renal damage, electromyography and tremorograms to assess tremor, 

oculography to measure visual disturbances, and sperm counts and tests of motility to assess toxic effects 

on sperm (Guzelian 1985; Larson et al. 1979b; Taylor et al. 1978). However, these biomarkers are not 

specific for either mirex or chlordecone. Measurement of serum bile acids may be helpful in assessing 

hepatobiliary function after exposure to chlordecone. Examination of this possibility and further 

investigation of other serum biomarkers of effect in populations exposed to mirex or chlordecone would 

be helpful.

Absorption, Distribution, Metabolism, and Excretion. No data were located regarding 

absorption of mirex in humans following inhalation, oral, or dermal exposure. Limited epidemiological 

data were located regarding the distribution and excretion of mirex following inhalation, oral, and dermal 

exposure. Mirex is not metabolized by humans or animals. There are a number of animal studies 

describing absorption, distribution, metabolism, and excretion of mirex following oral exposure. 

Information is available to assess the relative rates and extent of these toxicokinetic parameters by the oral 

route. Most of the toxicokinetic data, however, involve acute exposures to mirex; only very limited data 

deal with intermediate or chronic exposures. Additional intermediate and chronic data would be useful to 

adequately assess the rates and extent of the toxicokinetic parameters for these durations. Limited animal 

data were located regarding the absorption, distribution, and excretion of mirex following inhalation 

exposure. Additional acute-, intermediate-, and chronic-duration data would be useful to adequately 

assess the relative rates and extent of the toxicokinetic parameters by this route. No animal data were 

located for the toxicokinetic parameters by the dermal exposure route.

Limited occupational data exist regarding absorption, distribution, metabolism, and/or excretion of 

chlordecone by humans. There are a number of animal studies describing the absorption, distribution, 

metabolism, and excretion of chlordecone following oral exposure. Most of these data concern acute 

exposures. However, the available data are sufficient to assess the relative rates and extent of the 

pharmacokinetics following oral exposure. Dermal absorption occurs only to a limited extent. No studies 

were located regarding distribution, metabolism, or excretion following dermal exposure. No animal data 

were located regarding absorption, distribution, metabolism, or excretion of chlordecone following 
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6. ADEQUACY OF THE DATABASE

inhalation exposure. Additional acute-, intermediate-, and chronic-duration data would be useful to 

adequately compare the toxicokinetic parameters across all routes of exposure.

Comparative Toxicokinetics. The absorption, distribution, metabolism, and excretion of mirex and 

chlordecone have been studied in animals. However, information on the toxicokinetics of mirex and 

chlordecone in humans is very limited. Furthermore, little information is available regarding interspecies 

differences in the kinetics of mirex. Toxicokinetic studies have been performed for chlordecone using 

multiple animal species. Based on the available data, rats, guinea pigs, and hamsters are not good animal 

models for studying chlordecone metabolism in humans because they do not convert chlordecone to 

chlordecone alcohol (Fariss et al. 1980; Guzelian et al. 1981; Houston et al. 1981). Gerbils and pigs were 

found to be the most practical animal models of chlordecone metabolism in humans because they 

converted chlordecone to chlordecone alcohol (Houston et al. 1981; Soine et al. 1983). Additional studies 

of various animal species would be useful to determine the most appropriate animal model(s) to predict 

the toxicokinetics of mirex and chlordecone in humans.

Children’s Susceptibility. Results from animal studies suggest that the fetus and newborn may be 

more sensitive than adults to mirex or chlordecone toxicity. Mirex administered within 1 week after birth 

caused a high incidence of cataracts and other lesions of the lens in experimental animals. Infants and 

young children should be monitored for potential mirex- or chlordecone-related effects, particularly in 

areas with potential for significant exposure to these persistent pesticides.

Physical and Chemical Properties. The physical and chemical properties of mirex and chlordecone 

are sufficiently documented to permit estimation of their environmental fate. No further information is 

necessary.

Production, Import/Export, Use, Release, and Disposal. Mirex and chlordecone are no longer 

being produced or used in the United States. Mirex was most commonly used from 1962 to 1976 as an 

insecticide to control fire ants. Mirex was also used as a flame retardant from 1959 to 1972 in various 

coatings, plastics, rubber, paint, paper, and electrical goods. Until 1976, chlordecone was used as an 

insecticide on bananas, non-bearing citrus trees, tobacco, and ornamental shrubs. It was also used in 

household products such as ant and roach traps. However, all registered products containing mirex and 

chlordecone were canceled in 1977 and 1978, respectively. Since mirex and chlordecone are not 

flammable and are very stable in the environment, many disposal methods have proven unsuccessful. 

Since mirex is not identified by EPA as a hazardous waste under SARA Title III, no regulatory 
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6. ADEQUACY OF THE DATABASE

information is available for the disposal of mirex. However, the recommended method of disposal for 

mirex is incineration. Efficient disposal methods exist for chlordecone. Chlordecone is considered an 

EPA hazardous waste and must be disposed of according to EPA regulations.

Environmental Fate. Mirex and chlordecone released to the environment partition to soil and 

sediment. Small amounts may remain dissolved in water. Mirex and chlordecone released to the 

atmosphere are eventually deposited on soil or surface waters. On the surface of soil or water, mirex 

undergoes photolysis with the subsequent loss of a chlorine atom. Both compounds are resistant to 

aerobic degradation, although some anaerobic biodegradation does occur. When not exposed to sunlight 

or anaerobic conditions, mirex and chlordecone persist in soil, particularly sediments, for many years. 

Additional information on the persistence of mirex and chlordecone in water and soil would be useful.

Bioavailability from Environmental Media. Both mirex and chlordecone can be absorbed 

following oral exposure, although chlordecone is more readily absorbed than mirex. No data were 

located regarding absorption of mirex following dermal exposure. Limited animal data indicate that 

dermal absorption of chlordecone is low. Information regarding the bioavailability of mirex and 

chlordecone from oral exposure via contaminated food sources and dermal contact with contaminated 

soils would be helpful, particularly for populations living near areas where mirex and/or chlordecone 

were used in the past.

Food Chain Bioaccumulation. Both mirex and chlordecone are highly lipophilic and, therefore, 

have high bioconcentration potentials. They are bioaccumulated in aquatic food chains with virtually no 

degradation of the compounds by exposed organisms. Uptake and bioaccumulation of mirex in terrestrial 

food chains have also been shown to occur. No further information is necessary. Only limited 

information is available on uptake and bioaccumulation of chlordecone in terrestrial food chains, and little 

uptake of chlordecone by plants was observed. Additional information on uptake of chlordecone in plants 

under field conditions would be helpful.

Exposure Levels in Environmental Media. Environmental monitoring data are available for mirex 

levels in air, water, soil, and sediment. Limited information on mirex concentrations in groundwater is 

available; however, because mirex binds tightly to organic matter in soil, additional leaching data are not 

necessary. Data on atmospheric releases and levels of chlordecone are available only for 2 years (1974–

1975) of its production at the Hopewell, Virginia facility; however, since chlordecone production in the 

United States ceased in 1975 and because most of the chlordecone produced was exported or was used in 
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6. ADEQUACY OF THE DATABASE

insect bait traps so that it was not widely dispersed in the environment, no additional current information 

on chlordecone in the atmosphere is required. Historic chlordecone levels in surface waters, soils, and 

sediments in the vicinity of the Hopewell, Virginia facility have been well characterized. Because 

chlordecone binds tightly to organic matter in soil, leaching into groundwater is not anticipated to occur 

extensively. Minimal information was found on the uptake of mirex and chlordecone by plants grown 

under field conditions. Adequate information on mirex and chlordecone levels in fish and shellfish are 

available. Further information on foods other than fish and shellfish, particularly in foods grown in areas 

where mirex was used as a pesticide, would be helpful in estimating current human and animal intake.

Exposure Levels in Humans. Mirex has been detected in human adipose tissue, blood, and milk. 

Because of the lipophilic nature of mirex, most determinations of exposure are based on residues found in 

adipose tissue. Higher levels in tissue have been correlated with areas of mirex usage, manufacture, or 

disposal at waste sites. Chlordecone has not been detected in human adipose tissue or in blood samples 

from the general population, although it has been detected in human milk samples. Adequate information 

is available regarding chlordecone levels in blood of occupationally exposed workers and their families 

during 1974–1975 employed at the Hopewell, Virginia site. Additional information for mirex and 

chlordecone would be helpful in determining areas with greatest potential for human exposure.

Exposures of Children. Fetuses and nursing infants may be exposed to mirex or chlordecone via their 

mothers. Available animal data indicate that early stages of life may be relatively sensitive timepoints for 

mirex or chlordecone toxicity. Areas where mirex or chlordecone may persist in soil or food sources 

should be monitored for potential pre- and postnatal exposure.

Analytical Methods. Improvements in detection sensitivity for mirex and chlordecone in 

environmental media would be useful for monitoring these pesticides in areas with potential for 

significant exposure.

6.3 Ongoing Studies 

No ongoing studies were identified for mirex or chlordecone.
MIREX AND CHLORDECONE 209

CHAPTER 7. REGULATIONS AND GUIDELINES

Pertinent international and national regulations, advisories, and guidelines regarding mirex and 

chlordecone in air, water, and other media are summarized in Table 7-1. This table is not an exhaustive 

list, and current regulations should be verified by the appropriate regulatory agency.

ATSDR develops MRLs, which are substance-specific guidelines intended to serve as screening levels by 

ATSDR health assessors and other responders to identify contaminants and potential health effects that 

may be of concern at hazardous waste sites. See Section 1.3 and Appendix A for detailed information on 

the MRLs for mirex and chlordecone.

Table 7-1. Regulations and Guidelines Applicable to Mirex and Chlordecone

Agency Description Information Reference

Air

EPA RfC No data IRIS 1992, 2009

WHO Air quality guidelines No data WHO 2010

Water & Food

EPA Drinking water standards and health advisories No data EPA 2012

National primary drinking water regulations No data

RfD 

Mirex 0.0002 mg/kg/day IRIS 1992

Chlordecone 0.0003 mg/kg/day IRIS 2009

WHO Drinking water quality guidelines Mirex excluded from 

guideline value 

derivation because 

unlikely to occur in 

drinking water

WHO 2017

FDA EAFUS No dataa FDA 2013

Cancer

ACGIH Carcinogenicity classification No data ACGIH 2016

HHS Carcinogenicity classification

Mirex Reasonably 

anticipated to be a 

human carcinogenb

NTP 2016b

Chlordecone Reasonably 

anticipated to be a 

human carcinogenb

NTP 2016a

EPA Carcinogenicity classification

Mirex No data IRIS 1992
MIREX AND CHLORDECONE 210

7. REGULATIONS AND GUIDELINES

Table 7-1. Regulations and Guidelines Applicable to Mirex and Chlordecone

Agency Description Information Reference

Chlordecone Likely to be 

carcinogenic to 

humans

IRIS 2009

IARC Carcinogenicity classification

Mirex Group 2Bc IARC 1979

Chlordecone Group 2Bc IARC 1979

Occupational

ACGIH TLV No data ACGIH 2016

OSHA PEL (8-hour TWA) for general industry, 

construction, and shipyards

No data OSHA 2016a, 2016b, 

2017

NIOSH REL (up to 10-hour TWA)

Chlordecone 0.001 mg/m3d NIOSH 2016

Emergency Criteria

EPA AEGLs-air No data EPA 2016

DOE PACs-air DOE 2016a

Mirex

PAC-1e 6.3 mg/m3

PAC-2e 69 mg/m3

PAC-3e 410 mg/m3

Chlordecone

PAC-1e 1.6 mg/m3

PAC-2e 17 mg/m3

PAC-3e 100 mg/m3

aThe EAFUS list of substances contains ingredients added directly to food that FDA has either approved as food 

additives or listed or affirmed as GRAS.

bBased on sufficient evidence of carcinogenicity from studies in experimental animals.

cGroup 2B: Possibly carcinogenic to humans. dPotential occupational carcinogen.

eDefinitions of PAC terminology are available from U.S. Department of Energy (DOE 2016b).

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = acute exposure guideline levels; 

DOE = Department of Energy; EAFUS = Everything Added to Food in the United States; EPA = Environmental 

Protection Agency; FDA = Food and Drug Administration; GRAS = generally recognized as safe; HHS = Department 

of Health and Human Services; IARC = International Agency for Research on Cancer; IRIS = Integrated Risk 

Information System; NIOSH = National Institute for Occupational Safety and Health; NTP = National Toxicology 

Program; OSHA = Occupational Safety and Health Administration; PAC = Protective Action Criteria; 

PEL = permissible exposure limit; REL = recommended exposure limit; RfC = inhalation reference concentration; 

RfD = oral reference dose; TLV = threshold limit values; TWA = time-weighted average; WHO = World Health 

Organization
MIREX AND CHLORDECONE 211

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MIREX AND CHLORDECONE A-1

APPENDIX A. ATSDR MINIMAL RISK LEVEL WORKSHEETS

MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the 

most sensitive health effect(s) for a specific duration for a given route of exposure. An MRL is an 

estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk 

of adverse noncancer health effects over a specified route and duration of exposure. MRLs are based on 

noncancer health effects only; cancer effects are not considered. These substance-specific estimates, 

which are intended to serve as screening levels, are used by ATSDR health assessors to identify 

contaminants and potential health effects that may be of concern at hazardous waste sites. It is important 

to note that MRLs are not intended to define clean-up or action levels.

MRLs are derived for hazardous substances using the NOAEL/uncertainty factor approach. They are 

below levels that might cause adverse health effects in the people most sensitive to such chemicalinduced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and chronic 

(≥365 days) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal 

route of exposure are not derived because ATSDR has not yet identified a method suitable for this route 

of exposure. MRLs are generally based on the most sensitive substance-induced endpoint considered to 

be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or 

birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not 

mean that adverse health effects will occur.

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals.
MIREX AND CHLORDECONE A-2

APPENDIX A

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Office of Innovation and Analytics, Toxicology Section, expert panel peer reviews, and agency-wide 

MRL Workgroup reviews, with participation from other federal agencies and comments from the public. 

They are subject to change as new information becomes available concomitant with updating the 

toxicological profiles. Thus, MRLs in the most recent toxicological profiles supersede previously 

published MRLs. For additional information regarding MRLs, please contact the Office of Innovation 

and Analytics, Toxicology Section, Agency for Toxic Substances and Disease Registry, 1600 Clifton 

Road NE, Mailstop S102-1, Atlanta, Georgia 30329-4027.
MIREX AND CHLORDECONE A-3

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Mirex

CAS Numbers: 2385-85-5

Date: October 2020

Profile Status: Final

Route: Inhalation

Duration: Acute

MRL Summary: There are insufficient data for derivation of an acute-duration inhalation MRL.

Rationale for Not Deriving an MRL: No acute-duration inhalation studies were identified for mirex.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-4

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Mirex

CAS Numbers: 2385-85-5

Date: October 2020

Profile Status: Final

Route: Inhalation

Duration: Intermediate

MRL Summary: There are insufficient data for derivation of an intermediate-duration inhalation MRL.

Rationale for Not Deriving an MRL: No intermediate-duration inhalation studies were identified for 

mirex.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-5

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Mirex

CAS Numbers: 2385-85-5

Date: October 2020

Profile Status: Final

Route: Inhalation

Duration: Chronic

MRL Summary: There are insufficient data for derivation of a chronic-duration inhalation MRL.

Rationale for Not Deriving an MRL: No chronic-duration inhalation studies were identified for mirex.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-6

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Mirex

CAS Numbers: 2385-85-5

Date: October 2020

Profile Status: Final

Route: Oral

Duration: Acute

MRL Summary: There are insufficient data for derivation of an acute-duration oral MRL.

Rationale for Not Deriving an MRL: No acute-duration oral MRL was derived for mirex because 

serious effects (arrhythmias in neonatal pups from maternal exposure during gestation) were observed at 

the lowest dose tested (0.1 mg/kg/day) (Grabowski 1983). ATSDR does not derive MRLs based on 

serious effects in the absence of identified NOAEL values.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-7

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Mirex

CAS Numbers: 2385-85-5

Date: October 2020

Profile Status: Final

Route: Oral

Duration: Intermediate

MRL Summary: There are insufficient data for derivation of an intermediate-duration oral MRL.

Rationale for Not Deriving an MRL: Intermediate-duration oral studies in humans are lacking for mirex. 

The most suitable animal study provides a LOAEL of 0.67 mg/kg/day for endocrine effects (dilation of 

rough endoplasmic reticulum cisternae of the thyroid) in weanling Sprague-Dawley rats (Singh et al. 

1985). Application of a total uncertainty factor of 1,000 (10 for extrapolation from a NOAEL to a 

LOAEL, 10 for animal to human extrapolation, and 10 for human variability)and a modifying factor of 

3 to be protective of mirex-induced developmental toxicity, including arrhythmias in neonatal pups 

following maternal exposure during gestation at a dose level as low as 0.1 mg/kg/day in the absence of an 

identified NOAEL (Grabowski 1983) would yield an intermediate-duration oral MRL of 

0.0001 mg/kg/day. This potential MRL is lower than the chronic-duration oral MRL of 

0.0003 mg/kg/day derived from an NTP (1990) study in rats (see chronic-duration oral MRL). Another 

candidate study for derivation of an intermediate-duration oral MRL for mirex identifies a LOAEL of 

0.49 mg/kg/day for cataracts in female rat pups (4/10 versus 0/14 controls) (Chu et al. 1981b). The 

parental rats had been administered mirex in the diet for 91 days prior to mating and during mating (males 

and females) and throughout gestation and lactation (females). This LOAEL of 0.49 mg/kg/day is 

considered a serious LOAEL and the study did not identify a NOAEL. Therefore, no intermediateduration oral MRL was developed for mirex.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-8

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Mirex

CAS Numbers: 2385-85-5

Date: October 2020

Profile Status: Final

Route: Oral

Duration: Chronic

MRL 0.0003 mg/kg/day

Critical Effect: Histopathologic liver lesions

Reference: NTP 1990

Point of Departure: NOAEL of 0.075 mg/kg/day

Uncertainty Factor: 100

Modifying Factor: 3

LSE Graph Key: 79

Species: Rat

MRL Summary: An MRL of 0.0003 mg/kg/day has been derived for chronic-duration oral exposure to 

mirex based on dose-related hepatic changes from a 2-year oral study of male and female F344/N rats 

(NTP 1990). The NOAEL of 0.075 mg/kg/day was divided by a total uncertainty factor of 100 (10 for 

animal to human extrapolation and 10 for human variability) and a modifying factor of 3 (to protect for 

developmental toxicity).

Selection of the Critical Effect: Available animal data identify the liver and kidney as critical targets of 

mirex toxicity following chronic-duration oral exposure. Potential candidate studies for deriving a 

chronic-duration oral MRL for mirex are summarized in Table A-1; the lowest LOAEL is 0.75 mg/kg/day 

for hepatic effects and the corresponding NOAEL is 0.075 mg/kg/day.

Table A-1. NOAELs and LOAELs Identified in Chronic-Duration Oral Studies of 

Mirex

Endpoint Effect

NOAEL

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Body weight 11% lower mean body weight in female 

rats treated for 2 years

1.95 3.85 NTP 1990

Body weight No effect in rats treated for 21 months 0.37 Chu et al. 1981c

Hepatic No effect in rats treated for 21 months 0.37 Chu et al. 1981c

Hepatic Focal and centrilobular necrosis; fatty 

metamorphosis; dilation of sinusoids in 

rats treated for 2 years

0.075 0.75 NTP 1990

Hepatic Megalocytosis in rats treated for 

18 months followed by 6 months of 

recovery

3.6 Ulland et al. 1977

Renal Increased severity of nephrotoxicity in rats 

treated for 2 years

0.75 1.95 NTP 1990
MIREX AND CHLORDECONE A-9

APPENDIX A

Table A-1. NOAELs and LOAELs Identified in Chronic-Duration Oral Studies of 

Mirex

Endpoint Effect

NOAEL

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Renal Increased incidence of epithelial 

hyperplasia of the renal pelvis in rats 

treated for 2 years

0.075 0.75 NTP 1990

LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level

Selection of the Principal Study: NTP (1990) was selected as the principal study for deriving a chronicduration oral MRL for mirex because it identified the lowest reliable LOAEL for liver effects, a clearly 

sensitive effect of mirex toxicity.

Summary of the Principal Study:

NTP. 1990. Toxicology and carcinogenesis studies of mirex (CAS No. 2385-85-5) in F344/N rats (feed 

studies). Research Triangle Park, NC: U.S. Department of Health and Human Services, Public Health 

Service, National Institutes of Health, National Toxicology Program. NTP TR 313.

Groups of male and female F344/N rats (52/sex/group; approximately 7–8 weeks of age) were 

administered mirex (95% purity) in the diet at 0, 0.1, 1.0, 10, 25, or 50 ppm for 104 weeks (first study). 

During the first 6 months of the study, additional groups of groups of female rats were started on 0, 50, or 

100 ppm mirex in the diet (second study), based on the lack of observable toxic effects in the initial 

groups of female rats. Based on body weight and food consumption data, the study authors estimated 

average mirex doses to 0.1, 1, 10, 25, and 50 ppm groups from the first study at 0.007, 0.07, 0.7, 1.8, and 

3.8 mg/kg/day, respectively, for the males and 0.007, 0.08, 0.7, 2.0, and 3.9 mg/kg/day, respectively, for 

the females (for the combined sexes, the author estimated doses at 0.007, 0.075, 0.75, 1.95, and 

3.85 mg/kg/day, respectively). Estimated doses to the 50 and 100 ppm groups of females from the second 

study were 3.9 and 7.7 mg/kg/day, respectively. Animals were monitored for survival, clinical signs, 

body weight, and food intake. All rats were subjected to gross pathologic examination and all major 

organs and tissues were processed for histopathologic examination.

Survival of 1.95 and 3.85 mg/kg/day male rats was significantly less than that of controls (19/52 and 

15/52, respectively, compared to 44/52 controls), most deaths occurred after treatment weeks 86–87. 

Survival was not affected in mirex-dosed females. By week 100, mean body weights of 1.95 and 

3.85 mg/kg/day surviving males were 11–18% less than that of controls and mean body weights of 

3.9 and 7.7 mg/kg/day females were 12–18% less than that of controls. The most notable compoundrelated histopathologic lesions were observed in the liver of male and female rats and included doserelated increased incidence of fatty metamorphosis, cytomegaly, angiectasis (males only), and necrosis. 

The NOAEL for liver effects was 0.075 mg/kg/day and the LOAEL was 0.75 mg/kg/day for focal and 

centrilobular necrosis, fatty metamorphosis, and dilation of sinusoids. Incidences of nephropathy 

occurred at similar frequency in controls and mirex-dosed groups; however, the severity was judged to be 

greater in the 1.95, 3.9, and 7.7 mg/kg/day groups. Hyperplasia of the renal pelvis epithelium occurred at 

significantly increased incidence in male rats of the 10, 25, and 50 ppm groups (5/52, 14/51, and 9/52, 

respectively, versus 0/51 among controls). Incidences of neoplastic nodules in the liver were significantly 

greater in 0.75, 1.95, and 3.85 mg/kg/day groups of males than controls (14/52, 15/52, and 26/52, 

respectively, versus 3/52 in control males). Incidences of neoplastic liver nodules in the female rats of the 

first study were not significantly different from that of controls. However, the incidence among control 
MIREX AND CHLORDECONE A-10

APPENDIX A

females (10/52 or 19%) was significantly greater than the historical control incidence (2.8%). In the 

second study that included 0, 3.9, and 7.7 mg/kg/day groups of female rats, incidences of neoplastic liver 

nodules (usually consisting of enlarged hepatocytes with eosinophilic or clear cytoplasm arranged in 

irregular distorted cords one or two cell layers thick, but some consisting of cells with basophilic 

cytoplasm) were 23/52 (44%), and 30/52 (58%), respectively, versus 2/52 (4%) within a concurrent 

control group. Incidences of transitional cell papillomas of the renal pelvis of male rats occurred with a 

positive trend (p<0.02). The incidence in the 3.85 mg/kg/day males was 3/52 (6%) compared to 

0/51 (0%) among controls and was noted to be higher than the highest incidence previously observed in 

controls (1/48 or 2%). Incidences of pheochromocytomas of the adrenal gland occurred with a positive 

trend and the incidences in 1.95 and 3.85 mg/kg/day male rats were significantly greater than that of 

controls. Incidences of mononuclear cell leukemia in analysis of all female rats in the first and second 

studies (combined) were significantly increased in the 0.75, 1.95, 3.9, and 7.7 mg/kg/day groups (14/52 or 

27%, 18/52 or 35%, 27/104 or 26%, and 14/52 or 27%) versus 14/104 (13%) among controls.

Selection of the Point of Departure: The treatment-related increased incidence of renal pelvis 

hyperplasia identified in the 2-year dietary study of rats (NTP 1990) was not considered an appropriate 

basis for deriving a chronic-duration oral MRL for mirex because the hyperplasia was observed in areas 

of the kidney that also exhibited tumors. Therefore, the hyperplasia may represent a preneoplastic lesion. 

However, the liver lesions (focal and centrilobular necrosis, fatty metamorphosis, dilation of sinusoids) 

identified in the same study (NTP 1990) are nonneoplastic effects that were selected as the critical effects 

for deriving a chronic-duration oral MRL. The NOAEL of 0.075 mg/kg/day for liver effects was selected 

as the point of departure for deriving a chronic-duration oral MRL for mirex.

Uncertainty Factor: The NOAEL of 0.075 mg/kg/day was divided by a total uncertainty factor of 100:

• 10 for animal to human extrapolation

• 10 for human variability

Modifying Factor: A modifying factor of 3 was applied to be protective of mirex-induced developmental 

toxicity (see Section 2.17), including arrhythmias in neonatal pups following maternal exposure during 

gestation at a dose level as low as 0.1 mg/kg/day in the absence of an identified NOAEL (Grabowski 

1983).

Other Additional Studies or Pertinent Information that Lend Support: Adverse hepatic effects were 

reported in a number of intermediate- or chronic-duration animal studies that employed oral exposure to 

mirex (Bell and Mehendale 1985; Chu et al. 1980c, 1981a, 1981b; Curtis and Hoyt 1984; Dai et al. 2001; 

Davison et al. 1976; Gaines and Kimbrough 1970; Larson et al. 1979a; Mehendale 1981; Ulland et al. 

1977).

Agency Contacts (Chemical Managers): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-11

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Chlordecone

CAS Numbers: 143-50-0

Date: October 2020

Profile Status: Final

Route: Inhalation

Duration: Acute

MRL Summary: There are insufficient data for derivation of an acute-duration inhalation MRL.

Rationale for Not Deriving an MRL: No acute-duration inhalation studies were identified for 

chlordecone.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-12

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Chlordecone

CAS Numbers: 143-50-0

Date: October 2020

Profile Status: Final

Route: Inhalation

Duration: Intermediate

MRL Summary: There are insufficient data for derivation of an intermediate-duration inhalation MRL.

Rationale for Not Deriving an MRL: No intermediate-duration inhalation studies were identified for 

chlordecone.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-13

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Chlordecone

CAS Numbers: 143-50-0

Date: October 2020

Profile Status: Final

Route: Inhalation

Duration: Chronic

MRL Summary: There are insufficient data for derivation of a chronic-duration inhalation MRL.

Rationale for Not Deriving an MRL: No chronic-duration inhalation studies were identified for 

chlordecone.

Agency Contact (Chemical Manager): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-14

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Chlordecone

CAS Numbers: 143-50-0

Date: October 2020

Profile Status: Final

Route: Oral

Duration: Acute

MRL 0.01 mg/kg/day

Critical Effect: Neurological effects

Reference: EPA 1986a

Point of Departure: NOAEL of 1.25 mg/kg/day

Uncertainty Factor: 100

LSE Graph Key: 12

Species: Rat

MRL Summary: An acute-duration oral MRL of 0.01 mg/kg/day was derived for chlordecone based on 

neurological effects (increased startle response) observed in young adult male Fischer 344 rats in a 10-day 

gavage study conducted by EPA (1986a). The MRL is based on a NOAEL of 1.25 mg/kg/day and a total 

uncertainty factor of 100 (10 for animal to human extrapolation and 10 for human variability).

Selection of the Critical Effect: Numerous studies have evaluated the toxicity of chlordecone following 

acute-duration oral exposure. Many studies reported treatment-related neurological effects or 

developmental effects. Other studies collectively identified the following targets: body weight, 

cardiovascular system, hematological system, musculoskeletal system, liver, renal system, endocrine 

system, immunological system, and female reproductive system.

Recent reports evaluated development of the reproductive system following gavage treatment of pregnant 

mice with chlordecone at 0.1 mg/kg/day during gestation days 6.5–15.5. Gely-Pernot et al. (2018) 

reported significantly decreased numbers of spermatozoa in adult F1 and F3 mice (note only the parental 

[F0] dams were administered chlordecone). Legoff et al. (2019) reported delayed vaginal opening and 

adverse ovarian follicular effects in F1 mice. Both studies only tested a single dose; thus, dose-response 

relationships cannot be evaluated. The lack of dose-response data along with weaknesses in the reporting 

of the study design and results preclude using either study as the basis of an MRL. Study weaknesses 

include the lack of examination for potential maternal toxicity, although the study authors stated that the 

selected dose level (0.1 mg/kg/day) “has no effect on murine health;” lack of information regarding 

numbers of pregnant mice/group, numbers of litters produced, numbers of litters contributing to the 

quantitative data reported; and use of only four progeny/group in some of the analyses.

A summary of the lowest reliable LOAELs for each endpoint is presented in Table A-2. A comparison of 

the LOAEL values across endpoints supports the identification of the nervous system as the most 

sensitive target of toxicity.
MIREX AND CHLORDECONE A-15

APPENDIX A

Table A-2. Lowest LOAELs Identified in Acute-Duration Oral Studies of 

Chlordecone

Endpoint Effect

NOAEL 

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Body weight 15% depressed maternal body 

weight gain in rats gavaged daily 

on gestation days 7–16

2 Chernoff and 

Rogers 1976

Hematological Decreased neutrophils in rats 

exposed for 10 days

5 10 Smialowicz et al. 

1985

Hepatic Increased serum alkaline 

phosphatase, ALT, gammaglutamyl transferase in rats 

gavaged daily for 10 days

5 10 EPA 1986a

Renal Increased blood urea nitrogen in 

rats gavaged daily for 10 days

5 10 EPA 1986a

Endocrine Depletion of epinephrine in adrenal 

medulla of rats treated for 8 days in 

diet

17 Baggett et al. 1980

Immunological Decreases in spleen and thymus 

weights, leukocyte counts, natural 

killer cell activity, Concanavalin A 

responsiveness in rats gavaged 

daily for 10 days

5 10 EPA 1986a

Neurological Increased startle response in young 

adult male rats gavaged daily for 

10 days

1.25 2.5 EPA 1986a

Reproductive Persistent estrus in rats gavaged 

once

35 Swanson and 

Woolley 1982

Induction of persistent vaginal 

estrus in mice repeatedly gavaged 

for 4 or 6 weeks

2 Swartz et al. 1988

Developmental 86% decreased postnatal day 3 

pup survival following daily gavage 

treatment of maternal rats during 

gestation days 7–16

10 EPA 1986a

ALT = alanine aminotransferase; LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverseeffect level

Selection of the Principal Study: The lowest reliable LOAEL values were identified for body weight,

neurological effects, and effects on the female reproductive system. Chernoff and Rogers (1976) reported 

decreases in maternal body weight gain in rat dams administered 2 mg/kg/day chlordecone on gestation 

days 7–16. Swartz et al. (1988) reported the induction of persistent vaginal estrus in sexually mature 

mice administered chlordecone by gavage at 2 mg/kg/day, 5 days/week for 2 weeks. EPA (1986a) 

reported increased startle response in young adult male rats administered 2.5 mg/kg/day chlordecone for 

10 days. These comparable LOAELs are at least 4 times lower than the LOAELs for hematological, 

hepatic, renal, immunological, and developmental effects. The EPA (1986a) study was selected as the 

principal study for deriving an acute-duration oral MRL for chlordecone because it identified a NOAEL 

(1.25 mg/kg/day).
MIREX AND CHLORDECONE A-16

APPENDIX A

Summary of the Principal Study:

EPA. 1986a. Final report on the evaluation of four toxic chemicals in an ‘in vivo/in vitro’ toxicological 

screen: Acrylamide, chlordecone, cyclophosphamide, and diethylstilbestrol. Research Triangle Park, 

NC: U.S. Environmental Protection Agency, Health Effects Research Laboratory. EPA600186002.

Groups of young adult male Fischer 344 rats (10/group) were administered chlordecone (in corn oil 

vehicle) by gavage for 10 days at 0, 0.625, 1.25, 2.5, 5.0, or 10.0 mg/kg/day. Animals were monitored for 

survival and body weight. Motor activity (performance in a figure 8 maze) and acoustic startle response 

were evaluated at 1 day following the final dose treatment. Urine was collected for urinalysis and blood 

was drawn for serum chemistry. At sacrifice, selected organ weights were determined. At 

≥2.5 mg/kg/day, the amplitude of the acoustic startle response was significantly increased. At the other 

two doses, the amplitude was increased with all decibel stimuli. Motor activity in a figure-8 maze was 

decreased at the highest dose tested. Terminal body weight was depressed by 12% at 10 mg/kg/day. 

Relative liver weight was significantly increased at 5 and 10 mg/kg/day (15–16% higher than controls). 

Selected serum chemistry parameters were statistically significantly different from controls only in the

high-dose group.

Selection of the Point of Departure: The NOAEL of 1.25 mg/kg/day was selected as the point of 

departure for deriving an acute-duration oral MRL for chlordecone.

Uncertainty Factor: The NOAEL of 1.25 mg/kg/day was divided by a total uncertainty factor of 100:

• 10 for animal to human extrapolation

• 10 for human variability

Other Additional Studies or Pertinent Information that Lend Support: As stated above, numerous 

animal studies reported neurological effects associated with acute-duration oral exposure to chlordecone 

(Albertson et al. 1985; Aldous et al. 1984; Baggett et al. 1980; Chang-Tsui and Ho 1979; Desaiah et al. 

1980a; Egle et al. 1979; End et al. 1981; Fujimori et al. 1982a; Hoskins and Ho 1982; Huang et al. 1980; 

Jordan et al. 1981; Klingensmith and Mehendale 1982a; Mactutus et al. 1984; Mishra et al. 1980; 

Smialowicz et al. 1985; Swanson and Wooley 1982; Tilson et al. 1985).

Agency Contacts (Chemical Managers): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-17

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Chlordecone

CAS Numbers: 143-50-0

Date: October 2020

Profile Status: Final

Route: Oral

Duration: Intermediate

MRL 0.003 mg/kg/day

Critical Effect: Neurological and male reproductive effects

Reference: Linder et al. 1983

Point of Departure: NOAEL of 0.26 mg/kg/day

Uncertainty Factor: 100

LSE Graph Key: 57

Species: Rat

MRL Summary: An MRL of 0.003 mg/kg/day has been derived for intermediate-duration oral exposure 

to chlordecone based on neurological and male reproductive effects from a 90-day oral study of male 

Sprague-Dawley rats (Linder et al. 1983). The NOAEL of 0.26 mg/kg/day was divided by a total 

uncertainty factor of 100 (10 for animal to human extrapolation and 10 for human variability).

Selection of the Critical Effect: Studies that evaluated chlordecone toxicity in humans did not include 

dose-response data; therefore, human data were not considered for MRL derivation. Treatment-related 

effects on the liver, nervous system, body weight, cardiovascular system, endocrine system, reproductive 

system, and development have been consistently associated with intermediate-duration oral exposure of 

laboratory animals to chlordecone. A summary of the lowest LOAELs for each endpoint is presented in 

Table A-3.

Table A-3. Lowest LOAELs Identified in Intermediate-Duration Oral Studies of 

Chlordecone

Endpoint Effect

NOAEL

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Body weight 13% decreased body weight gain in 

rats treated for 3 months in diet

1.17 Cannon and 

Kimbrough 1979

Hepatic Focal necrosis in rats treated for 

3 months in diet

1.17 Cannon and 

Kimbrough 1979

Endocrine Reversible hyperplasia of adrenal 

cortex in rats treated for 3 months in 

diet

1.17 Cannon and 

Kimbrough 1979

Neurological Hyperexcitability, mild tremors in rats 

treated for 90 days in diet

0.26 0.83 Linder et al. 1983

Reproductive 46–48% decreased sperm motility and 

viability; 19% decreased epididymal 

sperm concentration in rats treated for 

90 days in diet

0.26 0.83 Linder et al. 1983
MIREX AND CHLORDECONE A-18

APPENDIX A

Table A-3. Lowest LOAELs Identified in Intermediate-Duration Oral Studies of 

Chlordecone

Endpoint Effect

NOAEL

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Developmental Decreased postnatal survival in pups 

from parental mice treated for up to 

130 days in diet

1.9 7 Huber 1965

LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level

A comparison of the LOAEL values across endpoints supports the identification of the nervous system 

and male reproductive system as the most sensitive targets of toxicity. The identification of the 

neurotoxicity and reproductive toxicity as sensitive endpoints for chlordecone is supported by several 

other intermediate-duration studies, which are summarized in Tables A-4 and A-5, respectively. 

Table A-4. Selected LOAELs for Neurological Effects Identified in IntermediateDuration Oral Studies of Chlordecone

Species 

(strain) Effect

NOAEL

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Rat (SpragueDawley)Tremors in rats treated for 15 days in 

diet

4.7 Agarwal and 

Mehendale 1984a

Rat (Sherman) Tremors, hyperexcitability, 

exaggerated startle response in rats 

treated for 3 months in diet

1.17 M

1.62 F

Cannon and 

Kimbrough 1979

Rat (ZivacMiller)Tremors, decreased operant behavior 

in rats repeatedly gavaged for 90 days

1 Dietz and McMillan 

1979

Rat (Wistar) Tremors (dose-related earlier onset 

and increased severity) in rats treated 

for up to 6 months in diet

2.1 M

2.4 F

Larson et all 1979b

Rat (SpragueDawley)Hyperexcitability, mild tremors in rats 

treated for 90 days in diet

0.26 0.83 Linder et al. 1983

Rat (SpragueDawley)Tremors, hypersensitivity to noise and 

stress in rats treated for 16 days in diet

3.95 Mehendale et al. 

1978

Rat (Fischer 

344)

Increased startle response in rats 

repeatedly gavaged for 15 weeks

2.8 4.1 Pryor et al. 1983

Rat (Fischer 

344)

Exaggerated startle response in rats 

treated for 90 days in diet

1.0 Squibb and Tilson 

1982a

Mouse 

(BALB/c)

Tremor in mice treated for 2–

12 months in diet

1.9 5.6 Huber 1965

LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level
MIREX AND CHLORDECONE A-19

APPENDIX A

Table A-5. Lowest LOAELs for Reproductive Effects Identified in IntermediateDuration Oral Studies of Chlordecone

Species 

(strain) Effect

NOAEL

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Rat (Sherman) Decreased number of litters born to 

control males mated to females treated 

for 3 months in diet

1.62 Cannon and 

Kimbrough 1979

Rat (Wistar) Testicular atrophy in 4/5 males treated 

for 3 months in diet

2.1 Larson et al. 1979b

Rat (SpragueDawley)46–48% decreased sperm motility and 

viability; 19% decreased epididymal 

sperm concentration in rats treated for 

90 days in diet

0.26 0.83 Linder et al. 1983

Mouse 

(BALB/c)

36% decrease in second litters in mice 

treated for 5 months (including 1 month 

premating) in diet

0.94 Good et al. 1965

Mouse 

(BALB/c)

8% decrease in litter size and 19% 

increase in pair-days to litter among 

mice treated for 130 days (1 month 

premating) in diet

1.9 Huber 1965

Mouse (CD-1) Increased ovulation, persistent vaginal 

estrus in mice gavaged for 4 or 

6 weeks (5 days/week)

2 Swartz et al. 1988

LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level

Selection of the Principal Study: The study of Linder et al. (1983) identified the lowest LOAEL 

(0.83 mg/kg/day) for both tremors and impaired sperm parameters; the NOAEL was 0.26 mg/kg/day. 

This multiple dose study was selected as the principal study for derivation of an intermediate-duration 

oral MRL for chlordecone.

Summary of the Principal Study:

Linder RE, Scotti TM, McElroy WK, et al. 1983. Spermotoxicity and tissue accumulation of 

chlordecone (Kepone) in male rats. J Toxicol Environ Health 12:183-192.

Groups of 20 adult male Sprague-Dawley rats were administered technical grade chlordecone (purity not 

specified) in the diet at 0, 5, 15, or 30 ppm for 90 days. Rats were monitored for clinical signs, body 

weight, and food intake. The study authors estimated chlordecone doses to the 5, 15, and 30 ppm groups 

to have been 0.26, 0.83, and 1.67 mg/kg/day, respectively. After the 90-day treatment period, 

10 rats/group were sacrificed; testes, epididymides, prostate, and seminal vesicles were weighed; 

epididymal fluid was extracted for evaluation of spermatozoal motility and viability. Reproductive 

tissues were then processed for histologic examination. The other 10 rats/group were returned to normal 

diet and each bred to two untreated virgin females during a 14-day posttreatment period. Mated females 

were sacrificed on gestation day 20 and fetal weights, fetal viability, and total implants were determined. 

Male rats used for breeding were sacrificed at 4.5 months after cessation of treatment for evaluation of 

recovery from chlordecone treatment.
MIREX AND CHLORDECONE A-20

APPENDIX A

One 0.83 mg/kg/day rat died on treatment day 84; one rat each in the 0.26 and 1.67 mg/kg/day groups 

died during the recovery period (recovery days 64 and 30, respectively). Clinical signs of neurotoxicity,

including hyperexcitability and mild tremors, were observed in rats of the 0.83 and 1.67 mg/kg/day 

groups (incidences not included in the study report). The 1.67 mg/kg/day group sacrificed at 90 days 

exhibited approximately 7% lower mean final body weight than controls (not considered an adverse effect 

because the decrease was <10%). The 1.67 mg/kg/day group of rats exhibited significantly lower 

absolute weights of seminal vesicles and prostate (12 and 24%, respectively, less than controls). Sperm 

concentration (sperm count) and incidences and type of morphologically abnormal spermatozoa were 

similar between controls and all chlordecone-treated groups. However, within the 0.83 and 

1.67 mg/kg/day groups, decreases in sperm motility (48 and 39%, respectively, less than controls), sperm 

viability (46 and 33%, respectively, less than controls), and epididymal concentration (19% less than 

controls for both 0.83 and 1.67 mg/kg/day groups) were observed. There were no chlordecone treatmentrelated effects on reproductive performance (number of males siring litters, live litters, average litter size, 

average number of implants, percent resorptions, or fetal weight). At the end of the recovery period, 

sperm parameters and reproductive organ weights were similar to those of controls. The study identified 

a NOAEL of 0.26 mg/kg/day and a LOAEL of 0.83 mg/kg/day for clinical signs of neurotoxicity 

(tremors) and effects on sperm parameters. The LOAEL for effects on sperm parameters is not 

considered a serious LOAEL due to the lack of effects on reproductive performance.

Selection of the Point of Departure: The NOAEL of 0.26 mg/kg/day was selected as the point of 

departure for deriving an intermediate-duration oral MRL for chlordecone.

Benchmark dose (BMD) analysis of the neurological effects in the principal study (Linder et al. 1983) 

was precluded by lack of incidence data for the treatment-related tremors. BMD analysis was conducted 

on the datasets for sperm motility and sperm viability (Table A-6) to identify potential points of departure 

for deriving an intermediate-duration oral MRL for chlordecone.

Table A-6. Sperm Motility and Viability Data for Sprague-Dawley rats 

Administered Chlordecone in the Diet for 90 Days

Dose (mg/kg/day) 0 0.26 0.83 1.67

Number of rats 10 10 10 10

Percent motile sperma 37.0±3.9 33.2±3.8 19.2±4.4b 22.6±5.5b

Percent live sperma 46.0±4.7 36.2±3.3 25.0±3.3b 30.9±4.8b

aMean ± standard error of the mean (SEM). bSignificantly different from control (p<0.05).

Source: Linder et al. 1983

The data for sperm motility and for sperm viability were fit to all available continuous models in EPA’s 

Benchmark Dose Software (BMDS, version 3.1.2). The following procedure for fitting continuous data 

was used: the simplest model (linear) was first applied to the data while assuming constant variance; if 

the data were consistent with the assumption of constant variance (p≥0.1), then the fit of the linear model 

to the means was evaluated and the polynomial, power, and Hill models were fit to the data while 

assuming constant variance. Adequate model fit was judged by four criteria: goodness-of-fit p-value 

(p>0.1), visual inspection of the dose-response curve, scaled residual at the data point (except the control) 

closest to the predefined benchmark response (BMR), and BMDL that was not 10 times lower than the 

lowest non-zero dose. Among all models providing adequate fit to the data, the lowest BMDL (the lower 

limit of a one-sided 95% confidence interval [CI] on the BMD) was selected as a reasonably conservative 
MIREX AND CHLORDECONE A-21

APPENDIX A

point of departure when differences between the BMDLs estimated from these models are >3-fold; 

otherwise, the BMDL from the model with the lowest Akaike's information criterion (AIC) was chosen. 

For both datasets, a BMR of 1 standard deviation (SD) change from the control was used.

Table A-7 presents the results of the BMD modeling with constant variance of the sperm motility data. 

Although most models provided adequate statistical fit, visual inspection of the plotted data indicated a 

poor fit of the estimated mean values to the measured mean values for the two dose levels closest to the 

BMD and BMDL. 

Table A-7. Results of BMD Analysis (with Constant Variance) of Percent 

Motile Sperm in Rats Exposed to Chlordecone in the Diet for 90 Days 

(Linder et al. 1983)

Model

BMD1SDa

(mg/kg)

BMDL1SDa

(mg/kg)

Test 4 

p-Valueb AIC

Scaled residualsc

Dose near 

BMD

Control 

group

Exponential 2d 1.27 0.63 0.185 330.23 0.95 0.34

Exponential 3d 1.27 0.63 0.185 330.23 0.94 0.34

Exponential 4d 0.65 0.20 0.209 330.44 -0.90 -0.25

Exponential 5 NA 331.19 0.00 0.00

Hilld,e 0.564 329.19 0.00 0.01

Polynomial Degree 3d 1.55 0.93 0.124 331.03 0.80 0.61

Polynomial Degree 2d 1.55 0.93 0.124 331.03 0.80 0.61

Powerd 1.55 0.93 0.124 331.03 0.80 0.61

Linear 1.55 0.93 0.124 331.03 0.80 0.61

aBMD and BMDL values for models that do not provide adequate fit are not included in this table. bValues <0.1 fail to meet adequate fit. cScaled residuals at doses immediately below and above the BMD. dRestricted model.

eThe Hill model was not considered adequate since less than five dose groups were used.

AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the exposure dose associated with the 

selected benchmark response; BMDL = 95% lower confidence limit on the BMD (subscripts denote benchmark 

response: i.e., 1SD = exposure dose associated with a 10% relative deviation from control)

The results of BMD analysis of sperm viability are presented in Table A-8Error! Reference source not 

found.. For the sperm viability data, the Exponential Model 4 was the only model to provide adequate 

statistical fit to the mean data. However, visual inspection of the plotted data from Exponential Model 4 

indicated a poor fit of the estimated mean values to the measured mean values for sperm viability. 

Therefore, the BMDL estimated from this model was not considered suitable as the basis of the MRL. 
MIREX AND CHLORDECONE A-22

APPENDIX A

Table A-8. Results of BMD Analysis (with Constant Variance) of Percent Sperm 

Viability in Rats Exposed to Chlordecone in the Diet for 90 Days (Linder et al. 

1983)

Model

BMD1SDa

(mg/kg)

BMDL1SDa

(mg/kg)

Test 4 

p-Valueb AIC

Scaled residualsc

Dose near 

BMD

Control 

group

Exponential 2d 0.0331 326.91 1.25 1.11

Exponential 3d 0.0331 326.91 1.25 1.11

Exponential 4d 0.2064 323.68 0.33 -0.08

Exponential 5 0.32 0.10 NA 325.23 0.00 0.05

Hilld 0.2857 323.23 0.00 0.00

Polynomial Degree 3d 0.0218 327.73 1.04 1.36

Polynomial Degree 2d 0.0218 327.73 1.04 1.36

Powerd 0.0218 327.73 1.04 1.36

Linear 0.0218 327.73 1.04 1.36

aBMD and BMDL values for models that do not provide adequate fit are not included in this table. bValues <0.1 fail to meet adequate fit. cScaled residuals at doses immediately below and above the BMD. dRestricted model.

AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the exposure dose associated with the 

selected benchmark response; BMDL = 95% lower confidence limit on the BMD (subscripts denote benchmark 

response: i.e., 1SD = exposure dose associated with a 10% relative deviation from control)

A NOAEL/LOAEL approach to deriving an intermediate-duration oral MRL for chlordecone was applied 

because a BMD approach was precluded by lack of adequate modeling results. 

Uncertainty Factor: The NOAEL of 0.26 mg/kg/day was divided by a total uncertainty factor of 100:

• 10 for animal to human extrapolation

• 10 for human variability

Other Additional Studies or Pertinent Information that Lend Support: Squibb and Tilson (1982a) 

reported chlordecone-induced exaggerated startle response in male rats administered chlordecone in the 

diet for 90 days at 1.0 mg/kg/day). Cannon and Kimbrough (1979) reported tremors, hyperactivity, and 

exaggerated startle response among male and female rats receiving chlordecone from the diet for 

3 months at 1.17 and 1.62 mg/kg/day, respectively (lowest exposure level tested). Good et al. (1965) 

reported decreased numbers of second litters produced by mice at a chlordecone dose level as low as 

0.94 mg/kg/day. Cannon and Kimbrough (1979) reported decreased number of litters born to control 

males mated to chlordecone-treated females dosed at 1.62 mg/kg/day. Larson et al. (1979b) reported 

testicular atrophy in male rats administered chlordecone for 3 months at 2.1 mg/kg/day.

Agency Contacts (Chemical Managers): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE A-23

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Chlordecone

CAS Numbers: 143-50-0

Date: October 2020

Profile Status: Final

Route: Oral

Duration: Chronic

MRL 0.0009 mg/kg/day

Critical Effect: Renal effects

Reference: Larson et al. 1979b

Point of Departure: NOAEL of 0.089 mg/kg/day

Uncertainty Factor: 100

LSE Graph Key: 75

Species: Rat

MRL Summary: An MRL of 0.0009 mg/kg/day was derived for chronic-duration oral exposure to 

chlordecone based on renal effects in rats administered chlordecone in the diet for up to 2 years (Larson et 

al. 1979b). The NOAEL of 0.089 mg/kg/day was divided by a total uncertainty factor of 100 (10 for 

animal to human extrapolation and 10 for human variability).

Selection of the Critical Effect: Treatment-related effects on body weight, hematological system, liver, 

renal system, and nervous system, and dermal irritation have been associated with chronic-duration oral 

exposure of laboratory animals to chlordecone. A summary of the lowest LOAELs for each endpoint is 

presented in Table A-9. A comparison of the LOAEL values across endpoints supports the identification 

of the renal system as the most sensitive target of toxicity.

Table A-9. Lowest LOAELs Identified in Chronic-Duration Oral Studies of 

Chlordecone

Endpoint Effect

NOAEL

(mg/kg/day)

LOAEL 

(mg/kg/day) Reference

Body weight >10% depressed body weight in rats 

treated for 1 or 2 years in diet

0.89 2.2 Larson et al. 1979b

Hematological Anemia in male rats treated for 

80 weeks in diet

0.56 NCI 1976

Hepatic Fatty infiltration and degeneration in 

male rats treated for 80 weeks in diet

0.56 NCI 1976

Renal Proteinuria and increased severity of 

glomerulosclerosis in rats treated for 

up to 2 years in diet

0.089 0.45 Larson et al. 1979b

Dermal Dermatitis in rats treated for 80 weeks 

in diet

0.56 NCI 1976

Neurological Tremors in rats treated for 80 weeks in 

diet

0.56 NCI 1976

LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level
MIREX AND CHLORDECONE A-24

APPENDIX A

Results from several studies were considered in the selection of the critical effect for derivation of a 

chronic-duration oral MRL for chlordecone. Larson et al. (1979b) administered chlordecone in the diet to 

rats for up to 2 years and reported depressed body weight gain, decreased hematocrit levels, and tremors 

at 2.2 mg/kg/day; fatty changes in the liver at 0.89 mg/kg/day; and proteinuria and increased severity of 

glomerulosclerosis in the kidney at 0.45 mg/kg/day. In an 80-week study of rats administered 

chlordecone in the diet (NCI 1976), adverse dermal, hepatic, hematological, and neurological effects were 

observed at the lowest dose tested (0.56 and 1.4 mg/kg/day for males and females, respectively). 

Similarly-treated mice exhibited adverse hepatic and neurological effects at the lowest dose tested 

(3.4 and 3.5 mg/kg/day for males and females, respectively). Larson et al. (1979b) also treated dogs for 

up to 128 weeks at doses up to 1.2 mg/kg/day and observed no neurological effects. Chu et al. (1981c) 

reported histopathological thyroid lesions in male Sprague-Dawley rats treated with chlordecone in the 

diet for 21 months at 0.07 mg/kg/day. However, the study report indicated that 4/10 control rats exhibited 

thyroid lesions (mild degenerative and proliferative changes in follicular epithelium without alteration in 

colloid density) and that 4/6 chlordecone-treated rats exhibited mild histological changes that may have 

included decreased colloid density. Thus, it is not clear whether a significant difference existed between 

controls and chlordecone-treated rats regarding thyroid lesions. Therefore, the thyroid lesion data were 

not considered for MRL derivation.

Selection of the Principal Study: Larson et al. (1979b) was selected as the principal study for deriving a 

chronic-duration oral MRL for chlordecone because it identified a NOAEL (0.089 mg/kg/day) associated 

with the lowest LOAEL (0.45 mg/kg/day for renal effects). The kidney effect observed in rats treated for 

up to 2 years represents the lowest reliable LOAEL (0.45 mg/kg/day) among the candidate treatmentrelated adverse effects from chronic-duration oral exposure to chlordecone, and was therefore selected as 

the critical effect for deriving a chronic-duration oral MRL for chlordecone. 

Summary of the Principal Study:

Larson PS, Egle JL Jr, Hennigar CR, et al. 1979b. Acute, subchronic, and chronic toxicity of 

chlordecone. Toxicol Appl Pharmacol 48:29-41.

Groups of Wistar rats (40/sex/group) were administered chlordecone in the diet for up to 2 years at 0, 5, 

10, 25, 50, or 80 ppm. Other groups of male and female Wistar rats (40/sex/group) were administered 

chlordecone in the diet for up to 2 years at 0 or 1 ppm (estimated chlordecone doses of 0 and 

0.089 mg/kg/day, respectively) and similarly evaluated. Estimated chlordecone doses of 0, 0.089, 0.45, 

0.89, 2.2, 4.5, and 7.1 mg/kg/day were calculated for the 1, 5, 10, 25, 50, and 80 ppm dietary 

concentrations, respectively, using a time-weighted average (TWA) of reported body weights (0.254 kg) 

and a food consumption rate (0.0226 kg/day) calculated using EPA’s (1988) allometric equation. After 

1 year, five rats/sex/dose group were sacrificed. All rats in the 4.5 and 7.1 mg/kg/day groups died by 

week 25. Proteinuria was noted in all 0.45, 0.89, and 2.2 mg/kg/day groups at all intervals after 3 months 

except in males at 21 and 24 months when control levels were elevated, and in females at 24 months 

when the levels in only the 0.89 and 2.2 mg/kg/day were elevated. There was no indication of proteinuria 

in the 0.089 mg/kg/day of male or female rats. The severity of observed glomerulosclerosis was 

increased in both males and females at ≥0.45 mg/kg/day. Non-statistically significantly increased kidney 

weight relative to body weight was reported. The NOAEL for kidney effects was 0.089 mg/kg/day. At 

1- and 2-year sacrifice, NOAELs of 0.45 and 0.89 mg/kg/day and their respective LOAELs 

(0.89 mg/kg/day for fatty changes in the liver and 2.2 mg/kg/day for depressed hematocrit levels) were 

identified.

Selection of the Point of Departure for the MRL: The NOAEL of 0.089 mg/kg/day was selected as the 

point of departure for deriving a chronic-duration oral MRL for chlordecone. The proteinuria and 
MIREX AND CHLORDECONE A-25

APPENDIX A

glomerulosclerosis severity data were not amenable to BMD modeling because standard deviations were 

not reported.

Uncertainty Factor: The NOAEL of 0.089 mg/kg/day was divided by a total uncertainty factor of 100:

• 10 for animal to human extrapolation

• 10 for human variability

Other Additional Studies or Pertinent Information that Lend Support to this MRL: Although other 

available chronic-duration oral studies did not identify renal effects in chlordecone-treated animals, 

adverse dermal, hepatic, hematological, and/or neurological effects were observed at doses in the range of 

0.4–2.6 mg/kg/day.

Agency Contacts (Chemical Managers): Obaid Faroon, D.V.M., Ph.D.
MIREX AND CHLORDECONE B-1

APPENDIX B. LITERATURE SEARCH FRAMEWORK FOR MIREX AND 

CHLORDECONE

The objective of the toxicological profile is to evaluate the potential for human exposure and the potential 

health hazards associated with inhalation, oral, or dermal/ocular exposure to mirex and chlordecone.

B.1 LITERATURE SEARCH AND SCREEN 

A literature search and screen was conducted to identify studies examining health effects, toxicokinetics, 

mechanisms of action, susceptible populations, biomarkers, and chemical interactions data for mirex and 

chlordecone. ATSDR primarily focused on peer-reviewed articles without publication date or language 

restrictions. Non-peer-reviewed studies that were considered relevant to the assessment of the health 

effects of mirex and chlordecone have undergone peer review by at least three ATSDR-selected experts 

who have been screened for conflict of interest. The inclusion criteria used to identify relevant studies 

examining the health effects of mirex and chlordecone are presented in Table B-1.

Table B-1. Inclusion Criteria for the Literature Search and Screen

Health Effects

Species

Human

Laboratory mammals

Route of exposure

Inhalation

Oral

Dermal (or ocular)

Parenteral (these studies will be considered supporting data)

Health outcome

Death

Systemic effects

Body weight effects 

Respiratory effects

Cardiovascular effects

Gastrointestinal effects

Hematological effects

Musculoskeletal effects

Hepatic effects

Renal effects

Dermal effects

Ocular effects

Endocrine effects

Immunological effects

Neurological effects

Reproductive effects

Developmental effects

Other noncancer effects
MIREX AND CHLORDECONE B-2

APPENDIX B

Table B-1. Inclusion Criteria for the Literature Search and Screen

Cancer

Toxicokinetics

Absorption

Distribution

Metabolism

Excretion

PBPK models

Biomarkers

Biomarkers of exposure

Biomarkers of effect

Interactions with other chemicals

B.1.1 Literature Search

The current literature search was intended to update the draft toxicological profile for mirex and 

chlordecone released for public comment in May 2019. The following main databases were searched in 

October 2019:

• PubMed 

• National Library of Medicine’s TOXLINE

• Scientific and Technical Information Network’s TOXCENTER

The search strategy used the chemical names, Chemical Abstracts Service (CAS) numbers, 

synonyms, and Medical Subject Headings (MeSH) terms for mirex and chlordecone. The query 

strings used for the literature search are presented in Table B-2. 

The search was augmented by searching the Toxic Substances Control Act Test Submissions (TSCATS), 

NTP website, and National Institute of Health Research Portfolio Online Reporting Tools Expenditures 

and Results (NIH RePORTER) databases using the queries presented in Table B-3. Additional databases 

were searched in the creation of various tables and figures, such as the TRI Explorer, the Substance 

priority list (SPL) resource page, and other items as needed. Regulations applicable to mirex and 

chlordecone were identified by searching international and U.S. agency websites and documents.

Review articles were identified and used for the purpose of providing background information and 

identifying additional references. ATSDR also identified reports from the grey literature, which included 

unpublished research reports, technical reports from government agencies, conference proceedings and 

abstracts, and theses and dissertations. 

Table B-2. Database Query Strings 

Database

search date Query string

PubMed

10/2019 ("Mirex"[mh] OR 2385-85-5[rn] OR "Chlordecone"[mh] OR 143-50-0[rn] OR 

"1,1a,2,2,3,3a,4,5,5,5a,5b,6-Dodecachlorooctahydro-1,3,4-metheno-1Hcyclobuta(cd)pentalene"[tw] OR "1,2,3,4,5,5-Hexachloro-1,3-cyclopentadiene dimer"[tw] 
MIREX AND CHLORDECONE B-3

APPENDIX B

Table B-2. Database Query Strings 

Database

search date Query string

OR "1,3,4-Metheno-1H-cyclobuta(cd)pentalene, 1,1a,2,2,3,3a,4,5,5,5a,5b,6-

dodecachlorooctahydro-"[tw] OR "1,3,4-Metheno-1H-cyclobuta(cd)pentalene, 

dodecachlorooctahydro-"[tw] OR "1,3-Cyclopentadiene, 1,2,3,4,5,5-hexachloro-, dimer"[tw] 

OR "Bichlorendo"[tw] OR "CG-1283"[tw] OR "Cyclopentadiene, hexachloro-, dimer"[tw] OR 

"Dechlorane"[tw] OR "Dodecachlorooctahydro-1,3,4-metheno-1Hcyclobuta(cd)pentalene"[tw] OR "Dodecachloropentacyclo(3.2.2.0(sup 2,6),0(sup 

3,9),0(sup 5,10))decane"[tw] OR 

"Dodecachloropentacyclo(5.2.1.0(2,6).0(3,9).0(5,8))decane"[tw] OR 

"Dodecachloropentacyclo(5.2.1.02,6.03,9.05,8)decane"[tw] OR 

"Dodecachloropentacyclodecane"[tw] OR "Dodecaclor"[tw] OR "Ferriamicide"[tw] OR "Fire 

Ant Bait"[tw] OR "GC 1283"[tw] OR "Hexachlorocyclopentadiene dimer"[tw] OR "HRS 

1276"[tw] OR "HRS l276"[tw] OR "Mirex"[tw] OR "Paramex"[tw] OR "Pentacyclodecane, 

dodecachloro-"[tw] OR "Perchlordecone"[tw] OR "Perchlorodihomocubane"[tw] OR 

"Perchloropentacyclo(5.2.1.0(2,6).0(3,9).0(5,8))decane"[tw] OR 

"Perchloropentacyclo(5.2.1.0(sup 2,6).0(sup 3,9).0(sup 5,8))decane"[tw] OR 

"Perchloropentacyclo(5.3.0.0(2,6).0(3,9).0(4,8))decane"[tw] OR 

"Perchloropentacyclodecane"[tw] OR "1,1a,3,3a,4,5,5,5a,5b,6-Decachlorooctahydro-1,3,4-

metheno-2H-cyclobuta(cd)pentalen-2-one"[tw] OR "1,2,3,4,5,5,6,7,8,9,10,10-

Dodecachlorooctahydro-1,3,4-metheno-2-cyclobuta(c,d)pentalone"[tw] OR "1,3,4-

Metheno-2H-cyclobuta(cd)pentalen-2-one, 1,1a,3,3a,4,5,5,5a,5b,6-decachlorooctahydro-

"[tw] OR "2,3,3a,4,5,6,7,7a,8,8a-Decachloro-3a,4,7,7a-tetrahydro-4,7-methanoinden-1-

one"[tw] OR "Chlordecone"[tw] OR "Ciba 8514"[tw] OR "Clordecone"[tw] OR "Compound 

1189"[tw] OR "Decachloro-1,3,4-metheno-2H-cyclobuta(cd)pentalen-2-one"[tw] OR 

"Decachloroketone"[tw] OR "Decachlorooctahydro-1,3,4-methano-2Hcyclobuta(cd)pentalen-2-one"[tw] OR "Decachlorooctahydro-1,3,4-metheno-2Hcyclobuta(cd)pentalen-2-one"[tw] OR "Decachlorotetracyclodecanone"[tw] OR 

"Decachlorotetrahydro-4,7-methanoindeneone"[tw] OR "GC 1189"[tw] OR "General 

chemicals 1189"[tw] OR "Kepone"[tw] OR "Kepone-2-one, decachlorooctahydro-"[tw] OR 

"Merex"[tw] OR "1,2,3,5,6,7,8,9,10,10-Decachloro(5.2.1.0(sup 2,6).0(sup 3,9).0(sup 

5,8))decano-4-one"[tw] OR "Decachloropentacyclo(5.2.1.0(2,6).0(3,9).0(5),(8))decan-4-

one"[tw] OR "Decachloropentacyclo(5.2.1.0(sup 2,6).0(sup 3,9).0(sup 5,8))decan-4-

one"[tw] OR "Decachloropentacyclo(5.3.0.0(sup 2,6).0(sup 4,10).0(sup 5,9))decan-3-

one"[tw] OR "Perchloropentacyclo(5.3.0.0(2,6).0(3,9).0(4,8))decan-5-one"[tw]) AND 

(2017/04/01:3000[mhda] OR 2017/04/01:3000[crdt] OR 2017/04/01:3000[edat] OR 

2016/04/01:3000[dp]) 

("1,1a,2,2,3,3a,4,5,5,5a,5b,6-Dodecachloroactahydro-1,3,4-metheno-1Hcyclobuta[cd]pentalene"[tw] OR "Dodecachlor"[tw] OR "Dodecachlorooctahydro-1,3,4-

metheno-2H-cyclobuta(cd)pentalene"[tw] OR 

"Dodecachloropentacyclo[5.3.0.0(2.6).0(3.9).0(4.8)]decane"[tw] OR 

"Perchloropentacyclo[5.2.1.02,6.03,9.05,8]decane"[tw] OR 

"Perchloropentacyclo[5.3.0.02,6.03,9.04,8]decane"[tw] OR "1,1a,3,3a,4,5,5,5a,5b,6-

Decachloro-octahydro-1,3,4-metheno-2H-cyclobuta(cd)pentalen-2-one"[tw] OR 

"1,1a,3,3a,4,5,5a,5b,6-Decachlorooctahydro-1,3,4-metheno-2H-cyclobuta [cd]pentalen-2-

one"[tw] OR "1,3,4-Metheno-2H-cyclobuta[cd]pentalen-2-one, 1,1a,3,3a,4,5,5,5a,5b,6-

decachlorooctahydro-"[tw] OR "1,3,4-Metheno-2H-cyclobuta[cd]pentalen-2-one, 

1,1a,3,3a,4,5,5a,5b,6-decachlorooctahydro-"[tw] OR "1,3,4-Metheno-2Hcyclobuta[cd]pentalen-2-one, decachlorooctahydro-"[tw] OR "1,3,4-Metheno-2H-cyclobutal 

[cd]pentalen-2-one, 1,1a,3,3a,4,5,5,5a,5b,6-decachloro-octahydro-"[tw] OR "1,3,4-

Metheno-2H-cyclobutal[cd]pentalen-2-one, 1,1a,3,3a,4,5,5,5a,5b,6-decachloroctahydro-

"[tw] OR "Decachloroctalhydro-1,3,4-metheno-2H-cyclobuta(cd)pentalen-2-one"[tw] OR 
MIREX AND CHLORDECONE B-4

APPENDIX B

Table B-2. Database Query Strings 

Database

search date Query string

"Decachloropentacyclo[5.2.1.02,6.03,9.05,8]decan-4-one"[tw]) AND (1993:3000[dp] OR 

1993:3000[mhda] OR 1993:3000[edat] OR 1993:3000[crdat]))

Toxline

10/2019 "Mirex" OR 2385-85-5[rn] OR "Chlordecone" OR 143-50-0[rn]

Year of Publication 2016 through 2019

"1,1a,2,2,3,3a,4,5,5,5a,5b,6-Dodecachlorooctahydro-1,3,4-metheno-1Hcyclobuta(cd)pentalene" OR "1,2,3,4,5,5-Hexachloro-1,3-cyclopentadiene dimer" OR 

"1,3,4-Metheno-1H-cyclobuta(cd)pentalene, 1,1a,2,2,3,3a,4,5,5,5a,5b,6-

dodecachlorooctahydro-" OR "1,3,4-Metheno-1H-cyclobuta(cd)pentalene, 

dodecachlorooctahydro-" OR "1,3-Cyclopentadiene, 1,2,3,4,5,5-hexachloro-, dimer" OR 

"Bichlorendo" OR "CG-1283" OR "Cyclopentadiene, hexachloro-, dimer" OR "Dechlorane" 

OR "Dodecachlorooctahydro-1,3,4-metheno-1H-cyclobuta(cd)pentalene"

Year of Publication 2016 through 2019

"Dodecachloropentacyclo(3.2.2.0(sup 2,6),0(sup 3,9),0(sup 5,10))decane" OR 

"Dodecachloropentacyclo(5.2.1.0(2,6).0(3,9).0(5,8))decane" OR 

"Dodecachloropentacyclo(5.2.1.02,6.03,9.05,8)decane" OR 

"Dodecachloropentacyclodecane" OR "Dodecaclor" OR "Ferriamicide" OR "Fire Ant Bait" 

OR "GC 1283" OR "Hexachlorocyclopentadiene dimer" OR "HRS 1276" OR "HRS l276" 

OR "Mirex" OR "Paramex" OR "Pentacyclodecane, dodecachloro-"

Year of Publication 2016 through 2019

"Perchlordecone" OR "Perchlorodihomocubane" OR 

"Perchloropentacyclo(5.2.1.0(2,6).0(3,9).0(5,8))decane" OR 

"Perchloropentacyclo(5.2.1.0(sup 2,6).0(sup 3,9).0(sup 5,8))decane" OR 

"Perchloropentacyclo(5.3.0.0(2,6).0(3,9).0(4,8))decane" OR "Perchloropentacyclodecane" 

OR "1,1a,3,3a,4,5,5,5a,5b,6-Decachlorooctahydro-1,3,4-metheno-2Hcyclobuta(cd)pentalen-2-one" OR "1,2,3,4,5,5,6,7,8,9,10,10-Dodecachlorooctahydro-1,3,4-

metheno-2-cyclobuta(c,d)pentalone" OR "1,3,4-Metheno-2H-cyclobuta(cd)pentalen-2-one, 

1,1a,3,3a,4,5,5,5a,5b,6-decachlorooctahydro-"

Year of Publication 2016 through 2019

"2,3,3a,4,5,6,7,7a,8,8a-Decachloro-3a,4,7,7a-tetrahydro-4,7-methanoinden-1-one" OR 

"Chlordecone" OR "Ciba 8514" OR "Clordecone" OR "Compound 1189" OR "Decachloro1,3,4-metheno-2H-cyclobuta(cd)pentalen-2-one" OR "Decachloroketone" OR 

"Decachlorooctahydro-1,3,4-methano-2H-cyclobuta(cd)pentalen-2-one" OR 

"Decachlorooctahydro-1,3,4-metheno-2H-cyclobuta(cd)pentalen-2-one" OR 

"Decachlorotetracyclodecanone" OR "Decachlorotetrahydro-4,7-methanoindeneone" OR 

"GC 1189" OR "General chemicals 1189"

Year of Publication 2016 through 2019

"Kepone" OR "Kepone-2-one, decachlorooctahydro-" OR "Merex" OR 

"1,2,3,5,6,7,8,9,10,10-Decachloro(5.2.1.0(sup 2,6).0(sup 3,9).0(sup 5,8))decano-4-one" 

OR "Decachloropentacyclo(5.2.1.0(2,6).0(3,9).0(5),(8))decan-4-one" OR 

"Decachloropentacyclo(5.2.1.0(sup 2,6).0(sup 3,9).0(sup 5,8))decan-4-one" OR 

"Decachloropentacyclo(5.3.0.0(sup 2,6).0(sup 4,10).0(sup 5,9))decan-3-one" OR 

"Perchloropentacyclo(5.3.0.0(2,6).0(3,9).0(4,8))decan-5-one"

Year of Publication 2016 through 2019

"1,1a,2,2,3,3a,4,5,5,5a,5b,6-Dodecachloroactahydro-1,3,4-metheno-1Hcyclobuta(cd)pentalene" OR "Dodecachlor" OR "Dodecachlorooctahydro-1,3,4-metheno2H-cyclobuta(cd)pentalene" OR 

"Dodecachloropentacyclo(5.3.0.0(2.6).0(3.9).0(4.8))decane" OR 
MIREX AND CHLORDECONE B-5

APPENDIX B

Table B-2. Database Query Strings 

Database

search date Query string

"Perchloropentacyclo(5.2.1.02,6.03,9.05,8)decane" OR 

"Perchloropentacyclo(5.3.0.02,6.03,9.04,8)decane"

Year of Publication 1993 through 2019

"1,1a,3,3a,4,5,5,5a,5b,6-Decachloro-octahydro-1,3,4-metheno-2H-cyclobuta(cd)pentalen2-one" OR "1,1a,3,3a,4,5,5a,5b,6-Decachlorooctahydro-1,3,4-metheno-2H-cyclobuta 

(cd)pentalen-2-one" OR "1,3,4-Metheno-2H-cyclobuta(cd)pentalen-2-one, 

1,1a,3,3a,4,5,5,5a,5b,6-decachlorooctahydro-" OR "1,3,4-Metheno-2Hcyclobuta(cd)pentalen-2-one, 1,1a,3,3a,4,5,5a,5b,6-decachlorooctahydro-" OR "1,3,4-

Metheno-2H-cyclobuta(cd)pentalen-2-one, decachlorooctahydro-"

Year of Publication 1993 through 2019

"1,3,4-Metheno-2H-cyclobutal(cd)pentalen-2-one, 1,1a,3,3a,4,5,5,5a,5b,6-decachlorooctahydro-" OR "1,3,4-Metheno-2H-cyclobutal(cd)pentalen-2-one, 1,1a,3,3a,4,5,5,5a,5b,6-

decachloroctahydro-" OR "Decachloroctalhydro-1,3,4-metheno-2H-cyclobuta(cd)pentalen2-one" OR "Decachloropentacyclo(5.2.1.02,6.03,9.05,8)decan-4-one"

Year of Publication 1993 through 2019

Toxcenter

10/2019 FILE 'TOXCENTER' ENTERED AT 11:37:01 ON 08 OCT 2019

CHARGED TO COST=EH038.06.01.LB.02

L1 6689 SEA FILE=TOXCENTER 2385-85-5 OR 143-50-0 

L2 6678 SEA FILE=TOXCENTER L1 NOT TSCATS/FS 

L3 6545 SEA FILE=TOXCENTER L2 NOT PATENT/DT 

L4 206 SEA FILE=TOXCENTER L3 AND ED>=20170401 

L48 36 SEA FILE=TOXCENTER L4 AND MEDLINE/FS 

L49 170 SEA FILE=TOXCENTER L4 NOT MEDLINE/FS 

L50 179 DUP REM L48 L49 (27 DUPLICATES REMOVED)

 ANSWERS '1-179' FROM FILE TOXCENTER

L*** DEL 36 S L4 AND MEDLINE/FS

L*** DEL 36 S L4 AND MEDLINE/FS

L51 36 SEA FILE=TOXCENTER L50 

L*** DEL 170 S L4 NOT MEDLINE/FS

L*** DEL 170 S L4 NOT MEDLINE/FS

L52 143 SEA FILE=TOXCENTER L50 

L53 143 SEA FILE=TOXCENTER (L51 OR L52) NOT MEDLINE/FS 

 D SCAN L53
MIREX AND CHLORDECONE B-6

APPENDIX B

Table B-3. Strategies to Augment the Literature Search

Source Query and number screened when available

TSCATS via ChemView

10/2019 Compounds searched: 2385-85-5, 143-50-0

NTP

10/2019 "2385-85-5" "143-50-0" "Mirex" "Chlordecone"

"Dechlorane" "Dodecachloropentacyclodecane" "Dodecaclor" "Kepone"

"Fire Ant Bait" "Paramex" "Perchloropentacyclodecane" "Decachloroketone"

"Decachlorooctahydro-1,3,4-metheno-2H-cyclobuta(cd)pentalen-2-one" 

"Perchlordecone" "Clordecone" "Ferriamicide"

"Dodecachlor"

Regulations.gov

10/2019 Compounds searched: 2385-85-5, 143-50-0

Other Identified throughout the assessment process

The 2019 results were: 

• Number of records identified from PubMed, TOXLINE, and TOXCENTER (after duplicate 

removal): 331

• Number of records identified from other strategies: 10

• Total number of records to undergo literature screening: 431

B.1.2 Literature Screening 

A two-step process was used to screen the literature search to identify relevant studies on mirex and 

chlordecone: 

• Title and abstract screen

• Full text screen

Title and Abstract Screen. Within the reference library, titles and abstracts were screened manually for 

relevance. Studies that were considered relevant (see Table B-1 for inclusion criteria) were moved to the 

second step of the literature screening process. Studies were excluded when the title and abstract clearly 

indicated that the study was not relevant to the toxicological profile. 

• Number of titles and abstracts screened: 431

• Number of studies considered relevant and moved to the next step: 75

Full Text Screen. The second step in the literature screening process was a full text review of individual 

studies considered relevant in the title and abstract screen step. Each study was reviewed to determine 

whether it was relevant for inclusion in the toxicological profile. 

• Number of studies undergoing full text review: 75

• Number of studies cited in the pre-public draft of the toxicological profile: 602

• Total number of studies cited in the profile: 584

A summary of the results of the literature search and screening is presented in Figure B-1.
MIREX AND CHLORDECONE B-7

APPENDIX B

Figure B-1. October 2019 Literature Search Results and Screen for Mirex and 

Chlordecone
MIREX AND CHLORDECONE C-1

APPENDIX C. USER'S GUIDE

Chapter 1. Relevance to Public Health

This chapter provides an overview of U.S. exposures, a summary of health effects based on evaluations of 

existing toxicologic, epidemiologic, and toxicokinetic information, and an overview of the minimal risk 

levels. This is designed to present interpretive, weight-of-evidence discussions for human health 

endpoints by addressing the following questions:

1. What effects are known to occur in humans?

2. What effects observed in animals are likely to be of concern to humans?

3. What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites?

Minimal Risk Levels (MRLs)

Where sufficient toxicologic information is available, ATSDR derives MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans.

MRLs should help physicians and public health officials determine the safety of a community living near 

a hazardous substance emission, given the concentration of a contaminant in air or the estimated daily 

dose in water. MRLs are based largely on toxicological studies in animals and on reports of human 

occupational exposure.

MRL users should be familiar with the toxicologic information on which the number is based. 

Section 1.2, Summary of Health Effects, contains basic information known about the substance. Other 

sections, such as Section 3.2 Children and Other Populations that are Unusually Susceptible and 

Section 3.4 Interactions with Other Substances, provide important supplemental information.

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen endpoint are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

of 10 must be employed. Additional uncertainty factors of 10 must be used both for human variability to 

protect sensitive subpopulations (people who are most susceptible to the health effects caused by the 

substance) and for interspecies variability (extrapolation from animals to humans). In deriving an MRL, 

these individual uncertainty factors are multiplied together. The product is then divided into the 

inhalation concentration or oral dosage selected from the study. Uncertainty factors used in developing a 
MIREX AND CHLORDECONE C-2

APPENDIX C

substance-specific MRL are provided in the footnotes of the levels of significant exposure (LSE) tables

that are provided in Chapter 2. Detailed discussions of the MRLs are presented in Appendix A.

Chapter 2. Health Effects

Tables and Figures for Levels of Significant Exposure (LSE)

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species and MRLs to humans for noncancer 

endpoints. The LSE tables and figures can be used for a quick review of the health effects and to locate 

data for a specific exposure scenario. The LSE tables and figures should always be used in conjunction 

with the text. All entries in these tables and figures represent studies that provide reliable, quantitative 

estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs).

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE tables and figures follow. The numbers in the left column of the legends correspond to 

the numbers in the example table and figure.

TABLE LEGEND

See Sample LSE Table (page C-5)

(1) Route of exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. 

Typically, when sufficient data exist, three LSE tables and two LSE figures are presented in the 

document. The three LSE tables present data on the three principal routes of exposure

(i.e., inhalation, oral, and dermal). LSE figures are limited to the inhalation and oral routes. Not 

all substances will have data on each route of exposure and will not, therefore, have all five of the 

tables and figures. Profiles with more than one chemical may have more LSE tables and figures.

(2) Exposure period. Three exposure periods—acute (<15 days), intermediate (15–364 days), and 

chronic (≥365 days)—are presented within each relevant route of exposure. In this example, two 

oral studies of chronic-duration exposure are reported. For quick reference to health effects 

occurring from a known length of exposure, locate the applicable exposure period within the LSE 

table and figure.

(3) Figure key. Each key number in the LSE table links study information to one or more data points 

using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 51 identified NOAELs and less serious LOAELs (also see the three

"51R" data points in sample LSE Figure 2-X).

(4) Species (strain) No./group. The test species (and strain), whether animal or human, are identified 

in this column. The column also contains information on the number of subjects and sex per 

group. Chapter 1, Relevance to Public Health, covers the relevance of animal data to human 

toxicity and Section 3.1, Toxicokinetics, contains any available information on comparative 

toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are extrapolated 

to equivalent human doses to derive an MRL.

(5) Exposure parameters/doses. The duration of the study and exposure regimens are provided in 

these columns. This permits comparison of NOAELs and LOAELs from different studies. In 

this case (key number 51), rats were orally exposed to “Chemical X” via feed for 2 years. For a 
MIREX AND CHLORDECONE C-3

APPENDIX C

more complete review of the dosing regimen, refer to the appropriate sections of the text or the 

original reference paper (i.e., Aida et al. 1992).

(6) Parameters monitored. This column lists the parameters used to assess health effects. Parameters 

monitored could include serum (blood) chemistry (BC), behavioral (BH), biochemical changes 

(BI), body weight (BW), clinical signs (CS), developmental toxicity (DX), enzyme activity (EA), 

food intake (FI), fetal toxicity (FX), gross necropsy (GN), hematology (HE), histopathology 

(HP), lethality (LE), maternal toxicity (MX), organ function (OF), ophthalmology (OP), organ 

weight (OW), teratogenicity (TG), urinalysis (UR), and water intake (WI).

(7) Endpoint. This column lists the endpoint examined. The major categories of health endpoints 

included in LSE tables and figures are death, body weight, respiratory, cardiovascular, 

gastrointestinal, hematological, musculoskeletal, hepatic, renal, dermal, ocular, endocrine, 

immunological, neurological, reproductive, developmental, other noncancer, and cancer. "Other

noncancer" refers to any effect (e.g., alterations in blood glucose levels) not covered in these 

systems. In the example of key number 51, three endpoints (body weight, hematological, and 

hepatic) were investigated.

(8) NOAEL. A NOAEL is the highest exposure level at which no adverse effects were seen in the 

organ system studied. The body weight effect reported in key number 51 is a NOAEL at

25.5 mg/kg/day. NOAELs are not reported for cancer and death; with the exception of these two 

endpoints, this field is left blank if no NOAEL was identified in the study.

(9) LOAEL. A LOAEL is the lowest dose used in the study that caused an adverse health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help 

readers identify the levels of exposure at which adverse health effects first appear and the 

gradation of effects with increasing dose. A brief description of the specific endpoint used to 

quantify the adverse effect accompanies the LOAEL. Key number 51 reports a less serious 

LOAEL of 6.1 mg/kg/day for the hepatic system, which was used to derive a chronic exposure, 

oral MRL of 0.008 mg/kg/day (see footnote "c"). MRLs are not derived from serious LOAELs. 

A cancer effect level (CEL) is the lowest exposure level associated with the onset of 

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious 

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report 

doses not causing measurable cancer increases. If no LOAEL/CEL values were identified in the 

study, this field is left blank.

(10) Reference. The complete reference citation is provided in Chapter 8 of the profile.

(11) Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. For example, footnote "c" indicates that the LOAEL of 6.1 mg/kg/day in key 

number 51 was used to derive an oral MRL of 0.008 mg/kg/day.

FIGURE LEGEND

See Sample LSE Figure (page C-6)

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods.

(13) Exposure period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the chronic exposure period are illustrated.
MIREX AND CHLORDECONE C-4

APPENDIX C

(14) Endpoint. These are the categories of health effects for which reliable quantitative data exist. 

The same health effect endpoints appear in the LSE table.

(15) Levels of exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3 or ppm and oral exposure is reported in 

mg/kg/day.

(16) LOAEL. In this example, the half-shaded circle that is designated 51R identifies a LOAEL 

critical endpoint in the rat upon which a chronic oral exposure MRL is based. The key number 

51 corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 6.1 mg/kg/day (see entry 51 in the sample LSE table) to 

the MRL of 0.008 mg/kg/day (see footnote "c" in the sample LSE table).

(17) CEL. Key number 59R is one of studies for which CELs were derived. The diamond symbol 

refers to a CEL for the test species (rat). The number 59 corresponds to the entry in the LSE 

table.

(18) Key to LSE figure. The key provides the abbreviations and symbols used in the figure.
MIREX AND CHLORDECONE

C-5

APPENDIX C
MIREX AND CHLORDECONE

C-6

APPENDIX C
MIREX AND CHLORDECONE D-1

APPENDIX D. QUICK REFERENCE FOR HEALTH CARE PROVIDERS

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous 

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation 

of available toxicologic and epidemiologic information on a substance. Health care providers treating 

patients potentially exposed to hazardous substances may find the following information helpful for fast 

answers to often-asked questions.

Primary Chapters/Sections of Interest

Chapter 1: Relevance to Public Health: The Relevance to Public Health Section provides an overview 

of exposure and health effects and evaluates, interprets, and assesses the significance of toxicity 

data to human health. A table listing minimal risk levels (MRLs) is also included in this chapter.

Chapter 2: Health Effects: Specific health effects identified in both human and animal studies are 

reported by type of health effect (e.g., death, hepatic, renal, immune, reproductive), route of 

exposure (e.g., inhalation, oral, dermal), and length of exposure (e.g., acute, intermediate, and 

chronic). 

NOTE: Not all health effects reported in this section are necessarily observed in the clinical 

setting. 

Pediatrics: 

Section 3.2 Children and Other Populations that are Unusually Susceptible

Section 3.3 Biomarkers of Exposure and Effect

ATSDR Information Center 

Phone: 1-800-CDC-INFO (800-232-4636) or 1-888-232-6348 (TTY) 

Internet: http://www.atsdr.cdc.gov

The following additional materials are available online:

Case Studies in Environmental Medicine are self-instructional publications designed to increase primary 

health care providers’ knowledge of a hazardous substance in the environment and to aid in the 

evaluation of potentially exposed patients (see https://www.atsdr.cdc.gov/csem/csem.html). 

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene 

(prehospital) and hospital medical management of patients exposed during a hazardous materials 

incident (see https://www.atsdr.cdc.gov/MHMI/index.asp). Volumes I and II are planning guides 

to assist first responders and hospital emergency department personnel in planning for incidents 

that involve hazardous materials. Volume III—Medical Management Guidelines for Acute 

Chemical Exposures—is a guide for health care professionals treating patients exposed to 

hazardous materials.

Fact Sheets (ToxFAQsTM) provide answers to frequently asked questions about toxic substances (see 

https://www.atsdr.cdc.gov/toxfaqs/Index.asp).
MIREX AND CHLORDECONE D-2

APPENDIX D

Other Agencies and Organizations

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease, 

injury, and disability related to the interactions between people and their environment outside the 

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, GA 

30341-3724 • Phone: 770-488-7000 • FAX: 770-488-7015 • Web Page: 

https://www.cdc.gov/nceh/.

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational 

diseases and injuries, responds to requests for assistance by investigating problems of health and 

safety in the workplace, recommends standards to the Occupational Safety and Health 

Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains 

professionals in occupational safety and health. Contact: NIOSH, 395 E Street, S.W., Suite 9200, 

Patriots Plaza Building, Washington, DC 20201 • Phone: 202-245-0625 or 1-800-CDC-INFO 

(800-232-4636) • Web Page: https://www.cdc.gov/niosh/.

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for 

biomedical research on the effects of chemical, physical, and biologic environmental agents on 

human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive, 

Research Triangle Park, NC 27709 • Phone: 919-541-3212 • Web Page: 

https://www.niehs.nih.gov/.

Clinical Resources (Publicly Available Information)

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics 

in the United States to provide expertise in occupational and environmental issues. Contact: 

AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 

• FAX: 202-347-4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/.

The American College of Occupational and Environmental Medicine (ACOEM) is an association of 

physicians and other health care providers specializing in the field of occupational and 

environmental medicine. Contact: ACOEM, 25 Northwest Point Boulevard, Suite 700, Elk 

Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266 • Web Page: 

http://www.acoem.org/.

The American College of Medical Toxicology (ACMT) is a nonprofit association of physicians with 

recognized expertise in medical toxicology. Contact: ACMT, 10645 North Tatum Boulevard, 

Suite 200-111, Phoenix AZ 85028 • Phone: 844-226-8333 • FAX: 844-226-8333 • Web Page: 

http://www.acmt.net.

The Pediatric Environmental Health Specialty Units (PEHSUs) is an interconnected system of specialists 

who respond to questions from public health professionals, clinicians, policy makers, and the 

public about the impact of environmental factors on the health of children and reproductive-aged 

adults. Contact information for regional centers can be found at http://pehsu.net/findhelp.html.

The American Association of Poison Control Centers (AAPCC) provide support on the prevention and 

treatment of poison exposures. Contact: AAPCC, 515 King Street, Suite 510, Alexandria VA 

22314 • Phone: 701-894-1858 • Poison Help Line: 1-800-222-1222 • Web Page: 

http://www.aapcc.org/.
MIREX AND CHLORDECONE E-1

APPENDIX E. GLOSSARY

Absorption—The process by which a substance crosses biological membranes and enters systemic 

circulation. Absorption can also refer to the taking up of liquids by solids, or of gases by solids or liquids.

Acute Exposure—Exposure to a chemical for a duration of ≤14 days, as specified in the Toxicological 

Profiles.

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact.

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium.

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment.

Benchmark Dose (BMD) or Benchmark Concentration (BMC)—is the dose/concentration 

corresponding to a specific response level estimate using a statistical dose-response model applied to 

either experimental toxicology or epidemiology data. For example, a BMD10 would be the dose 

corresponding to a 10% benchmark response (BMR). The BMD is determined by modeling the doseresponse curve in the region of the dose-response relationship where biologically observable data are 

feasible. The BMDL or BMCL is the 95% lower confidence limit on the BMD or BMC. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period.

Biomarkers—Indicators signaling events in biologic systems or samples, typically classified as markers 

of exposure, effect, and susceptibility.

Cancer Effect Level (CEL)—The lowest dose of a chemical in a study, or group of studies, that 

produces significant increases in the incidence of cancer (or tumors) between the exposed population and 

its appropriate control.

Carcinogen—A chemical capable of inducing cancer.

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-control study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without the outcome.

Case Report—A report that describes a single individual with a particular disease or exposure. These 

reports may suggest some potential topics for scientific research, but are not actual research studies.

Case Series—Reports that describe the experience of a small number of individuals with the same 

disease or exposure. These reports may suggest potential topics for scientific research, but are not actual 

research studies.
MIREX AND CHLORDECONE E-2

APPENDIX E

Ceiling Value—A concentration that must not be exceeded. 

Chronic Exposure—Exposure to a chemical for ≥365 days, as specified in the Toxicological Profiles.

Clastogen—A substance that causes breaks in chromosomes resulting in addition, deletion, or 

rearrangement of parts of the chromosome.

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome, and who are disease-free at start of follow-up. Often, at 

least one exposed group is compared to one unexposed group, while in other cohorts, exposure is a 

continuous variable and analyses are directed towards analyzing an exposure-response coefficient.

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at a specific point in time.

Data Needs—Substance-specific informational needs that, if met, would reduce the uncertainties of 

human health risk assessment.

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism.

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the response or amount of the response.

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

effect occurs. Effects include malformations and variations, altered growth, and in utero death.

Epidemiology—The investigation of factors that determine the frequency and distribution of disease or 

other health-related conditions within a defined human population during a specified period. 

Excretion—The process by which metabolic waste products are removed from the body. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome.

Half-life—A measure of rate for the time required to eliminate one-half of a quantity of a chemical from 

the body or environmental media.

Health Advisory—An estimate of acceptable drinking water levels for a chemical substance derived by 

EPA and based on health effects information. A health advisory is not a legally enforceable federal 

standard, but serves as technical guidance to assist federal, state, and local officials.

Immediately Dangerous to Life or Health (IDLH)—A condition that poses a threat of life or health, or 

conditions that pose an immediate threat of severe exposure to contaminants that are likely to have 

adverse cumulative or delayed effects on health.
MIREX AND CHLORDECONE E-3

APPENDIX E

Immunotoxicity—Adverse effect on the functioning of the immune system that may result from 

exposure to chemical substances. 

Incidence—The ratio of new cases of individuals in a population who develop a specified condition to 

the total number of individuals in that population who could have developed that condition in a specified 

time period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles.

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube.

In Vivo—Occurring within the living organism.

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been reported 

to have caused death in humans or animals.

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population.

Lethal Dose(LO) (LDLo)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals.

Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a 

defined experimental animal population.

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical 

is expected to cause death in 50% of a defined experimental animal population.

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control.

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus.

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function.

Metabolism—Process in which chemical substances are biotransformed in the body that could result in 

less toxic and/or readily excreted compounds or produce a biologically active intermediate.

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure.

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk 

Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1.
MIREX AND CHLORDECONE E-4

APPENDIX E

Morbidity—The state of being diseased; the morbidity rate is the incidence or prevalence of a disease in 

a specific population.

Mortality—Death; the mortality rate is a measure of the number of deaths in a population during a 

specified interval of time.

Mutagen—A substance that causes mutations, which are changes in the DNA sequence of a cell’s DNA. 

Mutations can lead to birth defects, miscarriages, or cancer.

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions.

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

hazardous substance.

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Although effects may be produced at this dose, they 

are not considered to be adverse.

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution.

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An odds ratio that is greater than 1 is considered to indicate greater risk of 

disease in the exposed group compared to the unexposed group.

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

regulatory limit on the amount or concentration of a substance not to be exceeded in workplace air 

averaged over any 8-hour work shift of a 40-hour workweek.

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests (insects or other organisms harmful to cultivated plants or animals).

Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate 

(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides 

the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body.

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body.

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic 

endpoints. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 
MIREX AND CHLORDECONE E-5

APPENDIX E

Physiologically Based Pharmacokinetic (PBPK) Model—A type of physiologically based doseresponse model that is comprised of a series of compartments representing organs or tissue groups with 

realistic weights and blood flows. These models require a variety of physiological information, including 

tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates, and possibly 

membrane permeabilities. The models also utilize biochemical information, such as blood:air partition 

coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry 

models.

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which a group is followed over time and the pertinent 

observations are made on events occurring after the start of the study. 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentration for up to a 10-hour workday during a 40-hour 

workweek.

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation RfC is expressed in units of mg/m3 or ppm.

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily oral exposure of the human population to a potential hazard that is likely to be without risk of 

deleterious noncancer health effects during a lifetime. The oral RfD is expressed in units of mg/kg/day. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). RQs are 

(1) ≥1 pound or (2) for selected substances, an amount established by regulation either under CERCLA or 

under Section 311 of the Clean Water Act. Quantities are measured over a 24-hour period.

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a hazardous substance. The toxicity may be directed to the reproductive organs and/or 

the related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual 

behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the 

integrity of this system.

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort.

Risk—The possibility or chance that some adverse effect will result from a given exposure to a hazardous 

substance.

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, existing health 

condition, or an inborn or inherited characteristic that is associated with an increased occurrence of 

disease or other health-related event or condition.
MIREX AND CHLORDECONE E-6

APPENDIX E

Risk Ratio/Relative Risk—The ratio of the risk among persons with specific risk factors compared to the 

risk among persons without risk factors. A risk ratio that is greater than 1 indicates greater risk of disease 

in the exposed group compared to the unexposed group.

Short-Term Exposure Limit (STEL)—A STEL is a 15-minute TWA exposure that should not be 

exceeded at any time during a workday. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population.

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical.

Teratogen—A chemical that causes structural defects that affect the development of an organism.

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which it is believed that nearly all workers may be repeatedly 

exposed, day after day, for a working lifetime without adverse effect. The TLV may be expressed as a 

Time-Weighted Average (TLV-TWA), as a Short-Term Exposure Limit (TLV-STEL), or as a ceiling 

limit (TLV-C).

Time-Weighted Average (TWA)—An average exposure within a given time period. 

Toxicokinetic—The absorption, distribution, metabolism, and elimination of toxic compounds in the 

living organism.

Toxics Release Inventory (TRI)—The TRI is an EPA program that tracks toxic chemical releases and 

pollution prevention activities reported by industrial and federal facilities. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL),

Reference Dose (RfD), or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis (3 being the approximate logarithmic 

average of 10 and 1).

Xenobiotic—Any substance that is foreign to the biological system.
MIREX AND CHLORDECONE F-1

APPENDIX F. ACRONYMS, ABBREVIATIONS, AND SYMBOLS

AAPCC American Association of Poison Control Centers

ACGIH American Conference of Governmental Industrial Hygienists

ACOEM American College of Occupational and Environmental Medicine

ACMT American College of Medical Toxicology

ADI acceptable daily intake

ADME absorption, distribution, metabolism, and excretion

AEGL Acute Exposure Guideline Level

AIC Akaike’s information criterion 

AIHA American Industrial Hygiene Association 

ALT alanine aminotransferase

AOEC Association of Occupational and Environmental Clinics

AP alkaline phosphatase

AST aspartate aminotransferase

atm atmosphere

ATSDR Agency for Toxic Substances and Disease Registry

AWQC Ambient Water Quality Criteria

BCF bioconcentration factor

BMD/C benchmark dose or benchmark concentration

BMDX dose that produces a X% change in response rate of an adverse effect

BMDLX 95% lower confidence limit on the BMDX

BMDS Benchmark Dose Software 

BMR benchmark response

BUN blood urea nitrogen 

C centigrade

CAA Clean Air Act

CAS Chemical Abstract Services

CDC Centers for Disease Control and Prevention

CEL cancer effect level

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act

CFR Code of Federal Regulations

Ci curie

CI confidence interval

cm centimeter

CPSC Consumer Products Safety Commission

CWA Clean Water Act

DNA deoxyribonucleic acid

DOD Department of Defense

DOE Department of Energy

DWEL drinking water exposure level

EAFUS Everything Added to Food in the United States

ECG/EKG electrocardiogram

EEG electroencephalogram

EPA Environmental Protection Agency

ERPG emergency response planning guidelines 

F Fahrenheit

F1 first-filial generation

FDA Food and Drug Administration

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FR Federal Register
MIREX AND CHLORDECONE F-2

APPENDIX F

FSH follicle stimulating hormone

g gram

GC gas chromatography

gd gestational day

GGT γ-glutamyl transferase 

GRAS generally recognized as safe

HEC human equivalent concentration 

HED human equivalent dose 

HHS Department of Health and Human Services 

HPLC high-performance liquid chromatography

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer

IDLH immediately dangerous to life and health

IRIS Integrated Risk Information System 

Kd adsorption ratio

kg kilogram

kkg kilokilogram; 1 kilokilogram is equivalent to 1,000 kilograms and 1 metric ton

Koc organic carbon partition coefficient

Kow octanol-water partition coefficient

L liter

LC liquid chromatography

LC50 lethal concentration, 50% kill

LCLo lethal concentration, low

LD50 lethal dose, 50% kill

LDLo lethal dose, low

LDH lactic dehydrogenase

LH luteinizing hormone

LOAEL lowest-observed-adverse-effect level

LSE Level of Significant Exposure

LT50 lethal time, 50% kill

m meter

mCi millicurie

MCL maximum contaminant level

MCLG maximum contaminant level goal

MF modifying factor

mg milligram

mL milliliter

mm millimeter

mmHg millimeters of mercury

mmol millimole

MRL Minimal Risk Level

MS mass spectrometry

MSHA Mine Safety and Health Administration

Mt metric ton

NAAQS National Ambient Air Quality Standard

NAS National Academy of Science

NCEH National Center for Environmental Health

ND not detected

ng nanogram

NHANES National Health and Nutrition Examination Survey

NIEHS National Institute of Environmental Health Sciences
MIREX AND CHLORDECONE F-3

APPENDIX F

NIOSH National Institute for Occupational Safety and Health

NLM National Library of Medicine

nm nanometer

nmol nanomole

NOAEL no-observed-adverse-effect level

NPL National Priorities List

NR not reported

NRC National Research Council

NS not specified

NTP National Toxicology Program

OR odds ratio

OSHA Occupational Safety and Health Administration

PAC Protective Action Criteria

PAH polycyclic aromatic hydrocarbon

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PEHSU Pediatric Environmental Health Specialty Unit

PEL permissible exposure limit

PEL-C permissible exposure limit-ceiling value

pg picogram

PND postnatal day

POD point of departure

ppb parts per billion

ppbv parts per billion by volume

ppm parts per million

ppt parts per trillion

REL recommended exposure level/limit

REL-C recommended exposure level-ceiling value

RfC reference concentration

RfD reference dose

RNA ribonucleic acid

SARA Superfund Amendments and Reauthorization Act

SCE sister chromatid exchange

SD standard deviation

SE standard error

SGOT serum glutamic oxaloacetic transaminase (same as aspartate aminotransferase or AST)

SGPT serum glutamic pyruvic transaminase (same as alanine aminotransferase or ALT)

SIC standard industrial classification

SMR standardized mortality ratio

sRBC sheep red blood cell

STEL short term exposure limit

TLV threshold limit value

TLV-C threshold limit value-ceiling value

TRI Toxics Release Inventory

TSCA Toxic Substances Control Act

TWA time-weighted average

UF uncertainty factor

U.S. United States

USDA United States Department of Agriculture

USGS United States Geological Survey

USNRC U.S. Nuclear Regulatory Commission
MIREX AND CHLORDECONE

F-4

APPENDIX F

VOC volatile organic compound

WBC white blood cell

WHO World Health Organization > greater than ≥ greater than or equal to = equal to < less than ≤ less than or equal to % percent α alpha β beta γ gamma δ delta

μm micrometer

μg microgram q1* cancer slope factor – negative + positive

(+) weakly positive result (–) weakly negative result