TOXICOLOGICAL PROFILE FOR
 

PENTACHLOROPHENOL
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 2001 
PENTACHLOROPHENOL ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
PENTACHLOROPHENOL iii 

UPDATE STATEMENT
 

Toxicological profiles are revised and republished as necessary, but no less than once every three years. 

For information regarding the update status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch
 

1600 Clifton Road NE, E-29
 

Atlanta, Georgia 30333
 


PENTACHLOROPHENOL vi 

*Legislative Background 

The toxicological profiles are developed in response to the Superfund Amendments and 

Reauthorization Act (SARA) of 1986 (Public law 99-499) which amended the Comprehensive 

Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). This 

public law directed ATSDR to prepared toxicological profiles for hazardous substances most commonly 

found at facilities on the CERCLA National Priorities List and that pose the most significant potential 

threat to human health, as determined by ATSDR and the EPA. The availability of the revised priority 

list of 275 hazardous substances was announced in the Federal Register on November 17, 1997 (62 FR 

61332). For prior versions of the list of substances, see Federal Register notices dated April 29, 1996 (61 

FR 18744); April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 

43619); October 17, 1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 

48801); and February 28, 1994 (59 FR 9486). Section 104(i)(3) of CERCLA, as amended, directs the 

Administrator of ATSDR to prepare a toxicological profile for each substance on the list. 
 

 

PENTACHLOROPHENOL vii 

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 will find the following information helpful for fast 

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating 

patients about possible exposure to a hazardous substance. It explains a substance’s relevant 

toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of 

the general health effects observed following exposure. 

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, and 

assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type of 

health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length of 

exposure (acute, intermediate, and chronic). In addition, both human and animal studies are 

reported in this section. 

NOTE: Not all health effects reported in this section are necessarily observed in 

the clinical setting. Please refer to the Public Health Statement to identify 

general health effects observed following exposure. 

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health 

issues: 

Section 1.6 How Can (Chemical X) Affect Children? 

Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? 

Section 3.7 Children’s Susceptibility 

Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-888-42-ATSDR or 404-498-0110 Fax: 404-498-0057 

E-mail: atsdric@cdc.gov Internet: http://www.atsdr.cdc.gov 

The following additional material can be ordered through the ATSDR Information Center: 

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an 

exposure history and how to conduct one are described, and an example of a thorough exposure 

history is provided. Other case studies of interest include Reproductive and Developmental 

Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide 

Toxicity; and numerous chemical-specific case studies. 
PENTACHLOROPHENOL viii 

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. 

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 (ToxFAQs) provide answers to frequently asked questions about toxic substances. 

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. 

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, 200 Independence Avenue, 

SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch, 

Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998 

• Phone: 800-35-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. 

Referrals 

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, 55 West Seegers Road, Arlington Heights, IL 

60005 • Phone: 847-818-1800 • FAX: 847-818-9266. 
PENTACHLOROPHENOL ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHORS(S):
 

Lori L. Miller, M.P.H.
 

ATSDR, Division of Toxicology, Atlanta, GA
 

Lisa D. Ingerman, Ph.D.
 

Mona Singh, Ph.D.
 

Syracuse Research Corporation, North Syracuse, NY
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS:
 

1.	 Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and classifying 

end points. 

2.	 Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific minimal risk levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3.	 Data Needs Review. The Research Implementation Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

PENTACHLOROPHENOL xi 

PEER REVIEW
 

A peer review panel was assembled for pentachlorophenol. The panel consisted of the following 

members: 

1. Dr. Donald Morgan, Professor Emeritus in Preventive Medicine, University of Iowa Medical 

School, 1650 Koehler Drive NW, #247, Cedar Rapids, IA 52405; 

2. Dr. Norman Rawlings, Professor of Veterinary Physiological Sciences, Department of Veterinary 

Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4 

Canada; 

3. Dr. Thomas Thompson, Manager of Environmental Sciences, Saskatchewan Health Provincial 

Laboratory, 3211 Albert Street, Regina, SK S4S 5W6 Canada; 

4.	 Dr. Loren Koller, Professor, College of Veterinary Medicine, Oregon State University, 105 

Magruder Hall, Corvallis, OR 97331-4802; 

5.	 Dr. Philip Leber, Goodyear Tire & Rubber Company, 1485 East Archwood Avenue, Akron, OH 

44306; 

6.	 Dr. John Lech, Professor, Pharmacology and Toxicology, Medical College of Wisconsin, 8701 

Watertown Park Road, Milwaukee, WI 53226; and 

7.	 Dr. Frederick Oehme, Professor, Comparative Toxicology Laboratories, 1800 Denison Avenue, 

Kansas State University, Manhattan, KS 66506-5606. 

These experts collectively have knowledge of pentachlorophenol's physical and chemical properties, 

toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer 

reviewers' comments and determined which comments will be included in the profile. A listing of the 

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their 

exclusion, exists as part of the administrative record for this compound. A list of databases reviewed and 

a list of unpublished documents cited are also included in the administrative record. 

The citation of the peer review panel should not be understood to imply its approval of the profile's final 

content. The responsibility for the content of this profile lies with the ATSDR. 

PENTACHLOROPHENOL xiii 

CONTENTS
 

FOREWORD ...................................................................... v 
 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS ................................. vii 
 

CONTRIBUTORS ................................................................... ix 
 

PEER REVIEW ..................................................................... xi 
 

LIST OF FIGURES ................................................................ xvii 
 

LIST OF TABLES .................................................................. xix 
 

1. PUBLIC HEALTH STATEMENT .................................................... 1 
 

1.1 	 WHAT IS PENTACHLOROPHENOL? ..................................... 1 
 

1.2	 WHAT HAPPENS TO PENTACHLOROPHENOL WHEN IT ENTERS THE
 

ENVIRONMENT? ..................................................... 2 
 

1.3 	 HOW MIGHT I BE EXPOSED TO PENTACHLOROPHENOL? ................. 3 
 

1.4	 HOW CAN PENTACHLOROPHENOL ENTER AND LEAVE MY BODY? ....... 4 
 

1.5	 HOW CAN PENTACHLOROPHENOL AFFECT MY HEALTH? ................ 4 
 

1.6	 HOW CAN PENTACHLOROPHENOL AFFECT CHILDREN? ................. 6 
 

1.7	 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO
 

PENTACHLOROPHENOL? .............................................. 7 
 

1.8	 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN
 

EXPOSED TO PENTACHLOROPHENOL? ................................. 9 
 

1.9	 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO
 

PROTECT HUMAN HEALTH? ........................................... 9 
 

1.10 	 WHERE CAN I GET MORE INFORMATION? ............................. 11 
 

2. RELEVANCE TO PUBLIC HEALTH ............................................... 13 
 

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO
 

PENTACHLOROPHENOL IN THE UNITED STATES ....................... 13 
 

2.2	 SUMMARY OF HEALTH EFFECTS ..................................... 14 
 

2.3 	 MINIMAL RISK LEVELS .............................................. 17 
 

3. HEALTH EFFECTS .............................................................. 21 
 

3.1	 INTRODUCTION ..................................................... 21 
 

3.2	 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ............ 21 
 

3.2.1	 Inhalation Exposure ............................................. 23 
 

3.2.1.1 Death .................................................. 23 
 

3.2.1.2 Systemic Effects ......................................... 24 
 

3.2.1.3 Immunological and Lymphoreticular Effects ................... 26 
 

3.2.1.4 Neurological Effects ...................................... 27 
 

3.2.1.5 Reproductive Effects ...................................... 28 
 

3.2.1.6 Developmental Effects ..................................... 29 
 

3.2.1.7 Cancer ................................................. 29 
 

3.2.2	 Oral Exposure .................................................. 31 
 
 

 

PENTACHLOROPHENOL xiv 

3.2.2.1 Death .................................................. 31 
 

3.2.2.2 Systemic Effects ......................................... 32 
 

3.2.2.3 Immunological and Lymphoreticular Effects ................... 57 
 

3.2.2.4 Neurological Effects ...................................... 60 
 

3.2.2.5 Reproductive Effects ...................................... 62 
 

3.2.2.6 Developmental Effects ..................................... 63 
 

3.2.2.7 Cancer ................................................. 65 
 

3.2.3	 Dermal Exposure ............................................... 68 
 

3.2.3.1 Death .................................................. 68 
 

3.2.3.2 Systemic Effects ......................................... 70 
 

3.2.3.3 Immunological and Lymphoreticular Effects ................... 73 
 

3.2.3.4 Neurological Effects ...................................... 73 
 

3.2.3.5 Reproductive Effects ...................................... 73 
 

3.2.3.6 Developmental Effects ..................................... 74 
 

3.2.3.7 Cancer ................................................. 74 
 

3.2.4	 Other Routes of Exposure ......................................... 74 
 

3.3	 GENOTOXIC EFFECTS ................................................ 75 
 

3.4 	 TOXICOKINETICS ................................................... 80 
 

3.4.1 	 Absorption .................................................... 81 
 

3.4.1.1 Inhalation Exposure ....................................... 81 
 

3.4.1.2 Oral Exposure ........................................... 82 
 

3.4.1.3 Dermal Exposure ......................................... 83 
 

3.4.2 	 Distribution .................................................... 84 
 

3.4.2.1 Inhalation Exposure ....................................... 85 
 

3.4.2.2 Oral Exposure ........................................... 86 
 

3.4.2.3 Dermal Exposure ......................................... 87 
 

3.4.2.4 Other Routes of Exposure .................................. 88 
 

3.4.3 	 Metabolism .................................................... 89 
 

3.4.3.1 Inhalation Exposure ....................................... 91 
 

3.4.3.2 Oral Exposure ........................................... 91 
 

3.4.3.3 Dermal Exposure ......................................... 93 
 

3.4.3.4 Other Routes of Exposure .................................. 93 
 

3.4.4 	 Elimination and Excretion ........................................ 94 
 

3.4.4.1 Inhalation Exposure ....................................... 94 
 

3.4.4.2 Oral Exposure ........................................... 96 
 

3.4.4.3 Dermal Exposure ......................................... 98 
 

3.4.4.4 Other Routes of Exposure .................................. 99 
 

3.4.5	 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) 

Models ...................................................... 100 
 

3.5	 MECHANISMS OF ACTION ........................................... 101 
 

3.5.1 	 Pharmacokinetic Mechanisms ..................................... 101 
 

3.5.2 	 Mechanisms of Toxicity ......................................... 103 
 

3.5.3 	 Animal-to-Human Extrapolations .................................. 106 
 

3.6 	 ENDOCRINE DISRUPTION ........................................... 106 
 

3.7	 CHILDREN’S SUSCEPTIBILITY ....................................... 108 
 

3.8	 BIOMARKERS OF EXPOSURE AND EFFECT ............................ 111 
 

3.8.1	 Biomarkers Used to Identify or Quantify Exposure to Pentachlorophenol . . 112
 

3.8.2	 Biomarkers Used to Characterize Effects Caused by Pentachlorophenol .... 114 
 

3.9 	 INTERACTIONS WITH OTHER CHEMICALS ............................ 115 
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ................. 116 
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS ........................... 118 
 
 

PENTACHLOROPHENOL xv 

3.11.1 Reducing Peak Absorption Following Exposure ...................... 118 
 

3.11.2 Reducing Body Burden .......................................... 119 
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects ............. 119 
 

3.12 ADEQUACY OF THE DATABASE ..................................... 119 
 

3.12.1 Existing Information on Health Effects of Pentachlorophenol ............ 120 
 

3.12.2 Identification of Data Needs ...................................... 122 
 

3.12.3 Ongoing Studies ............................................... 135 
 

4. CHEMICAL AND PHYSICAL INFORMATION ...................................... 137 
 

4.1 CHEMICAL IDENTITY ............................................... 137 
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES ............................. 137 
 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL ............................ 141 
 

5.1 PRODUCTION ...................................................... 141 
 

5.2 IMPORT/EXPORT ................................................... 141 
 

5.3 USE ............................................................... 141 
 

5.4 DISPOSAL ......................................................... 143 
 

6. POTENTIAL FOR HUMAN EXPOSURE ........................................... 145 
 

6.1 OVERVIEW ........................................................ 145 
 

6.2 RELEASES TO THE ENVIRONMENT ................................... 147 
 

6.2.1 Air .......................................................... 147 
 

6.2.2 Water ........................................................ 151 
 

6.2.3 Soil ......................................................... 151 
 

6.3 ENVIRONMENTAL FATE ............................................ 152 
 

6.3.1 Transport and Partitioning ....................................... 153 
 

6.3.2 Transformation and Degradation .................................. 156 
 

6.3.2.1 Air ................................................... 156 
 

6.3.2.2 Water ................................................. 157 
 

6.3.2.3 Sediment and Soil ....................................... 159 
 

6.3.2.4 Other Media ............................................ 161 
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT .......... 162 
 

6.4.1 Air .......................................................... 162 
 

6.4.2 Water ........................................................ 162 
 

6.4.3 Sediment and Soil .............................................. 163 
 

6.4.4 Other Environmental Media ...................................... 164 
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ............. 165 
 

6.6 EXPOSURES OF CHILDREN .......................................... 172 
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ................ 176 
 

6.8 ADEQUACY OF THE DATABASE ..................................... 176 
 

6.8.1 Identification of Data Needs ...................................... 177 
 

6.8.2 Ongoing Studies ............................................... 182 
 

7. ANALYTICAL METHODS ....................................................... 185 
 

7.1 BIOLOGICAL MATERIALS ........................................... 185 
 

7.2 ENVIRONMENTAL SAMPLES ........................................ 187 
 

7.3 ADEQUACY OF THE DATABASE ..................................... 193 
 

7.3.1 Identification of Data Needs ...................................... 198 
 

7.3.2 Ongoing Studies ............................................... 199 
 

8. REGULATIONS AND ADVISORIES .............................................. 201 
 
PENTACHLOROPHENOL xvi 

9. REFERENCES ................................................................. 213 
 

10. GLOSSARY .................................................................. 263 
 

APPENDICES
 

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS ....................... A-1 
 

B. USER’S GUIDE ......................................................... B-1 
 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS ........................... C-1 
 

D. INDEX ................................................................ D-1 
 
PENTACHLOROPHENOL xvii 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Pentachlorophenol - Oral ............................. 47 
 

3-2. Proposed Metabolic Scheme for Pentachlorophenol .................................... 90 
 

3-3. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance ................................................ 102 
 

3-4. Existing Information on Health Effects of Pentachlorophenol ........................... 121 
 

6-1. Frequency of NPL Sites with Pentachlorophenol Contamination ......................... 146 
 

PENTACHLOROPHENOL xix 

LIST OF TABLES 

3-1. Levels of Significant Exposure to Pentachlorophenol - Oral ............................. 33 
 

3-2. Results of Analyses of Impurities Present in the Pentachlorophenol Used in National Toxicology
 

Program (NTP) Feeding Studies and the Types of Tumors They Induce .................... 51 
 

3-3. Genotoxicity of Pentachlorophenol In Vivo .......................................... 76 
 

3-4. Genotoxicity of Pentachlorophenol and its Metabolites In Vitro .......................... 77 
 

4-1. Chemical Identity of Pentachlorophenol and Pentachlorophenate ........................ 138 
 

4-2. Physical and Chemical Properties of Pentachlorophenol and Sodium Pentachlorophenate ..... 139 
 

5-1. Facilities that Produce, Process, or Use Pentachlorophenol ............................. 142 
 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use 

Pentachlorophenol ............................................................ 149 
 

7-1. Analytical Methods for Determining Pentachlorophenol and Metabolites in Biological 

Samples ..................................................................... 188 
 

7-2. Analytical Methods for Determining Pentachlorophenol and Metabolites in Environmental 

Samples ..................................................................... 194 
 

8-1. Regulations and Guidelines Applicable to Pentachlorophenol ........................... 203 
 

PENTACHLOROPHENOL 1 

1. PUBLIC HEALTH STATEMENT
 

This public health statement tells you about pentachlorophenol and the effects of exposure. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in 

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for 

long-term federal cleanup activities. Pentachlorophenol has been found in at least 313 of the 

1,585 current or former NPL sites. However, the total number of NPL sites evaluated for this 

substance is not known. As more sites are evaluated, the sites at which pentachlorophenol is 

found may increase. This information is important because exposure to this substance may harm 

you and because these sites may be sources of exposure. 

When a substance is released from a large area, such as an industrial plant, or from a container, 

such as a drum or bottle, it enters the environment. This release does not always lead to 

exposure. You are exposed to a substance only when you come in contact with it. You may be 

exposed by breathing, eating, or drinking the substance, or by skin contact. 

If you are exposed to pentachlorophenol, many factors determine whether you’ll be harmed. 

These factors include the dose (how much), the duration (how long), and how you come in 

contact with it. You must also consider the other chemicals you’re exposed to and your age, sex, 

diet, family traits, lifestyle, and state of health. 

1.1 WHAT IS PENTACHLOROPHENOL? 

Pentachlorophenol is a synthetic substance, made from other chemicals, and does not occur 

naturally in the environment. It is made by only one company in the United States. At one time, 

it was one of the most widely used biocides in the United States. Since 1984, the purchase and 

use of pentachlorophenol has been restricted to certified applicators. It is no longer available to 

the general public. Application of pentachlorophenol in the home as an herbicide and pesticide 

accounted for only 3% of its consumption in the 1970s. Before use restrictions, 
PENTACHLOROPHENOL 2 

1. PUBLIC HEALTH STATEMENT 

pentachlorophenol was widely used as a wood preservative. It is now used industrially as a 

wood preservative for power line poles, cross arms, fence posts, and the like. 

Pure pentachlorophenol exists as colorless crystals. It has a very sharp characteristic phenolic 

smell when hot but very little odor at room temperature. Most people can begin to smell 

pentachlorophenol in water at less than 12 parts pentachlorophenol per million parts of water 

(ppm). Impure pentachlorophenol (the form usually found at hazardous waste sites) is dark gray 

to brown and exists as dust, beads, or flakes. Pentachlorophenol can be found in two forms: 

pentachlorophenol itself or as the sodium salt of pentachlorophenol. The sodium salt dissolves 

easily in water, but pentachlorophenol does not. These two forms have some different physical 

properties, but are expected to have similar toxic effects. 

Humans are generally exposed to technical-grade pentachlorophenol, which usually contains 

such toxic impurities as polychlorinated dibenzo-p-dioxins and dibenzofurans. Table 3-2 lists 

the impurities found in three different grades of pentachlorophenol. 

For more information on the physical and chemical properties of pentachlorophenol, see 

Chapter 4. For more information on its production, use, and disposal, see Chapter 5. 

1.2	 WHAT HAPPENS TO PENTACHLOROPHENOL WHEN IT ENTERS THE 

ENVIRONMENT? 

Pentachlorophenol is released to the air by evaporation from treated wood surfaces and factory 

(chemical manufacturing plants and wood preservation plants) waste disposal. It enters surface 

water and groundwater from factories, wood-treatment facilities, and hazardous waste sites. It 

also enters the soil as a result of spills, disposal at hazardous waste sites, and its use as a 

pesticide. The physical and chemical properties of the compound suggest that not much will 

evaporate into the atmosphere and that most of it will move with water and generally stick to soil 

particles. Movement of pentachlorophenol in soils depends on the soil's acidity. The compound 

can be present in fish or other species used for food, as demonstrated by the ongoing food 

monitoring program of the Food and Drug Administration (FDA). In air, soil, and surface water, 
PENTACHLOROPHENOL 3 

1. PUBLIC HEALTH STATEMENT 

pentachlorophenol lasts for hours to days. The compound is broken down in soil and surface 

water by microorganisms, and in air and surface water by sunlight, to other compounds, some of 

which may be harmful to humans. 

More information on the releases, occurrence, and movement of pentachlorophenol in the 

environment can be found in Chapters 5 and 6. 

1.3 HOW MIGHT I BE EXPOSED TO PENTACHLOROPHENOL? 

In addition to workplace exposures, humans can be exposed to very low levels of pentachlorophenol through indoor and outdoor air, food, soil, and drinking water. Exposure may also result 

from dermal contact with wood treated with preservatives that contain pentachlorophenol. 

Levels in the workplace, near certain hazardous waste sites, and near sites of accidental spills are 

usually higher than in the general environment. 

Exposure to pentachlorophenol by eating contaminated food is limited. The average intake in 

food is estimated to be 0.0105 milligrams of pentachlorophenol for a 70 kg human. Daily intake 

by drinking contaminated water is also low and is estimated to be about 0.021 mg for a 70 kg 

human. In its survey of various population groups in 1986–1991, the ongoing food monitoring 

program of the FDA observed a substantial decrease in the daily intakes of pentachlorophenol. 

We do not have much information on the levels of pentachlorophenol in indoor and outdoor air, 

but the general population is estimated to breathe in about 0.063 mg/day. People who work or 

live near pentachlorophenol sources are exposed to higher levels. A 1984 report cites the 

measured concentration of pentachlorophenol in the indoor air of pressure-treated log homes 

brushed with pentachlorophenol in the range of 0.5–10 parts per trillion (ppt, 1 ppt is 

1 million times less than 1 ppm) and in the air of industrially dipped, nonpressure-treated log 

homes at 34–104 ppt. Levels of pentachlorophenol in the air at wood-treatment facilities and 

lumber mills are much higher, and workers exposed at these places are estimated to breathe in 

10.5–154.0 mg/day. Workers who handle treated lumber can take in about 35.0 mg/day through 

the skin. 
PENTACHLOROPHENOL 4 

1. PUBLIC HEALTH STATEMENT 

For more information on exposure to pentachlorophenol, see Chapter 6. 

1.4 HOW CAN PENTACHLOROPHENOL ENTER AND LEAVE MY BODY? 

Pentachlorophenol easily enters your body through your lungs when you breathe it, through your 

digestive tract after you eat contaminated food or water, or through your skin. The most 

significant ways are through breathing and skin contact. After a short exposure period, 

pentachlorophenol quickly leaves your body (studies in humans show that half the amount taken 

in is usually gone within 33 hours). It does not seem to build up in the body very much. Most of 

the pentachlorophenol taken into your body does not break down, but instead leaves in your 

urine. Much smaller amounts leave in your feces. Only a small amount escapes through your 

exhaled air. Some of the pentachlorophenol taken into your body is joined with other natural 

chemicals that make the pentachlorophenol less harmful. The combined product can then leave 

your body more easily. 

Chapter 3 contains more information on how pentachlorophenol enters and leaves your body. 

1.5 HOW CAN PENTACHLOROPHENOL AFFECT MY HEALTH? 

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people 

who have been harmed, scientists use many tests. 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and 

released by the body; for some chemicals, animal testing may be necessary. Animal testing may 

also be used to identify health effects such as cancer or birth defects. Without laboratory 

animals, scientists would lose a basic method to get information needed to make wise decisions 

to protect public health. Scientists have the responsibility to treat research animals with care and 

compassion. Laws today protect the welfare of research animals, and scientists must comply 

with strict animal care guidelines. 
PENTACHLOROPHENOL 5 

1. PUBLIC HEALTH STATEMENT 

Some, but not all, of the harmful effects associated with exposure to pentachlorophenol are due 

to impurities present in commercial pentachlorophenol. Short exposures to large amounts of 

pentachlorophenol in the workplace or through the misuse of products that contain it can cause 

harmful effects on the liver, kidneys, blood, lungs, nervous system, immune system, and 

gastrointestinal tract. Contact with pentachlorophenol (particularly in the form of a hot vapor) 

can irritate the skin, eyes, and mouth. If large enough amounts enter the body, heat is produced 

by the cells in the body, causing an increase in body temperature. The body temperature can 

increase to dangerous levels, causing injury to various organs and tissues and even death. This 

effect is the result of exposure to pentachlorophenol itself and not the impurities. The lengths of 

exposure and the levels that cause harmful effects have not been well defined. Long-term 

exposure to low levels such as those that occur in the workplace can cause damage to the liver, 

kidneys, blood, and nervous system. Studies in animals also suggest that the endocrine system 

and immune system can also be damaged following long-term exposure to low levels of 

pentachlorophenol. All of these effects get worse as the level of exposure increases. 

Decreases in the number of newborn animals, harmful effects on reproductive organs of the 

mothers, decreases in the number of successful pregnancies, and increases in the length of 

pregnancy were observed in animals exposed to pentachlorophenol while they were pregnant. 

Harmful effects on reproductive organs of the females were also seen in animals exposed to 

pentachlorophenol while they were not pregnant. We do not know if pentachlorophenol 

produces all of the same effects in humans that it causes in animals. 

An increased risk of cancer has been shown in some laboratory animals given large amounts of 

pentachlorophenol orally for a long time. There is weak evidence that pentachlorophenol causes 

cancer in humans. The International Agency for Research on Cancer (IARC) has determined 

that pentachlorophenol is possibly carcinogenic to humans, and the EPA has classified 

pentachlorophenol as a probable human carcinogen. 

Chapters 2 and 3 contain more information on the health effects linked with exposure to pentachlorophenol. 
PENTACHLOROPHENOL 6 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN PENTACHLOROPHENOL AFFECT CHILDREN? 

This section discusses potential health effects from exposures during the period from conception 

to maturity at 18 years of age in humans. 

Children might be exposed to pentachlorophenol by eating fish and other foods contaminated 

with the substance, by accidentally or intentionally eating soil or drinking water contaminated 

with the substance, or by drinking breast milk contaminated with the substance. Tests have not 

been performed to measure pentachlorophenol in breast milk in the United States, although small 

amounts have been found in the milk of chemical workers in Eastern Europe. Children might 

also be exposed to pentachlorophenol by breathing air in homes that contain wood that has been 

treated with the substance or by skin contact with contaminated soils or with the exposed surface 

of wood that has been treated with the substance. For most people, food is the most important 

source of intake of pentachlorophenol, and most of this intake is from root vegetables. Based on 

analyses of foods representative of the diets of different age/gender population groups, daily 

intakes of pentachlorophenol from the diet, although low overall, are higher in infants and 

toddlers than in teenagers and adults. Daily intakes of pentachlorophenol from food have 

decreased over time. 

Newborn children who were accidentally exposed to diapers and bedding that were contaminated 

with pentachlorophenol had high fevers, a large amount of sweating, a hard time with breathing, 

and harmful effects on their nervous system and liver, and some died. In the newborn animals of 

mothers that were given pentachlorophenol by mouth, slight changes were seen in the formation 

of bones and their weight was decreased at weaning. One study in animals showed that large 

amounts of pentachlorophenol taken by mouth can damage the testes, but it is unknown whether 

such large amounts affect the ability of animals to have babies. The immune system was 

suppressed in family members, including children as young as 8 years old, who were exposed to 

pentachlorophenol while living in log homes. Absorption of pentachlorophenol is expected by 

all routes of exposure, and the harmful effects of pentachlorophenol should be qualitatively 

similar over all routes of exposure; these effects might also occur in children exposed to low 

levels of pentachlorophenol by any route. There is not enough information to know whether 
PENTACHLOROPHENOL 7 

1. PUBLIC HEALTH STATEMENT 

children under 18 years of age differ from adults in their sensitivity to the health effects of 

pentachlorophenol. One study in animals found that small amounts of pentachlorophenol may 

cross the placenta, and it is possible that it can reach and cross the placenta in humans. 

1.7	 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO 

PENTACHLOROPHENOL? 

If your doctor finds that you have been exposed to significant amounts of pentachlorophenol, ask 

whether your children might also be exposed. Your doctor might need to ask your state health 

department to investigate. 

Pentachlorophenol was a widely used pesticide and a wood preservative (utility poles) for a long 

time. It is no longer present in any product you can buy today. It can be applied only by 

certified applicators. Although it is no longer commonly used, traces of pentachlorophenol are 

still found in small amounts in air, water, and soil. It is also found at some hazardous waste 

sites. 

Up until 1980, you could buy pentachlorophenol-containing pesticides. Since then, it has been 

regulated and can only be used in a restricted number of places. You may have old containers of 

pesticides in your attic, basement, or garage that contain pentachlorophenol. Removing these old 

containers will reduce your family’s risk of exposure to pentachlorophenol. You should dispose 

of these old containers in an appropriate manner through your county’s hazardous waste facility. 

Otherwise, place them out of reach of young children to prevent accidental exposures. You 

should never store pesticides or household chemicals in containers that children would find 

attractive to eat or drink from, such as soda bottles. 

Your children may be exposed to pentachlorophenol if an unqualified person applies pesticides 

containing it around your home. In some cases, the improper use of pesticides banned for use in 

homes has turned homes into hazardous waste sites. Make sure that any person you hire is 

licensed and, if appropriate, certified to apply pesticides. Your state licenses each person who is 

qualified to apply pesticides according to EPA standards and further certifies each person who is 
PENTACHLOROPHENOL 8 

1. PUBLIC HEALTH STATEMENT 

qualified to apply “restricted use” pesticides. Ask to see the license and certification. Also ask 

for the brand name of the pesticide, a Material Safety Data Sheet (MSDS), the name of the 

product’s active ingredient, and the EPA registration number. Ask whether EPA has designated 

the pesticide “for restricted use” and what the approved uses are. This information is important 

if you or your family react to the product. 

Though pentachlorophenol has been found in some foods, its levels are low. You can minimize 

the risk of your family’s exposure by peeling and thoroughly washing fruits and vegetables 

before cooking. 

Small children have a tendency to eat soil, and to put their hands and foreign objects in their 

mouths. This could result in their exposure to pentachlorophenol that may be present in the soil 

and on objects. Children may be exposed to pentachlorophenol by absorption through the skin. 

Pentachlorophenol is known to be rapidly absorbed by the skin from the soil. You should 

prevent children from putting their hands and foreign objects in their mouths and you should 

discourage your children from eating dirt. Make sure they wash their hands frequently. Very 

low levels of pentachlorophenol have been detected in house and carpet dust. Keeping the house 

clean and free of dust will reduce your family’s exposure to pentachlorophenol. 

Pentachlorophenol was used for treating wood. It is no longer used for treating wood used in 

and around homes. But it is still used for treating wood utility poles and railroad ties. If you live 

near a utility pole or railroad tracks, you should prevent your children from playing, climbing, or 

sitting on them especially in the hot summer months. Old playground equipment may contain 

pentachlorophenol, and children may be exposed dermally when playing on it. If you have old 

treated wood in or around your house, covering it with epoxy paint may reduce the risk of your 

family’s exposure to pentachlorophenol. Wood treated with pentachlorophenol (e.g., railway 

ties) should not be used for landscaping, especially near gardens or private wells 
PENTACHLOROPHENOL 9 

1. PUBLIC HEALTH STATEMENT 

1.8	 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO PENTACHLOROPHENOL? 

Pentachlorophenol and its products can be measured in the blood, urine, and tissues of exposed 

persons. Because urine and blood samples are easily collected, testing these fluids is the best 

way to find out whether a person has been exposed. Neither test is usually available at a doctor's 

office because both require the use of special equipment. Although these tests can prove that a 

person has been exposed, they cannot be used to tell how severe any health effects might be. 

Because pentachlorophenol leaves the body fairly quickly, these tests are best for finding 

exposures that occurred within the last several days. Exposure at hazardous waste sites usually 

includes exposure to other organic compounds, such as hexachlorobenzene, that could break 

down into pentachlorophenol. On the other hand, measurement of blood and urine levels for 

pentachlorophenol and its products in groups of exposed people and nonexposed people is a 

good way to tell whether exposure to pentachlorophenol or members of the same chemical 

family occurred. 

Chapter 7 contains more information on tests for measuring pentachlorophenol in the body. 

1.9	 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. 

Regulations can be enforced by law. Federal agencies that develop regulations for toxic 

substances include the Environmental Protection Agency (EPA), the Occupational Safety and 

Health Administration (OSHA), and the Food and Drug Administration (FDA). 

Recommendations provide valuable guidelines to protect public health but cannot be enforced by 

law. Federal organizations that develop recommendations for toxic substances include the 

Agency for Toxic Substances and Disease Registry (ATSDR) and the National Institute for 

Occupational Safety and Health (NIOSH). 
PENTACHLOROPHENOL 10 

1. PUBLIC HEALTH STATEMENT 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or 

food that are usually based on levels that affect animals; then they are adjusted to help protect 

people. Sometimes these not-to-exceed levels differ among federal organizations because of 

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal 

studies, or other factors. 

Recommendations and regulations are also periodically updated as more information becomes 

available. For the most current information, check with the federal agency or organization that 

provides it. Some regulations and recommendations for pentachlorophenol include the 

following: 

The federal government has set regulatory standards and guidelines to protect workers from the 

possible health effects of pentachlorophenol in air. OSHA has set a legally enforceable limit of 

0.5 milligrams per cubic meter (mg/m3) in workroom air to protect workers during an 8-hour 

shift over a 40-hour work week. 

The federal government has also set regulatory standards and guidelines to protect the public 

from the possible health effects of pentachlorophenol in drinking water. EPA decided that the 

amount in the drinking water should not be more than 0.022 milligram per liter (mg/L) and that 

any release of more than 10 pounds to the environment should be reported. For short-term 

exposures, EPA decided that drinking water levels should not be more than 1.0 mg/L for 1 day or 

0.3 mg/L for 10 days. EPA also estimates that for an average-weight adult, exposure to 

0.03 mg/kg/day will probably not cause any noncancer health effects. EPA is now working to 

measure the levels of pentachlorophenol found at abandoned waste sites. 

For more information on criteria and standards for pentachlorophenol exposure, see Chapter 8. 
PENTACHLOROPHENOL 11 

1. PUBLIC HEALTH STATEMENT 

1.10 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department or 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology 

1600 Clifton Road NE, Mailstop E-29 

Atlanta, GA 30333 

* Information line and technical assistance 

Phone: 1-888-42-ATSDR (1-888-422-8737)
 

Fax: 1-404-498-0057
 

ATSDR can also tell you the location of occupational and environmental health clinics. These 

clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to 

hazardous substances. 

* To order toxicological profiles, contact 

National Technical Information Service
 

5285 Port Royal Road
 

Springfield, VA 22161
 

Phone: (800) 553-6847 or (703) 605-6000
 

PENTACHLOROPHENOL 13 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PENTACHLOROPHENOL 

IN THE UNITED STATES 

Pure pentachlorophenol exists as colorless crystals that are poorly soluble in water, but dissolve in 

organic solvents such as alcohol, ether, and benzene. Typically, commercial grade pentachlorophenol is 

86% pure. Contaminants generally consist of other polychlorinated phenols, polychlorinated dibenzop-dioxins (CDDs), and polychlorinated dibenzofurans (CDFs), which are formed during the 

manufacturing process and can impart a darker color to the crystals. To increase its water solubility, 

pentachlorophenol has often been manufactured and marketed as a sodium salt. Pentachlorophenol was, 

in the past, one of the most heavily used pesticides in the United States, but is now regulated as a 

restricted-use pesticide and is no longer contained in wood preserving solutions or in insecticides or 

herbicides available for home and garden use. Its use is restricted to the treatment of utility poles, railroad 

ties, and wharf pilings. Pentachlorophenol is found in all environmental media as a result of its past 

widespread use; current releases to the environment are more limited as a result of changing use patterns. 

In addition, a number of other environmental contaminants, including hexachlorobenzene, pentachlorobenzene, pentachloronitrobenzene, and hexachlorocyclohexane isomers, are known to be metabolized to 

pentachlorophenol. 

Humans may be exposed to pentachlorophenol in occupational settings through inhalation of 

contaminated workplace air and dermal contact with the compound or with wood products treated with 

the compound. General population exposure may occur through contact with contaminated 

environmental media, particularly in the vicinity of wood treatment facilities and hazardous waste sites. 

Important routes of exposure appear to be inhalation of contaminated air, inhalation exposure to 

pentachlorophenol that has volatilized from treated wood surfaces, ingestion of contaminated 

groundwater used as a source of drinking water, ingestion of contaminated food, and dermal contact with 

contaminated soils or wood products treated with the compound. Children are likely to be exposed to 

pentachlorophenol by the same routes as adults. In addition, small children are generally more likely than 

adults to have significant contact with soil and have less concern with hygiene than adults. ATSDR 

believes that the primary route of human exposure to pentachlorophenol at hazardous waste sites is 

ingestion of contaminated media, and to a lesser extent, inhalation and dermal contact with contaminated 

media. Pentachlorophenol has been identified in at least 313 of the 1,585 hazardous waste sites that have 
PENTACHLOROPHENOL 14 

2. RELEVANCE TO PUBLIC HEALTH 

been proposed for inclusion on the EPA National Priorities List (NPL). However, the number of sites 

evaluated for pentachlorophenol is not known. 

2.2 SUMMARY OF HEALTH EFFECTS 

Adverse health effects have been observed in humans and experimental animals following short- and 

long-term exposure to pentachlorophenol by the inhalation, oral, and dermal exposure routes. Reports of 

inhalation and/or dermal exposure in humans and oral exposure studies in animals make up the bulk of 

the available toxicity data. The liver, thyroid, immune system, reproductive system, and the developing 

organism are the primary targets of pentachlorophenol toxicity. Case reports of individuals acutely 

exposed to pentachlorophenol via inhalation and dermal contact and longer-term occupational exposure 

via inhalation and/or dermal contact identify a number of adverse health effects. The observed effects 

include symptoms associated with uncoupling of oxidative phosphorylation (tachycardia, increased 

respiratory rate, labored breathing, profuse sweating, fever, metabolic acidosis), liver effects, and 

impaired immune function. The lack of information on exposure characterization and the possible 

concomitant exposure to other chemicals in the studies reporting these effects somewhat clouds their 

interpretation. However, acute and longer-term oral studies in experimental animals provide support for 

these health effects. Since humans are generally exposed to technical-grade pentachlorophenol, which 

usually contains such toxic impurities as polychlorinated dibenzo-p-dioxins and dibenzofurans, some of 

the effects observed in humans (or the severity and dose-response characteristics of the effects) may be 

related, at least in part, to the presence of the impurities. Animal studies with both technical-grade and 

purified pentachlorophenol have demonstrated that, within the ranges of doses tested, some of the toxic 

effects attributed to pentachlorophenol were actually due to the impurities. Because human exposure is 

generally to technical-grade pentachlorophenol, studies on technical-grade pentachlorophenol are 

considered relevant. 

In addition to the liver, thyroid, immune, reproductive, and developmental effects, exposure to 

pentachlorophenol is also associated with carcinogenic, renal, and neurological effects. The results of 

several epidemiology studies suggest that pentachlorophenol may be a human carcinogen. This 

assessment is supported by the findings in chronic oral rodent studies of increased incidences of liver 

tumors (hemangiosarcomas, adenomas, and carcinomas) and adrenal gland pheochromocytomas in mice 

and mesotheliomas and nasal squamous cell carcinomas in rats. No increases in gene mutations have 

been observed in a variety of in vivo or in vitro studies. Clastogenic effects have been observed in a 

number of in vitro studies. The EPA classifies pentachlorophenol in group B2 (probable human 
 

 

PENTACHLOROPHENOL 15 

2. RELEVANCE TO PUBLIC HEALTH 

carcinogen) and IARC classifies it in group 2B (possibly carcinogenic to humans). Several studies have 

reported adverse health effects in children accidentally exposed to pentachlorophenol. The observed 

effects were symptoms of oxidative phosphorylation uncoupling (high fever, profuse sweating, increased 

respiratory rate, labored breathing, tachycardia, hepatomegaly, and irritability) and death. Thus, the 

effects observed in children are similar to those seen in adults. However, the data are inadequate to assess 

whether children are more susceptible than adults to the toxicity of pentachlorophenol. 

Hepatic Effects. A number of case reports describe liver effects in individuals exposed to technicalgrade pentachlorophenol either occupationally or in the home via inhalation and/or dermal contact. The 

types of hepatic effects noted in the case reports include enlarged liver, jaundice, centrilobular 

degeneration, and elevated serum biliary acid concentrations. Liver enlargement was also observed in 

newborns exposed for a short time via contaminated diapers and bed linen in a hospital nursery. In 

addition, elevated urinary porphyrin and delta-amino levulinic acid concentrations and elevated levels of 

serum alanine aminotransferase and aspartate aminotransferase have been reported in epidemiological 

studies. 

Animal studies have confirmed the identification of the liver as one of the primary targets of pentachlorophenol toxicity. Increased liver weights, increased serum enzymes, and histological alterations 

(centrilobular hepatocellular hypertrophy and vacuolization, necrosis, degeneration, and periportal 

fibrosis) have been observed in rats and mice exposed to pure and technical-grade pentachlorophenol. 

Thyroid Effects. There are limited data on the effect of pentachlorophenol on thyroid function in 

humans. An inverse relationship between triiodothyronine levels and blood pentachlorophenol levels was 

found in women with gynecological and/or endocrinological disorders; who lived in homes with wood 

ceilings and wood panels treated with a wood preservative containing pentachlorophenol. However, the 

triiodothyronine levels were frequently within the normal range and it is likely that they were also 

exposed to other chemicals. 

In animal studies, decreases in circulating and free concentrations of triiodothyronine and thyroxine have 

been observed in rats and sheep orally exposed to pure or technical-grade pentachlorophenol for an 

intermediate duration and first and second generation mink exposed to pentachlorophenol (purity not 

reported) in a multigeneration study. The chronic-duration oral MRL is based on alterations in thyroid 

hormone levels (see Section 2.3). 
 

 

PENTACHLOROPHENOL 16 

2. RELEVANCE TO PUBLIC HEALTH 

Developmental Effects. Developmental effects (congenital eye cataracts) have been observed in the 

children of male sawmill workers exposed to a mixture of sodium salts of pentachlorophenol and 

tetrachlorophenol; however, other chemicals, in particular CDDs, may have contributed to the occurrence 

of these effects. However, animal studies provide strong evidence that pentachlorophenol is a 

developmental toxicant following oral exposure. Developmental effects are frequently observed at doses 

that cause decreases in maternal body weight gain. However, decreases in fetal or pup body weight have 

been observed at doses that do not result in maternal toxicity. Increases in fetal/neonatal mortality, and 

soft tissue and skeletal malformations/variation (subcutaneous edema, diaphragmatic hernia, dilation of 

kidneys, lumbar spurs, and delays in ossification), and decreases in offspring growth have been observed 

in rats and sheep. Pure pentachlorophenol appears to be slightly more developmentally toxic than 

technical-grade pentachlorophenol. The maternal dose of technical grade pentachlorophenol that would 

be lethal to 50% of embryos was over two times higher than for pure pentachlorophenol. The acuteduration oral MRL, see Section 2.3 for details, was based on the increased occurrence of delayed skull 

ossification in rats. 

Reproductive Effects. No studies were found that adequately assessed the reproductive toxicity of 

pentachlorophenol in humans. A possible association between pentachlorophenol exposure and 

reproductive effects was found in women exposed to technical-grade pentachlorophenol from outgassing 

wood panels treated with a wood preservative containing pentachlorophenol; however, study limitations, 

particularly lack of exposure characterization and possible exposure to other chemicals, preclude using 

these study to establish a causal relationship. A number of animal studies provide evidence that the 

reproductive system is a sensitive target of pentachlorophenol toxicity. A decrease in fertility was 

observed in first generation rats administered pentachlorophenol by gavage in a two-generation study; no 

alterations in fertility were observed in the parental generation in this study. In contrast, no effects on 

fertility were observed in another multigeneration study in which mink were exposed to lower doses of 

pentachlorophenol. Several other studies have reported alterations in reproductive tissues. The observed 

effects include decreased testes weight and focal/multifocal mononuclear cell infiltrate in the epididymis 

in first generation rats, focal degeneration of the seminiferous tubules in sheep, and increased severity of 

uterine and oviduct cysts in sheep and mink. Histological alterations were not observed in rats orally 

exposed to pure or technical-grade pentachlorophenol for an intermediate or chronic duration. 
 

PENTACHLOROPHENOL 17 

2. RELEVANCE TO PUBLIC HEALTH 

Immunological Effects. Immunological effects have been reported in humans exposed via 

inhalation and/or dermal contact with pentachlorophenol and in animals following oral exposure. A 

number of immunological effects (e.g., activated T-cells, autoimmunity, immunosuppression, B-cell 

dysregulation) have been reported in families living in pentachlorophenol-treated log homes and male 

factory workers involved in brushing technical-grade pentachlorophenol onto wood strips. A number of 

animal studies indicate that oral exposure to technical-grade pentachlorophenol affects a wide range of 

immune functions, such as humoral and cellular immunity, susceptibility to tumor induction, and 

complement activity. However, studies that tested both technical-grade and pure pentachlorophenol 

provide strong evidence that the immune effects are related to the level of impurities in the technicalgrade product (e.g., CDDs and CDFs). There is some evidence that pure pentachlorophenol is an 

immunotoxicant in rats. Enhanced mitogen-induced T- and B-lymphocyte blastogenesis and suppression 

of the antibody response against sheep red blood cells has been observed in rats orally exposed to pure 

pentachlorophenol (>99% pure with no detectable dioxin impurities) for 28 days. However, studies in 

mice suggest that pure pentachlorophenol has relatively little immunotoxic activity. 

2.3 MINIMAL RISK LEVELS 

Inhalation MRLs 

Inhalation MRLs for acute, intermediate, or chronic exposure have not been derived. While target organs 

have been identified in humans following inhalation exposure to technical-grade pentachlorophenol, the 

exposure levels at which these effects occur have not been quantified. No data exist on the toxicity of 

pentachlorophenol following inhalation exposure in animals from which MRLs could be developed. 

Oral MRLs 

C For acute oral exposure, an MRL of 0.005 mg/kg/day has been derived for pentachlorophenol. 

This MRL is based on a developmental toxicity study in which groups of pregnant rats were administered 

pure or technical-grade pentachlorophenol in corn oil by gavage on gestational days 6–15. At the lowest 

pure pentachlorophenol dose tested (5 mg/kg/day), a significant increase in the occurrence of delayed 

ossification of the skull was observed. At higher doses ($15 mg/kg/day), significant increases in the 

occurrence of subcutaneous edema, lumbar spurs, and skeletal anomalies in the ribs, sternebrae, and 

vertebrae were observed. Increased fetal resorptions and decreased fetal body weight were observed at 
PENTACHLOROPHENOL 18 

2. RELEVANCE TO PUBLIC HEALTH 

$30 mg/kg/day. Decreases in maternal body weight gain were observed at $30 mg/kg/day. Similar 

results were found in rats exposed to technical-grade pentachlorophenol. However, increased fetal 

resorptions and skeletal anomalies were observed at $15 mg/kg/day. The MRL was derived by dividing 

the lowest-observed-adverse-effect level (LOAEL) of 5 mg/kg/day pure pentachlorophenol by an 

uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for interspecies extrapolation, and 10 for human 

variability). Similar developmental effects have been observed in another rat developmental toxicity 

study. In this study, significant increases in the occurrence of resorptions, and soft tissue and skeletal 

malformations and variations, and decreases in fetal body weight were observed in the offspring of rats 

that were administered by gavage 80 mg/kg/day technical-grade (89% pure) pentachlorophenol on 

gestational days 6–15. This study identified a no-observed-adverse-effect level (NOAEL) of 

30 mg/kg/day. Intermediate-duration oral developmental toxicity studies in rats have also reported 

increased fetal/neonatal mortality, malformations and/or variations, and decreased growth. 

C An intermediate-duration oral MRL of 0.001 mg/kg/day has been derived for pentachlorophenol. 

This MRL is based on a LOAEL of 1 mg/kg/day for reproductive effects in mink exposed to 

pentachlorophenol (purity not reported) in the diet for 3 weeks prior to mating and throughout gestation 

and lactation. At the only dose tested, 1 mg/kg/day, decreases in the proportion of mated females 

accepting a second mating and mink that whelped were observed. No effect on the proportion of mink 

accepting the first mating or the proportion of mink with visible implantation sites were found. An 

increase in the severity cystic uterine glands was also observed in the pentachlorophenol-exposed mink. 

The MRL was derived by dividing a LOAEL of 1 by an uncertainty factor of 1000 (10 for use of a 

LOAEL, 10 for interspecies extrapolation, and 10 for human variability). 

As discussed in the previous section, reproductive effects have also been observed in rats and sheep orally 

exposed to pentachlorophenol for intermediate or chronic durations, but the results have been 

inconsistent. Significant decreases in the number of rats mated and in the ratio of pregnant rats to number 

of rats in cohabitation were observed in a two-generation rat study. The effects were observed in the first 

generation of rats exposed to 60 mg/kg/day, but not in the parental generation. In contrast, no effects on 

fertility were observed in a multi-generation study in mink exposed to 1 mg/kg/day pentachlorophenol in 

the diet or in sheep or sheep offspring (only females were exposed) exposed to 1 mg/kg/day 

pentachlorophenol in the diet. Histological alterations in female reproductive tissues have also been 

observed in sheep; increased severity of oviductal intraepithelial cysts in sheep exposed to 2 mg/kg/day 

pentachlorophenol by gavage twice weekly for 43 days and lymphocyte infiltration into the endometrium 
PENTACHLOROPHENOL 19 

2. RELEVANCE TO PUBLIC HEALTH 

were observed in sheep exposed to 1 mg/kg/day pentachlorophenol in the diet for 5 weeks prior to mating 

and during pregnancy and lactation. However, no histological alterations were observed in female mink 

exposed to 1 mg/kg/day pentachlorophenol in the diet in a multi-generation study. 

Liver and developmental effects also appear to be sensitive end points of pentachlorophenol following 

intermediate-duration oral exposure; the lowest adverse effect levels for these effects are 10-fold higher 

than the reproductive effects reported in mink. Significant increases in relative liver weight and the 

occurrence of centrilobular hepatocellular hypertrophy have been reported in rats and mice exposed to 

<10 mg/kg/day pure or technical-grade pentachlorophenol. At higher doses, hepatocyte degeneration and 

necrosis have been observed. Developmental effects (decreased pup body weight) have also been 

observed in rat offspring at 10–15 mg/kg/day. 

C For chronic oral exposure, an MRL of 0.001 mg/kg/day has been derived for pentachlorophenol. 

This MRL was based on a LOAEL of 1 mg/kg/day (only dose tested) for significantly decreased serum 

thyroxine concentrations first generation males and both males and females of the second generation, and 

decreased relative thyroid weight second generation females when mink were administered pentachlorophenol of unspecified purity continuously in the diet in a multigeneration reproduction study. Several 

studies support the identification of the thyroid gland as a sensitive target of pentachlorophenol toxicity. 

Oral gavage administration of pure pentachlorophenol to young adult female rats over a 28-day period at 

doses of 3 or 30 mg/kg produced decreases in circulating and free concentrations of the thyroid hormones 

triiodothyronine and thyroxine in serum, a decrease in serum thyroid stimulating hormone, decreases in 

intrathyroidal levels of triiodothyronine and thyroxine, a decrease in the thyroxine:triiodothyronine ratio 

in serum, and a reduction in thyroidal hormone stores. Technical-grade pentachlorophenol, tested only at 

a dose of 3 mg/kg, produced the same effects, except for the reduction in free triiodothyronine in serum 

(data for free serum thyroxine were not reported). A decrease in maternal serum thyroxine concentration 

throughout pregnancy and lactation and a significant increase in maternal thyroid gland follicle size were 

found in female sheep administered 1 mg/kg/day pentachlorophenol (purity not indicated) in the diet 

5 weeks prior to mating and throughout pregnancy and lactation until 2 weeks after weaning of the lambs. 

Additionally, increased thyroxine levels were observed in their ewe and ram lambs that also received 

postnatal exposure to pentachlorophenol. The chronic-duration MRL was derived by dividing the 

LOAEL of 1 mg/kg/day by an uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for interspecies 

extrapolation, and 10 for human variability). 

Dermal MRLs 
PENTACHLOROPHENOL 20 

2. RELEVANCE TO PUBLIC HEALTH 

Appropriate methodology does not currently exist to develop MRLs for dermal exposure. This is most 

often because of the difficulty in identifying reliable, absorbed doses from most dermal studies. The 

paucity of dermal studies is in part due to the difficulty in constructing animal models which limit 

exposure exclusively to the dermal route. An approach to deriving dermal MRLs from oral or inhalation 

data through route-to-route extrapolation is currently being evaluated for potential use by the agency. 
PENTACHLOROPHENOL 21 

3. HEALTH EFFECTS 

3.1 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 pentachlorophenol. 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. 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

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 first by route of exposure (inhalation, 

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, 

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure 

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). 

Levels of significant exposure 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 

lowest-observed-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 end point 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 end points. 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 
PENTACHLOROPHENOL 22 

3. HEALTH EFFECTS 

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. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user's perspective. Public health officials and others concerned with 

appropriate actions to take at hazardous waste sites may want information on levels of exposure 

associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no 

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans 

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of pentachlorophenol are indicated in Table 3-1 and Figure 3-1. Because cancer effects could occur at lower exposure 

levels, Figure 3-1 also shows a range for the upper bound of estimated excess risks, ranging from a risk of 

1 in 10,000 to 1 in 10,000,000 (10-4 to 10-7), as developed by EPA. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been 

made for pentachlorophenol. An MRL is defined as an estimate of daily human exposure to a substance 

that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified 

duration of exposure. 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 within a given route of 

exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. 

MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral 

routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990a), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic 

bronchitis. As these kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 
PENTACHLOROPHENOL 23 

3. HEALTH EFFECTS 

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

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 

Since humans are generally exposed to technical-grade pentachlorophenol, which usually contains such 

toxic impurities as polychlorinated dibenzo-p-dioxins and dibenzofurans (see Table 3-2), some of the 

effects observed in humans (or the severity and dose-response characteristics of the effects) may be 

related, at least in part, to the presence of the impurities. Animal studies with both technical-grade and 

purified pentachlorophenol have demonstrated that, within the ranges of doses tested, some of the toxic 

effects attributed to pentachlorophenol were actually due to the impurities. Because human exposure is 

generally to technical-grade pentachlorophenol and because ATSDR's intent is to protect human health, 

studies on both technical-grade and purified pentachlorophenol preparations are reviewed, and special 

reference is made to those adverse effects seen in humans that are believed to be a result of the 

contaminants. 

3.2.1 Inhalation Exposure 

Only limited data were available on the inhalation toxicity of pentachlorophenol in humans. Most of the 

information available for humans comes from cases of acute poisoning following home use of pentachlorophenol-containing products such as wood preservatives or herbicides in the garden (home and 

garden use of pentachlorophenol is no longer approved by EPA), and following occupational exposure in 

agricultural and wood-treatment industries. Many of these poisoning incidences involved inhalation and 

dermal exposure to pentachlorophenol. Below is a discussion of the case reports and studies in which 

inhalation is the primary route of exposure; the remaining studies are discussed in Section 3.2.3, Dermal 

Exposure. Exposure concentrations and duration, as well as information on other exposures and 

contaminants present in technical-grade pentachlorophenol, are often not available in these studies. Thus, 

no studies were considered suitable for presentation in a table describing significant levels of inhalation 

exposure to pentachlorophenol. 

3.2.1.1 Death 

Data on the lethality of pentachlorophenol in humans is limited to a case report of a man who died 

following 3 weeks of daily occupational exposure to pentachlorophenol dust (purity not reported) (Gray 

et al. 1985). 
 

 

 

PENTACHLOROPHENOL 24 

3. HEALTH EFFECTS 

Death has been reported in experimental animals following acute inhalation of sodium pentachlorophenate aerosol. The reported LC50 (45 minutes) for rats is 14 mg/m3

 (11.7 mg/kg) (Hoben et al. 1976b). 

3.2.1.2 Systemic Effects 

No studies were located regarding any systemic effects in animals after inhalation exposure to pentachlorophenol. No studies were located regarding cardiovascular, gastrointestinal, musculoskeletal, or 

renal effects in humans after inhalation exposure to pentachlorophenol. It should be noted that many of 

the systemic effects observed following occupational exposure which are discussed below resulted from 

uses of pentachlorophenol that are no longer accepted and that the pentachlorophenol used in these 

instances had a composition (e.g., presence of more impurities) different from the pentachlorophenol that 

is currently used. 

Respiratory Effects. In humans, chronic high-dose occupational exposure to pentachlorophenol 

causes inflammation of the upper respiratory tract and bronchitis (Baader and Bauer 1951; Klemmer et al. 

1980). The purity of pentachlorophenol in these cases was not specified, and inhalation of pentachlorophenol contaminants (chlorinated dibenzo-p-dioxins and dibenzofurans) and other compounds (such as 

dieldrin, chromium, fluorine, arsenic, copper, boron, and tin compounds) present in workplace air was 

likely and may have contributed to the respiratory response observed. Furthermore, the inflammation 

observed may have also been the result of physical irritation from the inhalation of particulate matter. 

Hematological Effects. In a chronic occupational study, increased numbers of immature leukocytes 

and basophils were observed in workers exposed to technical-grade pentachlorophenol; however, these 

parameters were still within normal limits (Klemmer et al. 1980). 

Hepatic Effects. In an epidemiology study of male and female pentachlorophenol-production 

workers, higher urinary excretion of coproporphyrins, compared with unexposed controls, was associated 

with workers with chloracne involved in the production of pentachlorophenol (Hryhorczuk et al. 1998). 

In another epidemiology study, Cheng et al. (1993) found elevated urinary porphyrin and delta-amino 

levulinic acid concentrations among male workers who produced technical-grade pentachlorophenol, but 

there were no differences in these parameters between the workers with chloracne and those without. 
 

PENTACHLOROPHENOL 25 

3. HEALTH EFFECTS 

Endocrine Effects. In a brief report, Gerhard et al. (1991) noted that elevated blood levels of pentachlorophenol (>25 μg/L) and/or lindane (>100 ng/L) were found in 22 of 90 women with histories of 

habitual abortion, unexplained infertility, menstrual disorders, or the onset of menopause. Exposure 

duration was 4.6–10 years, and exposure occurred via offgassing (from wooden ceiling and wall panels 

and from carpets and leather upholstery treated with wood preservatives) as well as via dermal contact 

with these treated materials. Pentachlorophenol blood levels were highest in the women with infertility 

(mean=73 μg/L) and lower in those with menstrual dysfunction (42 μg/L). Seventeen of the 22 women 

also exhibited adrenocortical insufficiency, and 6 of these women had thyroid dysfunction as assessed by 

measurement of thyroid stimulating hormone releasing hormone (no further details were provided). 

Conclusions cannot be drawn from these data because a control group was not used and statistical 

analyses were not performed. Gerhard et al. (1998) also examined several endocrine end points among 

89 women with repeated miscarriages. An inverse correlation was found between triiodothyronine levels 

and pentachlorophenol levels. It should be noted that this is a preliminary study; study design limitations 

include lack of a matched control group, lack of control for other confounding factors, only 15% of the 

women had pentachlorophenol levels that were above the reference level of 25 μg/L, no information was 

provided on possible sources of exposure to pentachlorophenol, and elevated levels of other chlorinated 

hydrocarbons (e.g., PCBs, DDT) were also present in some of the women. In a third study by Gerhard et 

al. (1999) of a group of women with gynecological and/or endocrinological disorders, a decrease in 

triiodothyronine levels were found in women with elevated pentachlorophenol serum levels (median level 

of 3.59 μg/L); although the levels were lower than levels found in age-, geographical region-, and 

condition-matched controls, the mean and median triiodothyronine levels were within the normal range. 

An euthyroid goiter was also observed in 50% of these subjects as compared to 30% in the controls. 

Other statistically significant alterations in endocrine hormones included an increase in adrenocorticotropic hormone (ACTH)-stimulated cortisol levels and decreases in follicle stimulating hormone, 

testosterone, hydroepiandrosterone, hydroepiandrosterone sulfate, 17-hydroxypregnenolone, and 

17-hydroxyprogesterone levels. As with the triiodothyronine levels, the hormone levels were within the 

normal range. The source of pentachlorophenol was wood ceilings that were treated with wood 

preservatives; it is likely that these women were also exposed to other chemicals in the wood 

preservative. 

No studies were located regarding endocrine effects in animals after inhalation exposure to pentachlorophenol. 
 

 

PENTACHLOROPHENOL 26 

3. HEALTH EFFECTS 

Dermal Effects. Occupationally-exposed workers at a wood-treatment plant exhibited a statistically 

significant increase in low-grade inflammation of skin and subcutaneous tissue, and severe eruptions of 

the skin. However, it is possible these symptoms resulted from exposure to contaminants in pentachlorophenol (chlorinated dibenzo-p-dioxins, dibenzofurans) and other materials such as dieldrin, chromium, 

fluorine, arsenic, copper, boron, and tin compounds (Baader and Bauer 1951; Klemmer et al. 1980). 

Hosenfeld et al. (1986) reported the presence of skin abnormalities (type not specified) in some residents 

of log homes treated with pentachlorophenol (purity not indicated). 

Numerous occupational exposure studies have reported chloracne, characterized by extensive cysts and 

pus forming abscesses on the face, chest, abdomen, and proximal part of the extremities in sodium 

pentachlorophenate (Seghal and Ghorpade 1983) and pentachlorophenol (Cheng et al. 1993; Hryhorczuk 

et al. 1998; O’Malley et al. 1990) production workers. It is likely that these workers were also exposed to 

chlorinated dibenzo-p-dioxins and dibenzofurans, which are known to induce chloracne in humans. 

Ocular Effects. Inflammation of the conjunctival membrane of the eyes was observed in workers 

exposed to technical-grade pentachlorophenol at a wood treatment plant (Klemmer et al. 1980). 

3.2.1.3 Immunological and Lymphoreticular Effects 

In an epidemiologic study, McConnachie and Zahalsky (1991) evaluated 18 lymphocyte phenotype 

frequencies, proliferative responses of peripheral lymphocytes to mitogens and allogenic stimulator 

lymphocytes, serum immunoglobulin levels, and autoantibody levels in 38 people ages 8–60 (21 males) 

and 9–60 (17 females) from 10 families who had been exposed to pentachlorophenol (purity not 

indicated) in their pentachlorophenol-treated log homes for periods of 1–13 years. Fifteen of the 

individuals were children ages 8–18. The mean serum concentration of pentachlorophenol in the 

individuals who still lived in log homes at the time of the study was 884 μg/L; this was higher than the 

mean of 420 μg/L found in another study of people living in log homes and a mean level of 40 μg/L 

reported for members of the general public with no known exposure to pentachlorophenol (Cline et al. 

1989). Comparison of the pentachlorophenol-exposed individuals with controls indicated that the 

exposed individuals had activated T-cells, autoimmunity, immunosuppression, and B-cell dysregulation. 

T-cell activation was indicated by statistically-significant increases of more than 50% in the proportion of 

lymphocytes with T-cell activation markers, as detected by monoclonal antibodies, in pentachlorophenolexposed individuals compared with controls. Autoantibodies were detected in 8 of 38 pentachlorophenolexposed subjects, and there was increased expression of a monoclonal-antibody-detected marker 
PENTACHLOROPHENOL 27 

3. HEALTH EFFECTS 

associated with autoimmunity in the pentachlorophenol-exposed group. Functional immunosuppression 

was indicated by statistically-significant decreases of 24–41% in the proliferative response of peripheral 

lymphocytes of pentachlorophenol-exposed individuals, compared with controls, to three different 

mitogens and to allogeneic stimulation in mixed-lymphocyte culture. A statistically-significant increase 

in natural killer cell function was also reported in pentachlorophenol-exposed women compared with 

women of the control group. This study is limited by the absence of reported serum pentachlorophenol 

concentrations in members of the control group and the lack of control for potential confounders such as 

smoking, hypertension, and alcohol use. Gerhard et al. (1991) reported “immunological disorders” (no 

further details were given) in 15 of 22 women attending a clinic for reproductive and/or endocrinological 

disorders. The women were exposed to pentachlorophenol by the outgassing of wood products in the 

home. 

No studies were located regarding immunological effects in animals after inhalation exposure to pentachlorophenol. 

3.2.1.4 Neurological Effects 

There are limited data on the neurotoxicity of inhaled pentachlorophenol in humans. Signs of central 

nervous system toxicity (lethargy and tachypnea) and cerebral edema with focal swelling of the myelin 

sheath was observed in a worker exposed to pentachlorophenol dust (Gray et al. 1985). It is likely that 

these effects were secondary to hyperthermia, which resulted from pentachlorophenol-induced 

uncoupling of oxidative phosphorylation. 

A study by Peper et al. (1999) examined neurotoxicity in individuals exposed to wood preserving 

chemicals used to treat wood ceilings and wood paneling. An increase in subjective symptoms (increased 

fatigue, distractability, attenuated motivation, and depressed mood) and impaired performance on several 

objective tests of neurobehavioral performance (paired-associated learning with a distracting condition, 

verbal memory test with distraction, visual short term memory, and incidental learning of visual objects) 

were observed in 15 women with elevated pentachlorophenol (mean of 43.6 μg/L) and γ-hexachlorocyclohexane (0.085 μg/L) blood levels, as compared to a sex-, age-, education-, and intelligence-matched 

control group. Additionally, the results of the reading speed, naming speed, paired associated learning, 

and visual short-term memory tests were significantly associated with pentachlorophenol blood levels. 

Although this study provides some suggestive evidence of the neurotoxic potential of pentachlorophenol, 
PENTACHLOROPHENOL 28 

3. HEALTH EFFECTS 

interpretation of the results is complicated by co-exposure to high levels of γ-hexachlorocyclohexane 

(lindane) and other solvents and the small number of subjects. 

A reduction in median motor nerve conduction velocity was seen in male pentachlorophenol production 

workers, as compared to matched controls (Cheng et al. 1993). However, the reduction was only 

statistically significant in the subgroup of pentachlorophenol workers in the trichlorobenzene tank area 

where the highest levels of chlorinated dibenzo-p-dioxins (CDDs) were also found. In contrast, Triebeg 

et al. (1987) did not find significant alterations in motor or sensory nerve conduction velocities in the 

ulnar and/or median nerve in workers exposed to low levels (0.0003–0.18 mg/m3

) of technical-grade 

pentachlorophenol. 

In a case-control study of patients with Parkinson’s disease, Seidler et al. (1996) found significant 

associations of Parkinson’s disease with long-term (>15 years) exposure to wood paneling in the home, 

contact with wood preservatives in free time, and contact with wood preservatives at work. However, the 

association of Parkinson’s disease with exposure to pentachlorophenol is uncertain because the patients 

were more likely than control subjects to have used organochlorines and alkylated phosphates/ 

carbamates, and the patients reported more frequent exposure to heavy metals, solvents, exhaust fumes, 

and carbon monoxide than the control group. 

No studies were located regarding neurological effects in animals following inhalation exposure to pentachlorophenol. 

3.2.1.5 Reproductive Effects 

In a brief report, Gerhard et al. (1991) noted that elevated blood levels of pentachlorophenol (>25 μg/L) 

and/or lindane (>100 ng/L) were found in 22 of 90 women with histories of habitual abortion, 

unexplained infertility, menstrual disorders, or the onset of menopause. However, a causal relationship 

between pentachlorophenol exposure and the effects is uncertain because of concurrent exposures to other 

chemicals, the absence of matched controls, and lack of control for other confounding factors. Gerhard et 

al. (1999) also examined a group of 65 women with gynecological and/or endocrinological alterations and 

elevated serum pentachlorophenol levels (median level was 35.9 μg/L). Statistically significant decreases 

in follicle stimulating hormone and testosterone levels were found, as compared to age-, geographical-, 

region-, and condition-matched controls. Although the hormone levels were lower than in the control 

group, they were within the normal range of values. The women were exposed to pentachlorophenol via 
PENTACHLOROPHENOL 29 

3. HEALTH EFFECTS 

outgassing of wood ceilings treated with wood preservatives. It is likely that the women were also 

exposed to other components of the wood preservatives. 

No studies were located regarding reproductive effects in animals following inhalation exposure to pentachlorophenol. 

3.2.1.6 Developmental Effects 

Information on the developmental toxicity of pentachlorophenol in humans is limited to a study of male 

sawmill workers exposed to CDD-contaminated chlorophenate (a mixture of the sodium salts of 

pentachlorophenol and tetrachlorophenol) (Dimich-Ward et al. 1996). A significant correlation between 

presumed exposure to chlorophenate and an increased incidence of congenital eye cataracts were 

observed in the workers’ children. Because there were no data on exposure level, exposure to 

chlorophenate was estimated by 10 experienced workers based on each cohort member’s job title. 

No studies were located regarding developmental effects in animals after inhalation exposure to pentachlorophenol. 

3.2.1.7 Cancer 

Case reports suggest a possible association between cancer (Hodgkin's disease, soft tissue sarcoma, and 

acute leukemia) and occupational exposure to technical-grade pentachlorophenol (Fingerhut et al. 1984; 

Greene et al. 1978; Roberts 1983). These studies are limited by confounding factors such as concurrent 

exposure to other potentially carcinogenic chemicals, small sample size, follow-up periods too short to 

detect an excess cancer risk, mortality due to competing causes of death, and brief exposure periods. 

Several epidemiological studies found no association between inhalation of pentachlorophenol (purity not 

stated) in any form and cancer in humans (Gilbert et al. 1990; Jäppinen et al. 1989; Johnson et al. 1990; 

Robinson et al. 1985). For example, workers exposed to wood treating chemicals between the years of 

1960 and 1981 were evaluated for health-related problems. Eighty-eight wood treaters having exposures 

of 0.33–26.3 years, with a median of 6.5 years, were compared to 58 matched controls. No adverse 

health effects or increased incidence of mortality from exposure were detected even though the urinary 

pentachlorophenol excretion levels were clearly increased (174 ppb versus 35 ppb) (Gilbert et al. 1990). 

However, IRIS (1999) indicated that the study of Gilbert et al. (1990) cannot be used as evidence of no 
PENTACHLOROPHENOL 30 

3. HEALTH EFFECTS 

effect of the exposures based on their evaluation of various aspects of the experimental design and 

conduct. 

Johnson et al. (1990) found no association between soft tissue sarcoma and exposure to chlorophenols in 

a meta-analysis of deaths due to cancer in 15 cohort studies published 1979–1987. However, each of the 

individual studies had a low power to detect elevated risk estimates (Johnson et al. 1990). Because of the 

nature of the analysis performed by Johnson et al. (1990) (deaths due to cancer), their study excluded 

analysis of two studies, which had only incidence data, that found an association between exposure to 

technical-grade pentachlorophenol and soft tissue sarcoma (Eriksson et al. 1981; Hardell and Sandstrom 

1979). In a recent study, in which all data collection and coding were blinded as to cases or controls, 

Eriksson et al. (1990) found an association between soft tissue sarcoma and high-grade exposure (1 week 

or more continuously or at least 1 month totally over the years) to technical-grade pentachlorophenol. 

Compared with the high-grade pentachlorophenol association, a slightly stronger association was found 

for chlorophenols exposure and a weaker association was found for exposure to phenoxyacetic acids. In a 

meta-analysis of four of their previous case-control studies, Hardell et al. (1995) found a significant 

association between soft tissue sarcoma and exposure to pentachlorophenol (purity not specified). An 

increase in the occurrence of soft tissue sarcoma was also found in workers reporting exposure to 

phenoxyacetic acids or chlorophenols. Hoppin et al. (1998) found a significant association in men aged 

30–60 years between soft tissue sarcoma risk and ever having high-intensity chlorophenol exposure. 

However, their findings were also consistent with an association to some other component of cutting oils. 

Seventeen percent of the jobs rated as high intensity involved wood preservation, whereas 82% involved 

cutting oils. Due to the limited nature of the exposure information in this study, potential for dioxin 

exposure could not be evaluated. 

Hardell et al. (1994) also reported a significant association, in men of various professions, between nonHodgkin’s lymphoma and high-grade exposure (1 week or more continuously or at least 1 month in total 

over the years) to pentachlorophenol (purity not specified). Compared with the high-grade pentachlorophenol association, a slightly stronger association was found for high-grade exposure to chlorophenols. 

Hertzman et al. (1997) reported a borderline positive association between an increasing incidence of nonHodgkin’s lymphoma and increasing chlorophenate exposure among sawmill workers. The trend 

approached statistical significance. 

Ramlow et al. (1996) reported a significant association between death from kidney cancer and increasing 

exposure to technical-grade pentachlorophenol but indicated that the finding must be considered 
PENTACHLOROPHENOL 31 

3. HEALTH EFFECTS 

preliminary because of the small number of cases, lack of control for confounders, and absence of 

information concerning other occupational exposures. 

No studies were located regarding cancer in animals after inhalation exposure to pentachlorophenol. 

3.2.2 Oral Exposure 

Only two reports were found in the literature concerning adverse effects in humans of ingestion of pentachlorophenol (Cretney 1976; Haley 1977). However, pentachlorophenol (particularly the technicalgrade) has been shown to affect several organ systems in experimental animals. Target organs or systems 

of oral pentachlorophenol-induced toxicity in experimental animals include liver, kidney, central nervous 

system, endocrine system, immune system, and reproductive system; the developing organism is also a 

sensitive target of pentachlorophenol toxicity. Hematologic, cardiovascular, and respiratory effects have 

also been noted following oral administration of pentachlorophenol in experimental animals. Oral 

administration of pentachlorophenol also produced developmental effects in animals and cancer in rats 

and mice. 

Some of the effects of pentachlorophenol may be due, at least in part, to the uncoupling of oxidative 

phosphorylation by pentachlorophenol (see Section 3.5), which leads to hyperthermia and related effects. 

Some effects may also result from chlorinated dibenzo-p-dioxin and other impurities in technical-grade 

pentachlorophenol. The adverse effect of pure pentachlorophenol on thyroid homeostasis and the 

induction of oxidative deoxyribonucleic acid (DNA) damage by oral exposure to pentachlorophenol may 

also contribute to its spectrum of toxic effects. 

3.2.2.1 Death 

One case report that described a suicide from pentachlorophenol ingestion was found in the reviewed 

literature, but the amount of pentachlorophenol ingested was not specified (Cretney 1976). The lowest 

human lethal dose for pentachlorophenol (purity not specified) is estimated to be 1 gram (approximately 

17.0 mg/kg) (Driesbach 1980). 

Pentachlorophenol may cause death in experimental animals following ingestion. Death usually is a 

result of hyperthermia. There does not appear to be much difference in doses that cause death across 

species. The LD50 values were 80–120 mg/kg in rats (St. Omer and Gadusek 1987) and 117–177 mg/kg 
 

PENTACHLOROPHENOL 32 

3. HEALTH EFFECTS 

in mice (Borzelleca et al. 1985; Renner et al. 1986). Preweaned and adult rats have been reported to have 

lower oral LD50 values for technical-grade pentachlorophenol than juvenile rats (25–50 days old) (St. 

Omer and Gadusek 1987). The ranges of LD50 values in preweaned, juvenile, and adult rats were 50–180, 

220–230, and 80–120 mg/kg, respectively. The lethality of pentachlorophenol was greatly enhanced 

when it was administered in a fuel oil or corn oil vehicle (Deichmann et al. 1942). Absorption of 

chemicals such as pentachlorophenol that have substantial lipid solubility across skin and mucous 

membranes is increased by the presence of hydrocarbon or corn oil solvents. The greater toxicity of 

pentachlorophenol when dissolved in these vehicles may be due partly or entirely to more efficient 

absorption of pure pentachlorophenol. 

Deaths were also seen in a 30-day oral range-finding study in mice (NTP 1989), a 28-day oral rangefinding study in rats with highly purified pentachlorophenol (Chhabra et al. 1999; NTP 1999), and a 

6-month oral study in mice (NTP 1989). At the highest dietary concentration tested (12,500 ppm) in the 

30-day study in mice (NTP 1989), incidences of deaths were higher in animals fed pure pentachlorophenol (98.6% pure with <0.0002% chlorinated dibenzo-p-dioxins and dibenzofurans) and the purified 

EC-7 pentachlorophenol preparation (90% pure with <0.0002% chlorinated dibenzo-p-dioxins and 

dibenzofurans) than in animals fed technical-grade pentachlorophenol (90% pure with 0.18% chlorinated 

dibenzo-p-dioxins and dibenzofurans). 

All reliable LD50 values from acute duration studies and NOAELs/LOAELs for death in longer-duration 

studies are recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.2.2 Systemic Effects 

No studies were located regarding gastrointestinal, musculoskeletal, dermal, or ocular effects in humans 

or animals after oral exposure to pentachlorophenol. 

The highest NOAEL values and all reliable LOAEL values from each reliable study for systemic effects 

in each species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

Respiratory Effects. The National Toxicology Program (NTP) conducted a 6-month dietary rangefinding study (NTP 1989) with 3 different preparations of pentachlorophenol (technical-grade, Dowicide 

EC-7, and pure) in B6C3F1 mice (see analysis in Table 3-2). Increased incidences of nasal mucosal 

metaplasia/goblet cell hyperplasia, compared with controls, were seen in female mice that received 


















Table 3-2. Results of Analyses of Impurities Present in the Pentachlorophenol Used in Natio

Program (NTP) Feeding Studies and the Types of Tumors They Induce a,b

Impurity Technical grade Dowicide EC-7c Pure Tumor type Dichlorophenol – – – No data 

Trichlorophenold 100 ppm 70 ppm 100 ppm Liver, leukemiase , 

lymphomas 

Tetrachlorophenol 38,000 ppm 94,000 ppm 14,000 ppm Not carcinogenic 

Hexachlorobenzene 50 ppm 65 ppm 10 ppm Liver 

Thyroid/ Parathyroid Adrenal Kidney Lymphosarcomas 

Tetrachlorodibenzodioxin – <0.04 ppm <0.08 ppm Liver, thyroid Hexachlorodibenzodioxin 10.1 ppm 0.19 ppm <1 ppm Liver Heptachlorodibenzodioxin 296 ppm 0.53 ppm – No data Octachlorodibenzodioxin 1,386 ppm 0.69 ppm <1 ppm No data 

Pentachlorodibenzofuran 1.4 ppm – – No data 

Hexachlorodibenzofuran 9.9 ppm 0.13 ppm – No data 

Heptachlorodibenzofuran 88 ppm 0.15 ppm – No data 

Octachlorodibenzofuran 43 ppm – – No data 

Heptachlorohydroxydiphenyl ether 500 ppmf – 100 ppm No data 
Table 3-2. Results of Analyses of Impurities Present in the Pentachlorophenol Used in Natio

Program (NTP) Feeding Studies and the Types of Tumors They Induce a,b (contin

Impurity Technical grade Dowicide EC-7c Pure Tumor type Octachlorohydroxydiphenyl ether 19,100 ppm – 900 ppm No data Nanochlorohydroxydiphenyl ether 35,600 ppm – 2,100 ppm No data Hexachlorohydroxydibenzofuran 1,600 ppm – 1,100 ppm No data Heptachlorohydroxydibenzofuran 4,700 ppm – 2,200 ppm No data 

aSamples were dissolved in benzene, placed on a deactivated alumina column, and eluted with benzene. Further separation was carried 

aluminum oxide column; elution was with methylene chloride in hexane. Identification was performed by gas chromatography with an SP

column/mass spectrometry; quantitation was by comparison with spiked samples analyzed by gas chromatography with an SP1240 DA c

bDerived from NTP 1989cFour unidentified impurities with concentrations of 0.14, 0.057, 0.045, and 0.035 ppm were also detected.dIdentified as the 2,3,6-isomer; another isomer was believed to be present but was not identified.eData are for 2,4,6-isomer.fIncludes oxtachlorodiphenyl ether

– = not detected; EC-7 = Dow Company chemical name 
 

 

 

 

PENTACHLOROPHENOL 53 

3. HEALTH EFFECTS 

dietary doses of $64 mg/kg/day EC-7 (90% pure) and $67 mg/kg/day pure pentachlorophenol, but were 

not observed in the female mice exposed to 209 mg/kg/day technical-grade pentachlorophenol (which 

contains relatively high concentrations of chlorinated dibenzo-p-dioxins and dibenzofurans). The female 

mice appeared to be more sensitive to the nasal effects than the male mice. The LOAELs for nasal lesions 

were 148 and 381 mg/kg/day in the EC-7 and pure pentachlorophenol groups, respectively. 

Cardiovascular Effects. One report describing effects of ingestion of pentachlorophenol in humans 

was found in the literature (Haley 1977). In this case, an adult male intentionally ingested an estimated 

4–8 ounces of weed killer that contained 12% pentachlorophenol, 1.5% other chlorinated phenols, 

82% aromatic hydrocarbons, and 4.5% inert ingredients. Clinical signs observed upon subsequent 

hospital admission included tachycardia. This effect is possibly the result of pentachlorophenol's ability 

to uncouple oxidative phosphorylation, leading to hyperthermia. 

One early report described the occurrence of extensive vascular damage and heart failure in rats, rabbits, 

guinea pigs, and dogs following a single oral administration (dose not specified) of pentachlorophenol of 

unidentified purity (Deichmann et al. 1942). 

Hematological Effects. No studies were located regarding hematological effects in humans after 

oral exposure to pentachlorophenol. 

Various hematologic changes of questionable biological significance have been reported in animal 

studies. A depression in number of erythrocytes, a decrease in hemoglobin level, and a decrease in 

packed cell volume were observed in rats fed technical-grade pentachlorophenol for 90 days but not in 

those fed purified pentachlorophenol (Johnson et al. 1973). However, a decrease in white blood cell 

count was observed in pigs administered purified pentachlorophenol for 30 days (Greichus et al. 1979). 

Conflicting findings over time were reported in rats fed a purified pentachlorophenol preparation, which 

contained no tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and <0.03% of the other chlorinated dibenzop-dioxins, for 12 weeks (Knudsen et al. 1974). Increased hemoglobin and hematocrit were observed after 

6 weeks of treatment, followed by a decrease in hemoglobin and erythrocytes at study termination. 

Hepatic Effects. No studies were located regarding hepatic effects in humans after oral exposure to 

pentachlorophenol. 
 

PENTACHLOROPHENOL 54 

3. HEALTH EFFECTS 

The liver is a target organ for pentachlorophenol-induced toxicity in experimental animals. Evidence of 

biochemical (alterations in hepatic enzyme activities), and gross (increased liver weight), and 

histopathological (hypertrophy, vacuolization, hyperplasia, fibrosis, necrosis, and degeneration) effects is 

seen following acute, intermediate, and chronic oral exposure to pentachlorophenol in rodents. At low 

dosages, the observed liver effects are characteristic of enzyme induction. Increases in liver weight and 

hepatocellular hypertrophy and vacuolization have been observed in mice exposed to 41 mg/kg/day pure 

pentachlorophenol for 2 weeks (Umemura et al. 1996), in rats exposed to 1–40 mg/kg/day pure or 

technical-grade pentachlorophenol for an intermediate duration (Argus 1997/Bernard et al. 2001c; 

Blakley et al. 1998; Kimbrough and Linder 1978; Knudsen et al. 1974; Nishimura et al. 1982; NTP 

1999), in mice exposed to 9 mg/kg/day pure or technical-grade pentachlorophenol for 4–12 weeks 

(Kerkvliet et al. 1982; Umemura et al. 1996), and in pigs exposed to 10 mg/kg/day pure 

pentachlorophenol for 30 days (Greichus et al. 1979). 

The severity of the liver damage increased with increasing exposure concentrations. Intermediateduration exposure to doses of 7–48 mg/kg/day pure or technical-grade pentachlorophenol resulted in 

necrosis, periportal fibrosis, and hepatocellular degeneration in rats (Argus 1997/Bernard et al. 2001c; 

Kimbrough and Linder 1978; NTP 1989) and multifocal necrosis and hepatocellular degeneration in mice 

exposed to 67–105 mg/kg/day pure or technical-grade pentachlorophenol (Kerkvliet et al. 1982; NTP 

1989). Hepatocellular degeneration was observed in rats exposed to 10–60 mg/kg/day pure 

pentachlorophenol in the diet for 52 or 104 weeks (NTP 1999). The biochemical changes consisted of 

increases in the serum levels of alanine and aspartate aminotransferase at 40 and 67 mg/kg/day pure or 

technical-grade pentachlorophenol in rats (Nishimura et al. 1980) and mice (NTP 1989), respectively. 

The results of the Kimbrough and Linder (1978) study suggests that the impurities found in technicalgrade pentachlorophenol may influence its toxicity. The liver effects observed in this study included 

centrilobular hepatocyte hypertrophy at 1 mg/kg/day, periportal fibrosis at 7 mg/kg/day, and periportal 

fibrosis and bile duct proliferation at 48 mg/kg/day in rats exposed to technical-grade pentachlorophenol 

in the diet for 8 months. In contrast, minimal liver effects (centrilobular hepatocyte hypertrophy) were 

observed at the highest tested dose (32 mg/kg/day) of pure pentachlorophenol. It is possible that the 

tetrachlorophenol, hexachloro-p-dibenzodioxin, heptachloro-p-dibenzodioxin, octachloro-p-dibenzodioxin, hexachlorodibenzofuran, pentachlorodibenzofuran, and tetrachlorodibenzofuran present in the 

technical-grade pentachlorophenol influenced its hepatotoxicity. However, other studies that compared 

the hepatotoxicity of pure and technical-grade pentachlorophenol did not find differences in potency or 

the type of liver effects (Kerkvliet et al. 1982; NTP 1989). 
 

PENTACHLOROPHENOL 55 

3. HEALTH EFFECTS 

Renal Effects. No studies were located regarding renal effects in humans after oral exposure to pentachlorophenol. 

There is evidence of mild-to-moderate renal toxicity in experimental animals as a result of long-term oral 

administration of pentachlorophenol. The most frequently reported toxic effects seen in kidneys of 

rodents include increased organ weight and altered enzyme levels. Histopathologic effects are rarely 

seen. The possibility that impurities in pentachlorophenol may be responsible for the adverse effects 

observed is likely. Furthermore, some of the data discussed below have many inconsistencies. 

Purified pentachlorophenol (2 mg/kg/day, only dose tested, >99% pure with no detectable dioxin 

impurities) induced a small but significant increase in relative kidney weight in rats exposed twice weekly 

for 28 days (Blakley et al. 1998). 

When similar doses of technical-grade and purified pentachlorophenol (>99% pure) were fed to rats for 

8 months, the pure compound induced a slight, non-dose-related increase in kidney weight in males, 

whereas the technical-grade compound did not alter kidney weight in either sex (Kimbrough and Linder 

1978). When similar doses of technical-grade and pure pentachlorophenol (no detectable chlorinated 

dibenzo-p-dioxins) were fed to rats for 3 months, increased kidney weight was reported at 

10–30 mg/kg/day of the technical-grade preparation, but only at the 30 mg/kg/day dose of the pure pentachlorophenol (Johnson et al. 1973). In neither study were renal histopathological changes observed to 

accompany organ weight changes. Thus, the biological significance of these observations with regard to 

long-term toxicity is not known. 

Increased kidney weight and urine specific gravity and a dose-related incidence of kidney discoloration 

were observed in rats fed 1–30 mg/kg/day of Dowicide EC-7 (a purified pentachlorophenol containing 

<0.0002% chlorinated dibenzo-p-dioxins and dibenzofurans) for 24 months (Schwetz et al. 1978). 

Pigmentation per se is not considered an adverse effect. Biochemical changes indicative of renal toxicity 

have also been reported in pentachlorophenol-treated animals. For example, after 15 days of oral 

exposure to purified pentachlorophenol at 10 or 15 mg/kg/day, young pigs exhibited statistically 

significant increased levels of blood urea nitrogen, but this effect was no longer significant after 30 days 

of treatment (Greichus et al. 1979). Proximal tubular alkaline phosphatase activity was decreased after 

1 month of twice-weekly gavage doses (40–160 mg/kg/day) of 90% pure pentachlorophenol (sodium salt; 

impurities not identified) administered to rats, but this effect was no longer evident after 3 months of 
 

PENTACHLOROPHENOL 56 

3. HEALTH EFFECTS 

treatment (Nishimura et al. 1980). The biological significance of these apparently transient renal effects 

with regard to long-term toxicity is not known. 

Endocrine Effects. No studies were located regarding endocrine effects in humans after oral 

exposure to pentachlorophenol. 

Significant alterations in thyroid hormone levels have been observed in several intermediate- and chronicduration animal studies. Oral gavage administration of pure pentachlorophenol to young adult female rats 

over a 28-day period at a dose of 30 mg/kg produced decreases in circulating and free concentrations of 

the thyroid hormones triiodothyronine and thyroxine in serum, a decrease in serum thyroid stimulating 

hormone, decreases in intrathyroidal levels of triiodothyronine and thyroxine, a decrease in the ratio of 

serum thyroxine to triiodothyronine, and a reduction in thyroidal hormone stores. Decreases in 

circulating and free thyroxine were also observed at 3 mg/kg/day. Technical-grade pentachlorophenol, 

tested only at a dose of 3 mg/kg, produced the same effects as 30 mg/kg of pure pentachlorophenol 

except the reduction in free T3 in serum (data for free serum T4 were not reported). Technical-grade 

pentachlorophenol, in addition, produced an increase in thyroid epithelial-cell height (Jekat et al. 1994). 

In a multigeneration study in mink, significant decreases in serum thyroxine levels were observed in the 

F1 males and the F2 males and females exposed to 1 mg/kg/day pentachlorophenol (purity not reported) 

(Beard and Rawlings 1998). A decrease in relative thyroid weight was also observed in the F2 female 

mink. This LOAEL of 1 mg/kg/day was used to derive a chronic-duration oral MRL of 0.001 mg/kg/day, 

as described in the footnote in Table 3-1. 

Alterations in thyroid hormone levels were also observed in a series of studies in sheep. A significant 

decrease in thyroxine levels was observed in female sheep administered 2 mg/kg/day pure 

pentachlorophenol by gavage twice weekly for 36 days (Rawlings et al. 1998). Exposure of female sheep 

to 1 mg/kg/day pentachlorophenol (purity not reported) for 5 weeks premating and throughout gestation 

and lactation, resulted in significant decreases in serum thyroxine levels in the mothers (Beard et al. 

1999b), in the ram lambs that were also exposed for 20 weeks post weaning (Beard et al. 1999a), and in 

the ewe lambs also exposed for 67 weeks post weaning (Beard and Rawlings 1999). No alterations in 

thyroid stimulating hormone levels or the response to thyroid releasing hormone were observed in the 

female offspring. However, in response to thyroid stimulating hormone, there were reductions in the 

magnitude and duration of the thyroxine response and in the maximum triiodothyronine level and net 

triiodothyronine increase. 
 

 

 

PENTACHLOROPHENOL 57 

3. HEALTH EFFECTS 

There are limited data on the toxicity of pentachlorophenol to other endocrine tissues. A significant 

increase in mean serum insulin concentrations was seen in sheep receiving twice weekly gavage doses of 

2 mg/kg/day (Rawlings et al. 1998). No alterations in cortisol levels were observed in ram lambs (Beard 

et al. 1999a). 

Body Weight Effects. Significant ($10%) decreases in body weight gain were observed in several 

studies where both technical-grade and pure pentachlorophenol were administered orally for intermediate 

or chronic durations to rats or mice (Chhabra et al. 1999; Kimbrough and Linder 1978; Nishimura et al. 

1980; NTP 1989, 1999; Welsh et al. 1987). Suppression of body weight gain by oral administration of 

pentachlorophenol was also reported in maternal animals, fetuses, and neonates. 

Metabolic Effects. There are limited data on the metabolic toxicity of pentachlorophenol. Nishimura 

et al. (1980) reported significant increases in blood glucose levels and decreases in hepatic glycogen 

levels in rats administered 40 mg/kg/day technical-grade sodium pentachlorophenate by gavage twice 

weekly for 1 to 3 months. 

Other Systemic Effects. In the intermediate-duration studies conducted by NTP (1989), granular 

eosinophilic pigment was observed in the epithelial cells of the urinary bladder of rats exposed to 

technical-grade pentachlorophenol, EC-7 (90% pure), and pure pentachlorophenol; the increase in 

pigment was not accompanied by inflammation. 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans following oral exposure to pentachlorophenol. 

Evidence for pentachlorophenol-induced alterations in immune function was obtained from studies 

conducted in experimental animals. The available data indicate that, at doses of 0.5–100 mg/kg/day, 

pentachlorophenol affects a wide range of immune functions, such as humoral and cellular immunity, 

susceptibility to tumor induction, and complement activity. Detailed studies in mice indicate that the 

majority of the immunotoxic effects of pentachlorophenol appear to be related to the level of impurities in 

the technical-grade product (e.g., polychlorinated dibenzo-p-dioxins and dibenzofurans) (Kerkvliet et al. 

1982, 1985a; NTP 1989; White and Anderson 1985). However, a recent study in rats provides evidence 

that pure pentachlorophenol (>99% with no detectable dioxin impurities) can affect immune function 
PENTACHLOROPHENOL 58 

3. HEALTH EFFECTS 

(Blakley et al. 1998). Studies that compared effects of technical-grade to pure pentachlorophenol are 

reviewed below in an attempt to illustrate immunotoxic effects attributable to pentachlorophenol. 

Female B6C3F1 mice exposed daily to 10–100 mg/kg of technical-grade pentachlorophenol by gavage for 

2 weeks exhibited a dose-related suppression of in vivo antibody response (IgM plaque-forming cells 

[PFC]) to sheep red blood cells (SRBC) when mice were immunized during exposure (Holsapple et al. 

1987). This response was not seen following exposure to purified pentachlorophenol at a dose of 

100 mg/kg. It was further observed that spleen cells from mice treated with technical-grade pentachlorophenol could still produce antibodies following in vitro immunization, indicating that the suppression 

seen following in vivo immunization was not due to a direct effect on antibody-forming cells. 

Purified pentachlorophenol (>99% pure with no detectable dioxin impurities) administered to male F344 

rats twice weekly for 28 days at a dose of 2 mg/kg/treatment significantly enhanced mitogen-induced Tand B-lymphocyte blastogenesis and significantly suppressed the antibody response against injected 

sheep red blood cells when the response was expressed per viable spleen cell (Blakley et al. 1998). 

In 6-month dietary range-finding studies (NTP 1989) with 3 different preparations of pentachlorophenol 

(technical-grade, Dowicide EC-7, or pure) in B6C3F1 mice (see Table 3-2), the antibody response to 

sheep red blood cell injection was decreased at doses of technical-grade pentachlorophenol 

$48 mg/kg/day in males but was not affected in males by dosing with Dowicide EC-7 or pure pentachlorophenol. Antibody response data were not reported for females. In the same studies, significant 

increases in relative spleen weight were not seen in dosed females, but were seen in males at doses of 

376 mg/kg/day technical-grade pentachlorophenol, $49 mg/kg/day Dowicide EC-7, and $225 mg/kg/day 

pure pentachlorophenol. 

Effects of dietary administration of both technical-grade and purified pentachlorophenol for 10–12 weeks 

on the ability of male B6C3F1 mice to resist syngeneic tumor growth, an indication of an organism's state 

of immunosurveillance, were studied (Kerkvliet et al. 1982). Technical-grade preparation induced a 

significant dose-independent enhancement of susceptibility to methylcholanthrene-induced sarcoma 

1412 tumor growth, whereas the purified preparation had no effect on this parameter. In another test of 

immunocompetence, treated mice were studied for their ability to resist secondary tumor growth induced 

by Maloney sarcoma virus (MSV). After exposure to technical-grade pentachlorophenol, animals were 

inoculated with MSV, which resulted in transient subcutaneous injection-site tumors. Upon subsequent 

challenge with MSV-transformed tumor cells, a significant increase in mortality and secondary tumor 
PENTACHLOROPHENOL 59 

3. HEALTH EFFECTS 

susceptibility was seen in animals treated with technical-grade pentachlorophenol but not in animals 

administered purified pentachlorophenol. This result suggests a detrimental effect of components of the 

technical-grade pentachlorophenol on both primary and secondary T-cell-dependent cytotoxic immune 

response. An increase in secondary splenic tumors was seen in animals treated with both grades of pentachlorophenol at a dose of 25 mg/kg/day. This was interpreted as a more sensitive indicator of 

immunocompetence suppression by purified pentachlorophenol. In a third test designed to evaluate 

macrophage competence, resistance to encephalomyocarditis virus (EMCV) was also studied in mice 

treated with both grades of pentachlorophenol. No effect was seen on susceptibility of either group of 

animals to EMCV-induced mortality. The investigators concluded that immunomodulatory effects 

observed with pentachlorophenol were due primarily, but not exclusively, to contaminants present in the 

technical-grade preparation. 

To further investigate the role of these impurities in immunotoxicity induced by technical-grade pentachlorophenol, the antibody (IgM) response to an SRBC challenge in C57BL/6 mice given single oral 

doses of both grades of pentachlorophenol was studied (Kerkvliet et al. 1985a). In agreement with results 

seen by Holsapple et al. (1987), technical-grade pentachlorophenol induced a dose-related suppression of 

this response at a dose of 30 mg/kg/day whereas purified pentachlorophenol did not. Co-administration 

of heptachloro-p-dibenzodioxin (HpCDD), one of the most prevalent chlorinated dibenzo-p-dioxin 

impurities in technical-grade pentachlorophenol, with pure pentachlorophenol resulted in an immunosuppressive response that was similar in magnitude to that seen with technical-grade pentachlorophenol or 

HpCDD alone. These results provide good evidence that impurities (particularly HpCDD) are responsible 

for some of the immunotoxic effects attributed to technical-grade pentachlorophenol. Results from the 

next series of experiments conducted by these investigators further supported this hypothesis. Technicalgrade pentachlorophenol was fed to both C57BL/6 mice and DBA/2 mice for 6 weeks (Kerkvliet et al. 

1985a). The former strain has a high-affinity aryl hydrocarbon (Ah) receptor and the latter a low-affinity 

Ah receptor. The ability of chlorinated dibenzo-p-dioxin and dibenzofuran congeners (that are present as 

impurities in pentachlorophenol) to bind to this receptor correlates with their toxicity and their ability to 

induce P1-450 monooxygenase activity. Antibody response to SRBC was suppressed by 28% (p#0.01) 

and 72% (p#0.01) in the 2 groups of C57BL/6 mice with different levels of technical-grade pentachlorophenol, as opposed to 0 and 45% (p>0.01) in corresponding groups of D2 mice. Based on these results, 

the authors concluded that the immunosuppressive effect of technical-grade pentachlorophenol was 

probably mediated by contaminant chlorinated dibenzo-p-dioxins and dibenzofurans via interaction with 

the Ah receptor. 
PENTACHLOROPHENOL 60 

3. HEALTH EFFECTS 

In a study designed to evaluate effects of dietary exposure to technical-grade pentachlorophenol on T-cell, 

macrophage, and natural killer cell activity, C57BL/6 mice were administered technical-grade pentachlorophenol for 8 weeks prior to conducting a number of in vitro immunofunction tests (Kerkvliet et al. 

1985b). They found that T-cell and macrophage-mediated (cell-mediated) immunocompetence is 

relatively resistant to perturbation by technical-grade pentachlorophenol. The only statistically significant 

change seen was a reduction in lymphoproliferative response in mixed lymphocyte culture. This finding 

contrasts with marked effects that technical-grade pentachlorophenol has on antibody-mediated 

immunity. 

The complement component of the immune system in mice has also been found to be affected by 

exposure to technical-grade pentachlorophenol, but not Dowicide EC-7, a preparation of 90% pentachlorophenol that contains reduced levels of chlorinated dibenzo-p-dioxins and dibenzofurans (see 

Table 3-2) (White and Anderson 1985). In this study, technical-grade pentachlorophenol inhibited 

functional activity of all aspects of complement in a dose-dependent manner. This suppression was still 

seen up to 30 days after termination of treatment. 

The highest NOAEL values and all LOAEL values from each reliable study for immunological effects in 

each species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.2.4 Neurological Effects 

One report describing effects of ingestion of pentachlorophenol in humans was found in the literature 

(Haley 1977). In this case, an adult male intentionally ingested an estimated 4–8 ounces of weed killer 

that contained 12% pentachlorophenol, 1.5% other chlorinated phenols, 82% aromatic petroleums, and 

4.5% inert ingredients. Clinical signs observed upon subsequent hospital admission included pyrexia, 

diaphoresis, hyperkinesis, muscle twitching, tremors, epigastric tenderness, leg pain, tachypnea, and 

tachycardia. These neurologic symptoms may be the result of pentachlorophenol's ability to uncouple 

oxidative phosphorylation (including the resultant increase in body temperature, tachycardia, and 

tachypnea) rather than a direct toxic effect of pentachlorophenol on the central or peripheral nervous 

systems. 

Results from animal studies demonstrate that the central nervous system is adversely affected by pentachlorophenol, possibly as a result of hyperthermia induced by uncoupling of oxidative phosphorylation. 

At the neurochemical level, transient changes in activity of some brain enzymes and decreased glial 
PENTACHLOROPHENOL 61 

3. HEALTH EFFECTS 

glutathione levels were seen in rats administered technical-grade pentachlorophenol in drinking water for 

14 weeks (Savolainen and Pekari 1979). These findings suggest another biochemical component to 

technical-grade pentachlorophenol neurotoxicity. The possibility and extent of the role of technical-grade 

contaminants in producing these effects are not known, although the study authors concluded that the 

neurochemical changes were most likely associated with the body burden of chlorophenols. Inhibition of 

the uptake of thyroxine into the cerebrospinal fluid, as demonstrated in rats following intraperitoneal 

injection of pentachlorophenol is another possible component of pentachlorophenol neurotoxicity. 

Degenerative changes in 10% of the Types A and B fibers consisting of breaks in the myelin sheath of 

sciatic nerves and a variable loss of neurotubules, neurofilaments, and other axoplasmic components were 

observed in male rats administered 38 mg/kg/day pentachlorophenol (purity not reported) in drinking 

water for 90 days or 114 mg/kg/day for 120 days. Type C fibers were unaffected. These changes were 

more marked in the rats receiving the higher dose. No effects were observed in rats exposed to 

11.4 mg/kg/day for 60 days or 38 mg/kg/day for 60 days. While these results suggest that pentachlorophenol can cause neurotoxic changes in the morphology of peripheral nerves, since the purity of the 

pentachlorophenol tested was not specified, it is not possible to determine whether these changes were 

due to pentachlorophenol itself or impurities present in technical-grade pentachlorophenol. Other 

limitations associated with this study include a lack of protocol details (e.g., number of animals per 

group) and a lack of quantitative incidence data (Villena et al. 1992). 

The NTP (1989) conducted a 6-month dietary range-finding study with three different preparations of 

pentachlorophenol (technical-grade, Dowicide EC-7, or pure [see composition in Table 3-2]) in 

B6C3F1 mice. Neurobehavioral studies were conducted during exposure weeks 5 and 26. No pentachlorophenol-related neurobehavioral effects were observed at 5 weeks except for animals administered 

technical-grade pentachlorophenol, which showed a dose-dependent decrease in motor activity and 

rotarod performance. In contrast, exposure to all 3 pentachlorophenol preparations caused dose-related 

increases in both motor activity and startle response in female mice at 26 weeks, whereas only technicalgrade pentachlorophenol caused these effects in male mice. NTP (1989) did not provide actual doseresponse data. 

The LOAEL for neurological effects in rats following intermediate exposure is recorded in Table 3-1 and 

plotted in Figure 3-1. 
PENTACHLOROPHENOL 62 

3. HEALTH EFFECTS 

3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after oral exposure to pentachlorophenol. 

A number of animal studies have examined the reproductive toxicity of pentachlorophenol. The available 

data suggest that long-term exposure to pentachlorophenol can decrease fertility, although the mechanism 

does not appear to be through histological damage to reproductive tissue. In a two-generation study, 

decreased fertility (significant decreases in the number of rats mated and in the ratio of pregnant rats to 

the number of rats in cohabitation) was observed in the first generation of rats exposed to 60 mg/kg/day 

pentachlorophenol (purity not reported) administered by gavage (Argus 1997/Bernard et al. 2001c). No 

alterations in fertility were observed in the F1 generation exposed to 10 or 30 mg/kg/day or in the parental 

generation. The only other reproductive effects observed in this study were a significant decrease in 

testicular spermatid count, decreases in absolute testes weight and the ratio of testes weight to brain 

weight, and focal/multifocal mononuclear cell infiltrate in the epididymis in the F1 rats administered 

30 or 60 mg/kg/day. However, no alterations in the average number of motile or nonmotile sperm, 

epididymal or testicular sperm counts, or sperm morphology were observed in either generation. No 

alterations in reproductive tissues were observed in the female rats. Significant increases in the average 

day of preputial separation and vaginal patency were observed in the F1 generation, suggesting that in 

utero exposure to pentachlorophenol disrupted the normal development of the reproductive system. No 

adverse reproductive effects were observed in another multigeneration study in which mink were fed a 

diet containing 1 mg/kg/day pentachlorophenol (purity not reported) (Beard and Rawlings 1998). A 

single-generation mink study also conducted by this group reported significant decreases in the 

proportion of mated females accepting a second mating and the proportion of mink that whelped, 

although no effect on the proportion of mink that accepted the first mating or the proportion of mink with 

visible implantation sites were found (Beard et al. 1997). In both studies, the minks were exposed to 

1 mg/kg/day pentachlorophenol (purity not reported) in the diet for 3 weeks prior to mating. 

Additionally, no significant alterations in mating response, ovulation rate, follicle and corpus luteum size, 

gestation length, pregnancy rate, lambing rate, and lamb birth rate were observed in sheep exposed to 

1 mg/kg/day pentachlorophenol in the diet for 5 weeks premating and throughout the gestation and 

lactation periods (Beard et al. 1999b). No effect on fertility was observed in the offspring of these sheep, 

later mated to unexposed males (Beard and Rawlings 1999). 
PENTACHLOROPHENOL 63 

3. HEALTH EFFECTS 

Several reproductive toxicity and nonreproductive toxicity studies have reported histological alterations 

in reproductive tissues. The observed effects include focal degeneration of the seminiferous tubules and 

decreased sperm density in the epididymis body (but not in caput or cauda epididymis) in sheep exposed 

to 1 mg/kg/day pentachlorophenol (purity not reported) in the diet during gestation, lactation, and for 

20-weeks postnatally (Beard et al. 1999a), minimal to marked germinal epithelial degeneration and lack 

of spermatozoa in the seminiferous tubules of rats exposed to 270 mg/kg/day pure pentachlorophenol in 

the diet for 28 days (effects may have been secondary to poor condition of animals) (Chhabra et al. 1999; 

NTP 1999), increased severity of cystic uterine glands in mink exposed to 1 mg/kg/day pentachlorophenol (purity not reported) prior to mating and during gestation and lactation periods (Beard et al. 1997), 

increased severity of oviductal intraepithelial cysts in sheep administered 2 mg/kg/day pure pentachlorophenol by gavage twice weekly for 43 days (Rawlings et al. 1998), and lymphocyte infiltration into the 

endometrium in sheep exposed to 1 mg/kg/day pentachlorophenol (purity not reported) in the diet for 

5 weeks premating and during the gestation and lactation periods (Beard et al. 1999b). No histological 

alterations in reproductive tissues were observed in male or female rats chronically exposed to 

30 mg/kg/day pure pentachlorophenol in the diet for 2 years (Chhabra et al. 1999; NTP 1999). 

Additionally, no alterations in reproductive hormones (estradiol, testosterone, progesterone, follicle 

stimulating hormone, and/or luteinizing hormone levels) have been observed in mink (Beard et al. 1997) 

or sheep (Beard et al. 1999a). The LOAEL of 1 mg/kg/day for decreases in the proportion of females 

accepting a second mating and the number of mink that whelped and the increased severity of cystic 

uterine glands identified in the single-generation mink study was used to derive an intermediate-duration 

oral MRL of 0.001 mg/kg/day, as described in the footnote in Table 3-1. 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans after oral exposure to pentachlorophenol. 

A number of animal studies have examined the developmental toxicity of pentachlorophenol and provide 

evidence that gestational exposure can result in fetal/neonatal mortality, malformation/variations, 

decreased growth, and possibly functional deficits in rats and sheep. No developmental effects have been 

observed in rabbits administered up to 30 mg/kg/day 88–89% pure pentachlorophenol by gavage on 

gestational days 6–18 (Argus 1993a/Bernard et al. 2001c). Significant increases in postimplantation 

resorptions or embryo lethality were observed in rats administered 30 mg/kg/day pure pentachlorophenol 

or 15 mg/kg/day technical-grade (88.4% pure) pentachlorophenol by gavage on gestational days 
PENTACHLOROPHENOL 64 

3. HEALTH EFFECTS 

6–15 (Schwetz et al. 1974), in rats administered 80 mg/kg/day 89% pure pentachlorophenol by gavage on 

gestational days 6–15 (Argus 1993b/Bernard et al. 2001b), and in the offspring of rats exposed to 

46 mg/kg/day pure pentachlorophenol in the diet during mating and gestation (Welsh et al. 1987). A 

decrease in litter size and decreases in neonatal survival were observed in offspring of rats exposed for 

77 days prior to gestation and throughout the gestation and lactation periods to 30 mg/kg/day 90.4% pure 

pentachlorophenol in the diet (Schwetz et al. 1978), in rats exposed to 48 mg/kg/day 85.5% pure 

pentachlorophenol in the diet for 10 weeks prior to mating and throughout gestation and lactation (Exon 

and Koller 1982), and in F1 and F2 rat pups exposed to 60 mg/kg/day pentachlorophenol (purity not 

specified) (Argus 1997/Bernard et al. 2001c). Schwetz et al. (1974) reported marked changes in the sex 

ratio of rats exposed to pentachlorophenol; the majority of surviving rats were males. The ratios were 

3.6 and 4.9 in the rats administered 50 mg/kg/day technical-grade pentachlorophenol and 30 mg/kg/day 

pure pentachlorophenol, respectively, as compared to respective control values of 1.0 and 1.1. Other 

developmental toxicity studies have not found alterations in sex ratio (Argus 1993b/Bernard et al. 2001b, 

Argus 1997/Bernard et al. 2001c). 

The occurrence of malformations and variations has been reported in a small number of studies. Soft 

tissue (subcutaneous edema) and skeletal (lumbar spurs) anomalies were observed in the offsprings of rats 

exposed by gavage $15 mg/kg/day of technical-grade (88.4%) pentachlorophenol (Schwetz et al. 1974) 

and skeletal (variations in vertebral, sternal, and pelvic ossification, increased rib pairs, delays in sternal 

forelimb and hindlimb ossification) and soft tissue (diaphragmatic hernia, slight to moderate dilation of 

the kidneys) malformations and variations have been observed in rat offspring administered 

80 mg/kg/day, but not 30 mg/kg/day, 89% pure pentachlorophenol on gestational days 6–15 (Argus 

1993b/Bernard et al. 2001b). 

Decreases in growth have been reported in a number of developmental toxicity studies. Statistically 

significant decreases in fetal body weights were observed in the offspring of rats administered pure or 

technical-grade pentachlorophenol by gavage at doses of $30 mg/kg/day (Argus 1993b/Bernard et al. 

2001b; Courtney et al. 1976; Larsen et al. 1975; Schwetz et al. 1974). Decreases in pup weight have been 

observed in the offspring of rats administered 14 mg/kg/day 99% pure pentachlorophenol in the diet 

(Welsh et al. 1987), rats in a two-generation study administered 10 mg/kg/day pentachlorophenol (purity 

not specified) in the diet (Argus 1997/Bernard et al. 2001c), and in sheep fed 1 mg/kg/day 

pentachlorophenol (purity not reported) in the diet (Beard et al. 1999b). 
PENTACHLOROPHENOL 65 

3. HEALTH EFFECTS 

There is some limited evidence that gestational/lactational exposure to pentachlorophenol may impair the 

development of the reproductive system. Significant increases in the average day of vaginal patency in 

F1 females exposed to 60 mg/kg/day and preputial separation in F1 males exposed to 60 mg/kg/day 

(Argus 1997/Bernard et al. 2001c). Decreased fertility was also observed in the F1 generation. 

Schwetz et al. (1974) examined the differences in the developmental toxicity between pure and technicalgrade pentachlorophenol. The pure pentachlorophenol was slightly more toxic than the technical-grade 

pentachlorophenol in terms of maternal body weight gain, fetal resorptions, fetal body weight, and 

occurrence of fetal anomalies. The study authors estimated that the maternal dose that would be lethal to 

one half of the embryos was 16 mg/kg/day pure pentachlorophenol versus 44 mg/kg/day for technicalgrade pentachlorophenol. 

In many of the oral developmental toxicity studies, decreases in maternal body weight were observed at 

the same doses as the developmental effects in rats (Argus 1993b/Bernard et al. 2001b; Courtney et al. 

1976; Schwetz et al. 1974). However, in other rat studies (Argus 1997/Bernard et al. 2001c; Welsh et al. 

1987), the LOAEL for maternal toxicity was higher than the LOAEL for developmental effects 

(decreased fetal or pup body weight), suggesting that developmental toxicity can occur in the absence of 

maternal toxicity. 

The highest NOAEL values and all LOAEL values from each reliable study for developmental toxicity in 

each species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.2.7 Cancer 

Lampi et al. (1992) demonstrated significantly elevated risk ratios, compared to reference populations, 

for non-Hodgkin’s lymphoma and soft tissue sarcoma among people who consumed fish from a lake 

contaminated with tri-, tetra-, and penta-chlorophenols and drank water from wells nearby. For 

non-Hodgkin’s lymphoma, there was a significant association with fish consumption. The population 

was not exposed to chlorinated dibenzodioxins or dibenzofurans. 

Carcinogenicity of orally administered pentachlorophenol has been tested in at least four studies using 

rats and mice (Inns et al. 1969; NCI 1968; NTP 1989, 1999 [data also reported by Chhabra et al. 1999]; 

Schwetz et al. 1978). The purity of pentachlorophenol in these studies varied; this is an important factor 

to consider because pentachlorophenol, during its production, is usually contaminated with chlorinated 
PENTACHLOROPHENOL 66 

3. HEALTH EFFECTS 

dibenzo-p-dioxins, some of which are animal carcinogens. NTP (1989) tested both technical-grade pentachlorophenol (TG-Penta), a 90% pure composite mixture of 3 technical-grades of pentachlorophenol, and 

Dowicide EC-7, a mixture containing 90% pure pentachlorophenol and fewer chlorinated dibenzop-dioxin impurities than TG-Penta (see Table 3-2). NCI (1968) tested Dowicide EC-7 as well. Schwetz 

et al. (1978) tested Dowicide EC-7. NTP (1999) tested pure pentachlorophenol (approximately 99% with 

one impurity, tetrachlorophenol). 

NCI administered Dowicide EC-7 (0 or 17 mg/kg/day) in the diet of weanling B6C3F1 mice for 78 weeks 

(NCI 1968), while NTP (1989) administered Dowicide EC-7 (0, 18, 37, or 118 mg/kg/day) in the diet of 

B6C3F1 mice for 103 weeks. No significant elevation in incidence of cancer occurred in the NCI study; 

however, in the NTP study, significant increases in incidence of tumors were observed. Male mice 

displayed significant dose-related increases in the incidence of adrenal medulla pheochromocytomas 

(benign and malignant) and hepatocellular adenomas and carcinomas. Female mice in the high-dose 

group displayed significant increases in incidences of hepatocellular adenoma and carcinoma, in 

pheochromocytomas (benign and malignant), and in hemangiosarcomas (spleen and liver). The 

differences between the two studies were that NCI tested for a shorter period of time, used fewer animals 

per group, had higher mortality in the dose group leaving fewer animals to be at risk of developing 

tumors, and used only one dose that was one-sixth of the highest dose used in the NTP study, and, 

therefore, was probably not the maximum tolerated dose. 

NTP (1989) also tested TG-Penta, a composite mixture of three technical-grades of pentachlorophenol. 

This mixture contained a higher percentage of chlorinated dibenzo-p-dioxin contaminants than did the 

Dowicide EC-7 mixture (see Table 3-2). Groups of male and female B6C3F1 mice were given diets that 

contained 0, 100, or 200 ppm TG-Penta (equivalent to 0, 18, or 35 mg/kg/day, respectively) or Dowicide 

EC-7 (as described above for 103 weeks). Survival was reduced in all groups, including controls, when 

compared to historical controls. Male mice displayed a significant increase over the male control 

incidence in tumors of the adrenal medulla (benign and malignant pheochromocytomas combined) and 

liver (adenomas and carcinomas combined). Treated female mice displayed a significant increase over 

female controls with regard to incidence of hemangiosarcomas of the spleen and liver. Chlorinated 

dibenzo-p-dioxins were found in the TG-Penta mixture at a concentration of 0.17%, but the mixture 

contained no 2,3,7,8-TCDD. Chlorinated dibenzo-p-dioxin exposure has been associated with an 

increased incidence of liver tumors in treated mice but not with pheochromocytomas or hemangiosarcomas (NCI/NTP 1980). Although this study is limited because of unusually low survival in the male 
PENTACHLOROPHENOL 67 

3. HEALTH EFFECTS 

TG-Penta control group, the occurrence of rare hemangiosarcomas was considered a carcinogenic 

response due to pentachlorophenol exposure. 

In the NTP (1999) study, groups of male and female F344 rats were given diets that contained 0, 200, 

400, or 600 ppm pentachlorophenol (approximately 99% pure with one impurity, tetrachlorophenol) in 

the diet (equivalent to doses of 0, 10, 20, or 30 mg/kg/day) for 105 weeks. A stop-exposure group was 

given a diet that contained 1,000 ppm pentachlorophenol for 52 weeks (equivalent to a dose of 

60 mg/kg/day) followed by a control diet through 105 weeks. At 2 years, a significantly increased 

incidence of malignant mesothelioma originating from the tunica vaginalis was present in 60 mg/kg/day 

stop exposure group males compared with controls, and the incidence exceeded the historical control 

range. Nasal squamous cell carcinomas were present in one control male, three 10 mg/kg/day males, one 

20 mg/kg/day male, and five 60 mg/kg/day males at 2 years, and the incidence in 1,000-ppm males 

exceeded the historical control range. 

In an earlier study, Dowicide EC-7 was administered to rats at dietary levels of 0, 1, 3, 10, or 

30 mg/kg/day in males and females for 22 months and 24 months, respectively (Schwetz et al. 1978). No 

significant increases in incidence of tumors were observed during this study. The study was limited, 

however because a small number of animals was tested, no data on survival were provided to evaluate if 

enough animals survived for a long enough period of time to develop tumors, and it is not known if the 

maximum tolerated dose was attained. 

The NTP (1999) study in F344 rats showed some evidence that purified pentachlorophenol 

(approximately 99% with one impurity, tetrachlorophenol) is carcinogenic, producing mesotheliomas and 

nasal squamous cell carcinomas. The most convincing evidence that 90% pure pentachlorophenol is 

carcinogenic to mice following ingestion comes from the NTP (1989) bioassay. This study was generally 

well conducted, taking into account the lifetime of the study animal, that gross necropsy and 

histopathology were completed on all suitable animals, and that percentages of the maximum tolerated 

dose were administered to determine carcinogenic response. It is limited because the unusually low 

survival of males in the TG-Penta control group left fewer control animals at long-term risk of developing 

tumors. 

EPA has classified pentachlorophenol as a Group B2 substance (probable human carcinogen) (IRIS 

2001). A cancer potency factor of 0.12 (mg/kg/day)-1 was calculated by IRIS (2001) based on the NTP 

(1989) data. This cancer potency factor translates to estimated upper-bound unit risk levels of 9x10-3, 
PENTACHLOROPHENOL 68 

3. HEALTH EFFECTS 

9x10-4, 9x10-5, 9x10-6, and 9x10-7 mg/kg/day for cancer risks of 1 in 1,000, 1 in 10,000, 1 in 100,000, 1 in 

1 million and 1 in 10 million respectively (see Figure 3-1). 

The CELs for pentachlorophenol are recorded in Table 3-1 and plotted in Figure 3-1, and the estimated 

upper-bound human cancer risk levels are plotted in Figure 3-1. 

3.2.3 Dermal Exposure 

Data on the toxicity of pentachlorophenol in humans exposed via dermal contact come from a number of 

case reports and studies in individuals applying wood preservative products containing pentachlorophenol, using pesticides containing sodium pentachlorophenate, or children exposed to pentachlorophenol 

used in the laundering of diapers and bedding. The primary route of exposure is believed to be dermal 

contact, although inhalation exposure also occurred. Studies in which inhalation exposure was the 

primary route and dermal contact the secondary route are discussed in Section 3.2.1 Inhalation Exposure. 

No studies considered suitable for presentation in a table describing significant levels of dermal exposure 

to pentachlorophenol were found. 

3.2.3.1 Death 

In most instances, death in humans exposed to pentachlorophenol was a result of occupational exposure 

or use of pentachlorophenol-containing products in the home by individuals who did not employ proper 

precautionary measures. All of these reports are limited in that the possibility of concurrent exposure to 

other potentially toxic substances in technical-grade pentachlorophenol and concurrent exposure to other 

toxic substances (e.g., lindane, dieldrin) cannot be excluded, and because the pentachlorophenol exposure 

level and duration cannot be quantified because appropriate measurements were not taken at the time. 

Deaths were also seen in human infants exposed to pentachlorophenol used in the laundering of diapers 

and bedding. Though the primary route of exposure in all of these studies was believed to be dermal, the 

probability that inhalation exposure also occurred must be considered. It should be noted that 

occupational exposure to pentachlorophenol has been strictly limited not only by use patterns but by 

application procedures, and all household uses of pentachlorophenol have been banned. Therefore, 

exposure to pentachlorophenol resulting in death as described in this section is currently improbable, with 

the exception of hazardous waste workers involved in the clean up of pentachlorophenol-containing 

ponds or soils. It should also be noted that the deaths discussed below resulted from the use of 
PENTACHLOROPHENOL 69 

3. HEALTH EFFECTS 

formulations that likely had a different composition (e.g., presence of more impurities) than the pentachlorophenol that is currently used. 

In a case report, nine infants in a small nursery for newborns exhibited an illness characterized by high 

fever, profuse sweating, increased respiratory rate, labored breathing, tachycardia, hepatomegaly, 

irritability followed by lethargy, metabolic acidosis, proteinuria, increased blood urea nitrogen, and 

pneumonia or bronchiolitis (Smith et al. 1996). Two of the infants died. At autopsy, both infants showed 

fatty metamorphosis of the liver and one showed fatty vacuolar changes in the renal tubules. The 

remaining infants recovered after exchange transfusions and transfer to another hospital. The clinical 

findings and deaths were attributed to the use of pentachlorophenol in a mixture of synthetic phenolic 

derivatives in the hospital laundry as an antimildew agent. Pentachlorophenol was found in freshly 

laundered diapers and in the serum and urine of the infants. 

Five cases of fatal blood dyscrasias were reported. Reports followed exposures to technical-grade pentachlorophenol or pentachlorophenol of undefined purity for 1-month to 4-year periods—three as a result of 

industrial exposure and two from home use (Roberts 1963, 1981, 1990). The cause of death in all cases 

was reported to be either aplastic anemia or red blood cell aplasia. Clinical signs, chemistries, and 

postmortem findings revealed functional and degenerative changes in most organ systems. Deaths 

attributed to pentachlorophenol were also reported in a male working as a wood preserver for 1 week 

(Bergner et al. 1965), 5 herbicide sprayers exposed once (Gordon 1956), and nine sawmill workers 

exposed for 3–30 days (Menon 1958). Deaths reported by Gray et al. (1985), Bergner et al. (1965), and 

Menon (1958) were all due to hyperthermia that resulted from uncoupling of oxidative phosphorylation 

by pentachlorophenol. Manifestations of overexposure were chiefly those associated with hyperthermia: 

flushing, intense thirst, sweating, weakness, and occasionally, muscle spasms. Toxic effects seen in these 

fatalities will be discussed in sections dealing with specific organ toxicity. Hyperthermia is the major 

factor leading to death following fatal pentachlorophenol exposure in humans. 

One report of death following dermal exposure in experimental animals was found in the reviewed 

literature (Deichmann et al. 1942). Eight out of 20 rabbits administered dermal applications of 4% pentachlorophenol (purity not indicated) in fuel oil for 6–61 weeks died of unspecified causes. The vehicle 

contained known toxic substances (e.g., polyaromatic hydrocarbons), which may have contributed to the 

lethal effects observed. 
 

 

 

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3. HEALTH EFFECTS 

3.2.3.2 Systemic Effects 

Most of the literature reviewed concerning systemic effects of dermal exposure to pentachlorophenol in 

humans described case reports of individuals exposed either occupationally or in the home during misuse 

of pentachlorophenol-containing solutions as a result of failure to adhere to appropriate precautionary 

measures. The predominant route of exposure in such cases is dermal, but the possibility of some 

inhalation exposure cannot be ruled out. All of these reports are limited because the possibility of 

concurrent exposure to other potentially toxic substances in technical-grades of pentachlorophenol cannot 

be excluded, and because the pentachlorophenol exposure level and duration were not quantified. Some 

of the effects observed may be secondary to hyperthermia generated by uncoupling of oxidative 

phosphorylation (see Section 2.5). 

No studies were located regarding cardiovascular, musculoskeletal, endocrine, or ocular effects in humans 

or respiratory, cardiovascular, gastrointestinal, musculoskeletal, hepatic, renal, endocrine, or ocular 

effects in animals after dermal exposure to pentachlorophenol. 

Respiratory Effects. In a case report, nine infants in a small nursery for newborns exhibited 

increased respiratory rate and labored breathing from exposure to pentachlorophenol in a mixture of 

synthetic phenolic derivatives in diapers and linens from the hospital laundry (Smith et al. 1996). It is 

likely that these effects are secondary to hyperthermia rather than a direct effect on the respiratory tract. 

Gastrointestinal Effects. Except for anecdotal reports of abdominal pain, nausea, and vomiting in 

humans occupationally exposed to pentachlorophenol of undefined purity (Gordon 1956; Menon 1958), 

no studies were located regarding gastrointestinal effects in humans or animals following dermal 

exposure to pentachlorophenol. 

Hematological Effects. Incidents of fatal hematological disorders were found in case reports 

following exposure (level and duration not specified) to technical-grade pentachlorophenol or pentachlorophenol of undefined purity as a result of predominantly dermal exposure. Thirteen cases of aplastic 

anemia, pure red blood cell aplasia, or severe pancytopenia with abnormal marrow have been reported in 

individuals using pentachlorophenol-containing wood preservative products, eight of which resulted in 

death (Roberts 1981, 1990). Aplastic anemia was also diagnosed in an individual using pentachlorophenol in the renovation of an old home (Rugman and Cosstick 1990). A case of intravascular hemolysis 

was attributed to use of a insecticide containing pentachlorophenol (Hassan et al. 1985). 
 

 

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3. HEALTH EFFECTS 

Hepatic Effects. Most of the studies reviewed concerning hepatic effects of dermal exposure to 

pentachlorophenol in humans described case reports of individuals exposed either occupationally or in the 

home following the use of pentachlorophenol-containing solutions by individuals who did not employ 

appropriate precautionary measures. Information regarding pentachlorophenol-induced hepatic toxicity 

in humans following dermal exposure, discussed below, is subject to some doubt regarding the extent to 

which the adverse effects seen can be attributed to pure pentachlorophenol. Hepatic enlargement has 

been observed in herbicide sprayers (Gordon 1956), and in neonates exposed for a short time via 

contaminated diapers and bed linen in a hospital nursery (Armstrong et al. 1969; Robson et al. 1969; 

Smith et al. 1996). Autopsy findings in those affected individuals who died revealed fatty infiltration of 

the liver (in the neonates) and severe centrilobular congestion with hepatocellular fat accumulation (in the 

chemical worker). Centrilobular degeneration was also observed in a liver specimen from a worker who 

dipped wood in a preservative that contained 4.1% pentachlorophenol every day for 1 week (Bergner et 

al. 1965). In an epidemiologic study of male factory workers who brushed technical-grade pentachlorophenol onto wood strips, sometimes without gloves, serum biliary acid concentrations were elevated in 

the high-exposure group, but not the low-exposure group, compared with controls. Exposure was 

assessed by measurement of pentachlorophenol concentrations in plasma and urine (Colosio et al. 1993b). 

The presence of elevated concentrations of bile acids in serum is a sensitive indicator of liver dysfunction 

(Franco et al. 1986). Evidence of liver damage was seen in an epidemiologic study of adult males 

occupationally exposed to pentachlorophenol in wood-treatment plants or as farmers or pest control 

operators in Hawaii (Klemmer 1972). This evidence consisted of elevated levels of serum alanine 

aminotransferase (ALT) and asparate aminotransferase (AST) following chronic, predominantly dermal 

exposure to technical-grade pentachlorophenol or pentachlorophenol of undefined purity. Hyperthermia 

induced by pentachlorophenol may be a major factor leading to liver injury. 

Renal Effects. Four reports were found that described renal toxic effects following dermal exposure 

to pentachlorophenol in humans. All involved either occupational exposure or accidental poisoning with 

the predominant route of exposure being dermal, but the possibility of inhalation exposure cannot be 

excluded. In one instance, a 3-year-old girl was exposed to pentachlorophenol of undefined composition 

via a pesticide-contaminated domestic water supply. Transient disruption of acid-base equilibrium and 

metabolic balance as evidenced by acidosis, aminoaciduria, and ketonuria suggested the occurrence of 

renal dysfunction in this child (Chapman and Robson 1965). In a case study of nine infants, metabolic 

acidosis, proteinuria, and increased blood urea nitrogen were found following exposure of the infants to 

pentachlorophenol of undefined composition in diapers and bedding at a hospital that used pentachlorophenol in the hospital laundry as an antimildew agent. Fatty vacuolar changes in the renal tubules were 
 

PENTACHLOROPHENOL 72 

3. HEALTH EFFECTS 

noted in one of the two infants that died (Smith et al. 1996). An autopsy conducted on a worker who 

dipped wood in a preservative that contained 4.1% pentachlorophenol every day for 1 week revealed mild 

renal tubular degeneration (Bergner et al. 1965). Finally, evidence for pentachlorophenol-induced 

impaired glomerular filtration and tubular function was reported in 18 workers employed at a woodtreatment facility (Begley et al. 1977). These findings consisted of depressed creatinine clearance and 

phosphorus reabsorption. Considerable improvement in these symptoms was seen following a 20-day 

absence from work. These data suggest that the renal toxicant effects of technical-grade pentachlorophenol are reversible. The extent to which contaminants of technical-grade pentachlorophenol are 

responsible for the effects discussed above is not known. Hyperthermia may also be a mechanism of 

renal injury in individuals that are acutely overexposed to pentachlorophenol. 

Dermal Effects. Transient localized redness and pain subsequent to immersion of the hands in a 0.4% 

pentachlorophenol solution for 10 minutes were exhibited by an adult male (Bevenue et al. 1967). Two 

cases of pemphigus vulgaris and one of chronic urticaria (both examples of severe skin lesions) attributed 

to nonoccupational chronic pentachlorophenol exposure (i.e., via contact with wood treated with pentachlorophenol) have been described (Lambert et al. 1986). The dermal effects discussed above may have 

resulted from impurities present in the pentachlorophenol resulting from the manufacturing process. 

Pentachlorophenol-induced toxic effects on the skin of experimental animals have also been reported. A 

single application of pentachlorophenol of unspecified purity (1,111 mg/kg in 95% ethyl alcohol or 

150 mg/kg in pale paraffin oil) resulted in gross changes such as pronounced edema and inflammation 

leading to wrinkling, cracking, desquamation, and hair loss. Microscopic changes observed include 

widespread foci of atrophy and necrosis, thinning and disappearance of upper skin layers, and 

hyperkeratinization and hypertrophy of hair follicles (Deichmann et al. 1942). Single dermal applications 

of 250 mg/kg of a 10% aqueous solution of sodium pentachlorophenate of unspecified purity to rabbits 

did not result in dermal irritation. Repeated application of lower doses of pentachlorophenol (40 mg/kg in 

mineral oil) to rabbits for 21 days induced no irritation, whereas daily application of 10–50 mg/kg of a 

4% solution of pentachlorophenol in fuel oil for 6–61 weeks resulted in pronounced dermal effects, and 

daily application of 63 mg/kg of an aqueous sodium pentachlorophenate solution for 32 days was without 

effect (Deichmann et al. 1942). No evidence of histologic changes in the epidermis or pilosebaceous unit 

were noted after application of 0.036 mg of sodium pentachlorophenate of unspecified purity to a 

9 cm2

 area of the dorsal skin of hairless dogs once daily for 7 days. The toxic effects of dermal exposure 

to pentachlorophenol appear to be most severe following high-dose, acute exposure to pentachlorophenol 

in fuel oil. 
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3. HEALTH EFFECTS 

Acne was observed in rabbits following application of technical-grade pentachlorophenol to the ear, but 

was not observed following application of pure pentachlorophenol (Johnson et al. 1973), suggesting that 

the effects were due to contaminants rather than the pentachlorophenol. 

3.2.3.3 Immunological and Lymphoreticular Effects 

Two cases of pemphigus vulgaris and one of chronic urticaria (skin diseases with an immunologic 

etiology) have been attributed to nonoccupational exposure to pentachlorophenol (Lambert et al. 1986). 

Alterations in immune function were reported in patients who had been exposed for more than 6 months 

to pentachlorophenol-containing pesticides (composition not defined) (Daniel et al. 1995) and workers 

who brushed technical-grade pentachlorophenol onto wood strips (Colosio et al. 1993b). 

No studies were located regarding immunological effects in animals following dermal exposure to pentachlorophenol. 

3.2.3.4 Neurological Effects 

Numerous signs of central nervous system toxicity have been reported in case reports of individuals 

exposed to high levels of pentachlorophenol via dermal contact and inhalation exposure. The observed 

effects include intermittent delirium and convulsions (Chapman and Robson 1965) and irritability 

(Robson et al. 1969; Smith et al. 1996). It is likely that these are effects secondary to hyperthermia due to 

pentachlorophenol-induced uncoupling of oxidative phosphorylation. 

No studies were located regarding neurological effects in animals following dermal exposure to pentachlorophenol. 

3.2.3.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans and animals following dermal exposure 

to pentachlorophenol. 
 

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3. HEALTH EFFECTS 

3.2.3.6 Developmental Effects 

No studies were located regarding developmental effects in humans and animals following dermal 

exposure to pentachlorophenol. 

3.2.3.7 Cancer 

Epidemiological studies and case reports described in Section 3.2.1.7 (in which dermal exposure was also 

likely) provide evidence that exposure to pentachlorophenol may be associated with soft tissue sarcomas 

and non-Hodgkin’s lymphoma in humans. 

Only one study was located in which investigators topically administered pentachlorophenol to animals 

(Boutwell and Bosch 1959). These investigators applied a 20% solution of commercial grade pentachlorophenol in benzene to shaved dorsal skin of mice twice a week for 13 weeks. Mice were previously 

treated with a dose of 0.3% dimethylbenzanthracene (DMBA) in benzene to induce skin cancer. No 

increase in DMBA-induced skin tumors resulted from pentachlorophenol treatment. This study was 

designed to determine if pentachlorophenol was a tumor promoter and was therefore severely limited in 

its ability to detect a carcinogenic effect caused by pentachlorophenol because of administration of an 

insufficient dose over a short treatment period. However, based on results of this study, pentachlorophenol was inactive as a promotor of skin tumors in mice. 

3.2.4 Other Routes of Exposure 

Endocrine Effects. Studies in animals have shown that acute (single-dose, intraperitoneal injection) 

pentachlorophenol administration causes a marked, statistically significant decrease in serum total 

thyroxine levels in rats (van Raaij et al. 1991a). This decrease peaked 6–24 hours after administration, 

and thyroxine levels slowly returned to control values within 96 hours after administration. Further in 

vitro studies by these investigators revealed that the likely mechanism of action for this anti-thyroid effect 

was competition for serum protein thyroxine binding sites (van Raaij et al. 1991b). 
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3. HEALTH EFFECTS 

3.3 GENOTOXIC EFFECTS 

Numerous in vivo and in vitro studies have assessed the genotoxic potential of pentachlorophenol, and the 

results of these studies are presented in Tables 3-3 and 3-4, respectively. Three studies examined the 

clastogenic activity of pentachlorophenol in workers primarily exposed via inhalation. A marginal 

increase in chromosomal aberrations was found in the lymphocytes of workers exposed to pentachlorophenol or its sodium salt (Bauchinger et al. 1982). In contrast, studies by Wyllie et al. (1982) and 

Ziemson et al. (1987) did not find significant increases in the occurrence of chromosomal aberrations in 

their studies of workers. The occurrence of sister chromatid exchange was not increased in the 

lymphocytes of workers (Bauchinger et al. 1982; Ziemson et al. 1987). No other human in vivo 

genotoxicity studies were located. An increase in DNA adduct formation was observed in the liver of 

mice orally exposed to pentachlorophenol (Sai-Kato et al. 1995; Umemura et al. 1996), but not in the 

kidney or spleen (Sai-Kato et al. 1995), and positive results were seen in a coat color spot test in mouse 

embryos treated transplacentally with pentachlorophenol (Fahrig et al. 1978). In other in vivo assays, no 

evidence of genotoxicity was observed; the assays included sex-linked recessive lethal mutations in 

Drosophila melanogaster (Fahrig 1974; Fahrig et al. 1978; Vogel and Chandler 1974), micronuclei 

formation in rats and mice (NTP 1999), and gene mutations and recombination in a mouse spot test 

(Fahrig and Steinkamp-Zucht 1996). 

No alterations in the occurrence of gene mutations (Andersen et al. 1972; Donnelly et al. 1998;Lemma 

and Ames 1975; Markiewicz et al. 1996; Moriya et al. 1983; NTP 1999; Simmon et al. 1977; Waters et al. 

1982) or DNA damage (Fahrig 1974; Waters et al. 1982) were observed in bacterial systems, with the 

exception of one study that reported positive activity in the rec assay using Bacillus subtilis (Waters et al. 

1982). In yeast, pentachlorophenol induced gene mutations (Fahrig 1974; Fahrig et al. 1978) and genetic 

recombination (Fahrig et al. 1978; Waters et al. 1982). Weak clastogenic activity was observed in 

chromosomal aberration assays in human lymphocyte (Fahrig 1974) and in chromosomal aberration and 

sister chromatid exchange assays in Chinese hamster ovary cells (NTP 1999). No significant increases in 

the occurrence of DNA damage (adduct formation or single-strand breaks) were seen in mammalian cells 

(Dalhaus et al. 1996; Ehrlich 1990; Wang and Lin 1995). 

A few studies were found regarding the genotoxic potential of pentachlorophenol metabolites. 

Tetrachloro-p-hydroquinone (TCHQ), (isomer not specified) but not tetrachlorocatechol, induced a doserelated and significant mutagenic response in Chinese hamster V-79 cells in the absence of exogenous 

metabolic activation (Jansson and Jansson 1991). The para isomer of TCHQ, but not the ortho isomer, 
Table 3-3. Genotoxicity of Pentachlorophenol In Vivo 

Species (test system) End point Results Reference Drosophila melanogaster spermatocytes Human lymphocytes (occupational exposure) Human lymphocytes (occupational exposure) Human lymphocytes (occupational exposure) Human lymphocytes (occupational exposure) Human lymphocytes (occupational exposure) B6C3F1 mouse (oral exposure) Mouse bone marrow (intraperitoneal exposure) Rat bone marrow (intraperitoneal exposure) Mouse embryonic cells (transplacental exposure) Mouse/spot test Mouse/spot test 

Sex-linked recessive lethal mutation Chromosomal aberrations Chromosomal aberrations Chromosomal aberrations Sister chromatid exchange Sister chromatid exchange DNA adduct formationMicronuclei Micronuclei Gene mutation 

Gene mutation Recombination 

– Fahrig 1974; Fahrig 

Chandler 1974

(+) Bauchinger et al. 19

– Wyllie et al. 1982

– Ziemsen et al. 1987

– Bauchinger et al. 19

– Ziemsen et al. 1987

+ Sai-Kato et al. 1995

– NTP 1999– NTP 1999

(+) Fahrig et al. 1978

– Fahrig and Steinkam

– Fahrig and Steinkam

 – = negative results; + = positive results; (+) = weakly positive results 
Table 3-4. Genotoxicity of Pentachlorophenol and its Metabolites In Vitro 

Results 

Species (test system) End point 

With activation 

Without activation Reference 

Pentachlorophenol Prokaryotic organisms: 

Salmonella typhimurium Gene mutation – – Donnelly et al. 1998; Mar

Moriya et al. 1983; NTP 11977; Waters et al. 1982 

S. typhimurium /spot test Gene mutation NT – Andersen et al. 1972; LemS. typhimurium (mouse host-mediated assay) 

Gene mutation – NT Buselmaier et al. 1973 

Invertebrate animal cells: Moriya et al. 1983; Simmo

Waters et al. 1982 

E. coli /spot test Serratia marcescens /spot test Bacillus subtilis /rec- assay E. coli pol A 

Eukaryotic organisms: 

Fungi: 

Saccharomyces cerevisiae MP-1 S. cerevisiae aAeZ S. cerevisiae MP-1/intergenic recombination 

Gene mutation 

DNA damage 

DNA damage 

DNA damage 

Gene mutation 

Recombination 

Recombination 

NT

NT

NT

NT

NT

NT

NT

 – 

– 

+ 

– 

+ 

+ 

– 

Waters et al. 1982 

Fahrig 1974 

Waters et al. 1982 

Waters et al. 1982 

Fahrig et al. 1978 Fahrig 1974 

Fahrig et al. 1978 

S. cerevisiae MP-1/intergenic recombination 

Recombination NT + Fahrig et al. 1978 

S. cerevisiae Recombination + + Waters et al. 1982 
Table 3-4. Genotoxicity of Pentachlorophenol and its Metabolites In Vitro (contin

Results 

With Without 

Species (test system) End point activation activation Reference 

Mammalian cells: 

Human lymphocytes Chromosomal 

aberrations 

NT (+) Fahrig 1974 

Chinese hamster ovary cells Chromosomal 

aberrations 

(+) – NTP 1999 

Chinese hamster ovary cells DNA damage NT – Ehrlich 1990 

Chinese hamster ovary cells Sister chromatid 

exchange 

– (+) NTP 1999 

Chinese hamster V79 cells DNA damage 

(8-OH-dG adduct) 

NT – Dahlhaus et al. 1996 

Chinese hamster V79 cells DNA damage 

(single-strand breaks) 

NT – Dahlhaus et al. 1996 

Mouse embryonic fibroblast cells DNA damage 

(single-strand breaks) 

(+) – Wang and Lin 1995 

Tetrachloro-o-benzoquinone Mammalian cells: 

Chinese hamster V79 cells DNA damage 

(8-OH-dG adduct) 

NT + Dahlhaus et al. 1996 

Chinese hamster V79 cells DNA damage 

(single-strand breaks) 

NT – Dahlhaus et al. 1996 

Tetrachloro-p-benzoquinone Mammalian cells: 

Chinese hamster V79 cells DNA damage 

(8-OH-dG adduct) 

NT + Dahlhaus et al. 1996 

Chinese hamster V79 cells DNA damage 

(single-strand breaks) 

NT + Dahlhaus et al. 1996 
Table 3-4. Genotoxicity of Pentachlorophenol and its Metabolites In Vitro (contin

Results 

Species (test system) End point 

With activation 

Without activation Reference 

Tetrachloro-o-hydroquinone Mammalian cells: 

Chinese hamster V79 cells Chinese hamster V79 cells 

Tetrachlorop-hydroquinone Mammalian cells: 

DNA damage 

(8-OH-dG adduct) 

DNA damage 

(single-strand breaks) 

NT NT 

– – 

Dahlhaus et al. 1996 Dahlhaus et al. 1996 

Chinese hamster ovary cells Chinese hamster V79 cells Chinese hamster V79 cells 

Tetrachlorohydroquinone Mammalian cells: 

DNA damage 

DNA damage 

(8-OH-dG adduct) 

DNA damage 

(single-strand breaks) 

NT 

NT NT 

+ 

+ + 

Ehrlich 1990 

Dahlhaus et al. 1996 Dahlhaus et al. 1996 

Chinese hamster V79 cells Gene mutation NT + Jansson and Jansson 19

– = negative result; + = positive result; (+) = weakly positive result; DNA = deoxyribonucleic acid; 8-OH-dG = 8-hydroxydeoxyguanosine; 
PENTACHLOROPHENOL 80 

3. HEALTH EFFECTS 

induced DNA damage in Chinese hamster V79 cells as evidenced by DNA single-strand breaks and an 

increase in the amount of 8-hydroxydeoxyguanosine in DNA (Dahlhaus et al. 1996). In the same study, 

the para isomer of tetrachlorobenzoquinone produced DNA single-strand breaks and an increase in the 

amount of 8-hydroxydeoxyguanosine in DNA, whereas the ortho isomer of this compound produced an 

increase in the amount of 8-hydroxydeoxyguanosine in DNA but did not produce DNA single-strand 

breaks (Dahlhaus et al. 1996). TCHQ was also found to exert a severe cytotoxic effect and cause marked 

DNA damage (i.e., single-strand breaks and/or alkali-labile sites) in Chinese hamster ovary cells; the 

parent compound was weakly cytotoxic but not genotoxic at comparable levels (Ehrlich 1990). 

3.4 TOXICOKINETICS 

Pentachlorophenol is efficiently absorbed following inhalation, oral, and dermal exposure. Absorbed 

pentachlorophenol is distributed to the liver, lungs, kidneys, blood, fat tissues, and brain. The binding of 

pentachlorophenol to plasma proteins plays a significant role in the distribution of pentachlorophenol 

(Braun et al. 1977; Gómez-Catalán et al. 1991). Results from animal and human studies indicate that 

pentachlorophenol is not completely metabolized, as evidenced by a large portion of the administered 

dose being excreted in urine unchanged in all species studied. Pentachlorophenol binds extensively to 

plasma proteins as discussed in Section 3.4.2.2. Pentachlorophenol has a greater binding affinity for 

thyretin, a major thyroxine transport protein in the rat, than thyroxine itself (den Besten et al. 1991), and 

the binding of pentachlorophenol to thyretin is likely responsible for its adverse effect on thyroid 

homeostasis. The available human and animal data indicate that metabolism of pentachlorophenol does 

occur in the liver, and the major pathways are conjugation to form the glucuronide and oxidative 

dechlorination to form tetrachlorohydroquinone (TCHQ). However, recent studies in rats and mice 

following oral administration of pentachlorophenol (Lin et al. 1997; Waidyanatha et al. 1994, 1996) 

suggest that the metabolism of pentachlorophenol can also proceed through the quinols TCHQ and 

Cl4CAT via microsomal cytochrome P 450 enzymes and that these quinols can be oxidized via 

semiquinone intermediates (tetrachloro-1,2-semiquinone [Cl4-1,2-SQ] and tetrachloro-1,4-semiquinone 

[Cl4-1,4-SQ]) into the corresponding quinones (tetrachloro-1,2-benzoquinone [Cl4-1,2-BQ] and 

tetrachloro-1,4-benzoquinone [Cl4-1,4-BQ]). Both the quinones and semiquinones are electrophilic and 

can bind to cellular macromolecules (Lin et al. 1997). Horseradish peroxidase catalyzed the oxidation of 

pentachlorophenol to Cl4BQ in vitro via a phenoxyl radical intermediate (Samokyszyn et al. 1995). The 

study authors suggest that this is a potential in vivo metabolic step that could be catalyzed by mammalian 

peroxidases, including prostaglandin H synthase, myeloperoxidase, salivary peroxidase, lactoperoxidase, 

or uterine peroxidase. 
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The primary route of pentachlorophenol elimination in all species studied, including humans, by all routes 

of exposure, is urine. Approximately 74 and 12% (total of 86%) of pentachlorophenol ingested by 

humans was eliminated as pentachlorophenol and its glucuronide conjugate, respectively (Braun et al. 

1979). In rodents, from 60– 83% of the administered oral dose is eliminated in the urine (Ahlborg et 

al. 1974; Braun et al. 1977; Larsen et al. 1972; Reigner et al. 1991); in monkeys, 45–75% of the 

administered oral dose is eliminated in the urine (Braun and Sauerhoff 1976) (see Section 3.4.4.2 for a 

discussion of the metabolites of pentachlorophenol excreted in each species). Fecal elimination of pentachlorophenol and its metabolites accounted for 4% of the administered oral dose in humans, 4–34% of the 

administered oral dose in rodents, and 4–17% in monkeys. Only trace amounts were eliminated in 

expired air. The pharmacokinetic profile of pentachlorophenol excretion following single doses is 

species- and possibly sex-dependent. Elimination was rapid and biphasic in rats (Braun et al. 1977; 

Reigner et al. 1991) and slow and first-order in monkeys and humans following oral exposure (Braun and 

Sauerhoff 1976; Braun et al. 1979). Enterohepatic circulation and plasma protein binding influence the 

elimination kinetics of pentachlorophenol, but no data are available to assess whether the elimination 

kinetics of pentachlorophenol are dependent on its concentration in blood. 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

There are limited data on the absorption of inhaled pentachlorophenol in humans. In an attempt to 

measure inhalation absorption of pentachlorophenol in humans, 2 volunteers were exposed to pentachlorophenol in an enclosed area for 45 minutes while they applied pentachlorophenol to wood with a 

brush (Casarett et al. 1969). Ambient pentachlorophenol concentrations in air were 0.230 and 

0.432 ng/m3

. The extent of pentachlorophenol absorption in these 2 subjects was calculated to be 88 and 

76% of the total potential inhaled dose, based on measurements of respiratory rates during exposure, total 

urinary pentachlorophenol recovered for up to 1 week postexposure, and tidal volume estimates. These 

data indicate that pentachlorophenol is readily absorbed through the lungs of humans. These data are 

supported by the finding of increased plasma and urine pentachlorophenol levels in exposed workers 

(Casarett et al. 1969; Jones et al. 1986; Pekari et al. 1991) and in residents of log homes treated with 

pentachlorophenol (Cline et al. 1989; Hosenfeld et al. 1986). 

Pulmonary absorption of pentachlorophenol in rats has been demonstrated to occur readily; 70–75% of 

radioactivity from a single 20-minute inhalation exposure (at a concentration calculated by the authors to 
PENTACHLOROPHENOL 82 

3. HEALTH EFFECTS 

be equivalent to 5.7 mg [14C]-pentachlorophenol/kg) was recovered in urine, plasma, liver, and lung by 

24 hours postexposure (Hoben et al. 1976c). 

3.4.1.2 Oral Exposure 

Results of studies in humans (Braun et al. 1979; Uhl et al. 1986) and animals (Ahlborg et al. 1974; Braun 

and Sauerhoff 1976; Braun et al. 1977; Meerman et al. 1983; Reigner et al. 1991) indicate that pentachlorophenol and its sodium salt are readily absorbed following oral administration. Oral absorption of 

pentachlorophenol (as the sodium salt in water) in humans was determined to be first order, with peak 

blood levels of 0.248 μg/mL pentachlorophenol being achieved within 4 hours of ingestion of 0.1 mg 

sodium pentachlorophenate/kg by four healthy male volunteers (Braun et al. 1979). The average half-life 

of absorption was calculated to be approximately 1.3 hours, indicating that oral absorption of pentachlorophenol in humans is rapid. 

Oral absorption of pentachlorophenol by rats and monkeys was compared following administration of 

single oral doses in corn oil of 10 mg [14C]-pentachlorophenol/kg (monkeys) (Braun and Sauerhoff 1976) 

and 10 or 100 mg [14C]-pentachlorophenol/kg (rats) (Braun et al. 1977). In both species, absorption 

through the gastrointestinal tract was rapid; females in both species exhibited faster absorption than males 

as evidenced by different rate constants of absorption. These rate constants were 1.95 hour-1 and 

1.52 hour-1 for male and female rats, respectively, and 0.215 hour-1 and 0.383 hour-1 for male and female 

monkeys, respectively. The half-lives of absorption were 3.64 and 1.81 hours, for male and female 

monkeys, respectively. Peak blood levels of approximately 60 μg pentachlorophenol/g plasma were 

achieved in both sexes of rat within 4–6 hours, and peak plasma levels of 10–30 μg pentachlorophenol/g 

plasma were reached by 12–24 hours in both sexes of monkey. Absorption of pentachlorophenol through 

the gastrointestinal tract was extensive in both species following administration of a single dose of 

[

14C]-pentachlorophenol as evidenced by more than 90% recovery of radioactivity in urine, feces, expired 

air, tissues, and carcass. 

Similar results were obtained in another study in rats using a lower dose (2.5 mg/kg) of pentachlorophenol (Reigner et al. 1991). Peak plasma concentrations (7.3±2.8 μg/mL) were achieved between 

1.5 and 2 hours after administration. Absorption appeared to be first order and fit a one-compartment 

model in three of five animals tested. Half-life of absorption varied between 0.25 and 1.50 hours. Based 

on the results of this study, the authors concluded that pentachlorophenol is virtually completely absorbed 

after oral administration in rats. These same investigators studied the pharmacokinetics of pentachloro­
PENTACHLOROPHENOL 83 

3. HEALTH EFFECTS 

phenol in B6C3F1 mice following the administration of a single gavage dose of 15 mg/kg (Reigner et al. 

1992b). Peak plasma concentrations (28±7 μg/mL) were achieved between 1.5 and 2 hours after 

administration. Half-life of elimination from the blood averaged 5.8±0.6 hours. Based on the results of 

this study, the study authors concluded that pentachlorophenol is virtually completely absorbed after oral 

administration in mice. 

Absorption of pentachlorophenol (>99%) from the gastrointestinal tract of F344 rats after gavage doses of 

9.5 or 38 mg/kg in an aqueous methylcellosolve vehicle was first order, with an absorption half-life of 

about 1.3 hours. The absorption rate of pentachlorophenol, determined after administration of 302 or 

1,010 ppm concentrations in the diet (approximately 21 or 64 mg/kg), was comparable to that obtained 

from aqueous methylcellosolve gavage formulations, but the bioavailability of pentachlorophenol 

administered in the diet (52% at 302 ppm and 30% at 1,010 ppm) was markedly lower than the 

bioavailability of pentachlorophenol administered by gavage (100% at 9.5 mg/kg and 86% at 38 mg/kg). 

Following gavage administration of a single dose of 9.5 or 38 mg/kg pentachlorophenol to the male rats, 

peak plasma concentrations of pentachlorophenol appeared in 2–4 hours and the concentration was dosedependent. In males administered pentachlorophenol in the diet for 5 days, diurnal variation was seen in 

the serum concentration of pentachlorophenol, with increases during the 12-hour dark period and 

decreases during the 12-hour light period (Yuan et al. 1994). 

The extent of absorption of pentachlorophenol or sodium pentachlorophenate from the gastrointestinal 

tract was studied in rats allowed free access to drinking water that contained a 1.4 millimolar (mM) 

solution of sodium pentachlorophenate (288 mg/L) or food that contained 350 ppm pentachlorophenol or 

sodium pentachlorophenate (Meerman et al. 1983). Based on analysis of pentachlorophenol plasma 

concentrations over a 24-hour period and comparison with parameters obtained after intravenous 

administration, the study authors concluded that absorption of pentachlorophenol and sodium pentachlorophenate under these conditions was essentially complete. 

3.4.1.3 Dermal Exposure 

Using human abdominal skin (dermis and epidermis) obtained at autopsy, it has been demonstrated that 

62% of pentachlorophenol in diesel oil solution penetrated skin in vitro, while only 16% of an aqueous 

solution of sodium pentachlorophenate penetrated skin (Hortsman et al. 1989). Thus, it appears that 

pentachlorophenol is absorbed to a much greater extent in an oily solution than in an aqueous solution 

following dermal exposure in humans. The only other available information on dermal absorption of 
PENTACHLOROPHENOL 84 

3. HEALTH EFFECTS 

pentachlorophenol and its salts by humans comes from occupational case studies in which elevated levels 

of pentachlorophenol have been detected in urine and plasma of workers who handle pentachlorophenoltreated wood and/or do not wear adequate personal protective gear when working in areas where pentachlorophenol is being sprayed (Jones et al. 1986). In addition, numerous case reports describe occurrence 

of severe toxicity and/or death in individuals whose exposure to pentachlorophenol is presumed to be 

predominantly via the dermal route (Gray et al. 1985; Robson et al. 1969; Smith et al. 1996; Wood et al. 

1983). 

Animal studies support the human findings that pentachlorophenol is absorbed across the skin. In a 

Rhesus monkey study, pentachlorophenol was well absorbed following percutaneous application in soil 

or in acetone (Wester et al. 1993). Under the conditions of this study (0.7 μg/cm2

 in soil and 0.8 μg/cm2 

in acetone of 14C-pentachlorophenol applied for 24 hours to abdominal skin), 24.4±6.4% of the applied 

dose in soil and 29.2±5.8% of the applied dose in acetone were absorbed. In an in vivo swine model, 

40 μg/cm2

 [14C-UL]-pentachlorophenol was applied occlusively or nonocclusively in a soil-based mixture 

to a clipped abdominal site of 8–10-week-old female pigs (Qiao et al. 1997). By 408 hours after dosing, 

total radiolabel absorption was 29.08% under nonocclusive conditions and 100.72% under occlusive 

conditions. When antibiotics (neomycin sulfate, bacitracin, and polymyxin B) were codosed with 

occlusively applied [14C-UL]-pentachlorophenol, total radiolabel absorption by 408 hours was 86.21%. 

The antibiotics were selected to provide a combined wide spectrum of antimicrobial and antifungal 

activity. If it assumed that the antibiotics had no direct effect on the dermal absorption of pentachlorophenol, then the inhibition of dermal absorption by the antibiotics suggests that degradation of pentachlorophenol by skin microorganisms may play a role in dermal absorption. The percentage of applied 

dose present in blood or plasma reached maxima at approximately 96 hours under occlusive conditions 

(with or without antibiotics) and 144 hours under nonocclusive conditions. These results indicate that 

pentachlorophenol is readily absorbed following dermal exposure and is bioavailable from soil. 

3.4.2 Distribution 

There are limited data on the distribution of pentachlorophenol in humans. The distribution of 

background levels of pentachlorophenol were measured in the urine and tissues collected during the 

autopsy of 21 humans (Grimm et al. 1981). The highest concentrations of pentachlorophenol were found 

in the liver (0.067 μg/g), kidneys (0.043 μg/g), brain (0.047 μg/g), spleen (0.019 μg/g), and body fat 

(0.013 μg/g). The median pentachlorophenol levels in the urine and blood were 0.0044 and 0.033 μg/mL, 

respectively. Low levels of pentachlorophenol were found in human breast milk from West Germany 
PENTACHLOROPHENOL 85 

3. HEALTH EFFECTS 

(Gebefugi and Korte 1983) and Slovakia (Veningerova et al. 1996). The source of pentachlorophenol 

was not specified. It is possible that the pentachlorophenol in breast milk was not due to pentachlorophenol exposure, but rather to exposure to other industrial chemical (e.g., hexachlorobenzene, 

hexachlorocyclohexane), which are metabolized to pentachlorophenol. Since pentachlorophenol was 

detected in 64% of urine samples gathered from 1,000 human adults living in the United States (Hill et al. 

1995), it is likely that pentachlorophenol is present in breast milk in U.S. citizens. Because pentachlorophenol is a metabolite of a number of environmental contaminants, it is not known if the pentachlorophenol present in the urine, breast milk, or tissues resulted from exposure to pentachlorophenol. The 

discussion of experimental animal studies follows. 

3.4.2.1 Inhalation Exposure 

Information regarding distribution of pentachlorophenol following inhalation exposure in animals is 

limited. Distribution of pentachlorophenol was evaluated following single and multiple (five) 20-minute 

inhalation exposures to concentrations calculated by the authors to be equivalent to a dose of 5.7 mg 

pentachlorophenol/kg body weight by measuring concentrations of pentachlorophenol in liver, lungs, 

blood, and urine only (Hoben et al. 1976c). Rapid distribution away from the site of exposure was 

apparent after a single exposure since only 1.8% of the administered dose was present in lungs 

immediately after exposure. By 24 hours postexposure, approximately 55% of the administered dose was 

recovered in urine, 7% in plasma, 9% in liver, and 0.7% in lung. These data indicate that pentachlorophenol was cleared rapidly, and only small amounts accumulated in the tissue samples studied. Repeatedexposure experiments support the observation that pentachlorophenol does not accumulate in rats 

following inhalation exposure. By 24 hours after the last (fifth) exposure, 70% of the administered dose 

was recovered in urine, 5% in plasma, 4% in liver, and 0.3% in lung. It is not clear from these data where 

pentachlorophenol was distributed immediately following exposure, but high levels in urine suggest that 

pentachlorophenol was cleared rapidly and did not reach an appreciable body burden following repeated 

exposure. Binding of pentachlorophenol to plasma proteins influences its distribution (see 

Section 3.4.2.2). Binding of pentachlorophenol to plasma proteins varies linearly with increasing dose 

following inhalation exposure (Hoben et al. 1976d). No studies were located regarding distribution of 

pentachlorophenol in animals following long-term inhalation exposure. 
PENTACHLOROPHENOL 86 

3. HEALTH EFFECTS 

3.4.2.2 Oral Exposure 

Distribution studies in rats conducted 9 days after oral administration of a single dose of 10 mg 

[

14C]-pentachlorophenol/kg body weight in corn oil demonstrated that the highest levels of radioactivity 

are found in liver and kidneys and lower levels are found in brain and fat tissue. Radioactivity was also 

detected in lungs, testes, ovaries, heart, and adrenal glands. Levels of radioactivity were uniformly higher 

in plasma and tissues of females as compared to males, though the distribution pattern was qualitatively 

the same (Braun et al. 1977). A similar distribution pattern was observed by Larsen et al. (1972) in rats 

40 hours after gavage administration of 37–41 mg [14C]-pentachlorophenol/kg body weight in corn oil. 

Larsen et al. (1975) administered a single oral dose of 60 mg/kg pentachloro[U-14C]phenol (99.54% 

radiochemical purity) to 14 rats on day 15 of gestation. Groups of 2 rats were sacrificed at 2, 4, 8, 12, 16, 

24, and 32 hours after dosing, and the distribution of administered dose was determined in blood serum, 

placentas, and fetuses. Tissue distributions, expressed as the percentage of administered dose per gram 

tissue, were 0.88% in blood serum, 0.20% in placentas, and 0.05% in fetuses at 2 hours after dosing. 

Peak amounts occurred in serum at 8 hours (1.12%), in placentas at 12 hours (0.28%), and in fetuses at 

12 hours (0.08%). By 32 hours after dosing, percentages of administered dose were 0.43% in serum, 

0.08% in placentas, and 0.04% in fetuses. The chemical nature of the radioactivity present in serum, 

placentas, and fetuses was not investigated. Since the administered pentachlorophenol did not have 100% 

radiochemical purity, it is possible that some of the radioactive material distributed in the fetuses was due 

to radioactive impurities. 

Following gavage administration of a single dose of 9.5 or 38 mg/kg pentachlorophenol (>99%) to male 

F344 rats, peak plasma concentrations of pentachlorophenol appeared in 2–4 hours and the concentration 

was dose dependent. In male F344 administered pentachlorophenol at 302 or 1,010 ppm concentrations 

in the diet (approximately 21 or 64 mg/kg) for 5 days, diurnal variation was seen in the serum 

concentration of pentachlorophenol, with increases during the 12-hour dark period and decreases during 

the 12-hour light period (Yuan et al. 1994). 

At the end of the 2-year dietary bioassay of pentachlorophenol (approximately 99% with one impurity, 

tetrachlorophenol) in F-344 rats (NTP 1999), mean plasma concentrations of pentachlorophenol were 

approximately proportional to pentachlorophenol concentrations in the feed, and plasma concentrations in 

females were higher than those in males. Plasma concentration of pentachlorophenol were 24, 44, and 
PENTACHLOROPHENOL 87 

3. HEALTH EFFECTS 

67 μg/mL in females and 17, 36, and 53 μg/mL in males at dietary concentrations of 200, 400, and 

600 ppm, respectively. 

Distribution of [14C]-pentachlorophenol was measured in 2 monkeys 360 hours after oral administration 

of a single dose of 10 mg [14C]-pentachlorophenol/kg body weight. Approximately 11% of administered 

radiolabel was found in the body at the time of analysis; 80% of this activity was in the liver and in the 

large and small intestines. These data suggest that the monkey differs from the rat with regard to 

distribution of orally absorbed pentachlorophenol. There appears to be extensive biliary secretion and 

enterohepatic circulation of pentachlorophenol in the monkey as evidenced by the long half-life of pentachlorophenol in the body of monkeys and the fact that most of the radiolabel still present in the body 

360 hours after administration was in the liver and large and small intestines (Braun and Sauerhoff 1976). 

Binding of pentachlorophenol to plasma proteins plays a significant role in the distribution of pentachlorophenol. Tissue/plasma ratios and renal clearance rates following oral administration of pentachlorophenol were much lower than would be predicted, based on the octanol/water partition coefficient 

and glomerular filtration rate (Braun et al. 1977). This could be explained by extensive binding of pentachlorophenol to plasma proteins. The authors subsequently demonstrated using an in vitro diafiltration 

technique that 95% of pentachlorophenol in plasma is protein bound (Braun et al. 1977). In another 

experiment in rats, 97.1±2.0% of the administered dose of pentachlorophenol was found bound to plasma 

proteins as compared to plasma lipoproteins (Gómez-Catalán et al. 1991). Protein binding may result in 

lower levels being distributed to tissues (i.e., liver and kidney) for metabolism and excretion and 

increased retention in the body. 

3.4.2.3 Dermal Exposure 

The distribution of radiolabelled pentachlorophenol was examined in female pigs following occlusive 

application of 40 μg/cm2

 [14C-UL]-pentachlorophenol (Qiao et al. 1997). The distribution of radiolabel 

17 days after dosing was as follows (highest to lowest): liver, lung, ovary, gall bladder, kidney, spleen, 

uterus, urinary bladder, heart, diaphragm, and brain. A large amount of the label was retained in the 

body, approximately 50–67% of the absorbed label was present in the tissues 17 days after exposure. 
PENTACHLOROPHENOL 88 

3. HEALTH EFFECTS 

3.4.2.4 Other Routes of Exposure 

Distribution of radioactivity in mice following intraperitoneal and subcutaneous administration of single 

doses of [14C]-pentachlorophenol has been reported (Jakobson and Yllner 1971). Only 0.4–6% of the 

administered dose was found in tissues 96 hours after intraperitoneal injection of 14.8–37.2 mg 

[

14C]-pentachlorophenol/kg body weight. The highest concentrations of radiolabel were found in the gall 

bladder, liver, stomach wall, and gastrointestinal contents, indicating the occurrence of biliary secretion of 

pentachlorophenol. Lesser amounts of radiolabel were found in the kidneys, heart, and brain. A similar 

distribution pattern was observed after subcutaneous administration of 50 mg [14C]-pentachlorophenol/kg 

body weight. The concentration of radiolabel in the liver remained high 1 week after dosing. These data 

are similar to those obtained after oral administration of pentachlorophenol. 

Dose- and time-dependent uptake of pentachlorophenol (purity not stated) into the cerebrospinal fluid of 

rats was demonstrated following single intraperitoneal injections of pentachlorophenol into rats at doses 

up to 17 mg/kg. Since similar doses of pentachlorophenol also significantly decreased the uptake of 

radiolabeled T4 into cerebrospinal fluid, the study authors suggested that pentachlorophenol may interact 

with the T4 binding site of transthyretin and compete with T4 for uptake into cerebrospinal fluid (van 

Raaij et al. 1994). This is a plausible explanation since the affinity of pentachlorophenol for the T4 

binding site on transthyretin is 2.5-fold greater than that of T4 itself (den Besten et al. 1991). 

Based on plasma concentrations and clearance rates, the volume of distribution of pentachlorophenol was 

estimated to be relatively small and approximately correspond to the volume of distribution of albumin 

and volume of extracellular fluid following intravenous injection of a single dose of 2.5 mg/kg to rats 

(Reigner et al. 1991). Similar results were obtained in mice (Reigner et al. 1992b). Following 

intravenous administration of 5 mg/kg pentachlorophenol (>99% purity) into rats, plasma concentrations 

tended to be slightly higher in males than in females during the first 12 hours. The volume of distribution 

was 0.13±0.006 L/kg in males and 0.19±0.04 L/kg in females, but the difference was not statistically 

significant (Yuan et al. 1994). 

Reigner et al. (1993) investigated the binding of radiolabeled pentachlorophenol to serum proteins in vitro 

using ultrafiltration. The percent unbound pentachlorophenol in serum was 1.37 in mice, 0.85 in rats, 

0.67 in monkeys, 0.53 in humans, and 0.43 in cows. These percentages correlated inversely with the total 

protein levels in the same serum samples. Percent unbound pentachlorophenol also correlated inversely 

with serum albumin concentrations with the exception of the cow, which had a lower albumin 
PENTACHLOROPHENOL 89 

3. HEALTH EFFECTS 

concentration than humans. These data suggest that the distribution of pentachlorophenol may be 

restricted due to extensive plasma protein binding. 

3.4.3 Metabolism 

Results from animal and human studies indicate that pentachlorophenol is not extensively metabolized, as 

evidenced by a large portion of the administered dose being excreted in urine unchanged in all species 

studied. Extensive plasma protein binding of pentachlorophenol discussed in Section 3.3.2.2 may 

account for the low degree of metabolism because protein-bound material is not readily distributed to 

tissues. However, available human and animal data indicate that metabolism of pentachlorophenol does 

occur in the liver, and the major pathways are conjugation to form glucuronide and oxidative 

dechlorination to form TCHQ. A summary of possible metabolic pathways for pentachlorophenol is 

presented in Figure 3-2. 

UDP-glucuronosyl transferase and sulfotransferases are involved in phase II metabolism of pentachlorophenol. Both of these enzymes are thought to be developmentally regulated (Leeder and Kearns 1997). 

Although the ontogeny of UDP-glucuronosyl transferase is isoform-specific, the adult level of activity 

seems to be achieved in humans by 6–18 months of age (Leeder and Kearns 1997). Ontogeny for the 

sulfotransferases seems to be more rapid than that for UDP-glucuronosyl transferase, and the activity for 

some isoforms of sulfotransferase may exceed adult levels during infancy and early childhood (Leeder 

and Kearns 1997). 

Mehmood et al. (1996) has provided evidence that human cytochrome P450 3A4 may metabolize pentachlorophenol to TCHQ in phase I metabolism of pentachlorophenol; however, the initial purity of the 

pentachlorophenol used in this study was not indicated. In humans, this enzyme has low activity in the 

first month of life, with approach toward adult levels by 6–12 months of postnatal age; adult activity may 

be exceeded between 1–4 years of age and then activity progressively declines, reaching adult levels at 

the conclusion of puberty (Leeder and Kearns 1997). By Western immunoblotting using monoclonal 

antibodies to identify the different P 450 isozymes, pure pentachlorophenol (>99%)was identified as an 

inducer of cytochrome P450 3A7 in studies in cultured rat hepatocytes, quail hepatocytes, and human 

hepatoma (Hep G2) cells (Dubois et al. 1996). In humans, functional activity of cytochrome P450 3A7 in 

the fetus is approximately 30–75% of adult levels (Leeder and Kearns 1997). 
URINARY METABOLITES 

COOH 

O H 

Glucuronic H

OH Acid HOH O H HO 

Cl Cl Cl Cl OH

URINE 

Cl Cl Cl Cl OH H

PCP Cl Cl H2SO4 PCP -Glu 

HOH 

O SO3H 

Cytochrome P450 Cl Cl 

Cl Cl 

Cl PCP - S 

COOH 

O H O OH Glucuronic H

Cl Cl Cl Cl Acid HOH O H HO

Cl Cl OH 

Cl Cl Cl Cl 2H O Cl Cl OH H OH TCQ TCHQ H2SO4 OH 

TCP -Glu 

HOH 

O SO3H 

Cl Cl 

Cl Cl 

OH TCP - S 

COOH 

Glucuronic
 O OH Acid HOH
 

Cl
 H Cl H 

Cl 

O H

O H HO

HOH 

H

Cl 

H OH 

Cl Cl 2H Cl Cl 

Cl TriCQ O OH 

OH TriCHQ H2SO4 

TriCP -Glu 

HOH 

O SO3H 

Cl H 

URINE Cl Cl

OH TriCP - S 

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3. HEALTH EFFECTS 

Figure 3-2. Proposed Metabolic Scheme for Pentachlorophenol 

PCP = pentachlorohenol; PCP-Glu = pentachlorophenol-β-glucuronide; PCP-S = pentachlorophenylsulfate;
 

TCHQ = tetrachloro-p-hydroquinone; TCP-Glu = tetrachlorophenol-β-glucuronide; TCP-S = tetrachlorophenylsulfate;
 

TCQ = tetrachloroquinone; Tri CHQ = trichloro-p-hydroquinone; Tri CP-Glu = trichlorophenyl-β-glucuronide;
 

Tri CP-S = trichlorophenylsulfate; Tri CQ = trichloro-p-quinone
 
PENTACHLOROPHENOL 91 

3. HEALTH EFFECTS 

3.4.3.1 Inhalation Exposure 

Ahlborg et al. (1974) analyzed urine from 2 workers employed as spraymen 24 hours after exposure to 

sodium pentachlorophenate that was presumably via the inhalation route. Both unchanged pentachlorophenol and TCHQ were identified (relative proportions were not specified), but no mention was made 

regarding the possible presence of glucuronide conjugates. Thus, at least oxidative dechlorination of 

pentachlorophenol occurs in humans exposed via inhalation. In rats, 70–75% of inhaled pentachlorophenol is excreted unchanged in urine following a single exposure (Hoben et al. 1976a). 

3.4.3.2 Oral Exposure 

Oral administration of small doses of pentachlorophenol (0.02–0.31 mg pentachlorophenol/kg) of $99% 

purity to volunteers resulted in excretion of unchanged pentachlorophenol (78% of administered dose) 

and pentachlorophenol glucuronide (12% of the administered dose) in urine and feces (Braun et al. 1979; 

Uhl et al. 1986). No TCHQ was identified. 

Studies in rats indicate that both metabolic pathways described above were operative following oral 

administration of pentachlorophenol, but most of the administered dose was excreted unchanged (Ahlborg 

et al. 1974; Braun et al. 1977; Renner 1989; Renner and Hopfer 1990). The following urinary metabolites 

were recovered and identified by gas chromatography from female Sprague-Dawley rats dosed with 

pentachlorophenol (>99% pure) for 28 days: 2,3,4,5-tetrachlorophenol; 2,3,4,6-tetrachlorophenol; 

2,3,5,6-tetrachlorophenol; tetrachlorocatechol (Cl4CAT); trichloro-1,4-benzenediol; tetrachloro1,4-benzenediol; tetrachlororesorcinol; trichlorohydroquinone; TCHQ; and traces of trichloro1,4-benzoquinone and tetrachloro-1,4-benzoquinone. The major metabolite was TCHQ, which was 

excreted mainly as a glucuronide conjugate (Renner and Hopfer 1990). Based on the urinary metabolites 

identified, the study authors concluded that the main metabolic pathway for pentachlorophenol in the rat 

was pentachlorophenol to 2,3,5,6-tetrachlorophenol to TCHQ, with a minor pathway being pentachlorophenol to 2,3,4,6- and 2,3,4,5-tetrachlorophenol to trichlorohydroquinone. Pentachlorophenol 

(conjugated with glucuronic acid and unconjugated) and TCHQ (conjugated with glucuronic acid and 

unconjugated) were recovered from urine and quantified by high-performance liquid chromatography and 

confirmed by using capillary gas chromatography from female Sprague-Dawley rats dosed with pentachlorophenol (>99% pure) for 28 days (Renner and Hopfer 1990). Unconjugated pentachlorophenol 

accounted for 36–58% of pentachlorophenol recovered, and 10–19% of the TCHQ excreted was 

unconjugated. Concentrations of both pentachlorophenol and TCHQ in urine fell to negligible amounts 
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3. HEALTH EFFECTS 

within one week after cessation of treatment. The study authors concluded that conjugation of pentachlorophenol with glucuronide and the metabolism of pentachlorophenol to TCHQ in rats results in more 

rapid excretion than in species that excrete unchanged pentachlorophenol (e.g., monkey) (see discussion 

below). 

In other studies in rats, 48% of the 100 mg [14C]-pentachlorophenol/kg administered orally to rats was 

recovered as unchanged pentachlorophenol in urine, 10% was TCHQ, and 6% was pentachlorophenolglucuronide. No TCHQ-glucuronide was detected (Braun et al. 1977). Similar results were obtained in 

rats and mice when a single dose of 25 mg [14C]-pentachlorophenol was administered by gavage, except 

that TCHQ conjugates (not positively identified as glucuronides) were identified in urine (Ahlborg et al. 

1974). These investigators found that 41–43% of the administered radiolabel was recovered in the urine 

as unchanged pentachlorophenol in rats and mice, 5% as TCHQ in rats, and 24% as TCHQ in mice. An 

unspecified proportion of radioactivity was found in urine as conjugated pentachlorophenol and TCHQ, 

but it could not be determined whether these were glucuronide conjugates. Other investigators have 

reported results in rats that differ from those of Braun et al. (1977). Approximately 60% of a 2.5 mg/kg 

dose of pentachlorophenol was recovered in the urine of Sprague-Dawley rats after 72 hours, mostly as 

conjugated pentachlorophenol and TCHQ, with only 5.3±0.2% of the dose recovered as unchanged pentachlorophenol (Reigner et al. 1991). Treatment of urine with sulfuric acid indicated that sulfate conjugates 

of pentachlorophenol and TCHQ accounted for about 90% of conjugated pentachlorophenol and TCHQ 

(glucuronide conjugates reported by Braun et al. [1977]). Metabolites and unchanged pentachlorophenol 

in feces accounted for 10% of the administered dose. 

It has been demonstrated that the monkey differs from the rat and mouse in that virtually all radioactivity 

recovered in urine following oral administration of 10 mg [14C]-pentachlorophenol/kg was associated with 

pentachlorophenol; no TCHQ or glucuronide conjugates were identified (Braun and Sauerhoff 1976). 

These data suggest that pentachlorophenol is not metabolized to any great degree by the monkey. 

Binding of pentachlorophenol to specific components of liver cells or differential distribution of pentachlorophenol to different cellular organelles can affect its metabolic fate or that of other xenobiotics and 

ultimately regulate the manifestation of toxic effects. Arrhenius et al. (1977) administered a single dose 

of gas-chromatographically pure pentachlorophenol (40 mg/kg) by stomach tube to rats, killed them 

16 hours later, separated subcellular fractions, and determined that the relative concentration of pentachlorophenol in microsomes was 6 times greater than in mitochondria. Since maximum effects on 

inhibition of microsomal detoxification processes (requiring electron transport from flavin to cytochrome) 
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occur at a pentachlorophenol concentration (100 μM) that is 4 times greater than the concentration of 

pentachlorophenol required to cause maximum inhibition of oxidative phosphorylation in mitochondria 

(25 μM), Arrhenius et al. (1977) suggested that inhibition of mitochondrial oxidative phosphorylation and 

inhibition of microsomal detoxification by pentachlorophenol might be equally important. The 

possibility that the presence of pentachlorophenol in microsomes allows this substance to inhibit its own 

metabolism provides a possible explanation for the relative lack of pentachlorophenol metabolism seen in 

all species studied. Another possible explanation is that extensive plasma binding of pentachlorophenol 

limits distribution of pentachlorophenol to the liver for subsequent biotransformation. In either case, any 

perturbation that increases the level of free circulating pentachlorophenol may result in enhanced toxicity 

as well as an increased rate of biotransformation and elimination. For individuals living in close 

proximity to areas of potentially high pentachlorophenol exposure, concomitant exposure to chemicals or 

intentional ingestion of drugs that compete with pentachlorophenol for protein binding may enhance 

pentachlorophenol-induced toxicity. 

3.4.3.3 Dermal Exposure 

No studies were located regarding metabolism in humans or animals after dermal exposure to pentachlorophenol. 

3.4.3.4 Other Routes of Exposure 

Results of studies in rats and mice indicate that metabolism of pentachlorophenol following 

intraperitoneal injection is similar to that observed following oral exposure (Ahlborg et al. 1978; 

Jakobson and Yllner 1971). In vitro studies in both human and rat liver homogenates clearly demonstrate 

that pentachlorophenol is converted to TCHQ (Juhl et al. 1985). Using a genetic construct in which 

human cytochrome P450 3A4 is expressed in Saccharomyces cerevisiae strain AH22, Mehmood et al. 

(1996) demonstrated that human cytochrome P450 3A4 may metabolize pentachlorophenol to TCHQ; 

however, the initial purity of the pentachlorophenol used in this study was not indicated. By Western 

immunoblotting using monoclonal antibodies to identify the different P 450 isozymes, pure pentachlorophenol (>99%) was identified as an inducer of cytochrome P450 3A7 in studies in cultured rat 

hepatocytes, quail hepatocytes, and human hepatoma (Hep G2) cells (Dubois et al. 1996). 

Since studies with rat liver microsomes using 19F nuclear magnetic resonance have demonstrated the 

cytochrome P450-dependent oxidation of pentafluorophenol to tetrafluorobenzoquinone (den Besten et al. 
 

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3. HEALTH EFFECTS 

1993), it can be speculated that cytochrome P450 may also catalyze the oxidation of pentachlorophenol to 

tetrachlorobenzoquinone. 

Horseradish peroxidase catalyzed the oxidation of pentachlorophenol to Cl4BQ in vitro via a phenoxyl 

radical intermediate (Samokyszyn et al. 1995). The study authors suggest that this is a potential in vivo 

metabolic step that could be catalyzed by mammalian peroxidases, including prostaglandin H synthase, 

myeloperoxidase, salivary peroxidase, lactoperoxidase, or uterine peroxidase. 

The rate of pentachlorophenol-glucuronide conjugation in human liver microsomes is reported to be 

one-third of that found in rat liver microsomes (Lilienblum 1985), although phenobarbital-enhanced 

dechlorination of pentachlorophenol, phenobarbital, and 3-methylcholanthrene (another microsomal 

enzyme inducer) had little effect on the conjugation reaction in rat liver microsomes (Ahlborg et 

al. 1978). This indicated that the extent of glucuronide conjugation was governed by factors other than 

phenobarbital- and 3-methylcholanthrene-inducible microsomal enzyme activity. 

It has been proposed that accumulation of pentachlorophenol by lipid-containing tissues seen in vitro is 

due to conjugation with fatty acids (Leighty and Fentiman 1982). These investigators reported that pentachlorophenol conjugated with palmitic acid in an in vitro rat liver coenzyme A fortified microsomal 

system. This ester is also found in human fat (Ansari et al. 1985). The mechanism by which the 

palmitoyl-pentachlorophenol is formed in human fat has yet to be determined. The presence of this ester 

in human fat demonstrates that xenobiotics such as pentachlorophenol can be made more lipophilic and 

stored in the fat of humans rather than excreted by the kidneys, thereby providing a potential reservoir of 

toxin that could be released at a later time. 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

The available information regarding pentachlorophenol excretion following inhalation exposure in 

humans comes predominantly from occupational case studies. Data obtained by Bevenue et al. (1967) 

from measuring urinary levels of pentachlorophenol in residents of Honolulu (some with a history of 

occupational exposure to pentachlorophenol) indicated that elimination was biphasic, with urinary pentachlorophenol levels decreasing approximately 35% per day in the first 2 days. Urinary levels of pentachlorophenol measured in wood-treatment workers prior to, during, and after vacation implied a urinary 
PENTACHLOROPHENOL 95 

3. HEALTH EFFECTS 

half-life of elimination of 19–20 days following inhalation exposure (Begley et al. 1977). A 10-day halflife of pentachlorophenol excretion in urine was estimated from urinary levels of pentachlorophenol 

measured in a tannery worker 1 day after the last day of work-related pentachlorophenol exposure and 

during a subsequent holiday period (Barbieri et al. 1995). The results of studies conducted by Casarett et 

al. (1969) in occupationally exposed humans suggest that pentachlorophenol excretion kinetics differ 

between single high-level and chronic low-level exposure. Urinary half-lives of approximately 10 hours 

were displayed by 2 subjects following a 45-minute inhalation exposure resulting from painting 

household materials in an enclosed area, whereas urine pentachlorophenol levels in exposed workers 

decreased only by 60–80% when the workers were absent from work for up to 18 days. The authors 

hypothesized that slower elimination of pentachlorophenol in the chronic situation may be the result of 

the establishment of an equilibrium between lung, plasma proteins, urine, and tissue depots. 

A group of 7 sawmill workers (6 males and 1 female) exposed to a sodium chlorophenolate woodpreserving product containing 3% pentachlorophenol were monitored for serum and urinary 

concentrations of pentachlorophenol (as well as other chlorophenols) throughout a wood-treatment season 

of approximately 7 months and an additional 171 days after the termination of exposure for the season 

(Pekari et al. 1991). Maximal pentachlorophenol urine concentrations after the period of exposure were 

0.2–0.9 μmol/L. Approximately 76% of the pentachlorophenol in urine was conjugated. The elimination 

rate constant in these workers using a one-compartment model was 0.044±0.018/day with a 

corresponding half-life of 16 days for pentachlorophenol. The minimal urinary clearance for pentachlorophenol was 0.2 mL/minute and varied with urine flow. The study authors noted that the relatively high 

concentrations of pentachlorophenol found in the serum (23%) as compared to the low percentage of 

pentachlorophenol in the technical product (3%) indicates that pentachlorophenol accumulates in the 

serum, in accordance with its relatively long half-time (16 days as compared to 18 hours and 4.2 days for 

tri- and tetrachlorophenol, respectively). Breathing zone measurements of concentration of airborne 

contamination compared to quantitative urine measurements would greatly improve the quality of the 

study. 

Excretion of pentachlorophenol following inhalation exposure in animals has not been well documented. 

The elimination half-life of pentachlorophenol following a single 20-minute inhalation exposure to 

5.7 mg [14C]-pentachlorophenol/kg was 24 hours (Hoben et al. 1976c). Pentachlorophenol does not 

undergo appreciable biotransformation as most of the inhaled dose was found to be eliminated unchanged 

in the urine. The authors of this study also reported that repeated (five) exposures increased urinary 

output of pentachlorophenol. These results are not inconsistent with those of Casarett et al. (1969). 
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3. HEALTH EFFECTS 

Elimination of many toxicants from high body burdens follows first-order kinetics initially, but the 

pattern of elimination becomes much more complex as lower body burdens are attained. Accumulation 

with repeated exposure will occur if rate of absorption exceeds rate of elimination, irrespective of 

excretion kinetics or tissue storage. 

3.4.4.2 Oral Exposure 

Studies investigating excretion of pentachlorophenol by humans following ingestion of 0.016–0.31 mg 

pentachlorophenol/kg have yielded conflicting results. Uhl et al. (1986) found that pentachlorophenol 

was excreted slowly, displaying an elimination half-life in both blood and urine of 14 days and a renal 

clearance of 0.07 mL/minute following ingestion of 0.016–0.31 mg pentachlorophenol/kg in ethanol by 

volunteers. The authors concluded that slow elimination could be attributed to extensive plasma protein 

binding and tubular reabsorption. 

When Braun et al. (1979) studied excretion kinetics of pentachlorophenol (as the sodium salt) in 

volunteers who ingested 0.1 mg pentachlorophenol/kg, they found that the half-life of elimination was 

30.2 hours from plasma and 33.1 hours from urine for pentachlorophenol, and 12.7 hours from urine for 

the glucuronide conjugate. Approximately 74% of the administered dose was eliminated in urine as 

pentachlorophenol and 12% as pentachlorophenol-glucuronide within 168 hours postingestion, and 4% 

was recovered as pentachlorophenol and pentachlorophenol-glucuronide in feces. These investigators 

concluded that pentachlorophenol elimination in humans followed first-order kinetics with enterohepatic 

recirculation following oral exposure. One possible explanation for the different half-lives observed in 

the Uhl et al. (1986) and the Braun et al. (1979) studies is the different dosing procedures employed. 

Subjects in the Uhl et al. (1986) study were reported to have ingested pentachlorophenol "without 

restriction of diet," while Braun et al. (1979) reported that "food was withheld 8 hours before and 1 hour 

after ingestion of the dose." Dispersion in gut contents may have slowed absorption in the Uhl et al. 

(1986) subjects, while absorption of the full dose occurred over a much shorter interval in the Braun et al. 

(1979) subjects, thus accounting for the different half-lives observed. Other explanations for the 

differences observed between the two studies include the fact that sodium pentachlorophenate was used 

for the Braun et al. (1979) study and pentachlorophenol in ethanol was used for the Uhl et al. (1986) 

study, and the vehicle used in the Uhl et al. (1986) study (ethanol) may have altered the solubility of 

pentachlorophenol. 
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Elimination of pentachlorophenol in rats following oral exposure was shown to be rapid and biphasic, 

with urine being the major route of excretion (Braun et al. 1977). The authors of this study reported that 

within 8–9 days, 80% of the radioactivity from the single oral administration of 10 mg [14C]-pentachlorophenol/kg to rats was recovered in urine and 19% in feces; 64% was detected in urine and 34% in feces 

following single oral administration of 100 mg [14C]-pentachlorophenol/kg. Elimination half-lives were 

17 and 13 hours for the first phase and 40 and 30 hours for the second phase in low-dose males and 

females, respectively. Ninety percent of the radioactivity was eliminated in the first phase. High-dose 

males exhibited elimination half-lives of 13 and 121 hours for the first and second phases, respectively. 

High-dose females exhibited first-order kinetics with a half-life of 27 hours. No explanation was offered 

for the difference in kinetics seen in high-dose females. These data indicate that: (1) the rate of 

elimination in the slow phase only and the relative distribution of radioactivity in feces varied linearly 

with increasing dose, (2) females eliminated pentachlorophenol faster than males, and (3) plasma binding 

and hepatic retention could account for the prolonged second phase of elimination. 

Different results were reported in rats administered single doses of 37–41 mg [14C]-pentachlorophenol/kg 

(Larsen et al. 1972). While the half-lives of rapid phases of elimination were comparable, Larsen et 

al. (1972) reported a half-life of 102 days for the second phase. However, these data are questionable 

because Larsen et al. (1972) did not obtain 100% recovery in urine and assumed that fecal excretion was 

constant. Therefore, they only reported a total fecal excretion value after 10 days. 

Results similar to those obtained by Braun et al. (1977) were reported by Reigner et al. (1991, 1992b) 

with respect to urinary and fecal elimination of pentachlorophenol following single-dose exposure in rats 

and mice. In the Reigner et al. studies, 8–10% of the administered dose (2.5 and 15 mg/kg, respectively, 

for rats and mice) of pentachlorophenol was recovered in the feces. Therefore, biliary excretion must 

play some role in elimination of pentachlorophenol. 

Elimination of pentachlorophenol by monkeys was slow and followed first-order kinetics. Braun and 

Sauerhoff (1976) orally administered single doses of 10 mg [14C]-pentachlorophenol/kg to monkeys and 

monitored excretion of radioactivity for up to 360 hours after administration. They found that 10–20% of 

administered radioactivity was steadily excreted in the feces, attesting to a relatively high degree of 

biliary secretion. Urinary pentachlorophenol accounted for 70–80% of the administered radiolabel. The 

half-life of elimination was 40.8 hours in males and 92.4 hours in females. The long half-life was 

attributed to enterohepatic circulation with subsequent biliary secretion. 
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The role of enterohepatic circulation and biliary secretion in pentachlorophenol elimination in monkeys 

was further investigated by measuring the relative extent of excretion of pentachlorophenol in urine, 

feces, and bile before and after administration of cholestyramine, a substance that binds phenols (Ballhorn 

et al. 1981; Rozman et al. 1982). The cholestyramine was administered in the diet 24 hours after 

pentachlorophenol exposure. At 30 mg/kg/day, control excretion was 92.3% in urine and 7.7% in feces. 

Following cholestyramine administration, excretion was 12.1% renal and 86.9% fecal. At 50 mg/kg/day, 

control excretion was 79.9% renal and 20.1% fecal. Following cholestyramine administration, excretion 

was 15.4% renal and 84.6% fecal. Total excretion was also increased by cholestyramine administration. 

Total recovery of administered dose over a 6-day period increased from 26 to 45% at the low dose and 

from 15 to 31% at the high dose (Ballhorn et al. 1981). 

In a follow-up study, cholestyramine treatment reduced urinary excretion of pentachlorophenol from 

35 to 5% of the administered dose and increased fecal excretion from 3 to 54% of the administered dose. 

The increase in fecal excretion induced by cholestyramine exceeded the decrease in urinary excretion. 

Total excretion increased by 40%. Seventy percent was excreted in bile during the control period, and 

52% was excreted in bile after cholestyramine treatment (Rozman et al. 1982), suggesting that 

cholestyramine treatment also enhanced the excretion of pentachlorophenol across the intestinal wall. 

The following conclusions can be drawn from these studies: 

• In untreated monkeys, oral absorption of pentachlorophenol was followed by elimination via bile 

into the duodenum, reabsorption in the small intestine, and enterohepatic circulation and 

excretion, predominantly via the kidney. 

• Cholestyramine, which binds phenols, interrupted enterohepatic circulation by binding pentachlorophenol and/or its metabolites, resulting in predominantly fecal excretion. 

• Total excretion was increased after cholestyramine treatment, suggesting that it reduced the halflife of pentachlorophenol in the monkey by enhancing its elimination from the body. 

• Cholestyramine increased elimination of pentachlorophenol by sequestering it from enterohepatic 

circulation and increasing its excretion across the intestinal wall. 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion in humans after dermal exposure to pentachlorophenol. 

In an in vivo swine model, 40 μg/cm2

 [14C-UL]-pentachlorophenol was applied occlusively or 

nonocclusively in a soil-based mixture to a clipped abdominal site of 8–10-week-old female pigs (Qiao et 
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3. HEALTH EFFECTS 

al. 1997). As an additional dosing protocol, antibiotics (neomycin sulfate, bacitracin, and polymyxin B, 

selected to provide a combined wide spectrum of antimicrobial and antifungal activity) were codosed with 

occlusively-applied [14C-UL]-pentachlorophenol to determine if inhibition of dermal microbial activity 

would influence absorption and disposition. Only one-third to one-half of the absorbed dose was almost 

equally excreted through urinary and fecal routes at constant rates over the 408-hour study period. In 

general, both the urinary and fecal excretion rates were faster for occlusive than for nonocclusive 

conditions. At 408 hours, the excretion data indicated that occlusion significantly increased the urinary 

(4x) and fecal (2.5x) excretion. Codosing of antibiotics with occlusive pentachlorophenol application 

significantly decreased urinary and fecal excretion. Based on the excretion curves, the urinary excretion 

rates were 0.35, 1.29, and 0.65% dose/day for nonocclusive, occlusive, and occlusive-antibiotic 

conditions, respectively, and the fecal excretion rates were 0.47, 1.24, and 0.82% dose/day for 

nonocclusive, occlusive, and occlusive-antibiotic conditions, respectively. 

3.4.4.4 Other Routes of Exposure 

Kinetics of elimination of pentachlorophenol in rats following a single intravenous injection (Reigner et 

al. 1991) differ from those reported by Braun et al. (1977) following oral exposure. In the Reigner et al. 

(1991) study, the clearance rate of pentachlorophenol from plasma was 0.026±0.003 L/hour/kg. 

Elimination of pentachlorophenol from plasma was biphasic and fit a two-compartment model, with the 

half-life for the first phase being 0.67±0.46 hours and the half-life for the second phase being 

7.11±0.87 hours. Most of the pentachlorophenol was eliminated during the second phase. However, 

routes of excretion and main metabolites recovered in urine and feces were similar to those seen by these 

same investigators after oral administration (Reigner et al. 1991). The study authors proposed that 

specificity of the analytical methodology is one possible explanation for the difference in elimination 

kinetics seen between their study and the study by Braun et al. (1977), who, instead of taking multiple 

blood samples from the same animal, killed two animals at different times to get the kinetic profile. Use 

of pooled data such as this may have provided inaccurate data for modeling. 

Following intravenous administration of 5 mg/kg pentachlorophenol (>99% purity) into rats, the 

estimated mean terminal elimination half-life of pentachlorophenol was 5.6±0.37 hours in males and 

9.5±4.2 hours in females, but the difference was not significant (Yuan et al. 1994). 
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3. HEALTH EFFECTS 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (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 end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is 

adequately described, however, this simplification is desirable because data are often unavailable for 
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many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-3 shows a conceptualized representation of a PBPK model. 

No PBPK modeling studies were located for pentachlorophenol. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Pentachlorophenol is a nonpolar, lipophilic substance. While the exact mechanism of absorption is not 

known, it can be assumed that because of its lipophilicity it can easily cross cell membranes and be 

absorbed in lungs, gastrointestinal tract, and skin. Toxicokinetic studies in animals and humans 

demonstrate this to be the case (see Section 3.4.1). 

Binding of pentachlorophenol to plasma proteins plays a role in the distribution of pentachlorophenol. It 

has been demonstrated, using an in vitro diafiltration technique (Braun et al. 1977), that 95% of the pentachlorophenol in plasma is protein bound. Extensive plasma protein binding of pentachlorophenol may 

account for the low degree of metabolism seen with this compound (most pentachlorophenol is excreted 

unchanged) because protein-bound material is not readily distributed to tissues where it can be 

metabolized. van Raaij et al. (1994) demonstrated a dose- and time-dependent uptake of pentachlorophenol into the cerebrospinal fluid of rats following single intraperitoneal injections. Since similar doses 

of pentachlorophenol also significantly decreased the uptake of radiolabeled T4 into cerebrospinal fluid, 

the study authors suggested that pentachlorophenol may interact with the T4 binding site of transthyretin 

and compete with T4 for uptake into cerebrospinal fluid (van Raaij et al. 1994). This is a plausible 

explanation since the affinity of pentachlorophenol for the T4 binding site on transthyretin is 2.5-fold 

greater than that of T4 itself (den Besten et al. 1991). 
Skin 

Kidney 

Richly 

perfused 

tissues 

Slowly 

perfused 

tissues 

Fat 

Liver 

Lungs 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

GI 

Tract 

Vmax Km 

Urine 

Chemicals in air 

Inhaled chemical Exhaled chemical 

Ingestion 

Feces 

contacting skin 

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Figure 3-3. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a Hypothetical 

Chemical Substance
 

Source: adapted from Krishnan et al. 1994 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by 

inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 
PENTACHLOROPHENOL 103 

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3.5.2 Mechanisms of Toxicity 

It is widely believed that pentachlorophenol exerts its toxic effects, at least in part, by uncoupling 

mitochondrial oxidative phosphorylation, thereby causing accelerated aerobic metabolism and increased 

heat production. Pentachlorophenol has been found to bind to purified rat liver mitochondrial protein. 

This may induce conformational changes in enzymes involved in oxidative phosphorylation (Weinbach 

and Garbus 1965). The pattern of pentachlorophenol-induced toxicity often seen in humans and animals 

supports this proposed mechanism of action. A young worker who died following 3 weeks of exposure to 

pentachlorophenol dust in a chemical plant was found to have cerebral edema and fatty degeneration of 

liver and lungs at necropsy (Gray et al. 1985). The study authors concluded that these clinical findings 

are consistent with a hypermetabolic state resulting from a derangement of aerobic metabolism and 

characterized by hyperthermia, which can lead to tachycardia, tachypnea, hyperemia, diaphoresis, and 

metabolic acidosis. This is usually followed by death and rapid, profound rigor mortis. Toxicity 

resulting from uncoupling of oxidative phosphorylation was generally seen prior to death in animals 

acutely exposed to pentachlorophenol. These included accelerated respiration, hyperemia, cardiac and 

muscular collapse, asphyxial convulsions, death, and rapid rigor mortis (St. Omer and Gadusek 1987). 

The ultrastructural changes observed in mitochondria from liver cells of rats treated with technical-grade 

pentachlorophenol for 15 days are consistent with uncoupling of oxidative phosphorylation (Fleischer et 

al. 1980). 

The cell membrane is apparently a possible site of action for pentachlorophenol. Lipid bilayers of 

purified and total cell membranes have been reported to destabilize following sublethal pentachlorophenol 

treatment (Duxbury and Thompson 1987). This was evidenced by a 50% decrease in bulk lipid fluidity 

attributable to disruption of the bilayer by pentachlorophenol. These authors also found that pentachlorophenol partitions into the hydrophobic interior of the bilayer. Other membrane changes observed by these 

investigators included a decrease in phospholipid phosphate levels that they believe was a result of a 

selective chemical effect on phospholipase C. However, the authors concluded that this was only a 

sublethal effect since the cells remained viable. 

In another investigation of the physicochemical basis of pentachlorophenol membrane effects, membrane 

toxicity was associated with the pentachlorophenol-induced change in hydrogen ion permeability of the 

membrane lipid matrix (Smejtek 1987). The onset of toxic effects was correlated with the loss of 

membrane electrical resistance and a measurable amount of pentachlorophenol binding to the membrane. 
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Studies described above indicate that pentachlorophenol can disrupt membrane structure and function. 

These effects could conceivably occur throughout the body and could therefore explain the wide range of 

toxic effects associated with pentachlorophenol, including the uncoupling of oxidative phosphorylation. 

Oral and intraperitoneal administration of pentachlorophenol to animals causes adverse effects on thyroid 

homeostasis (e.g., decreased serum thyroxine) and on the thyroid gland (Beard and Rawlings 1998; Beard 

et al. 1999b; Jekat et al. 1994; van Raaij et al. 1991a). These effects may occur during gestation, 

pregnancy, and lactation (Beard and Rawlings 1998; Beard et al. 1999b). Further in vitro studies by van 

Raaij et al. (1991b) revealed that the likely mechanism of action for this anti-thyroid effect of pentachlorophenol was competition for serum protein thyroxine binding sites. van Raaij et al. (1994) 

subsequently demonstrated a dose- and time-dependent uptake of pentachlorophenol into the 

cerebrospinal fluid of rats following single intraperitoneal injections. Since similar doses of pentachlorophenol also significantly decreased the uptake of radiolabeled T4 into cerebrospinal fluid, the study 

authors suggested that pentachlorophenol may interact with the T4 binding site of transthyretin and 

compete with T4 for uptake into cerebrospinal fluid (van Raaij et al. 1994). This is a plausible 

explanation since the affinity of pentachlorophenol for the T4 binding site on transthyretin is 2.5-fold 

greater than that of T4 itself (den Besten et al. 1991). 

Such effects on thyroid parameters, combined with the activity of pentachlorophenol as a potent inhibitor 

of oxidative phosphorylation (Weinbach 1954), may be expected to have general adverse effects on basal 

metabolic rate and many critical processes including development, reproduction, nervous system function, 

and the specific functioning of endocrine and other organs. 

In addition, the effects of pentachlorophenol on thyroid homeostasis and the availability of T4 to the 

central nervous system may have adverse effects on development of the nervous system. Deficiencies in 

thyroxine during prenatal and postnatal life can cause decrements in intellectual function in children 

(Bargagna et al. 1997; Birrell et al. 1983; Kooistra et al. 1994), and hypothyroidism in animals leads to 

disorders in structural and functional development of the brain (Gould et al. 1990; Neveu and Arenas 

1996; Stein et al. 1991; Vega-Nunez et al. 1995). However, testing has not been performed on animals 

exposed to pentachlorophenol, either prenatally or postnatally, to examine the potential for the antithyroid effects of pentachlorophenol to produce adverse effects on neurobehavior. 

Recent studies in rats and mice involved the characterization of chlorinated protein adducts arising from 

pentachlorophenol metabolism following oral administration of pentachlorophenol (Lin et al. 1997; 
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3. HEALTH EFFECTS 

Waidyanatha et al. 1994, 1996). Results from these studies and previously summarized studies suggest 

that the metabolism of pentachlorophenol can proceed through the quinols TCHQ and Cl4CAT via 

microsomal cytochrome P 450 enzymes and that these quinols can be oxidized via semiquinone 

intermediates (tetrachloro-1,2-semiquinone [Cl4-1,2-SQ] and tetrachloro-1,4-semiquinone [Cl4-1,4-SQ]) 

into the corresponding quinones (tetrachloro-1,2-benzoquinone [Cl4-1,2-BQ] and tetrachloro-1,4-benzoquinone [Cl4-1,4-BQ]). Both the quinones and semiquinones are electrophilic and can bind to cellular 

macromolecules (Lin et al. 1997). The redox cycling associated with oxidation of TCHQ and reduction 

of Cl4-1,4-BQ generates oxygen radicals that caused an increase in 8-hydroxy-2-deoxyguanosine levels in 

liver DNA in mice that had been fed pentachlorophenol (Sai-Kato et al. 1995; Umemura et al. 1996) or 

TCHQ (Dahlhaus et al. 1994) in the diet for up to 4 weeks. It is possible that the formation of such 

adducts is involved in the induction of hepatic neoplasms in mice (NTP 1989). Lin et al. (1997) 

measured levels of chlorinated protein adducts arising from pentachlorophenol metabolism in the livers of 

mice and rats administered pentachlorophenol in the diet for up to 4 weeks. After aggregation of the 

estimated contributions of all quinone species derived from pentachlorophenol metabolism, mice had a 

four-fold greater dose to liver nuclei than rats, whereas rats had a three-fold greater dose to liver cytosol 

than mice. The increased nuclear dose to mouse liver compared to that of the rat suggests that the mouse 

is at greater risk to hepatic DNA damage from pentachlorophenol-derived quinones. Using a model to 

predict quinone and semiquinone production, Lin et al. (1999) estimated that at low doses of 

pentachlorophenol, the production of semiquinone adducts was proportionally greater in rats than mice; in 

mice, direct oxidation to quinones and the production of quinone adducts is favored in mice exposed to 

low doses of pentachlorophenol. These data suggest that both the types and amounts of adducts differ in 

rats and mice, which may account for the occurrence of liver tumors in mice but not in rats in bioassays 

conducted by NTP (1989, 1999). 

In an epidemiologic study of male factory workers who brushed pentachlorophenol onto wood strips, 

sometimes without gloves, serum biliary acid concentrations were elevated in the high-exposure group, 

but not the low-exposure group, compared with controls (Colosio et al. 1993b). This effect may have 

been caused in part by the impurities in the pentachlorophenol. The presence of elevated concentrations 

of bile acids in serum is a sensitive indicator of liver dysfunction (Franco et al. 1986). Since bile acids 

are essential for lipid transport, are the major products of cholesterol metabolism, and regulate the 

transcription of genes that control cholesterol homeostasis (Makishima et al. 1999; Parks et al. 1999), the 

elevation of serum bile acids by exposure to high levels of pentachlorophenol may have some effect on 

biochemical pathways involved in cholesterol metabolism and homeostasis. 
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3.5.3 Animal-to-Human Extrapolations 

Reigner et al. (1993) investigated the binding of radiolabeled pentachlorophenol to serum proteins in 

vitro, found that the percentage of unbound pentachlorophenol in serum was 1.37 in mice, 0.85 in rats, 

0.67 in monkeys, 0.53 in humans, and 0.43 in cows and found that these percentages correlated inversely 

with the total protein levels in the same serum samples. These investigators, assuming that pentachlorophenol itself is responsible for carcinogenicity in mice, developed a new method for interspecies 

extrapolation in which the interspecies differences in clearance and serum protein binding of pentachlorophenol were taken into account in interspecies scaling. Several pharmacokinetic parameters, including 

volume of distribution, unbound volume of distribution, clearance, unbound clearance, and unbound 

clearance time maximum life potential, were scaled to body weight. The method produced estimates of 

equivalent human doses of pentachlorophenol (derived from experimental doses in mice that caused 

increased tumor incidences in the NTP [1989] 2-year bioassay) that are up to four times smaller than 

those obtained using body surface area. 

3.6 ENDOCRINE DISRUPTION 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones, or otherwise 

interfere with the normal function of the endocrine system. Chemicals with this type of activity are most 

commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to 

disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. 

Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in 

light of the fact that hormone mimics exist in the natural environment. Examples of natural hormone 

mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These 

compounds are derived from plants and are similar in structure and action as endogenous estrogen. While 

there is some controversy over the public health significance of endocrine disrupting chemicals, it is 

agreed that the potential exists for these compounds to affect the synthesis, secretion, transport, binding, 

action, or elimination of natural hormones in the body that are responsible for the maintenance of 

homeostasis, reproduction, development, and/or behavior (EPA 1997). As a result, endocrine disruptors 

may play a role in the disruption of sexual function, immune suppression, and neurobehavioral function. 

Endocrine disruption is also thought to be involved in the induction of breast, testicular, and prostate 

cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992). 
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Several studies have documented effects of pentachlorophenol on thyroid homeostasis (Beard and 

Rawlings 1998, 1999; Beard et al. 1999a, 1999b; Jekat et al. 1994; van Raaij et al. 1991a). These effects 

include decreased serum thyroxine concentration (Beard and Rawlings 1998, 1999; Beard et al. 1999a, 

1999b; Jekat et al. 1994; van Raaij et al. 1991a), decreased thyroxine and triiodothyronine response to 

thyroid stimulating hormone (Beard and Rawling 1999), and decreased uptake of thyroxine into 

cerebrospinal fluid (van Raaij et al. 1994); these effects may be linked with a demonstrated competition 

of pentachlorophenol with the thyroxine binding site on transthyretin, a major thyroxine transport protein 

(den Besten et al. 1991). 

Developmental toxicity studies provide some limited evidence that pentachlorophenol has the ability to 

disrupt endocrine function. A marked increase in the sex ratio (most female fetuses did not survive) was 

observed in the offspring of rats administered pure or technical-grade pentachlorophenol on gestational 

days 6–15 (Schwetz et al. 1974). However, the finding was not confirmed in other developmental 

toxicity studies (Argus 1993b/Bernard et al. 2001b, Argus 1997/Bernard et al. 2001c). In a 

multigeneration study in rats, significant increases in the average day of vaginal patency and preputial 

separation were observed in the F1 offspring exposed to an unspecified purity pentachlorophenol (Argus 

1997/Bernard et al. 2001c). 

In an in vitro test system, pure pentachlorophenol inhibited the activity of the human progesterone 

receptor. Tran et al. (1996) transformed a yeast strain with an expression plasmid for the human 

progesterone (hPR) receptor and a reporter containing two progesterone response elements. In the 

resulting yeast strain, hPR-PRE, beta-galactosidase activity was measured as an indicator of stimulation 

of the hPR signaling pathway. When the signaling pathway was stimulated by progesterone, 1 μM pentachlorophenol (99% pure) significantly inhibited hPR activity. Competitive binding studies indicated that 

pentachlorophenol effectively competed with a radiolabeled synthetic progestin for binding to hPR. 

Investigation of the interaction of pentachlorophenol with the progesterone-signaling pathway in animals 

might be another avenue for future research. 

In rainbow trout hepatocytes, pentachlorophenol inhibited the induction of the estrogen receptor by 

estradiol and inhibited the induction of vitellogenin messenger RNA by estradiol (Flouriot et al. 1995). In 

short-term, whole-embryo assays using Xenopus laevis, pentachlorophenol significantly decreased the 

rates of tail resorption in metamorphs studied from day 50 (stage 60) to day 64 (stage 66) of development 

(Fort and Stover 1997). 
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3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. 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. 

Relevant animal and in vitro models are also discussed. 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6 Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 
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tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility while others may 

decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

There have been several reports of children accidentally exposed to pentachlorophenol; the children were 

predominantly exposed via dermal contact and, to a lesser extent, by the inhalation route. The observed 

health effects include symptoms of hyperthermia (high fever, profuse sweating, increased respiratory rate, 

labored breathing, tachycardia, hepatomegaly, and irritability) due to the uncoupling of oxidative 

phosphorylation and death in newborn infants following dermal contact with diapers and bedding washed 

in an antimildew agent containing pentachlorophenol (Robson et al. 1969; Smith et al. 1996) and in a 

child exposed to bath water contaminated with pentachlorophenol (Chapman and Robson 1965). The 

Chapman and Robson (1965) report provides suggestive evidence that young children may be more 

susceptible to the toxicity of pentachlorophenol than adults. All members of the child’s family bathed in 

the contaminated bath water over a 13-day period; however, the only symptoms reported in the other 

family members were nasal stuffiness and swollen, painful eyes. A study by McConnachie and Zahalsky 

(1991) also reported health effects in children. Alterations in immunological parameters were observed in 

individuals living in log homes treated with a wood preservative containing pentachlorophenol. Fifteen 

of the 38 subjects were children aged 8–18. This study cannot be used to assess whether children would 

be more susceptible to the toxicity of pentachlorophenol because no comparisons across age groups were 

made. In addition to these health effects, hematological disorders (Cheng et al. 1993; Hryhorczuk et al. 

1998; Klemmer et al. 1980; Roberts et al. 1981, 1990; Rugman and Cosstick 1991) and liver (Armstrong 

et al. 1969; Bergner et al. 1965; Colosio et al. 1993b; Gordon 1956; Robson et al. 1969; Smith et al. 

1996) effects have been observed in adults exposed to pentachlorophenol, and these are likely targets in 

children. An animal study that compared LD50 values provides evidence that infants may be more 

susceptible than children. Lower LD50 values were found in preweaning animals, as compared to juvenile 

rats (25–50 days); however, the LD50 value in adult rats was similar to the value for preweaning rats (St. 

Omer and Gadusek 1987). 
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There is some limited evidence that the developmental process in humans is altered by paternal exposure 

to pentachlorophenol. An increased risk of congenital eye cataracts was observed in the children of men 

presumably exposed to CDD-contaminated chlorophenate (Dimich-Ward et al. 1996); however, as 

discussed in Section 3.2.1.5, deficiencies in the study design limits interpretation of these results. Studies 

of potential developmental effects of pentachlorophenol in animals indicate that the developing organism 

is a sensitive target of toxicity. Fetal/neonatal mortality (Argus 1993b/Bernard et al. 2001b, Argus 1997/ 

Bernard et al. 2001c; Schwetz et al. 1974; Welsh et al. 1987), malformations/anomalies (Argus 1993b/ 

Bernard et al. 2001b; Schwetz et al. 1974), decreased growth (Argus 1993b/Bernard et al. 2001b; Beard et 

al. 1999b; Courtney et al. 1976; Larsen et al. 1975; Schwetz et al. 1974; Welsh et al. 1987), and possibly 

impaired development of the reproductive system (Argus 1997/Bernard et al. 2001c) have been observed 

in rats and sheep following gestational exposure. In most of these studies, the developmental effects 

occurred at maternally toxic doses; however, decreases in fetal body weight gain have been observed at 

doses that were not associated with maternal toxicity (Argus 1997/Bernard et al. 2001c; Welsh et al. 

1987). A number of studies in rats (Jekat et al. 1994) and sheep (Beard and Rawlings 1998; Beard et al. 

1999a, 1999b) have demonstrated that exposure to pentachlorophenol can result in decreased serum 

thyroxine and triiodothyronine levels. Deficiencies in thyroxine during prenatal and postnatal life can 

cause decrements in intellectual function in children (Bargagna et al. 1997; Birrell et al. 1983; Kooistra et 

al. 1994). It is not known if this will also occur following exposure to pentachlorophenol, and neurobehavioral testing has not been performed on animals exposed to pentachlorophenol either prenatally or 

postnatally. Such testing might be an avenue for future research. 

There is no information regarding pharmacokinetics of pentachlorophenol in children or regarding 

nutritional factors that may influence absorption of pentachlorophenol. There are no PBPK models for 

pentachlorophenol. Mehmood et al. (1996) has provided evidence that human cytochrome P450 3A4 

may metabolize pentachlorophenol to TCHQ in phase I metabolism of pentachlorophenol; however, the 

purity of the pentachlorophenol used in this study was not indicated. In humans, this enzyme has low 

activity in the first month of life, with approach toward adult levels by 6–12 months of postnatal age; 

adult activity may be exceeded between 1–4 years of age and then activity progressively declines, 

reaching adult levels at the conclusion of puberty (Leeder and Kearns 1997). By Western 

immunoblotting using monoclonal antibodies to identify the different P 450 isozymes, pure pentachlorophenol (>99%) was identified as an inducer of cytochrome P450 3A7 in studies in cultured rat 

hepatocytes, quail hepatocytes, and human hepatoma (Hep G2) cells (Dubois et al. 1996). In humans, 

functional activity of cytochrome P450 3A7 in the fetus is approximately 30–75% of adult levels (Leeder 

and Kearns 1997). UDP-glucuronosyl transferase and sulfotransferases are involved in phase II 
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metabolism of pentachlorophenol. Both of these enzymes are thought to be developmentally regulated 

(Leeder and Kearns 1997). Although the ontogeny of UDP-glucuronosyl transferase is isoform-specific, 

the adult level of activity seems to be achieved in humans by 6–18 months of age (Leeder and Kearns 

1997). Ontogeny for the sulfotransferases seems to be more rapid than that for UDP-glucuronosyl 

transferase, and the activity for some isoforms of sulfotransferase may exceed adult levels during infancy 

and early childhood (Leeder and Kearns 1997). Larsen et al. (1975) provided evidence that pentachlorophenol (0.05–0.08% of an oral dose administered on day 15 of gestation) may cross the placenta; the 

chemical nature of the radioactive material present in the fetuses was not investigated. 

Low levels of pentachlorophenol were found in human breast milk of women living in Germany or 

Slovakia (Gebefugi and Korte 1983; Veningerova et al. 1996). It is likely that pentachlorophenol will 

also be present in the breast milk of women living in the United States, particularly since pentachlorophenol has been detected in more than half of the urine samples of adults living in the United States (Hill 

et al. 1995). However, it is not known if the pentachlorophenol present in the breast milk or urine 

samples resulted from exposure to pentachlorophenol or to other industrial chemicals that are metabolized 

to pentachlorophenol. 

There is no reason to suspect the mechanism of action of pentachlorophenol is different in children. 

There are no specific biomarkers of exposure or effect for pentachlorophenol that have been validated in 

children or adults exposed as children. No studies were located regarding interactions of pentachlorophenol with other chemicals in children. 

There are no pediatric-specific methods for reducing peak absorption or reducing body burden following 

exposure to pentachlorophenol. 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. 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 
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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 or substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to pentachlorophenol are discussed in Section 3.8.1. 

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 effects caused 

by pentachlorophenol are discussed in Section 3.8.2. 

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 3.10. “Populations That Are Unusually Susceptible”. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Pentachlorophenol 

Since pentachlorophenol is excreted in the urine largely unchanged (Ahlborg et al. 1974; Braun et al. 

1979; Larsen et al. 1972; Reigner et al. 1991) and since it can be easily detected and quantified in the 

urine at concentrations as low as <1 ppb (Chou and Bailey 1986; Drummond et al. 1982; Edgerton et al. 

1979; EPA 1980b; Holler et al. 1989; NIOSH 1984b; Pekari and Aitio 1982; Rick et al. 1982; Siqueina 

and Fernicola 1981), pentachlorophenol in the urine is a useful biomarker of exposure. In addition, 
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pentachlorophenol can be easily detected and quantified in blood serum at concentrations as low as 

<1 ppb (Bevenue et al. 1968; EPA 1980b; Needham et al. 1981; NIOSH 1984b) and adipose tissue 

(Kuehl and Dougherty 1980; Needham et al. 1981; Ohe 1979; Shafik 1973). It has been demonstrated 

that pentachlorophenol is present in human adipose tissue as an ester of palmitic acid (Ansari et al. 1985). 

The detection limit for pentachlorophenol in adipose tissue is approximately 5 ppb (Kuehl and Dougherty 

1980; Ohe 1979; Shafik 1973). However, measuring pentachlorophenol in body fluids and tissues is not a 

specific biomarker for pentachlorophenol exposure because other compounds to which exposure may 

occur (e.g., hexachlorobenzene and lindane) may be metabolized to pentachlorophenol in the body. In 

addition, the available data do not permit the establishment of a quantitative relationship between levels 

of pentachlorophenol in the environment and levels in human fluids or tissues. However, it has been 

reported that repeated workday exposure to pentachlorophenol at a concentration of 0.5 mg/m3

 has 

resulted in a maximum steady state level of pentachlorophenol in plasma of about 0.5 mg/L (Wood et al. 

1983). Based on samples taken prior to 1989, background levels of up to 0.1 ppm pentachlorophenol 

could be found in blood and urine of members of the general population who had no recognized exposure 

to pentachlorophenol (Cranmer and Freal 1970; EPA 1989b; Hill et al. 1989; Kutz et al. 1978). 

TCHQ, a major urinary metabolite of pentachlorophenol, has potential use as an indicator of exposure to 

pentachlorophenol. It has been demonstrated that pentachlorophenol is converted to TCHQ by human 

microsomal enzymes (Juhl et al. 1985). In human and animal studies, TCHQ has been identified as the 

major urinary metabolite of pentachlorophenol (Ahlborg et al. 1974; Braun et al. 1977; Reigner et al. 

1991; Renner 1989). However, the presence of TCHQ in the urine is not specific to pentachlorophenol 

and would also be present following exposure to chemicals that are metabolized to pentachlorophenol. 

The presence of elevated levels of 8-hydroxydeoxyguanosine in the liver may serve as a nonspecific 

marker of oxidative DNA damage by pentachlorophenol. Administration of pentachlorophenol (98.6% 

pure) to mice in the diet for up to 4 weeks produced oxidative damage to hepatic nuclear DNA as 

evidenced by an increase in the amount of 8-hydroxydeoxyguanosine in DNA (Sai Kato et al. 1995; 

Umemura et al. 1996). A single oral dose of pentachlorophenol (98.6% pure) produced an increase in the 

amount of 8-hydroxydeoxyguanosine in liver DNA but not in kidney or spleen DNA (Sai-Kato et al. 

1995). 
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3.8.2 Biomarkers Used to Characterize Effects Caused by Pentachlorophenol 

Two of the major target organs for both humans and animals exposed to pentachlorophenol are liver and 

kidney. Clinical manifestations of hepatic and renal toxicity include elevated serum ALT and AST levels 

for toxicity to the liver (Armstrong et al. 1969; Bergner et al. 1965; Gordon 1956; Gray et al. 1985; 

Klemmer 1972; Robson et al. 1969) and increased enzyme levels, increased blood urea nitrogen, and loss 

of proximal tubular alkaline phosphatase activity for toxicity to the kidney (Greichus et al. 1979; 

Kimbrough and Linder 1978; Nishimura et al. 1980). Indices of changes in hepatic oxidative 

phosphorylation may also be useful as biomarkers for pentachlorophenol-induced liver changes (Ellinger 

et al. 1991). These effects are not specific for exposure to pentachlorophenol and have been associated 

with exposure to other compounds such as some chlorinated hydrocarbons. Therefore, the major use of 

these biomarkers is restricted to comparisons between work groups exposed to the chemical in the 

workplace and control subjects. Other data indicate that contaminants in the commercial grade product 

may play an important role in these observed hepatotoxic effects. 

Human case reports of pentachlorophenol exposure suggest that the central nervous system appears to be 

a target of pentachlorophenol exposure (Chapman and Robson 1965; Gray et al. 1985; Haley 1977; 

Robson et al. 1969). As discussed in Section 3.2.2.4, the neurologic syndrome observed following 

exposure to pentachlorophenol is possibly the direct result of hyperthermia generated by uncoupling of 

mitochondrial oxidative phosphorylation rather than a direct effect on the nervous system. The 

neurological syndrome observed following exposure to pentachlorophenol can be manifested by lethargy, 

tachypnea, tachycardia, intermittent delirium, convulsions, cerebral edema, focal swelling of the myelin 

sheath, and respiratory distress (Chapman and Robson 1965; Gray et al. 1985). However, these 

symptoms are not specific for pentachlorophenol exposure. 

In general, there is no simple relationship between nonfatal health effects and levels of pentachlorophenol 

detected in serum and urine. Serum levels of pentachlorophenol ranging from 23 to 162 mg/L (ppm) have 

been reported in cases of fatal overexposure to pentachlorophenol. Serum levels of pentachlorophenol 

below 1.3 mg/L have not been associated with any adverse health effects (Cline et al. 1989; Klemmer et 

al. 1980). 
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3.9 INTERACTIONS WITH OTHER CHEMICALS 

No studies were located regarding the direct toxic interactions of pentachlorophenol with other chemicals 

in humans, including children, or animals. No interactions between pentachlorophenol contaminants and 

the pure pentachlorophenol component of technical-grade pentachlorophenol have been demonstrated in 

some tests of immunotoxicity (Kerkvliet et al. 1985a). 

Pentachlorophenol may alter the toxicities of other compounds through its inductive action on 

microsomal metabolic enzymes (Vizethum and Goerz 1979). While this inductive effect has not 

specifically been demonstrated to alter the toxicity of other compounds, these types of alterations in 

enzyme activity may influence metabolism and toxicity of many compounds. Pentachlorophenol inhibits 

cytosolic sulfotransferases (Mulder and Scholtens 1977). Compounds such as n-hydroxy-2-acetylaminofluorene, which are activated by the formation of a sulfate ester, are considerably less toxic in 

animals pretreated with pentachlorophenol (Meerman et al. 1980). Pentachlorophenol, an inhibitor of 

arylsulfotransferase, significantly decreased 2-acetylaminofluorene-induced DNA damage in rat 

hepatocytes in vitro. In vivo, pentachlorophenol alone induced a significant increase in unscheduled liver 

DNA synthesis, but also caused a significant decrease in 2-acetylaminofluorene-induced unscheduled 

liver DNA synthesis (Monteith 1992). 

Male rats were given pentachlorophenol (91.6%) daily by gavage at a dose of 20 mg/kg. At 1, 2, 4, and 

5 weeks, the animals were given a single gavage dose of 2,6-dinitrotoluene, and urine was collected for 

24 hours and tested for mutagenicity in Salmonella typhimurium strain TA98. A statistically-significant 

increase in revertants at week 5 in pentachlorophenol-treated animals, compared with controls that did not 

receive pentachlorophenol, suggested that pentachlorophenol caused an increase in the excretion of 

mutagenic metabolites of 2,6-dinitrotoluene. A slight, but statistically-significant, decrease in 

nitroreductase activity in the small intestine was also reported in the pentachlorophenol-treated rats 

compared with controls (Chadwick et al. 1993). 

Since pentachlorophenol is metabolized to a small extent by hepatic microsomal enzymes, chemicals that 

alter the activity of these enzymes can modify metabolism, and subsequently, the toxicity of pentachlorophenol (see discussion above). For example, phenobarbital, a microsomal enzyme inducer, increases 

biotransformation of pentachlorophenol to TCHQ thereby reducing the level of pentachlorophenol in the 

body (Ahlborg et al. 1978). 
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A great deal of pentachlorophenol is bound to plasma proteins (Braun et al. 1977). Other agents that also 

have a high affinity for protein bonds (e.g., anticoagulants such as warfarin) could compete with and 

displace pentachlorophenol from proteins. This action could then result in a higher level of freecirculating pentachlorophenol that can be metabolized, or excreted, and/or induce toxic effects. However, 

this hypothesis has not been experimentally confirmed. 

Various agents have been used in experimental animals to try to decrease the toxicity of pentachlorophenol. Cholestyramine is known to bind phenols (Reiman and Walton 1970) and to enhance fecal 

elimination of chlordecone (Kepone) in rats and humans (Boylan et al. 1977). Rozman et al. (1982) 

found that cholestyramine enhances excretion of pentachlorophenol in Rhesus monkeys and recommends 

that its use be considered in cases of human pentachlorophenol overexposure. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to pentachlorophenol than will 

most persons exposed to the same level of pentachlorophenol in the environment. Reasons may include 

genetic makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette 

smoke). These parameters result in reduced detoxification or excretion of pentachlorophenol, or 

compromised function of organs affected by pentachlorophenol. Populations who are at greater risk due 

to their unusually high exposure to pentachlorophenol are discussed in Section 6.7, Populations With 

Potentially High Exposures. 

Groups possibly at greater-than-average risk of suffering from the toxic effects of pentachlorophenol 

include persons laboring in hot environments, persons with an inability or decreased ability to disperse 

body heat, geriatric and pediatric subpopulations, pregnant women, and those that are malnourished or 

consume an unbalanced diet. People with impaired liver and kidney function are likely to be susceptible 

to the toxic effects of any chemical/product that is metabolized and/or excreted by these organs, and 

therefore, may be unusually susceptible to the toxic effects of pentachlorophenol. 

Persons laboring in hot environments are unusually susceptible to the acute toxic effects of pentachlorophenol. One of the principal effects of pentachlorophenol is hyperthermia induced by the uncoupling of 

oxidative phosphorylation. The manifestations of overexposure to pentachlorophenol, particularly in 

persons laboring in a hot environment, are usually those associated with hyperthermia: flushing, intense 

thirst, sweating, weakness and, occasionally, muscle spasms. Persons working in hot environments are 
 

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unable to disperse excess body heat, resulting in potentially life-threatening hyperthermia. For example, 

occupational deaths reported by Bergner et al. (1965), Gray et al. (1985), and Menon (1958) were all due 

to hyperthermia, and the symptoms of hyperthermia described above were exhibited by affected workers 

prior to death. 

There is some evidence that young children are more susceptible than older children or adults to the toxic 

effects of pentachlorophenol often associated with the uncoupling of oxidative phosphorylation. In a 

study by Chapman and Robson (1965), signs of hyperthermia (resulting from the uncoupling of oxidative 

phosphorylation) were observed in a 3-year old child exposed to pentachlorophenol in contaminated bath 

water. However, no signs of hyperthermia were observed in older children or adults in the family. 

Preweaning and adult rats have been reported to have lower oral LD50s for technical-grade pentachlorophenol than juvenile rats (25–50 days old) (St. Omer and Gadusek 1987); similar differences in sensitivity 

are possible in humans. 

Age-related differences in the frequency or severity of toxic effects from pentachlorophenol exposure 

may arise from developmental regulation of cytochrome P-450s, which are involved in phase I 

metabolism of pentachlorophenol, and sulfotransferases and UDP-glucuronosyl transferase, which are 

involved in phase II metabolism of pentachlorophenol (see Section 3.7). 

Oral and intraperitoneal administration of pentachlorophenol to animals causes adverse effects on thyroid 

homeostasis (e.g., decreased serum thyroxine) and on the thyroid gland, and such effects may occur 

during gestation, pregnancy, and lactation. Pentachlorophenol also significantly decreased the uptake of 

radiolabeled thyroid hormone into cerebrospinal fluid (see Section 3.7). These effects of pentachlorophenol on the thyroid gland, thyroid homeostasis, and the availability of thyroid hormone to the central 

nervous system may have adverse effects on development of the nervous system. Deficiencies in 

thyroxine during prenatal and postnatal life can cause decrements in intellectual function in children 

(Bargagna et al. 1997; Birrell et al. 1983; Kooistra et al. 1994), and hypothyroidism in animals leads to 

disorders in structural and functional development of the brain (Gould et al. 1990; Neveu and Arenas 

1996; Stein et al. 1991; Vega-Nunez et al. 1995). 

Individuals with liver or kidney disease may be unusually susceptible to the toxic effects of pentachlorophenol. In certain fatal human cases, the victim was found to have renal insufficiency (Hayes 1982). 

Experiments have shown that rabbits made nephrotic experimentally were much more susceptible to the 

toxic effects of pentachlorophenol than were normal rabbits (Hayes 1982). Individuals exposed to other 
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chemicals that bind to plasma proteins (e.g., anticoagulants such as warfarin) may be at greater risk of 

suffering from pentachlorophenol-induced toxicity as well. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to pentachlorophenol. However, because some of the treatments discussed may be experimental 

and unproven, this section should not be used as a guide for treatment of exposures to pentachlorophenol. 

When specific exposures have occurred, poison control centers and medical toxicologists should be 

consulted for medical advice. The following texts provide specific information about treatment following 

exposures to pentachlorophenol: 

Ballhorn L, Rozman T, Rozman K, et al. 1981. Cholestryamine enhances fecal elimination of 

pentachlorophenol in Rhesus monkeys. Chemosphere 10:877-888. 

EPA. 1989b. Recognition and management of pesticide poisonings. 4th ed. Washington, DC: U.S. 

Environmental Protection Agency. EPA-540/9-88-001. 

Goodman AG, Rall TW, Nies AS, et al. 1990. Goodman & Gilman’s the pharmacological basis of 

therapeutics. 8th ed. New York, NY: Pergamon Press, 1635. 

Rozman T, Ballhorn L, Rozman K, et al. 1982. Effect of cholestyramine on the disposition of 

pentachlorophenol in Rhesus monkeys. J Toxicol Environ Health 10:277-283. 

3.11.1 Reducing Peak Absorption Following Exposure 

Means of limiting absorption of phenols include washing exposed skin and eyes and removing 

contaminated clothing in the case of dermal exposure, and inducing emesis, performing gastric lavage, 

and administering activated charcoal and a cathartic in the case of oral exposure (EPA 1989b). Emesis is 

induced only if the patient is fully alert and the pentachlorophenol has not been ingested in a solvent so 

that there is no chance that the stomach contents may be aspirated. If the patient is unconscious or 

vomiting cannot be induced, intubation, aspiration, and lavage of the stomach are suggested (EPA 

1989b). 
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3.11.2 Reducing Body Burden 

Various agents have been used in experimental animals to try to decrease the toxicity of pentachlorophenol by reducing body burden. Cholestyramine is known to bind phenols (Reiman and Walton 1970) 

and to enhance fecal elimination of chlordecone (Kepone) in rats and humans (Boylan et al. 1977). In 

studies performed on Rhesus monkeys, oral administration of cholestyramine enhanced fecal excretion of 

pentachlorophenol by interrupting enterohepatic circulation of pentachlorophenol and/or its metabolites 

(Ballhorn et al. 1981; Rozman et al. 1982). Thus cholestyramine administration may be an effective 

means of reducing the body burden of pentachlorophenol in humans (Goodman et al. 1990); it should be 

noted that testing would be required to determine whether or not cholestyramine treatment would be 

effective for humans. Hemodialysis and forced diuresis may not be effective means of reducing body 

burden of phenolic substances, and hemoperfusion has not been sufficiently tested as a means of 

accelerating elimination of phenols (EPA 1989b). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The naturally occurring antioxidants ellagic acid, epigallocatechin gallate, and vitamin C provided partial 

protection from pentachlorophenol-induced oxidative damage to liver DNA during daily oral 

administration of pentachlorophenol at 60 mg/kg/day for 5 days to male B6C3F1 mice (Sai-Kato et al. 

1995). Since these antioxidants are protective of animals, they may reduce toxic effects in humans. 

3.12 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 pentachlorophenol is available. Where adequate 

information is not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a 

program of research designed to determine the health effects (and techniques for developing methods to 

determine such health effects) of pentachlorophenol. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 
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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. 

3.12.1 Existing Information on Health Effects of Pentachlorophenol 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

pentachlorophenol are summarized in Figure 3-4. The purpose of this figure is to illustrate the existing 

information concerning the health effects of pentachlorophenol. Each dot in the figure indicates that one 

or more studies provide information associated with that particular effect. The dot does not necessarily 

imply anything about the quality of the study or studies, nor should missing information in this figure 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. 

Much of the literature reviewed concerning the health effects of pentachlorophenol in humans described 

case reports of individuals exposed occupationally, in log homes treated with pentachlorophenol as a 

preservative, or in the home following misuse of pentachlorophenol-containing solutions. The 

predominant route of exposure in such cases is often dermal, but the possibility of some degree of 

inhalation exposure cannot be ruled out. Therefore, Figure 3-4 reflects that information exists for both 

inhalation and dermal routes of exposure. However, all of these reports are limited because of the 

possibility of concurrent exposure to other potentially toxic substances, present as either contaminants in 

technical-grade pentachlorophenol (i.e., chlorinated dibenzo-p-dioxins and dibenzofurans), as other 

components in pentachlorophenol-containing mixtures (i.e., pesticides and herbicides), or simply other 

compounds also in the environment. Additionally, duration and level of exposure to pentachlorophenol 

generally cannot be quantified from information presented in these anecdotal reports. 

The database for health effects of pentachlorophenol following ingestion in experimental animals is 

substantial. However, as can be seen in Figure 3-4, very little information is available on the effects of 

inhalation and dermal exposure to pentachlorophenol in animals. Furthermore, the health effects 

associated with acute and intermediate exposure durations are more fully characterized than those 

associated with chronic exposure. Genotoxicity data on pentachlorophenol are available from both in 

vitro and in vivo studies. Finally, when evaluating much of the data on health effects of pentachlorophenol, the toxicity of its impurities (which may themselves present a hazard at disposal sites) must be 
PENTACHLOROPHENOL 121 

3. HEALTH EFFECTS 

Figure 3-4. Existing Information on Health Effects of Pentachlorophenol 
 

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3. HEALTH EFFECTS 

taken into account. However, it is now clear that pure pentachlorophenol is toxic to several organs and 

systems in rats and mice and is oncogenic in mice. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Information on the acute toxicity of pentachlorophenol in humans 

comes from a number of case reports involving home use of pentachlorophenol-containing products, such 

as wood preservatives or herbicides in the garden (Gordon 1956; Hassan et al. 1985) and from a series of 

reports of newborn infants exposed to pentachlorophenol from diapers and linens treated with an 

antimildew agent (Armstrong et al. 1969; Robson et al. 1969; Smith et al. 1996). In many of the cases, it 

is likely that the individuals were primarily exposed to technical-grade pentachlorophenol via dermal 

contact, although there may have also been some inhalation exposure. There are also cases of individuals 

ingesting pentachlorophenol (Cretney 1976; Dreisbach 1980; Haley 1977). In general, no information on 

exposure concentration, duration of exposure, exposure to other chemicals, or the impurities present in the 

technical-grade pentachlorophenol is available. A number of health effects were consistently observed in 

these individuals, including death, symptoms of hyperthermia generated by uncoupling of oxidative 

phosphorylation (e.g., tachycardia, increased respiratory rate, labored breathing, profuse sweating, fever, 

metabolic acidosis), hemolytic anemia, hepatic enlargement, and dermal toxicity (irritation and 

chloracne). 

The only available inhalation study in animals (Hoben et al. 1979b) reported death, but did not examine 

other end points. The lack of exposure information in the human studies and the inadequate animal study 

precluded deriving an acute-duration inhalation MRL. Additional inhalation studies are needed to 

characterize target organs and establish exposure-response relationships. 

Most of the available information on the acute toxicity of pentachlorophenol in animals comes from oral 

exposure studies. A number of adverse effects were observed in oral exposure studies including death 

(Borzelleca et al. 1985; Deichmann et al. 1942; Renner et al. 1986; St. Omer and Gadusek 1987), 

cardiovascular effects (extensive vascular damage and heart failure) (Deichmann et al. 1942), 

hepatotoxicity (increased relative liver weight) (Nishimura et al. 1982), impaired immune function 

(Holsapple et al. 1987; Kerkvliet et al. 1985a; White and Anderson 1985), reproductive toxicity (Schwetz 

et al. 1974), and developmental toxicity (Schwetz et al. 1974). The developing fetus was identified as the 

most sensitive target in rats following acute gavage exposure to pure pentachlorophenol (Schwetz et al. 

1974). The observed effects included delayed ossification at the lowest dose tested (5 mg/kg/day 
 

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administered on gestational days 6–15) and skeletal anomalies, decreased fetal body weights, increased 

male:female sex ratio, and increased resorptions at higher doses. The Schwetz et al. (1974) study is the 

basis for an acute-duration oral MRL of 0.005 mg/kg/day. 

Pentachlorophenol is well absorbed through the skin, and is expected to produce effects in the same 

tissues affected by exposure via other routes. Human reports describe numerous systemic effects in 

individuals predominantly exposed through dermal contact. Skin irritation was reported in a dermal study 

in rabbits (Deichmann et al. 1942). Additional studies via dermal exposure would be useful in 

determining target organs and dose-response relationships following acute-duration exposures. 

Intermediate-Duration Exposure. There is limited information on the toxicity of 

pentachlorophenol in humans following intermediate-duration exposure. Case reports of individuals 

exposed either occupationally or in the home during misuse of pentachlorophenol-containing solutions as 

a result of failure to adhere to appropriate precautionary measures provide some information on the 

toxicity of pentachlorophenol in humans. The observed effects include hematological alterations (aplastic 

anemia), hyperthermia (due to uncoupling of oxidative phosphorylation), hepatic enlargement, and 

impaired immune function (Daniel et al. 1995; Gray et al. 1985; Roberts 1963, 1981, 1990; Rugman and 

Cosstick 1990). Dermal contact is probably the primary exposure route in these cases, although the 

possibility of inhalation exposure cannot be ruled out. The interpretation of the reports is limited by the 

small number of subjects and the lack of information on exposure concentration, route, and duration, 

concomitant exposure to other chemicals, and description of impurities present in the commercial- or 

technical-grade pentachlorophenol. No studies were located that examined the toxicity of 

pentachlorophenol in humans following intermediate-duration oral exposure. 

No inhalation studies in animals were located. An intermediate-duration inhalation MRL was not derived 

due to the lack of human and/or animal data. A 90-day inhalation study is necessary to identify sensitive 

end points and dose-response relationships. 

Information on the toxicity of pentachlorophenol in animals following intermediate-duration exposure 

primarily comes from oral exposure studies. The results of these studies suggest that the reproductive 

system is the most sensitive target of toxicity following intermediate-duration exposure. An increase in 

the severity of cystic uterine glands and decreases in the proportion of female mink accepting a second 

mating and the number of mink that whelped have been observed in a single-generation mink study 

(Beard et al. 1997). Other sensitive end points include the liver (increased liver weight, centrilobular 
 

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hepatocyte hypertrophy and vacuolation, hepatocellular degeneration, and periportal fibrosis) (Blakley et 

al. 1998; Greichus et al. 1979; Johnson et al. 1973; Kerkvliet et al. 1982; Kimbrough and Linder 1978; 

Knudsen et al. 1974; Nishimura et al. 1980; Umemura et al. 1996), endocrine system (decreased 

thyroxine levels, increased thyroid gland follicle size) (Beard et al. 1999; Rawlings et al. 1998), immune 

system (Blakley et al. 1998; Kerkvliet et al. 1982, 1985a, 1985b; NTP 1989), and the developing fetus 

(decreased litter size, decreased fetal body weights, embryo lethality) (Argus 1997/Bernard et al. 2001c; 

Beard et al. 1999; Welsh et al. 1987). The studies in sheep suggest that the thyroid system is a sensitive 

target of pentachlorophenol toxicity. Additional studies are needed in conventional laboratory species to 

confirm the sensitivity of this organ and to evaluate the relevance of the effect to human health; other 

endocrine tissues should also be examined for potential effects. The LOAEL identified for reproductive 

effects in mink was used to derive an intermediate-duration oral MRL. Additional studies are needed to 

better define dose-response relationships and to identify no adverse effect levels. 

Information on the dermal toxicity of pentachlorophenol in animals is limited to a study that reported 

death and dermal irritation in rabbits following application of pentachlorophenol in fuel oil; the vehicle 

may have contributed to the observed effects (Deichmann et al. 1942). Studies examining systemic end 

points following dermal exposure would be useful to establish thresholds. 

Chronic-Duration Exposure and Cancer. Occupational exposure studies and reports of families 

living in log homes that were treated with pentachlorophenol provide information on the chronic toxicity 

of pentachlorophenol in humans. The reported effects include inflammation of the upper respiratory tract 

and bronchitis (Baader and Bauer 1951; Klemmer et al. 1980), reduced glomerular filtration rate and 

tubular function (Begley et al. 1977), hepatic effects (increased levels of biliary acid concentrations, 

urinary porphyrin, and serum alanine and aspartate transaminases) (Cheng et al. 1993; Colosio et al. 

1993a; Hryhorczuk et al. 1998; Klemmer 1972), and impaired immune function (McConnchie and 

Zahalsky 1991). It is likely that the individuals were exposed via inhalation and dermal contact. In 

general, the epidemiology studies involved exposure to technical-grade or undefined purity pentachlorophenol; therefore, other chemicals may have contributed to these effects. Little information on exposure 

concentrations is available. No chronic oral human studies were located. 

Chronic-duration animals studies are only available for the oral route. Liver effects (hepatocyte cystic 

degeneration, hepatodiaphragmatic nodules) (Chhabra et al. 1999; NTP 1999; Schwetz et al. 1978) and 

effects on the thyroid (decreased serum thyroxine and decreased relative thyroid weight) (Beard and 

Rawlings 1998, 1999; Beard et al. 1999a) were reported in these studies. A chronic-duration oral MRL of 
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0.001 mg/kg/day was calculated based on a LOAEL of 1 mg/kg/day for significantly decreased serum 

thyroxine concentrations in males of the first generation and males and females of the second generation, 

and decreased relative thyroid weight in females of the second generation when mink were administered 

pentachlorophenol of unspecified purity continuously in the diet in a multigeneration reproduction study 

(Beard and Rawlings 1998). A chronic-duration inhalation MRL was not developed because 

concentrations that cause toxic effects in humans were not quantified and no animal studies were 

identified. Chronic inhalation studies are necessary for establishing exposure-response relationships and 

identifying sensitive targets of toxicity. No dermal animal studies were identified; chronic dermal 

exposure studies would be useful for identifying sensitive targets of the toxicity and establishing 

exposure-response relationships. 

Epidemiology studies have not provided a firm association between pentachlorophenol exposure and an 

increased risk of cancer. Several occupational studies reported no association between inhalation of 

pentachlorophenol in any form and cancer in humans (Gilbert et al. 1990; Jappinen et al. 1989; Johnson et 

al. 1990; Robinson et al. 1985). However, each of the individual studies had a low power to detect 

elevated risk estimates. In contrast, other occupational studies reported an association between 

pentachlorophenol exposure and soft tissue sarcoma (Eriksson et al. 1990; Hardell et al. 1995; Hoppin et 

al. 1998; Lampi et al. 1992) or non-Hodgkin’s lymphoma (Hardell et al. 1994; Hertzman et al. 1997; 

Lampi et al. 1992). Many of these studies also reported significant associations between increased cancer 

risk and exposure to other chemicals (e.g., other chlorophenols, phenoxyacetic acids, cutting oil 

components). Additional follow-up of pentachlorophenol-exposed cohorts using epidemiological 

methods and study designs of sufficient power and discrimination to distinguish effects of 

pentachlorophenol from effects attributable to other possible causes would be useful for assessing the 

carcinogenic potential of pentachlorophenol in humans. Sufficient information exists from animal studies 

to support the conclusion that pentachlorophenol may cause cancer in humans. Significant increases in 

the incidence of hemangiosarcomas, liver adenomas and carcinomas, and adrenal gland 

pheochromocytomas were observed in mice (NTP 1989), and mesotheliomas and nasal squamous cell 

carcinomas were observed in rats orally exposed to pure pentachlorophenol (Chhabra et al. 1999; NTP 

1999). No information is available on the carcinogenic potential following inhalation or dermal exposure; 

chronic bioassays by these routes would be useful in determining whether pentachlorophenol induces 

cancer of the respiratory tract and skin, respectively. 

The suggestive human data and the positive carcinogenicity results from animal bioassays (Chhabra et al. 

1999; NTP 1989, 1999), along with genotoxicity data suggesting that pentachlorophenol is clastogenic, 
 

 

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3. HEALTH EFFECTS 

provide sufficient evidence to suggest that pentachlorophenol may be a human carcinogen. The 

International Agency for Research on Cancer (IARC 1999) has placed pentachlorophenol in group 2B 

(possibly carcinogenic to humans). EPA classified pentachlorophenol as a group B2 carcinogen 

(probable human carcinogen) (IRIS 2001). 

Genotoxicity. The available genotoxicity data indicate that pentachlorophenol may have genotoxic 

potential. Two studies investigated the genotoxicity of pentachlorophenol in humans; both of these are 

inadequate because of the small number of subjects studied (Bauchinger et al. 1982; Wyllie et al. 1975). 

The observed effects included a small increase in the frequency of dicentrics and acentrics, but no 

increases in sister chromatid exchange, and an increase in chromosome aberrations. In general, in vitro 

and in vivo studies have not reported evidence of genotoxicity. Pentachlorophenol did not induce gene 

mutations in Salmonella typhimurium (Donnelly et al. 1998; Markiewicz et al. 1996; NTP 1999; Simmon 

et al. 1977; Waters et al. 1982) or Escherichia coli (Anderson et al. 1972; Lemma and Ames 1975; 

Moriya et al. 1983; Simmon et al. 1977; Waters et al. 1982); or DNA damage in E. coli (Fahrig 1974), 

Bacillus subtilis (Waters et al. 1982), Chinese hamster ovary cells (Ehrlich 1990), Chinese hamster V79 

cells (Dahlhaus et al. 1996), or mouse embryonic fibroblast cells (Wang and Lin 1995). Several in vitro 

studies suggest that pentachlorophenol has clastogenic activity (Fahrig 1974; NTP 1999). Increases in the 

occurrence of chromosomal aberrations in human lymphocytes and Chinese hamster ovary cells and sister 

chromatid exchange in Chinese hamster ovary cells have occurred (NTP 1999). In Saccharomyces 

cerevisiae assays for recombination, positive and negative results have been found (Fahrig 1974; Fahrig et 

al. 1978; Waters et al. 1982), and positive results were found for induction of gene mutations (Fahrig et 

al. 1978). In in vivo studies, negative results have been found for gene mutations in a mouse spot test 

assay (Fahrig and Steinkamp-Zucht 1996), sex-linked recessive lethal mutations in Drosophila 

melanogaster (Sai-Kato et al. 1995; Umemura et al. 1996), and micronuclei occurrence in mouse and rat 

bone marrow (NTP 1999). Given the availability of a number of genetic toxicology studies, there is no 

apparent need for additional genotoxicity testing at this time. 

Reproductive Toxicity. The possible association between pentachlorophenol exposure and 

reproductive effects in women has been investigated by Gerhard et al. (1991). Elevated blood levels of 

pentachlorophenol were found in women with histories of reproductive effects (e.g., habitual abortions, 

unexplained infertility, menstrual disorders). However, a causal relationship cannot be established due to 

limitations such as the lack of information on the exposure route and exposure to other chemicals (e.g., 

increased levels of PCBs were detected in the blood). In addition, matched controls were not used and 
 

PENTACHLOROPHENOL 127 

3. HEALTH EFFECTS 

other confounding factors were not controlled. No other human studies examined reproductive end 

points. 

Adverse reproductive effects were observed in animals following oral exposure to technical-grade and 

pure pentachlorophenol. In a two-generation reproductive toxicity study in rats, decreased fertility was 

observed the first generation exposed to 60 mg/kg/day pentachlorophenol (purity not reported) (Argus 

1997/Bernard et al. 2001c). Decreased frequency of second mating, decreased birth rate for the second 

mating, and increased severity of cystic uterine gland were observed in mink exposed to 1 mg/kg/day 

(Beard et al. 1997). In contrast, no reproductive effects were observed in a multigeneration study in mink 

using the same dietary concentration (Beard and Rawlings 1998). No effect on fertility was observed in 

sheep exposed to 1 mg/kg/day prior to mating and throughout gestation and lactation (Beard et al. 1999b). 

No animal studies examined the reproductive toxicity of pentachlorophenol following inhalation or 

dermal exposure; studies by the inhalation and dermal routes would be valuable in establishing an 

exposure-response relationship for these exposure routes. The intermediate-duration oral MRL is based 

on a LOAEL for reproductive effects observed in the single-generation mink study (Beard et al. 1997). 

Developmental Toxicity. An increased risk of congenital eye cataracts was observed in the children 

of male sawmill workers presumably exposed to CDD-contaminated mixtures of the sodium salts of 

pentachlorophenol and tetrachlorophenol (chlorophenate) (Dimich-Ward et al. 1996). Interpretation of 

the study results is limited because exposure levels were not measured and a surrogate for chlorophenate 

exposure was used. No other human developmental toxicity studies were located. 

A number of animal studies reported developmental effects following oral exposure to pure or technicalgrade pentachlorophenol. The observed effects included fetal/neonatal mortality (Argus 1993b/Bernard 

et al. 2001b, Argus 1997/Bernard et al. 2001c; Schwetz et al. 1974; Welsh et al. 1987), 

malformations/anomalies (Argus 1993b/Bernard et al. 2001b; Schwetz et al. 1974), and decreased growth 

(Argus 1993b/Bernard et al. 2001b; Beard et al. 1993b; Courtney et al. 1976; Larsen et al. 1975; Schwetz 

et al. 1974; Welsh et al. 1987). A threshold for developmental toxicity has not been identified. A 

comparison between the adverse effects levels for developmental effects with those for systemic, immune, 

and reproductive effects, suggests that the fetus/neonate is a sensitive target for pentachlorophenol. Note 

that the acute duration oral MRL is based on a LOAEL for developmental effects (Schwetz et al. 1974). 

A common limitation of these developmental toxicity studies is that only one dose level was tested in 

most of these studies. Additional studies using a range of doses would be useful for establishing the 

threshold for developmental toxicity. Additionally, several oral studies provide evidence that the thyroid 
 

 

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3. HEALTH EFFECTS 

gland is sensitive to the toxicity of pentachlorophenol (Beard and Rawlings 1998; Beard et al. 1999; Jekat 

et al. 1994; Rawlings et al. 1998). It is not known whether this would also be a sensitive target in the 

developing organism. Developmental studies that assessed thyroid function and tested for potential 

neurobehavioral and neuropathological effects would be useful since deficiencies in thyroxine during 

prenatal and postnatal periods can cause decrements in intellectual function in children (Bargagna et al. 

1997; Birrell et al. 1983; Kooistra et al. 1994). The available developmental toxicity studies involve 

maternal exposure; no studies have examined the potential developmental effect of paternal exposure. No 

animal inhalation or dermal developmental toxicity studies are available for pentachlorophenol. Studies 

by these exposure routes would be useful for establishing dose-response relationships. 

Immunotoxicity. Several human studies provide suggestive evidence that pentachlorophenol is an 

immunotoxicant. Impaired mitogen-induced lymphocyte stimulation was observed in individuals 

exposed to pentachlorophenol-containing pesticides (Daniel et al. 1995); T-cell activation, autoimmunity, 

immunosuppression, and B-cell dysregulation were observed in family members living in pentachlorophenol-treated log homes (McConnachie and Zahalsky 1991); and decreased proliferative response to a 

mitogen was observed in factory workers exposed to high levels of pentachlorophenol (Colosio et al. 

1993b). Oral studies in animals provide strong evidence that technical-grade pentachlorophenol is an 

immunotoxicant, although none of the identified studies performed a complete immunotoxicity battery. 

Humoral and cellular immunity (Holsapple et al. 1987; Kerkvliet et al. 1985a; NTP 1989), susceptibility 

to tumor induction (Kerkvliet et al. 1982), and complement activity (White and Anderson 1985) have 

been adversely affected following oral exposure. Studies that tested both technical-grade and pure 

pentachlorophenol provide strong evidence that the immune effects are related to the level of impurities in 

the technical-grade product (e.g., CDDs, CDFs). Support for the immunotoxicity of pure pentachlorophenol is less conclusive, with some rat and mouse studies reporting altered immune function (Blakley et 

al. 1998; Kerkvliet et al. 1982) and other studies reporting no effects (Kerkvliet et al. 1985a; NTP 1989). 

No studies that tested the immunotoxicity of pentachlorophenol following inhalation or dermal exposure 

were located. The available data suggest that the immune system may be a sensitive target of toxicity 

following oral exposure to technical-grade pentachlorophenol and possibly pure pentachlorophenol. 

Neurotoxicity. In a number of case reports, neurological effects have been described in individuals 

likely exposed via inhalation and dermal contact. The symptoms of central nervous system neurotoxicity 

include intermittent delirium, fever, convulsions, profuse sweating, and increased respiratory rate and 

labored breathing (Chapman and Robson 1965; Robson et al. 1969; Smith et al. 1996). Similar 

neurological symptoms were reported in an individual intentionally ingesting a weed killer containing 
 

PENTACHLOROPHENOL 129 

3. HEALTH EFFECTS 

12% pentachlorophenol (Haley 1977). These effects are probably due to hyperthermia resulting from 

uncoupling of oxidative phosphorylation, rather than to a direct effect on the central nervous system. 

Neurological effects have also been observed in animals ingesting pentachlorophenol. Although a study 

examining a complete neurotoxicology battery of tests has not been identified, the available oral exposure 

data provide evidence that pentachlorophenol is a neurotoxicant at high doses. Oral exposure to relatively 

high doses of technical-grade or pure pentachlorophenol resulted in impaired motor activity and startle 

response in mice exposed to pentachlorophenol for 26 weeks, but not after 5 weeks (NTP 1989). 

Degenerative changes in the sciatic nerve myelin sheath were observed in rats administered 

pentachlorophenol of unspecified purity (Villena et al. 1992). No neurological studies involving 

inhalation or dermal exposure to pentachlorophenol were identified. 

Epidemiological and Human Dosimetry Studies. A number of studies have reported adverse 

health effects in humans following short- or long-term exposure to pentachlorophenol. The short-term 

data comes from case reports involving home use of pentachlorophenol-containing products such as wood 

preservative or herbicides in the garden (Gordon 1956; Hassan et al. 1985) or a series of reports of 

newborn infants exposed to pentachlorophenol from diapers and linens treated with an antimildew agent 

(Robson et al. 1969; Smith et al. 1996). Long-term toxicity information comes from families living in log 

homes that were treated with pentachlorophenol (McConnachi and Zahalsky 1991) and occupational 

exposure in agricultural and wood-treatment industries (Baader and Bauer 1951; Cheng et al. 1993; 

Colosio et al. 1993b; Hryhorczuk et al. 1998; Klemmer et al. 1980). As discussed previously, these 

studies are limited by incomplete exposure characterization. In general, information on exposure 

concentrations, exposure route, duration of exposure, possible concomitant exposure to other chemicals, 

and impurities present in technical-grade pentachlorophenol are not available. In most cases, exposure 

was by the inhalation and dermal routes. The consistently observed effects include death (Cretny 1976; 

Dreisbach 1980; Gordon 1956; Roberts 1981, 1990; Rugman and Cosstick 1990), inflammation of the 

upper respiratory tract and bronchitis (following inhalation exposure) (ACGIH 1991; Baader and Bauer 

1951; Klemmer et al. 1980), symptoms of hyperthermia generated by uncoupling of oxidative 

phosphorylation (e.g., tachycardia, increased respiratory rate, labored breathing, profuse sweating, fever, 

metabolic acidosis) (Bergner et al. 1965; Gordon 1956; Gray et al. 1985; Haley 1977; Hassan et al. 1985; 

Menon 1958; Robson et al. 1969; Smith et al. 1996), hemolytic anemia (Hassan et al. 1985; Roberts 1981, 

1990; Rugman and Cosstick 1990), hepatic enlargement (Bergner et al. 1965; Cheng et al. 1993; Colosio 

et al. 1993b; Gordon 1956; Hassan et al. 1985; Hryhorczuk et al. 1998; Smith et al. 1996), impaired 

immune function (Colosio et al. 1993b; Daniel et al. 1995; McConnachi and Zahalsky 1991), and dermal 
 

PENTACHLOROPHENOL 130 

3. HEALTH EFFECTS 

toxicity (irritation and chloracne) (Baader and Bauer 1951; Hosenfeld et al. 1986; Klemmer et al. 1980; 

Lambert et al. 1986; O’Malley et al. 1990). 

Additionally, several epidemiology studies have examined the carcinogenic potential of pentachlorophenol. These data are inconclusive with some studies reporting no association between cancer risk and 

exposure to pentachlorophenol (Gilbert et al. 1990; Jappinen et al. 1989; Johnson et al. 1990; Robinson et 

al. 1985) and other studies indicating a significant risk of soft tissue sarcoma (Eriksson et al. 1990; 

Hardell et al. 1995; Hoppin et al. 1998; Lampi et al. 1992) or non-Hodgkin’s lymphoma (Hardell et al. 

1994; Hertzman et al. 1997; Lampi et al. 1992). Hepatotoxicity (Blakley et al. 1998; Chhabra et al. 1999; 

Greichus et al. 1979; Johnson et al. 1973; Kerkvliet et al. 1982; Kimbrough and Linder 1978; Knudsen et 

al. 1974; Nishimura et al. 1982; NTP 1999; Schwetz et al. 1978; Umemura et al. 1996), impaired immune 

function (Blakley et al. 1998; Holsapple et al. 1987; Kerkvliet et al. 1982, 1985a, 1985b; NTP 1989; 

White and Anderson 1985), and increased incidence of malignant tumors (Chhabra et al. 1999; NTP 

1989, 1999) have also been reported in animal studies involving oral exposure. A number of other 

sensitive end points for animals, including thyroid toxicity, reproductive toxicity, and developmental 

toxicity, have not been fully investigated in humans. Additional epidemiological studies that provide 

sufficient information for exposure characterization and examine a number of systemic end points would 

be useful for establishing sensitive targets of toxicity in humans and dose-response relationship data. 

Biomarkers of Exposure and Effect. 

Exposure. Pentachlorophenol is excreted in the urine largely unchanged (Ahlborg et al. 1974; Braun et 

al. 1979; Larsen et al. 1972) and can easily be detected and quantified in the urine at concentrations as 

low as <1 ppb (Chou and Bailey 1986; Drummond et al. 1982; Edgerton et al. 1979; EPA 1980a; Holler 

et al. 1989; NIOSH 1984b; Pekari and Aitio 1982; Rick et al. 1982; Siqueina and Fernicola 1981). Thus, 

measurement of pentachlorophenol in the urine is a useful biomarker of exposure. In addition, 

pentachlorophenol can be easily detected and quantified in blood serum at concentrations as low as 

<1 ppb (Bevenue et al. 1968; EPA 1980a; Needham et al. 1981; NIOSH 1984b) and adipose tissue (Kuehl 

and Dougherty 1980; Needham et al. 1981; Ohe 1979; Shafik 1973). However, measuring pentachlorophenol in body fluids and tissues is not a specific biomarker for pentachlorophenol exposure because 

other compounds to which exposure may occur (e.g., hexachlorobenzene and lindane) may be 

metabolized to pentachlorophenol in the body. In addition, the available data do not permit the 

establishment of a quantitative relationship between levels of pentachlorophenol in the environment and 

levels in human fluids or tissues. Additionally, a major pentachlorophenol urinary metabolite, TCHQ, 
 

PENTACHLOROPHENOL 131 

3. HEALTH EFFECTS 

has potential use as an indicator of exposure to pentachlorophenol (Ahlborg et al. 1974; Braun et al. 1977; 

Juhl et al. 1985; Reigner et al. 1991; Renner 1989), although this biomarker is not specific for pentachlorophenol. Additional studies are needed to establish a relationship between exposure level and 

urinary concentration of TCHQ. 

Effect. The liver is a target organ for both humans and animals exposed to pentachlorophenol. Clinical 

manifestations of hepatic and renal toxicity include elevated serum ALT and AST levels for toxicity to 

the liver (Armstrong et al. 1969; Bergner et al. 1965; Gordon 1956; Gray et al. 1985; Klemmer 1972; 

Robson et al. 1969). Indices of changes in hepatic oxidative phosphorylation may also be useful as 

biomarkers for pentachlorophenol-induced liver changes (Ellinger et al. 1991). These effects are not 

specific for exposure to pentachlorophenol and have been associated with exposure to other compounds, 

such as some chlorinated hydrocarbons. Therefore, the major use of these biomarkers is restricted to 

comparisons in which pentachlorophenol-exposed and control groups can be identified (e.g., between 

workers exposed to chemical in the workplace and control subjects). Oral exposure of animals to 

pentachlorophenol induces a decrease of thyroxine levels in serum (Beard et al. 1999b; Jekat et al. 1994; 

Rawlings 1998). Comparison of the levels of thyroxine in control and pentachlorophenol-exposed 

populations could also serve as a nonspecific biomarker of pentachlorophenol effect. In general, there is 

no simple relationship between nonfatal health effects and levels of pentachlorophenol detected in serum 

and urine. Development of additional, more sensitive biomarkers that are specific for pentachlorophenol 

effects would be useful in monitoring populations at high risk. 

Absorption, Distribution, Metabolism, and Excretion. The absorption, distribution, 

metabolism, and excretion of pentachlorophenol have been investigated in humans and animals. 

Evidence for absorption of pentachlorophenol by humans after exposure by the inhalation and dermal 

routes is provided by the observation of elevated urine and plasma levels in workers (Casarett et al. 1969; 

Jones et al. 1986; Pekari et al. 1991) and residents of log homes treated with pentachlorophenol (Cline et 

al. 1989; Hosenfeld et al. 1986). A study of two humans exposed to pentachlorophenol vapors for 

45 minutes provides evidence that it is well absorbed (Casarett et al. 1969). Similarly, human studies also 

indicate that pentachlorophenol is readily absorbed following oral exposure (Braun et al. 1979; Uhl et al. 

1986). The results of inhalation (Hoben et al. 1976c) and oral (Ahlborg et al. 1974; Braun and Sauehoff 

1976; Braun et al. 1977; Meerman et al. 1983; Reigner et al. 1991) exposure studies in animals confirm 

the results of the human studies that pentachlorophenol is well absorbed following inhalation or oral 

exposure. In vivo animal studies (Qiao et al. 1997; Wester et al. 1993) are sufficient to characterize the 

extent of absorption of pentachlorophenol in soil. However, additional animal studies would be useful for 
 

PENTACHLOROPHENOL 132 

3. HEALTH EFFECTS 

determining the absorption efficiency of an aqueous solution of pentachlorophenol and neat 

pentachlorophenol. 

No human studies examined the distribution of pentachlorophenol following inhalation, oral, or dermal 

exposure. The distribution of pentachlorophenol following inhalation (Hoben et al. 1976c), oral (Braun et 

al. 1977; Gómez-Catalán et al. 1991; Larsen et al. 1975), or dermal (Qiao et al. 1997) exposure has been 

characterized in acute-duration studies in animals. Long-term studies examining distribution would be 

useful to determine if there are any duration-related differences in distribution. Pentachlorophenol has 

been found in human breast milk from German and Slovakian women (Gebefugi and Korte 1983; 

Veningerova et al. 1996). 

Results from human and animal studies indicate that pentachlorophenol is not extensively metabolized, as 

evidenced by a large portion of the administered dose being excreted in urine unchanged in humans 

exposed by the inhalation (Ahlborg et al. 1974) and oral (Braun et al. 1979; Uhl et al. 1986) routes and in 

animals exposed to pentachlorophenol by the inhalation (Hoben et al. 1976a) and oral (Ahlborg et al. 

1974; Braun et al. 1977; Renner 1989; Renner and Hopfer 1990) routes. The major metabolite is 

tetrachloro-p-hydroquinone (TCHQ) in humans exposed to pentachlorophenol by the inhalation route 

(Ahlborg et al. 1974) and in animals exposed to pentachlorophenol by the oral route (Ahlborg et al. 1974; 

Braun et al. 1977; Reigner et al. 1991; Renner and Hopfer 1990). Additional studies of metabolites 

formed in humans after exposure to pentachlorophenol by the dermal and oral routes and in animals after 

exposure to pentachlorophenol by the inhalation and dermal routes would be useful. The available human 

and animal data indicate that metabolism of pentachlorophenol occurs in the liver, and the major 

pathways are glucuronide conjugation and oxidative dechlorination to form TCHQ. However, recent 

studies in rats and mice following oral administration of pentachlorophenol (Lin et al. 1997; Waidyanatha 

et al. 1994, 1996) suggest that the metabolism of pentachlorophenol can also proceed through the quinols, 

TCHQ, and tetrachlorocatechol, via microsomal cytochrome P 450 enzymes, and that these quinols can 

be oxidized via semiquinone intermediates. Both the quinones and semiquinones are electrophilic and 

can bind to cellular macromolecules (Lin et al. 1997). Additional studies in animals to determine if 

chlorinated quinones and semiquinones are produced following inhalation and dermal exposures to 

pentachlorophenol would be useful. Studies in animals by the inhalation, oral, or dermal routes to 

examine the potential role of peroxidases in pentachlorophenol metabolism would also be useful. 

Additional studies examining the metabolism of pentachlorophenol following inhalation and dermal 

exposure would be useful for determining if there are route-specific differences in metabolism. 
 

PENTACHLOROPHENOL 133 

3. HEALTH EFFECTS 

No information was found on the relative amounts of excreted pentachlorophenol and its metabolites in 

urine and feces after humans or animals were exposed to pentachlorophenol by inhalation. 

Approximately 74 and 12% (total of 86%) of pentachlorophenol ingested by humans was eliminated in 

the urine as pentachlorophenol and its glucuronide conjugate, respectively (Braun et al. 1979). In 

rodents, from 60–83% of the administered oral dose is eliminated in the urine (Ahlborg et al. 1974; Braun 

et al. 1977; Larsen et al. 1972; Reigner et al. 1991); in monkeys, 45–75% of the administered oral dose is 

eliminated in the urine (Braun and Sauerhoff 1976). Fecal elimination of pentachlorophenol and its 

metabolites accounted for 4% of the administered oral dose in humans (Braun et al. 1979), 8–34% of the 

administered oral dose in rodents (Braun et al. 1977; Larsen et al. 1972; Reigner et al. 1991, 1992), and 

3–20% in monkeys (Ballhorn et al. 1981; Braun and Sauerhoff 1976; Rozman et al. 1982). Only trace 

amounts were eliminated in expired air. Excretion data in animals indicate that the kinetics of pentachlorophenol elimination in humans following oral exposure is similar to that seen in monkeys in that 

they are first order (Braun and Sauerhoff 1976; Braun et al. 1979); additional studies examining potential 

species differences would be useful. No studies were located regarding excretion in humans after dermal 

exposure to pentachlorophenol. After application of radioactively-labeled pentachlorophenol in a soilbased mixture to the skin of swine, one-third to one-half of the absorbed dose was almost equally 

excreted through urinary and fecal routes (Qiao et al. 1997). Additional studies on routes of elimination 

of pentachlorophenol following exposures of animals by the dermal and inhalation routes would be 

useful. Two animal studies (Braun and Sauerhoff 1978; Braun et al. 1974) found an apparent difference 

in elimination kinetics between males and females. Additional studies examining potential sex-related 

differences would be useful. 

Comparative Toxicokinetics. A series of studies conducted by Braun and associates (Braun and 

Sauerhoff 1976; Braun et al. 1977, 1979) suggest that there are toxicokinetic differences between humans, 

monkeys, and rats. The results of these studies suggest that the excretion of pentachlorophenol follows a 

linear, one-compartment model in humans and monkeys. In contrast, excretion in the rats was biphasic 

(two-compartment model). However, other pharmacological properties, such as maximum plasma 

concentration, absorption rate constant, volume of distribution, steady-state concentration, and the 

excretion of glucuronide conjugates were similar for humans and rats, but not for humans and monkeys. 

These data suggest that the rat may be a better model for humans than the monkey. Additional studies are 

needed to further evaluate species differences in the toxicokinetics of pentachlorophenol and to identify 

the most appropriate model for humans. 
 

 

PENTACHLOROPHENOL 134 

3. HEALTH EFFECTS 

Methods for Reducing Toxic Effects. Pentachlorophenol can be absorbed through inhalation, 

oral, or dermal routes. Methods are available for reducing absorption following oral and dermal exposure 

to pentachlorophenol; however, since gastrointestinal absorption of pentachlorophenol in humans is rapid 

(Braun et al. 1979), these methods (washing skin and eyes, emesis, lavage, activated charcoal, and 

catharisis) (EPA 1989, 1989b) are useful only immediately following exposure to the chemical. Based on 

animal studies, cholestyramine administration is recommended in cases of human pentachlorophenol 

overexposure to enhance elimination of pentachlorophenol (Goodman et al. 1990); however, its use in 

humans has not been sufficiently tested. Data on cholestyramine administration, hemoperfusion, and 

administration of sedatives and antipyretics as treatment methods would be useful. 

The mechanism of toxicity of pentachlorophenol is not clear. Although pentachlorophenol has been 

shown to uncouple oxidative phosphorylation, affect thyroid homeostasis, and produce oxidative damage 

to DNA, the extent to which these effects contribute to toxicity in the various organs and systems affected 

by pentachlorophenol is not clear. It is possible that these effects contribute to the toxicity spectrum seen 

in some organs, but are secondary unrelated to toxic effects seen in other organs. Therefore, additional 

studies on the relative contributions of these effects (uncoupling of oxidative phosphorylation, 

disturbances in thyroid homeostasis, and oxidative damage to DNA) to pentachlorophenol toxicity and 

examination of other potential mechanisms of toxicity (e.g., interactions with specific cell or tissue 

receptors) would be useful steps toward identifying methods that may reduce the toxic effects of 

pentachlorophenol. 

Children’s Susceptibility. Adverse effects on the nervous system, liver, kidneys, and respiratory 

system, and some deaths were associated with exposure of newborn children to pentachlorophenol in 

diapers and bedding (Smith et al. 1996), and suppression of the immune system was seen in older children 

exposed to pentachlorophenol (McConnachie and Zahalsky 1991). Additional studies to confirm and 

expand these findings would be useful. In animals, pentachlorophenol also causes a decrease in serum 

thyroxine levels, adverse effects on thyroid homeostasis, and inhibition of the uptake of thyroid hormone 

into the central nervous system. Long-term epidemiological studies of possible health effects in large 

cohorts of individuals who were exposed to pentachlorophenol as children would be useful, particularly 

with regard to reproductive function, the immune system, neurobehavioral testing, and cancer. 

Oral exposure studies in animals provide evidence that pentachlorophenol is a developmental toxicant. 

Gestational exposure to pentachlorophenol has resulted in decreased fetal and neonatal survival (Schwetz 

et al. 1978), decreased fetal and neonatal body weight (Argus 1993b/Bernard et al. 2001b, Argus 1997/ 
PENTACHLOROPHENOL 135 

3. HEALTH EFFECTS 

Bernard et al. 2001c; Beard et al. 1999b; Courtney et al. 1976; Larsen et al. 1975; Schwetz et al. 1978; 

Welsh et al. 1987), increased male:female sex ratio (Schwetz et al. 1974), delayed ossification (Schwetz 

et al. 1974), and skeletal anomalies (Schwetz et al. 1974, 1978). There is some suggestive evidence that 

effects on the thyroid can lead to neurological deficiencies in the offspring; a neurodevelopmental toxicity 

study is needed to assess this potentially sensitive end point. 

There are no studies to indicate whether the pharmacokinetics and metabolism of pentachlorophenol in 

children are different from those in adults, and there are no PBPK models for pentachlorophenol. 

However, given the large number of potential reactive metabolites that can be formed from pentachlorophenol and the different levels of active metabolites among rodent species (Lin et al. 1997), wellconducted studies on potential pharmacokinetic and metabolic differences between children and adults 

would be useful. A rationale for such studies is that UDP-glucuronosyl transferase and sulfotransferases, 

which are involved in phase II metabolism of pentachlorophenol, and two of the cytochrome P-450s, 

which are involved in the phase I metabolism of pentachlorophenol, are all thought to be developmentally 

regulated (Leeder and Kearns 1997). The need for a PBPK model for pentachlorophenol is not apparent 

at this time. There are some data to show that radiolabeled pentachlorophenol may cross the placenta of 

animals and enter the developing fetus (Larsen et al. 1975), and can be present in human breast milk 

(Gebefugi and Korte 1983; Veningerova et al. 1996). However, studies to confirm that pentachlorophenol crosses the placenta into developing fetuses and to characterize levels of pentachlorophenol in 

human breast milk in the United States would be useful. There are no studies to evaluate whether the 

mechanism of action of pentachlorophenol is different in children, but there is no apparent reason to 

suspect that it would be different. However, studies to determine whether children have a different 

susceptibility to health effects from pentachlorophenol than adults would be useful, starting with studies 

that compare immature animals to adult animals. 

Child health data needs relating to exposure are discussed in 6.8.1 Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

Information on the ongoing studies cited in this section was obtained from FEDRIP (2001). 

Dr. I. Hertz-Picciotto at the University of North Carolina is assessing the feasibility of self-administered 

devices for collection of breath, urine, tap water, and indoor air monitoring samples in studies of penta­
PENTACHLOROPHENOL 136 

3. HEALTH EFFECTS 

chlorophenol; generating data on background variability of body burdens and protein adducts from 

exposures to pentachlorophenol; and determining factors that influence such variability, including point 

sources of contamination and workplace, in addition to background factors such as sociodemographic, 

geographic, lifestyle, and home characteristics. 

Dr. S. M. Rappaport of the University of North Carolina at Chapel Hill is investigating the development 

and application of biomarkers of exposure to pentachlorophenol, including the levels of the parent 

compound in blood, exhaled air, and urine, and the levels of adducts with hemoglobin and serum 

albumin. 
PENTACHLOROPHENOL 137 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of pentachlorophenol is located in Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of pentachlorophenol is located in Table 4-2. 
Cl Cl

Cl Cl 

Cl 

Cl Cl

Cl Cl 

Cl 

PENTACHLOROPHENOL 138 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Pentachlorophenol and Pentachlorophenatea 

Characteristic Pentachlorophenol Sodium pentachlorophenate 

Synonym(s) 

Registered trade name(s)

 For 37% aqueous solutiona

 For polymeric formb 

Chemical formula 

Chemical structure 

Identification numbers: 

CAS Registry 

NIOSH RTECS 

EPA Hazardous Waste 

OHM/TADS 

DOT/UN/NA/IMCO 

HSDB 

NCI 

PCP; penchlorol; penta;
 

pentachlorophenate; 2,3,4,5,6­

pentachlorophenolb
 

Chlon; Dowicide 7; Dowicide
 

EC-7; Dura Treet II; EP 30;
 

Fungifen: 

Grundier Arbezol; Lauxtol;
 

Liroprem; Penta Concentrate;
 

Penta Ready; Penta WR;
 

Permasan; Santophen 20;
 

Woodtreatb
 

C6HCl5O 

OH 

87-86-5 

SM6300000 

U242; FO27 

7216842 

NA 2020 

894 

C54933; C55378; C56655 

Pentachlorophenol sodium; 

pentachlorophenol sodium salt: 

pentachlorophenoxy sodium: 

pentaphenate 

Dow Dormant Fungicide; Dowicide 

G; Dowicide 

G-St; Mystox D; Napclor-G; 

Santobrite; Sapco25 Weedbeads 

C6Cl5ONa 

O Na+ 

131-52-2 

SM6490000 

No data 

No data 

UN 2567; IMO6.1 

761 

No data 

a

All information obtained from HSDB 2001 except where noted. b

RTECS 1991 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; 

HSDB = Hazardous Substance Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; 

RTECS = Registry of Toxic Effects of Chemical Substances 
PENTACHLOROPHENOL 139 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Pentachlorophenol 

and Sodium Pentachlorophenatea 

Sodium 

Property Pentachlorophenol pentachlorophenate 

Molecular weight 266.35 288.34 

Color Colorless or white (pure); dark gray to White or tan 

brown (crude product) 

Physical state Crystalline solid (pure); pellets or powder Flakes or powder 

(crude product)b 

Melting point 190 EC No data 

Boiling point 309–310 EC (decomposes) No data 

Density 1.978 g/mL at 22 EC/4 EC No data 

Odor Phenolic; very pungent (only when hot) No data 

Odor threshold: 

Water 0.857 mg/L at 30 EC; No data 

12.0 mg/L at 60 EC b,c 

Solubility: 

Water 14 mg/L at 20 EC 330,000 mg/L at 25 EC 

Organic solvent(s) Very soluble in alcohol and ether; soluble Soluble in acetone and 

in benzene; slightly soluble in cold ethanol 

petroleum etherd 

Partition coefficients: 

Log Kow 5.01b No data 

Log Koc 4.5e No data 

Vapor pressure at 25 EC 0.00011 mmHgf No data 

Photolysis t1/2 = 48 hg t1/2 = 0.70 hh 

Henry's law constant at 25 EC 3.4x10-6 atm-m3/moli No data 

Autoignition temperature No data No data 

Flashpoint No data No data 

Flammability limits at 25 EC No data No data 

Incompatibilities No data No data 

Conversion factors (25 EC) No data No data 

Explosive limits No data No data 

a

All information obtained from HSDB 2001 unless otherwise noted. 

b

Verschueren 1983 

c

Hoak 1957 

d

Budavari et al. 1989 

e

Schellenberg et al. 1984

f

EPA 1979e 

g

Wong and Crosby 1981

h

Pignatello et al. 1983

i

Lyman et al. 1982 

PENTACHLOROPHENOL 141 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

Vulcan Chemicals, a division of Vulcan Materials Company (Wichita, Kansas), is the only current 

domestic manufacturer of pentachlorophenol (SRI 1998). Pentachlorophenol is produced by the stepwise 

chlorination of phenols in the presence of catalysts (anhydrous aluminum chloride or ferric chloride). 

Outside of the United States, it is also produced by the alkaline hydrolysis of hexachlorobenzene. 

Typically, commercial grade pentachlorophenol is 86% pure. Contaminants generally consist of other 

polychlorinated phenols, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans, which 

are formed during the manufacturing process (see Table 3-2). Pentachlorophenol has also been marketed 

in the past as a water-soluble sodium salt, a 5% emulsifiable concentrate, or a 3–40% solution in 

formulation with other chlorophenols, methylene bisthiocyanate, or copper naphthenate (IARC 1979). 

Production volumes for 1983–1986 were as follows: 45 million pounds in 1983; 42 million pounds in 

1984; 38 million pounds in 1985; and 32 million pounds in 1986 (Mannsville 1987). About 24 million 

pounds were manufactured in 1987 by Vulcan Materials (HSDB 2001). More recent production data are 

not available. For further information on facilities in the United States that manufacture or process 

pentachlorophenol, refer to Table 5-1. Table 5-1 is derived from Toxics Release Inventory (TRI) data 

and reports only those facilities that release pentachlorophenol. 

5.2 IMPORT/EXPORT 

The U.S. consumption of pentachlorophenol for 1986 was reported to be 28 million pounds (CMR 1987). 

In 1982, 121,000 pounds of pentachlorophenol were imported to the United States (328,000 pounds were 

imported in 1980). In 1985, 3 million pounds of pentachlorophenol were exported, and in 1986, 2 million 

pounds were exported (Mannsville 1987). More recent data on the import/export volumes of pentachlorophenol are not available. 

5.3 USE 

Pentachlorophenol was one of the most widely used biocides in the United States. It was registered for 

use by EPA as an insecticide (termiticide), fungicide, herbicide, molluscicide, algicide, disinfectant, and 

as an ingredient in antifouling paint (Cirelli 1978a), but it has been a restricted-use pesticide since July 

1984 (CELDS 1992; EPA 1984a). The principal use of pentachlorophenol is as a wood preservative 
PENTACHLOROPHENOL 142 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. Facilities that Produce, Process, or Use Pentachlorophenol 

Number of Minimum amount on Maximum amount on 

Statea facilities site in poundsb site in poundsb Activities and usesc 

AL 2 10,000 999,999 9 

AR 2 1,000 999,999 9, 13 

CA 1 100 999 13 

GA 1 10,000 99,999 9 

ID 1 10,000 99,999 13 

IL 1 1,000 9,999 13 

KY 1 10,000 99,999 13 

LA 2 10,000 999,999 9 

MD 1 10,000 99,999 1, 5 

MN 1 10,000 99,999 8 

MO 1 100,000 999,999 9 

MS 4 10,000 9,999,999 9, 12 

NC 2 10,000 999,999 8, 9 

NE 1 10,000 99,999 9 

NJ 1 1,000 9,999 13 

NV 1 10,000 99,999 9 

OH 1 1,000 9,999 13 

OR 3 10,000 99,999 9, 12, 13 

SC 2 10,000 999,999 9, 13 

SD 1 100,000 999,999 9 

TX 2 1,000 99,999 13 

UT 2 1,000 99,999 13 

Source: TRI99 2001 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state c

Activities/Uses: 

1. Produce 6. Impurity 10. Repackaging 

2. Import 7. Reactant 11. Chemical Processing Aid 

3. Onsite use/processing 8. Formulation Component 12. Manufacturing Aid 

4. Sale/Distribution 9. Article Component 13. Ancillary/Other Uses 

5. Byproduct 
PENTACHLOROPHENOL 143 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

(registered by EPA for power-line poles, cross arms, fence posts, and the like). The treatment of wood for 

utility poles represents 80% of the U.S. consumption of pentachlorophenol (CMR 1987). However, 

pentachlorophenol is no longer contained in wood preserving solutions or insecticides and herbicides 

available for home and garden use since it is a restricted-use pesticide. Pentachlorophenol is used for the 

formulation of fungicidal and insecticidal solutions and for incorporation into other manufactured 

pesticide products. These nonwood uses account for no more than 2% of U.S. pentachlorophenol 

consumption (Mannsville 1987). This wide spectrum of uses was partially attributed to the solubilities of 

the nonpolar pentachlorophenol in organic solvents, and the sodium salt in water. 

5.4 DISPOSAL 

After treatment with sodium bicarbonate or a sand-soda ash mixture, pentachlorophenol can be 

incinerated. Incineration of pentachlorophenol is one of the most important sources of polychlorinated 

dibenzo-p-dioxins and dibenzofurans, so care must be taken during this process (Karasek and Dickson 

1987). Pentachlorophenol has been designated as a hazardous substance, a hazardous pollutant, a toxic 

pollutant, and a hazardous waste by EPA. Disposal of pentachlorophenol is subject to EPA restrictions 

(EPA 1991, 1992). 

PENTACHLOROPHENOL 145 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Pentachlorophenol has been one of the most heavily used pesticides in the United States. The compound 

is found in all environmental media (air, soil, and water) as a result of its past widespread use. In 

addition, a number of other chemicals, including hexachlorobenzene, pentachlorobenzene, and benzene 

hexachloride isomers, are known to be metabolized to pentachlorophenol. Current releases of 

pentachlorophenol to the environment are more limited as a result of decreasing volumes used, changing 

use patterns (e.g., phase-out of slimicide use in water cooling towers), and waste treatment practices (e.g., 

closing of on-site evaporation ponds at wood-treatment facilities). Pentachlorophenol is currently 

regulated as a restricted-use pesticide. 

Pentachlorophenol is stable to hydrolysis and oxidation, but the compound is rapidly photolyzed by 

sunlight and can be metabolized by microorganisms, animals, and plants. Adsorption to soils and 

sediments is more likely to occur under acidic conditions than under neutral or basic conditions. The 

compound has been found to bioaccumulate to modest levels (e.g., bioconcentration factors of <1,000), 

but food chain biomagnification has not been observed. In recent decades, pentachlorophenol has been 

widely detected in human urine, blood, and adipose tissue among members of the general population. 

Human exposure to pentachlorophenol is believed to occur via inhalation of indoor and workplace air, 

ingestion of contaminated water and food, and direct dermal contact with pentachlorophenol-treated wood 

products. Since pentachlorophenol is no longer used in the treatment of wood products used in new 

residences and agricultural buildings, future indoor air exposure to this compound from these sources is 

likely to be minimal. 

Pentachlorophenol has been identified in at least 313 of the 1,585 hazardous waste sites that have been 

proposed for inclusion on the EPA National Priorities List (NPL) (HazDat 2001). However, the number 

of sites evaluated for pentachlorophenol is not known. The frequency of these sites can be seen in 

Figure 6-1. Of these sites, 312 are located within the United States and 1 is located in the Commonwealth 

of Puerto Rico (not shown). 
Figure 6-1. Frequency of NPL Sites with Pentachlorophenol Contamination 

Frequenc

NPL Site

Derived from HazDat 2001 
PENTACHLOROPHENOL 147 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2 RELEASES TO THE ENVIRONMENT 

Pentachlorophenol is ubiquitously distributed in the environment. It has been detected in surface waters 

and sediments, rainwater, drinking water, aquatic organisms, soils, and food, as well as in human milk, 

adipose tissue, and urine. The compound has been identified in at least 313 of the 1,585 hazardous waste 

sites on the NPL (HazDat 2001). 

The majority of pentachlorophenol annual releases during production and use are to the atmosphere 

(about 1.4 million pounds [620 metric tons]) from wood preservation plants and cooling towers, and to 

land (about 1.9 million pounds [890 metric tons]) from wood preservation and domestic use as a 

preservative. Pentachlorophenol is also released into the aquatic environment, especially in runoff waters 

and wood-treatment plant effluents. Based on the available information, discharges to water, both direct 

and through municipal waste water treatment facilities, were estimated to be about 26,000 pounds 

(12 metric tons) and 11,000 pounds (5 metric tons), respectively (EPA 1980f). It should be noted, 

however, that much of these data, and data discussed in the following sections, were collected before 

pentachlorophenol became a restricted-use pesticide. Current releases are more limited, as indicated by 

the releases reported to the Toxics Release Inventory (TRI). However, total current environmental 

releases may be higher than the TRI estimates because only certain types of facilities are required to 

report; the list of facilities is not exhaustive. 

The TRI data should be used with caution because only certain types of facilities are required to report. 

This is not an exhaustive list. 

6.2.1 Air 

Pentachlorophenol is released directly into the atmosphere via volatilization from treated wood products. 

Evaporation of pentachlorophenol-treated industrial process waters from cooling towers was an additional 

source of historical atmospheric releases of the compound. Historical atmospheric releases included those 

from cooling towers, where pentachlorophenol and its sodium salt were used as slimicides in cooling 

tower waters. However, pentachlorophenol and its salt are no longer commonly used for this purpose 

(Vulcan Chemicals 1989) since the early 1980s, when its use was restricted (EPA 1984b). 

Emissions during production are considered to be relatively insignificant in volume, and are 

geographically restricted to the Vulcan Materials facility in Wichita, Kansas (SRI 1998). Physical 
PENTACHLOROPHENOL 148 

6. POTENTIAL FOR HUMAN EXPOSURE 

removal mechanisms, such as wet deposition, are important processes that decrease pentachlorophenol 

concentrations in the atmosphere. 

Pentachlorophenol has historically been estimated to volatilize from the surface of pentachlorophenoltreated wood products at an estimated rate of 760,000 pounds (344 metric tons) annually, or roughly 2% 

of the total amount of preservative applied. These estimates are representative of usage of the compound 

in those applications in the 1970s (EPA 1980f). 

As much as 500,000 pounds annually (228 metric tons) of pentachlorophenol, used in cooling tower 

waters as an anti-fouling agent, have been released to the atmosphere through volatilization with heated 

water and steam in the past (EPA 1980f). However, pentachlorophenol is no longer commonly used for 

this purpose (Vulcan Chemicals 1989). 

According to the TRI, an estimated total of 1,306 pounds of pentachlorophenol, amounting to 1.3% of the 

total environmental release, was discharged to the atmosphere from manufacturing and processing 

facilities in the United States in 1999 (TRI99 2001) (Table 6-1). The TRI data should be used with 

caution because only certain types of facilities are required to report. This is not an exhaustive list. 

Volatilization from treated wood poles and other outdoor-use wood also occurs; 30–80% of the 

pentachlorophenol applied to coniferous wood by dip or brush treatments may be lost by volatilization 

within 12 months (Bunce and Nakai 1989). Ingram et al. (1986) reported increased volatilization of 

pentachlorophenol from treated wood with increased temperature; similar results with temperature change 

were seen with each of numerous solvent systems utilized for application of the compound. Volatilization 

of pentachlorophenol was dependent on the carrier solvents and the wood coatings utilized; maximum 

volatilization occurred when methylene chloride or 100% mineral spirits were used as carrier solvents, 

while the minimum volatilization occurred with the use of the cosolvent WC-144. 

Pentachlorophenol may be formed during the incineration of chlorine-containing waste material. Heeb et 

al. (1995) found that pentachlorophenol constituted 8% of polychlorinated phenols formed in the flue gas 

and 10% of the stack gas during the incineration of chlorine-containing waste material. It may also be 

released in stack emissions as a result of pyrolysis of polyvinyl chlorides (Blankenship et al. 1994). 
Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use Pent

Reported amounts released in pounds per yeara 

Number 

Stateb 

of facilities Airc Water 

Underground injection Land 

Total on-site released 

Total off-sreleasee 

AL 7 459 813 No data 0 1,272 3

AR 2 250 5 No data No data 255 1CA 2 5 No data No data No data 5 No da

FL 1 No data No data No data 2,000 2,000 No daGA 2 13 5 No data No data 18 1

ID 1 5 No data No data 43,000 43,005 No daIL 1 2 No data No data 0 2 

KY 1 10 No data No data 0 10 2

LA 2 8 34 No data No data 42 

MD 1 No data No data No data No data No data No daMN 1 1 No data No data No data 1 No daMO 1 255 0 No data No data 255 MS 4 10 112 No data 0 122 

NC 2 3 3 No data No data 6 1,4

NE 1 255 No data No data No data 255 No da

NJ 1 2 0 No data 0 2 NV 1 2 No data No data No data 2 No da

OH 1 2 1 No data No data 3 OR 4 16 251 No data 26,793 27,060 14,6SC 2 6 0 No data 11,911 11,917 
Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use Pent

(continued) 

Reported amounts released in pounds per yeara 

Number 

Stateb 

of facilities Airc Water 

Underground injection Land 

Total on-site released 

Total off-sreleasee 

SD 1 1 53 No data No data 54 1TX 2 0 0 5 No data 5 No da

UT 2 1 No data No data 15,133 15,134 2

WA 4 No data No data No data No data No data No da

Total 47 1,306 1,277 5 98,837 101,425 17,5

Source: TRI99 2001 aData in TRI are maximum amounts released by each facility.bPost office state abbreviations are used.cThe sum of fugitive and stack releases are included in releases to air by a given facility.dThe sum of all releases of the chemical to air, land, water, and underground injection wells. eTotal amount of chemical transferred off-site, including to publicly owned treatment works (POTW).
PENTACHLOROPHENOL 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.2 Water 

Pentachlorophenol releases to surface water occur through direct discharge and direct entry from 

numerous nonpoint sources, including treated wood. In addition, pentachlorophenol is transported to 

surface waters from the atmosphere by wet deposition, and from soil by runoff and leaching. 

Approximately 90% of wood-treatment plants evaporate their waste water and, consequently, have no 

direct discharge to surface waters. The remainder of the plants discharge to municipal waste water 

treatment facilities. Total annual pentachlorophenol releases to municipal waste water treatment facilities 

were estimated to be 12,000 pounds (5.3 metric tons) (EPA 1980g). 

About 2 metric tons of pentachlorophenol used as a biocide in cooling tower waters were estimated to 

have been discharged to surface waters in 1978 (EPA 1979a). In addition, industries such as leather 

tanning and textile factories may have released up to 4,400 pounds (2 metric tons) and 12,000 pounds 

(5.5 metric tons) of pentachlorophenol, respectively, in their waste water discharges to surface waters on 

an annual basis in the 1970s (EPA 1980f). Pentachlorophenol is no longer used in these applications 

(Weinberg 1997). 

Chlorination of phenolic compounds during water treatment has been reported to produce detectable 

levels of pentachlorophenol (Detrick 1977; Smith et al. 1976). In addition, common pesticides such as 

lindane, hexachlorobenzene, pentachlorobenzene, and pentachloronitrobenzene are known to be 

metabolized to pentachlorophenol by plants, animals, and/or microorganisms, but the contribution of the 

metabolism of these pesticides to environmental levels of pentachlorophenol is unknown (Dougherty 

1978). 

According to the TRI, an estimated total of 1,277 pounds of pentachlorophenol, amounting to 1.25% of 

the total environmental release, was discharged to water from manufacturing and processing facilities in 

the United States in 1999 (TRI99 2001) (Table 6-1). The TRI data should be used with caution because 

only certain types of facilities are required to report. This is not an exhaustive list. 

6.2.3 Soil 

Pentachlorophenol is released to soils as a result of its past use as a herbicide, leaching from treated wood 

products, atmospheric deposition in precipitation (such as rain and snow), spills at industrial facilities 

using pentachlorophenol, and at hazardous waste sites. 
PENTACHLOROPHENOL 152 

6. POTENTIAL FOR HUMAN EXPOSURE 

Most of the pentachlorophenol removed from effluent streams by waste water treatment processes is 

adsorbed to sludge solids. Sludges from wood preservation industries historically have been estimated to 

contain up to 31,500 pounds (14.3 metric tons) of pentachlorophenol annually. Pentachlorophenol in 

solid wastes from wood-treatment facility evaporation ponds was estimated to total an additional 

133,000 pounds (60.2 metric tons) annually in the 1970s (EPA 1980f). However, most wood-treatment 

facilities have closed, or are in the process of closing, on-site evaporation ponds (Vulcan Chemicals 

1989). 

According to the TRI, an estimated total of 98,837 pounds of pentachlorophenol, amounting to 97.5% of 

the total environmental release, was discharged to soil from manufacturing and processing facilities in the 

United States in 1999 (TRI99 2001) (Table 6-1). The TRI data should be used with caution because only 

certain types of facilities are required to report. This is not an exhaustive list. 

6.3 ENVIRONMENTAL FATE 

Pentachlorophenol released into the atmosphere from treated wood can be transported back to surface 

waters and soils via wet and dry deposition. Atmospheric pentachlorophenol is transformed via 

photolysis; the compound may slowly undergo free radical oxidation with an estimated half-life of 

approximately 2 months. 

In surface waters, pentachlorophenol undergoes biotransformation and photolysis, and is adsorbed to 

sediments. Hydrolysis, oxidation, and volatilization do not significantly affect surface water 

concentrations. 

In soils and sediments, pentachlorophenol is metabolized by acclimated microbes, under both aerobic and 

anaerobic conditions, or is adsorbed. Pentachlorophenol may also be methylated to form 

pentachloroanisole, a more lipid soluble compound. Adsorption of pentachlorophenol in soils is pH 

dependent. The compound has a pKa value of 4.7 and consequently exists in the ionic forms at 

environmentally relevant pH values. For example, at pH 4.7, pentachlorophenol is 50% ionized, whereas 

at pH 6.7, the compound is about 99% ionized (Crosby 1981). Adsorption decreases in neutral and basic 

soils and is strongest in acidic soils. Therefore, the compound is most mobile in neutral-to-basic mineral 

soils and least mobile in acidic organic soils. Volatilization and photolysis do not appear to be important 

transport and transformation processes for pentachlorophenol in soils. 
 

PENTACHLOROPHENOL 153 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.1 Transport and Partitioning 

A Henry’s law constant of 2.75x10-6 atm m3

/mol has been reported for pentachlorophenol; the value for 

the salt or ionic form of this compound is expected to be much less. Therefore, volatilization of the 

solvated anionic form from an aqueous system is not considered to be a significant transport mechanism 

under ambient conditions. Pignatello et al. (1983) reported that volatilization loss of pentachlorophenol 

as vapor and aerosol from treated river water in outdoor manufactured channels was #0.006% of the 

initial test concentration. Volatilization of pentachlorophenol from soil is also not expected to be a major 

transport pathway. Kilzer et al. (1979) determined the volatilization rates of pentachlorophenol from 

water and three soil types under laboratory conditions. The volatilization rates (expressed as percentage 

of applied pentachlorophenol per mL evaporated water) from water, sand, loam, and humus were 2.57, 

0.13, 0.31, and 0.10%, respectively, in the first hour after application of 50 μg/L pentachlorophenol. 

During the second hour, the volatilization rates were 2.11, 0.12, 0.15, and 0.12%, respectively. 

Pentachlorophenol is volatilized from treated wood surfaces. Walls in a closed room treated with 

pentachlorophenol released the chemical into the air, with concentrations reaching 1 ng/m3

 on the 

first day after treatment and 160 ng/m3

 on the fourth day (Gebefugi et al. 1976). 

The adsorption or mobility of pentachlorophenol in soils is controlled primarily by soil pH. The amount 

of pentachlorophenol adsorbed at a given pH increases with increasing organic content of the soil (Chang 

and Choi 1974). Pentachlorophenol is adsorbed to soil or sediment under acidic conditions, but the 

compound is mobile under neutral or alkaline conditions (Kuwatsuka and Igarashi 1975). Maximum 

adsorption has been reported at soil pH values of 4.6–5.1, with no adsorption above pH 6.8 (Choi and 

Aomine 1974). 

Schellenberg et al. (1984) investigated the adsorption of chlorinated phenols to natural sediments and 

aquifer materials. These authors demonstrated that adsorption of pentachlorophenol was highly 

dependent on the organic content of the adsorbent. An average Koc of 32,900 was measured for pentachlorophenol in lake sediment, river sediment, and aquifer materials. 

However, normalized partition coefficients (i.e., Koc) do not accurately predict adsorption for ionizable 

compounds such as pentachlorophenol since its adsorption does not increase linearly with increasing 

concentration (Christodoulatos et al. 1994). The use of the equation to normalize partition coefficients is 

not valid in such cases. Davis et al. (1994) investigated the retardation of pentachlorophenol in 
PENTACHLOROPHENOL 154 

6. POTENTIAL FOR HUMAN EXPOSURE 

groundwater at a former wood treating facility. Data were not well represented by the Freundlich or 

Langmuir isotherms. The authors observed that retardation of the compound in the aquifer was greater at 

lower concentrations (<40 μg/L) than at higher ones (>1000 or 10,000 μg/L), indicating that 

pentachlorophenol will move at rates closer to that of the groundwater when present at higher 

concentrations (>10,000 μg/L). The authors stated that the results indicated that at the lower 

concentrations found at plume peripheries, pentachlorophenol would be attenuated and then biodegraded, 

while at higher concentrations such as at the source, the compound would be mobile. 

Pentachlorophenol is applied to wood as a liquid formulation composed of pentachlorophenol dissolved 

in hydrocarbon diluents such as oils, kerosene, or mineral spirits. The presence of cosolvents such as 

alcohols or petroleum hydrocarbons decreases the adsorption of pentachlorophenol in soils by increasing 

its solubility in the soil solution (Christodoulatos et al. 1994). This may also be important at spill, 

storage, and hazardous waste sites where a large amount of cosolvent would be expected. Based on the 

results of a study of the mobility of pentachlorophenol, pentachlorodibenzodioxins, and 

pentachlorodibenzofurans in soils contaminated with wood-preserving oil, Jackson and Bisson (1990) 

indicated that decreased adsorption of the compounds in soil would result from the presence of a 

subsurface, contaminated oil phase. They predicted that upon contact with groundwater, the compounds 

would be partitioned into the aqueous phase. In a study of desorption of chlorophenols in contaminated 

soils, pentachlorophenol was desorbed more readily in the presence of methanol and exhibited a positive 

correlation with increasing methanol concentration (You and Liu 1996). 

Decreased adsorption may also occur without the presence of a cosolvent/contaminant such as methanol 

or a petroleum hydrocarbon. The release of soil organics and colloids in the presence of dissolved 

pentachlorophenol was investigated. When pentachlorophenol was added to soil at aqueous 

concentrations of 1,000–10,000 μg/L, surface organics (tentatively identified as fulvic acids) were 

solubilized and acted as a cosolvent, decreasing the adsorption of pentachlorophenol (Galil and Novak 

1995). Enhanced mobility of pentachlorophenol was also predicted from the observed increased stability 

of soil colloids that adsorbed 3–13% of the compound, but were released from soil particle surfaces into 

the soil solution. 

Pentachlorophenol can be leached from treated wood into surrounding soil. For example, Arsenault 

(1976) reported that pentachlorophenol migrated from the surface of utility poles to the adjacent soil, 

which had an average pentachlorophenol concentration of 654 mg/L. However, mobility in soil was 
PENTACHLOROPHENOL 155 

6. POTENTIAL FOR HUMAN EXPOSURE 

limited, as indicated by the average soil concentration of 3.4 mg/L pentachlorophenol at a distance of 

12 inches from the poles. 

In a review paper, McAllister et al. (1996) reported that available data on the plant uptake and 

transformation of pentachlorophenol are inconsistent among studies and are inconclusive with regard to 

the abilities of specific plants to take up the compound. It was observed that the biodegradation of 

pentachlorophenol by microorganisms and its adsorption to soil limit the availability of the compound for 

plant uptake. Among the pentachlorophenol metabolites found in plants are tetrachlorophenols and 

anisoles (McAllister et al. 1996); additionally, oxidation products (tetrachlorobenzenes), conjugated 

forms of chlorinated phenols, and insoluble metabolites (lignin-incorporated residues) have been 

observed (Engelhardt et al. 1986). 

Veith et al. (1985) demonstrated that chemicals with a log Kow value greater than 4.0 are likely to 

bioaccumulate in organisms and food chains. The log Kow presented in Chapter 4 is 5.01 for the 

un-ionized form, which suggests that pentachlorophenol will bioaccumulate. However, the extent of 

bioaccumulation will depend on the pH of the medium and physiological pH, since at higher pH levels, 

pentachlorophenol converts to the more water-soluble pentachlorophenate anion. Bluegill sunfish 

exposed to 100 μg/L pentachlorophenol accumulated the compound in various tissues (edible, nonedible, 

or whole fish) to levels of 10–350 times the ambient water concentration in a 16-day static/renewal 

bioassay. Pentachlorophenol was rapidly eliminated upon transfer of the test organisms to clean water 

(Pruitt et al. 1977). Pentachlorophenol was reported to have a bioconcentration factor (BCF) of 

81–461 in the soft tissue of a freshwater mussel; however, the compound was rapidly cleared by the test 

organisms (52% loss within 12 hours) (Makela et al. 1991). Other bioaccumulation tests with aquatic 

organisms include BCF values of 30–40 in carp muscle tissue and 300–400 in all other tissues (Gluth et 

al. 1985) and BCF values of 218 (whole fish) to 1,633 (fish lipid basis) for juvenile American flagfish 

(Smith et al. 1990). In the latter test, which was a flow-through bioassay, the half-life of 

pentachlorophenol in the tissues was reported to be about 16 hours. Bioaccumulation of pentachlorophenol in algae, aquatic invertebrates, and fish (with BCFs of up to 10,000) has been demonstrated. 

Representative BCFs are as follows: goldfish, 1,000; polychaete, 3,830; bluegill sunfish, 13; blue mussel, 

324; and eastern oyster, 78 (EPA 1986c). 

Biomagnification of pentachlorophenol in terrestrial or aquatic food chains has not been observed. In a 

110-day study with rainbow trout, where pentachlorophenol was administered in the diet at a maximum 

concentration of 3,000 μg/kg, maximum concentrations of the compound in fish tissues were 40 μg/kg 
PENTACHLOROPHENOL 156 

6. POTENTIAL FOR HUMAN EXPOSURE 

after 50 days and 20 μg/kg at the end of the test period. In a 28-day depuration test, tissue half-life of the 

compound was about 7 days. According to the investigators, these results suggest that pentachlorophenol 

bioconcentration in fish occurs primarily through direct uptake from water rather than through ingestion 

of food. The similar pentachlorophenol tissue concentration levels of prey and predator salmonid fish 

from Lake Ontario were cited as additional evidence of the limited food chain bioaccumulation of the 

compound (Niimi and Cho 1983). 

Pentachlorophenol bioconcentration by earthworms has also been studied by several investigators. In 

14-day exposure tests, BCFs of 3.4–13 were reported for uptake of pentachlorophenol adsorbed to soil 

particulates (Haque and Ebing 1988; van Gestel and Ma 1988). However, when bioconcentration was 

calculated on the basis of concentration of test compound in soil solution, BCF values of 426–996 were 

obtained (van Gestel and Ma 1988). 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

Atmospheric pentachlorophenol is probably photolyzed in the absence of water, although mechanisms for 

this reaction are not well known (Crosby and Hamadad 1971; Gab et al. 1975). Photolysis of sorbed or 

film-state pentachlorophenol in the presence of oxygen has also been observed (Gab et al. 1975). The 

reaction products were similar to those found in aqueous photolysis. Bunce and Nakai (1989) estimated 

the rate of photolysis in the atmosphere based on measured quantum yields (254 nm) in the laboratory, 

molar absorptivity values, and solar intensity values for midday in summer at 40 EN; the estimated loss of 

pentachlorophenol to vapor-phase photolysis was 6.2% per hour. This rate represents the maximum rate 

at 40 EN; the average rate of photolysis for pentachlorophenol will be lower. 

No empirical data were found describing the reactivity of pentachlorophenol to free radical oxidation in 

the atmosphere. Bunce and Nakai (1989) calculated the potential atmospheric degradation of 

pentachlorophenol due to hydroxyl radical attack. The estimated loss rate was 1.5% per hour (half-life of 

66 hours) as calculated from an estimated rate constant of 4.7x10-13 cm3

/molecule-sec, assuming a peak 

noon summer hydroxyl radical concentration of 6.2x106

 radicals/cm3. Based on the estimated relative 

rates of photolysis and degradation by hydroxyl radicals, it was concluded that the former process would 

likely be the dominant of the two. It is noted that the estimate by Bunce and Nakai did not take into 

account the adsorption of the compound to particulates in the atmosphere. Using the method of Meylan 
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6. POTENTIAL FOR HUMAN EXPOSURE 

and Howard (1993), a half-life of 58 days for the vapor-phase reaction of pentachlorophenol with 

hydroxyl radicals can be obtained from an estimated rate constant of 5.5x10-12 cm3

/molecule-sec and an 

average hydroxyl radical concentration of 5.5x105

 molecule/cm3. Adsorption of pentachlorophenol to 

particulate matter, however, will attenuate the rate of this process in the atmosphere. 

6.3.2.2 Water 

Photolysis and biodegradation are believed to be the dominant transformation processes for pentachlorophenol in aquatic systems. Hydrolysis and oxidation are not important mechanisms for removal of the 

compound from surface waters. 

The molecular structure of pentachlorophenol is indicative of its stability to hydrolysis or oxidation (EPA 

1979e). Wong and Crosby (1981) reported that pentachlorophenol did not hydrolyze in aqueous solutions 

(serving as dark controls in an aqueous photolysis study) at pH 3.3 or 7.3 when held at 26 EC for up to 

100 hours. 

Wong and Crosby (1981) reported that pentachlorophenol in aqueous solutions at 100 mg/L was 

photolyzed under laboratory ultraviolet (UV)-light irradiation with estimated half-lives of about 

100 hours at pH 3.3 and 3.5 hours at pH 7.3. Photolysis of pentachlorophenol in aqueous solution 

following exposure to sunlight was also rapid; in laboratory experiments, concentrations of pentachlorophenol in water were reduced from 9.3 to 0.4 mg/L in 24 hours, and approached zero at the end of 

48 hours (Arsenault 1976). Wong and Crosby (1981) also reported rapid photolysis in sunlight (July); 

pentachlorophenol in pH 7.3 aqueous solution at 100 mg/L photolyzed with a half-life of 48 hours (total 

elapsed time) and a total disappearance time of 10 days. Degradates formed during photolysis included 

tetrachlorophenols, three tetrachlorodiols and their respective quinones, chloranilic acid, and eventually 

2,3-dichloromaleic acid, which also undergoes photolysis, but at a slightly slower rate than 

pentachlorophenol. The final products from the complete photolytic degradation of pentachlorophenol 

were carbon dioxide and chloride ions. In outdoor tests conducted with river water in manufactured 

channels, Pignatello et al. (1983) demonstrated that photolysis of pentachlorophenol (applied as the 

sodium salt) was rapid at the water surface (half-life of 0.70 hour at a depth of 0.5 cm). However, 

photolysis was greatly attenuated with increasing depth of the water column (half-life of 9.63 hours at a 

depth of 13.8 cm). Photolytic degradation accounted for a 5–28% decrease in the initial test 

concentration of the compound after 3 weeks. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Pentachlorophenol is biotransformed in aqueous systems by acclimated microorganisms. In a 40-day 

study of sterile and nonsterile stream water samples that were not amended with acclimated microbial 

cultures, Baker et al. (1980) reported negligible biodegradation of pentachlorophenol at 0 and 20 EC. 

Pignatello et al. (1983) reported that microbial transformation became the primary removal mechanism of 

pentachlorophenol (applied as the sodium salt) added to river water in tests conducted in outdoor 

manufactured channels. After about a 3-week acclimation period, microbial transformation accounted for 

a 26–46% decline in the initial test concentration of pentachlorophenol. The majority of the microbes 

responsible for the mineralization of pentachlorophenol were associated with rock and macrophyte 

surfaces or surface sediments rather than existing in the water phase. In a follow-up study utilizing the 

same type of outdoor tests, Pignatello et al. (1985) found that biotransformation accounted for a 55–74% 

decrease in concentration of applied pentachlorophenol after a 3–5-week adaptation period. 

Biotransformation in the water column above sediments occurred at a greater rate under aerobic than 

under anaerobic conditions. Ingerslev et al. (1998) reported that in a study utilizing a battery of shake 

flasks tests, pentachlorophenol at 1 and 100 mg/L biodegraded in 10–30 days under aerobic conditions in 

surface water from an unpolluted stream after an acclimation period of approximately 55 days. The 

addition of either sterilized or unsterilized sediment to the samples resulted in reduced acclimation 

periods, but did not affect the postacclimation degradation rates in water. 

In a study using radiolabeled pentachlorophenol, Arsenault (1976) demonstrated that the compound was 

transformed to carbon dioxide, water, and hydrochloric acid in an activated sludge treatment plant. On a 

pilot-plant scale, the same investigator also showed that a waste stream from a wood-preserving facility 

containing 23 mg/L of pentachlorophenol could be treated successfully to produce a final effluent 

concentration of 0.4 mg/L of pentachlorophenol. 

In a microcosm study of unfiltered aquifer samples (geologic material and groundwater) contaminated 

with polycyclic aromatic hydrocarbons and pentachlorophenol, a loss was observed. Although reductions 

in the parent compound concentration occurred, only 1% of the applied radiolabeled pentachlorophenol 

had mineralized by 56 days (Mohammed et al. 1998). Neither nutrient addition nor sample sterilization 

had a significant effect on mineralization. The observed decreases in the pentachlorophenol 

concentrations were attributed to adsorption to particulate material and not to biodegradation. 

In four simulated lentic environments, Boyle et al. (1980) tested the effects of dissolved oxygen, light, 

pH, and the presence of a hydrosoil (i.e., pond soil/sediment) on the transformation of pentachlorophenol 

(applied as the sodium salt). The persistence of pentachlorophenol was associated with three 
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6. POTENTIAL FOR HUMAN EXPOSURE 

environmental variables: absence of light and hydrosoil; pH near or below pKa; and low oxygen 

concentration. Major reaction products were pentachloroanisole, 2,3,4,5-tetrachlorophenol, 2,3,4,6-tetrachlorophenol, and 2,3,5,6-tetrachlorophenol; only pentachloroanisole was found in the water phase, and 

then only in the aerobic systems maintained in light. 

6.3.2.3 Sediment and Soil 

Photolysis of pentachlorophenol on soil surfaces is not a major transformation process. Hebert and Miller 

(1990) reported that UV light was >90% attenuated in the surface 0.2 mm of soil. However, while they 

will not approach rates of photolysis observed in aqueous solution, photolytic losses on the soil surface 

may be increased under certain conditions. The effect of upward evaporative flux on the rates of 

photolytic loss of pentachlorophenol, applied at 1,500 μg/L, was examined in soils maintained at various 

moisture levels. It was observed that the rates of photolysis on soil increased when near-saturated 

conditions were utilized, which increased the evaporative flux and translocated the compound to the 

surface 0.5 mm of the soil where photochemical degradation occurs (Donaldson and Miller 1997). Under 

near-saturated flow conditions in loamy sand soil, up to 55% more degradation was observed in the 

irradiated samples than in the dark controls in 14 days. 

The rate of pentachlorophenol degradation from adsorption and metabolism in soil is not dependent on 

soil texture, clay content, free iron oxides, or the degree of base saturation; however, it is partially 

dependent on the ion exchange capacity of the soil (Engelhardt et al. 1986). The rate of pentachlorophenol transformation in laboratory tests is more rapid in soils with high organic content than in those 

with low organic content, and greater when moisture content is high and soil temperature approaches the 

optimum for microbial activity (Young and Carroll 1951). 

Biodegradation is considered the major transformation mechanism for pentachlorophenol in soil. Halflives are usually on the order of 2–4 weeks. Pentachlorophenol is metabolized rapidly by most 

acclimated microorganisms (Kaufman 1978). In a study by Edgehill and Finn (1983) inocula of a strain 

of pentachlorophenol-acclimated Arthrobacter bacteria was added to soils in laboratory and enclosed 

outdoor tests. The soils were amended with 120–150 mg pentachlorophenol/L and 34 kg pentachlorophenol/hectare, respectively. In the laboratory test conducted in the dark at 30 EC, the half-life of 

pentachlorophenol in inoculated samples was about 1 day, whereas the half-life in uninoculated samples 

was 12–14 days. Pentachlorophenol loss from uninoculated control plots in outdoor tests was 25% after 

12 days at ambient temperatures (8–16 EC), while losses from inoculated plots were 50–85%. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Pseudomonas biotransformed [14C]-pentachlorophenol rapidly and released radiolabeled carbon dioxide 

as well as the intermediate metabolites tetrachlorophenol and tetrachlorohydroquinone. In another study, 

strains of Pseudomonas putida and Acinetobacter calcoaceticus sp. were found to be able to use 

pentachlorophenol as a sole carbon and energy source (Martins et al. 1997) 

An investigation was conducted by Frisbie and Nies (1997) to determine whether aged pentachlorophenol 

residues from contaminated soil at a former wood-treatment site would be biodegraded in the laboratory 

under aerobic and anaerobic conditions by indigenous microbes from that site. Under aerobic conditions, 

both existing and newly added pentachlorophenol was biodegraded following a short acclimation period. 

The degradates 2-monochlorophenol and 4-monochlorophenol were rapidly degraded, but 3-monochlorophenol did not undergo significant degradation. Under anaerobic conditions, pentachlorophenol was 

degraded to 3-monochlorophenol, which accumulated and was then further degraded; however, 

approximately 30% of the initial pentachlorophenol was not degraded. 

Pentachlorophenol has been observed to degrade more rapidly in anaerobic environments than in aerobic 

ones. Pentachlorophenol degraded in a paddy soil at 28 EC with a half-life of about 3 weeks; reducing 

conditions increased the rate of reaction slightly (Ide et al. 1972). These observations were confirmed by 

Kuwatsuka and Igarashi (1975) in 10 different soil types. Pentachlorophenol biotransformation rates 

were higher under anaerobic (flooded) conditions than under aerobic (upland) conditions. The half-life 

for pentachlorophenol under flooded conditions ranged from 10 to 70 days, while under upland 

conditions, the range was 20–120 days, and the rate of reaction increased with the organic matter content. 

Pentachlorophenol transformation was assumed to proceed by both chemical and microbial means, based 

on the effects of sterilization, soil temperature, and nature of the reaction products, which included 

pentachloroanisole; 2,3,4,5-, 2,3,4,6-, and 2,3,5,6-tetrachlorophenol; and 2,3,4-, 2,3,5-, 2,3,6-, 2,4,5-, 

2,4,6-, and 3,4,5-trichlorophenol. The major products were 2,3,4,5-tetrachlorophenol, and 2,3,6- and 

2,4,6-trichlorophenol. Tetrachloro-p-benzoquinone and 2,6-dichlorohydroquinone have also been 

implicated as metabolic intermediates for pentachlorophenol (Reiner et al. 1978). 

The degradates 3,4- and 3,5-dichlorophenol were also observed in biodegradation studies of 

pentachlorophenol (Engelhardt et al. 1986). These authors noted that pentachloroanisole was a major 

degradate in aerobic soils, but was present in minor amounts in anaerobic soils. In anaerobic systems, 

pentachlorophenol is biodegraded only through reductive dechlorination, and the degradates 

3,5-dichlorophenol and 3-monochlorophenol may accumulate; complete dechlorination to phenol and its 

subsequent mineralization to methane and carbon dioxide have been observed (Frisbie and Nies 1997). In 
PENTACHLOROPHENOL 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

a review paper on microbial degradation of pentachlorophenol, McAllister et al. (1996) reported that the 

various intermediates found in numerous studies indicated that microbial degradation of the compound 

occurs by different mechanisms which are associated with specific microbial consortia. 

Pentachlorophenol is degraded under anaerobic conditions in sewage sludge and sediments. After 

6 months of operation, about 60% of the initial concentration of pentachlorophenol added to laboratoryscale, fixed-film reactors containing a digested municipal sewage sludge microbial inoculum was 

removed. Removal from reactors supplemented with glucose attained 98% of the initial charge over the 

same time frame. Trichlorophenol and tetrachlorophenol were observed as degradation products 

(Hendriksen et al. 1991). In other laboratory tests, reductive dechlorination of pentachlorophenol was 

found to be more rapid in freshwater sediments containing microbial communities adapted to dechlorinate 

2,4-dichlorophenol and 3,4-dichlorophenol than in nonadapted sediment microbial communities. 

Degradation products identified included 2,3,5,6-tetrachlorophenol, 2,3,5-trichlorophenol, 

3,5-dichlorophenol, 3-chlorophenol, and phenol (Bryant et al. 1991). Ingerslev et al. (1998) also reported 

more rapid degradation and shorter or no acclimation periods in freshwater sediments amended with 

activated sludge which was preexposed to pentachlorophenol at various levels. At concentrations ranging 

from 10 to 20,000 μg/L, the acclimation periods were reduced from 8.6–21.1 days to 0.1–3.2 days when 

sediments were amended with preexposed activated sludge compared with activated sludge which was not 

preexposed to pentachlorophenol; only at a toxic concentration of 74,000 μg/L was the acclimation period 

increased (15.5–59.4 days). At concentrations of 10, 100–2,500, and 20,000 μg/L, preexposure reduced 

the respective postacclimation half-lives from 32, 3.7–5.6, and 108 days to #2.2 days; at 74,000 μg/L, the 

postacclimation half-life decreased from 80 days to >51.6 days. 

6.3.2.4 Other Media 

Laboratory studies were conducted to determine the effect of artificial light and sunlight on concentrations of pentachlorophenol and chlorinated dibenzo-p-dioxins in wood treated with pentachlorophenol 

(Lamparski et al. 1980). Although chlorinated dibenzo-p-dioxins are known to be present in pentachlorophenol products as impurities, formation of octachlorodibenzo-p-dioxin (OCDD) as well as heptachlorodibenzo-p-dioxin (HpCDD) and hexachlorodibenzo-p-dioxin (HxCDD) was observed even when purified 

pentachlorophenol was irradiated. Based on the relative levels of the isomers observed, HxCDD and 

HpCDD were presumed to be degradation products of OCDD, not condensation products of tetrachlorophenol and pentachlorophenol. The formation of OCDD was greatly reduced when hydrocarbon oil was 

utilized as the carrier solvent in place of methylene chloride. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Pentachlorophenol historically has been widely detected in environmental media as a result of its 

widespread past use by industry, the agricultural sector, and the general public, as a cooling-tower 

algicide and fungicide, herbicide, molluscicide, paint preservative, plywood and fiberboard waterproofing 

agent, and drilling mud and photographic solution biocide. Pentachlorophenol is now regulated as a 

restricted-use pesticide. Therefore, it can only be purchased and used by certified applicators, and only 

for the applications covered by the applicator's certification. Pentachlorophenol is no longer available to 

the general public. Although the compound has been detected in indoor air, surface waters, groundwater, 

drinking water, soils, rainwater, and a variety of foods in older monitoring studies, current contamination 

of these media by the compound is probably more limited given the restricted current usage of 

pentachlorophenol and its limited environmental persistence. 

6.4.1 Air 

Limited information is available on the levels of pentachlorophenol in ambient air. EPA (1980f) 

estimated atmospheric concentrations of pentachlorophenol using air models. A cumulative concentration 

estimate based on all emission sources was 0.15–136 ng/m3

. The lower end of this range coincides with 

the upper end of the range of computed air concentration estimates based on pentachlorophenol 

concentrations in rainwater in Hawaii (0.002–0.063 ng/m3

) where pentachlorophenol has been used 

extensively as an herbicide and wood preservative. A Canadian study (Cessna et al. 1997) reported the 

amount of pentachlorophenol in air in Saskatchewan (Regina and Waskesiu) and Northwest Territories 

(Yellowknife). The concentrations of pentachlorophenol in the vicinity of Yellowknife ranged from 0.43 

to 3.68 ng/m3

, with a mean concentration of 1.53 ng/m3. At both the Regina and Waskesiu sites, the 

concentrations ranged from 0.06 to 0.58 ng/m3

 with a mean value of 0.30 ng/m3. 

6.4.2 Water 

Of 497 surface water observations in EPA's STORET database as of March 1979, 82% were at the 

detection limit; 84% of the remaining observations fell between 0.1 and 10 μg/L, with a total range of 

0.01–100 μg/L (EPA 1979b). These data imply that ambient levels of pentachlorophenol in surface water 

are usually below 1 μg/L, with much higher levels in more industrialized areas. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Pentachlorophenol levels monitored in surface water include the following: 0.1–0.7 μg/L in the 

Willamette River (Buhler et al. 1973); 9 μg/L in a river below a paper mill (Rudling 1970); 0.1–1 μg/L in 

the Great Lakes (EPA 1980f); <1 μg/L in a river at a sewage discharge site in Sacramento, California 

(Wong and Crosby 1978); 38–10,500 μg/L in a stream running through an industrial district in 

Pennsylvania (Fountaine et al. 1975); and 0.01–0.48 μg/L in streams in Hawaii (Young et al. 1976). 

Pentachlorophenol has also been detected in drinking waters at the following levels: 0.04–0.28 μg/L in 

Corvallis, Oregon (Buhler et al. 1973); a mean concentration of 0.07 μg/L in 108 samples surveyed by the 

National Organics Monitoring Survey (NOMS); and <1–800 μg/L (an average of 227 μg/L) in seven 

drinking water wells in Oroville, California (Wong and Crosby 1978). 

Pentachlorophenol was detected in raw effluent from a series of wood-treatment plants at levels ranging 

from 25,000 to 150,000 μg/L (Dust and Thompson 1972) and in influent (1–5 μg/L) and effluent 

(1–4 μg/L) at streams at a sewage plant in Corvallis, Oregon (Buhler et al. 1973). The compound has also 

been detected (concentrations unspecified) in surface water and groundwater samples taken at a woodtreatment facility in Arkansas (McChesney 1988), in the surface water (68 μg/L) at a wood-treatment 

facility in Louisiana (ATSDR 1995), in groundwater (up to 19,000 μg/L) at a wood-preserving site in 

South Carolina (ATSDR 1993a), in groundwater (0.6 μg/L) at an inactive landfill in Florida (ATSDR 

1993b), and in groundwater (up to 4,300 μg/L) at Camilla Wood Preserving Company, Camilla, Georgia 

(Anonymous 1999). 

6.4.3 Sediment and Soil 

Although several investigators (Fountaine et al. 1975; Pierce and Victor 1978) refer to possible soil 

contamination as a source of pentachlorophenol levels in water samples, very little data are available on 

actual measurements of pentachlorophenol in soil. Arsenault (1976) reported pentachlorophenol 

concentrations of 3.4–654 ppm in soil within 12 inches of treated utility poles. Pentachlorophenol was 

detected in the soil samples taken from a depth of 0–3 inches at (320–2,300 μg/kg) and in subsurface soil 

(820–200,000 μg/kg) at a wood-treatment facility, a NPL site, in Louisiana (ATSDR 1995). It was also 

found in soil at an inactive landfill in Florida, also a NPL site, at a maximum concentration of 

21,000 μg/kg (ATSDR 1993b). Pentachlorophenol was found in on-site (up to 13,000 μg/kg) and off-site 

(up to 1,300 μg/kg) soil samples from the Camilla Wood Preserving Company in Camilla, Georgia 

(Anonymous 1999) 
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6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.4 Other Environmental Media 

Levels of pentachlorophenol in food are examined as a part of FDA's ongoing food monitoring studies. 

In 1973–1974, 10 out of 360 composite food samples contained pentachlorophenol at 10–30 ppb: 1 in 

dairy products, 1 in cereals, 1 in vegetables, and 7 in sugar (Manske and Corneliussen 1976). In the next 

year, 13 out of 240 composites contained pentachlorophenol (10–40 ppb), again mostly in sugars 

(Johnson and Manske 1977). Pentachlorophenol was detected in all of a series of random samples of 

Florida food at levels of 1–1,000 ppb, principally in grain products (Dougherty and Piotrowska 1976). 

Pentachlorophenol was also detected at low levels in peanut butter (1.8–62 μg/kg) and chicken 

(6–12 μg/kg) (Farrington and Munday 1976). 

Pentachlorophenol concentrations in fish tissue for the years 1976–1979, reported in EPA's STORET 

database, ranged from below the limit of detection to 50 mg/kg. Mean concentrations by region were as 

follows: Lake Michigan, 0.002 mg/kg; lower Mississippi, 0.478 mg/kg; Pacific Northwest, 16.38 mg/kg; 

Alaska, 5.0 mg/kg; Western Gulf, not detected; and south central lower Mississippi, not detected (EPA 

1979b). 

Levels of pentachlorophenol ranging from 10 to 270 μg/L were reported in 9 out of 65 samples of 

children's paints in the Netherlands (Van Langeveld 1975). 

Another study (Thompson et al. 1997) estimated the amount of pentachlorophenol in the atmosphere by 

measuring the amount of pentachlorophenol in pine needles. The lipid coating of pine needles has been 

shown to absorb contaminants from the atmosphere and, therefore, measurement of pollutants in pine 

needles provides an indirect way of estimating the atmospheric pollutants. The pentachlorophenol 

concentrations in the vicinity of a utility pole storage site were found to range from 29 to 570 ng/g of the 

needles. In comparison, pentachlorophenol concentration in the pine needles from sites further away 

from the pole storage locations was found to be <0.5 ng/g. 

It should be noted that most of the data discussed above are 13–17 years old (more recent data are not 

available). Use of pentachlorophenol has decreased in the intervening years because of restrictions placed 

on its use. Therefore, levels of pentachlorophenol found in other environmental media have presumably 

decreased since the time these data were published. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Humans may be exposed to pentachlorophenol in occupational settings through inhalation of 

contaminated workplace air and dermal contact with the compound or with wood products treated with 

the compound. General population exposure may occur through contact with contaminated 

environmental media, particularly in the vicinity of hazardous waste sites. Important routes of exposure 

appear to be inhalation of contaminated air, ingestion of contaminated groundwater used as a source of 

drinking water, ingestion of contaminated food and soils, and dermal contact with contaminated soils or 

products treated with the compound. 

Before being regulated as a restricted-use pesticide, pentachlorophenol was used extensively in treating 

wood. Today, this use is restricted to the treatment of utility poles, railroad ties, and wharf pilings where 

it is widely used. Dermal exposure to pentachlorophenol by members of the general population may 

occur upon contact with these wood products. Since pentachlorophenol is readily absorbed through skin 

(Qiao et al. 1997; Wester et al. 1993), this represents a relevant route of low level exposure. 

Pentachlorophenol is known to volatilize from treated wood products (Bunce and Naki 1989) at a rate that 

is temperature-dependent (Ingram et al. 1986), and low level inhalation exposure may also occur with 

increased levels expected during the summer months. In older residences constructed with treated wood 

products, inhalation of contaminated indoor air may also be an important source of exposure. A reduction 

in volatilization of pentachlorophenol by coating the treated wood surfaces with varnishes and epoxy 

coatings was demonstrated by Ingram et al. (1986). In past years, pentachlorophenol has been detected in 

human adipose tissue, blood, and urine. 

Data have been collected on pentachlorophenol levels in human urine, blood, adipose tissue, and 

cerebrospinal fluid for both occupational and nonoccupational groups. While levels are much higher in 

occupationally exposed groups, tests on the general population consistently show evidence of low-level 

exposure. In an FDA study in Florida, Cranmer and Freal (1970) found an average pentachlorophenol 

urine level of 4.9 μg/L in the general population, compared with 119.9 μg/L in carpenters, boat builders, 

and spraymen. A range of 1,100–5,910 μg/L in the urine of Japanese pest control operators exposed to 

pentachlorophenol, compared with 10–50 μg/L in nonexposed workers was cited by Bevenue and 

Beckman (1967). A comparison of results from a study in Hawaii on pentachlorophenol in urine of three 

groups (occupational, nonoccupational, and a mixed population) was done by Bevenue et al. (1967). The 

pentachlorophenol level of 1,802 μg/L in the occupationally exposed population was almost 50 times 

higher than the nonoccupational group level of 40 μg/L. Hill et al. (1989) detected pentachlorophenol in 
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6. POTENTIAL FOR HUMAN EXPOSURE 

100% of urine samples taken from 197 children in Arkansas at a median concentration of 14 μg/L. 

Ninety-seven of these children lived in the vicinity of a herbicide plant while the remaining one hundred
 

were part of a control group of children who lived elsewhere. No difference was observed in the amount
 

of pentachlorophenol detected in the urine samples of these two groups. Pentachlorophenol was also
 

found in 100% of urine samples taken from 50 members of the general population of Barcelona, Spain, at
 

a mean concentration of 25 μg/L (Gómez-Catalán et al. 1987). 

An analysis of the urine samples of 1,000 adults residing in the United States detected pentachlorophenol
 

in 64% of the samples (Hill et al. 1995). The adults tested were a subset of those participating in the
 

National Health and Nutrition Examination Survey (NHANES III). The median pentachlorophenol
 

concentration in urine was found to be 1.5 ng/mL. A Canadian study compared results from urine
 

analysis studies of nonoccupationally exposed individuals residing in Saskatchewan, Canada, a region
 

with little lumber industry. In the first study with normal healthy individuals, performed in September
 

1992, 100% of the samples analyzed were found to contain detectable amounts of pentachlorophenol with
 

a median concentration of 1.3 ng/mL (Thompson and Treble 1994). A subsequent study, performed in
 

January 1995, also detected pentachlorophenol in 100% of the urine samples (Thompson and Treble
 

1996). The median concentration in this latter study was 0.5 ng/mL. A third urinary analysis study of
 

nonoccupationally exposed individuals residing in Saskatchewan also detected pentachlorophenol in 94%
 

of the urine samples at a median concentration of 0.5 ng/mL (Treble and Thompson 1996). 

Among a group of 16 patients with neurological symptoms, pentachlorophenol was detected in blood
 

serum and cerebrospinal fluid using a gas chromatograph with electron capture detection technique. 

Mean concentrations in these media were 22 μg/L (range, 4–60 μg/L) and 0.75 μg/L (range,
 

0.24–2.03 μg/L), respectively. Three people in the study group who reported contact with wood
 

preservative products had the highest serum levels of pentachlorophenol. Cerebrospinal fluid levels were
 

not correlated with serum levels or cerebrospinal protein levels (Jorens et al. 1991). 

The National Health and Nutrition Examination Survey II (NHANES II) and the National Human
 

Adipose Tissue Monitoring Survey (NHATS) analyzed blood and urine specimens from approximately
 

6,000 persons between the ages of 12–74 years in 64 communities throughout the United States for the
 

presence of a number of compounds, including pentachlorophenol, during the period of 1976–1980. The
 

initial results of the survey indicated that pentachlorophenol was detected in about 79% of urine samples
 

tested (Murphy et al. 1983), and that pentachlorophenol-related phenols were also detected at lower
 

frequencies. The mean pentachlorophenol value in urine samples tested during 1976–1979 was 6.3 μg/L
 
PENTACHLOROPHENOL 167 

6. POTENTIAL FOR HUMAN EXPOSURE 

with the maximum level of 193 μg/L(Kutz et al. 1978). Pentachlorophenol measured in urine was 

considered to be the result of exposure to pentachlorophenol, lindane, and hexachlorobenzene. More 

recent results of NHANES II indicate that pentachlorophenol was found in 71.6% of the urine samples 

collected from the general population at an estimated geometric mean concentration of 6.3 ng/mL. These 

results suggest that, during 1976–1980, almost 119 million individuals from the general population were 

exposed to pentachlorophenol. Males were found to have higher percentage quantifiable levels of 

pentachlorophenol and higher geometric mean concentrations in urine than females (Kutz et al. 1992). In 

a study of workers exposed to pentachlorophenol in the wood-preserving industry, Arsenault (1976) 

reported pentachlorophenol levels of 120–9,680 μg/L in urine, with a mean concentration of 1,683 μg/L. 

In another study, Ferreira et al. (1997) compared the concentration of pentachlorophenol in the urine and 

blood of a group of workers occupationally exposed to pentachlorophenol at a wood-transformation unit 

to those of a control group with no known exposure to pentachlorophenol. The mean level of 

pentachlorophenol in the occupationally exposed group was found to be 1,197 and 1,273 μg/L in urine 

and blood, respectively. The mean concentration of pentachlorophenol in the control group was 

considerably lower at 6.4 and 15.3 μg/L in urine and blood, respectively. The urine samples of wood 

workers from a wood factory in northern Italy were monitored before work at 8 a.m. and after the work 

shift at 5 p.m (Colosio et al. 1993a). The results indicated that a greater amount of pentachlorophenol 

was excreted in the morning (175 μg/L) than in the evening (106 μg/L). A subsequent study by Barbieri 

et al. (1995) obtained similar results from which a half-life of about 10 days was estimated for 

pentachlorophenol excretion in urine. 

A mean pentachlorophenol blood serum level of 420 μg/L was reported for residents of log homes, 

whereas a mean level of 40 μg/L was reported for members of the general public with no known exposure 

to the compound. For residents of the log homes, pentachlorophenol serum levels of children were found 

to average 1.8 times those of their parents. Pentachlorophenol urine concentrations for residents of log 

homes averaged 69 μg/L, whereas urine levels for the general population were found to be 3.4 μg/L. 

Inhalation was believed to be the most likely route of exposure to pentachlorophenol in log homes (Cline 

et al. 1989). Pentachlorophenol was also found in serum samples taken from members of the general 

population of Barcelona, Spain, at a mean concentration of 21.9 μg/L (Gómez-Catalán et al. 1987). In a 

separate study of 66 residents of log homes treated with pentachlorophenol in Kentucky, Hosenfeld et 

al. (1986) reported a geometric mean pentachlorophenol blood serum level of 47.6 μg/L and a geometric 

mean urine concentration of 21 μg per gram urinary creatinine. Pentachlorophenol was detected in blood 

and urine of all 66 residents. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Mean pentachlorophenol blood serum levels in workers using pentachlorophenol or pentachlorophenoltreated materials were found to range from 83 to 57,600 μg/L by Cline et al. (1989). This upper limit is 

approximately 100 times the value expected from exposure to the threshold limit value (TLV) (Braun et 

al. 1979). Workers were involved in the construction of log homes, repair of telephone lines, custodial 

care of log cabin museums, and in various operations in wood-preservative and chemical-packaging 

facilities. One worker from a chemical-packaging facility, with a whole blood pentachlorophenol level of 

23,000 μg/L, died of pentachlorophenol poisoning (Cline et al. 1989). 

A mean level of 26.3 μg/kg was found in adipose tissue from the general U.S. population and it was 

concluded that humans are continuously exposed to low levels of pentachlorophenol from the 

environment, food supplies, and disinfectants (Shafik 1973). The distribution and bioconcentration of 

pentachlorophenol in different tissues of humans was investigated by Geyer et al. (1987). By comparing 

daily intake of pentachlorophenol with tissue concentrations, bioconcentration ratios of 5.7, 3.3, 1.4, 1.4, 

and 1.0 were obtained in liver, brain, blood, spleen, and adipose tissue, respectively. Pentachlorophenol 

has also been found in human milk samples from West Germany at 0.03–2.8 μg/kg (Gebefugi and Korte 

1983). In a study of human tissues removed at autopsy, including testes, kidney, prostate glands, livers, 

and adipose tissue, pentachlorophenol was found in all tissues examined at a range of 7 ppb in 

subcutaneous fat to 4,140 ppb in testes (Wagner et al. 1991). 

Based on the pentachlorophenol levels in their 1977 food survey, FDA estimated an average dietary 

intake of 0.76 mg/day for a typical 15–20-year-old male, and EPA (1978a) calculated an average dietary 

intake of 1.5 mg/day and a maximum dietary intake of 18 mg/day. However, the actual intake will be 

lower than estimates because average dietary intakes were based on mean concentration of positive 

samples. Considering pentachlorophenol levels in fish, peanut butter, food packaging materials, jar lids, 

etc., the average intake of pentachlorophenol in food has been estimated to be 1.5 mg/day (EPA 1980f). 

Daily dietary intake of pentachlorophenol from contaminated food has been estimated by another source 

to be 0.1–6 μg/day (WHO 1987). Using a six-compartment environmental partitioning model, HattemenFrey and Travis (1989) reported that the food chain is the most important source of exposure to 

pentachlorophenol for the general population. They estimated average daily dietary intake of the 

compound to be 16 μg/day from ingestion of contaminated food, primarily root vegetables. 

Pentachlorophenol was detected in 15% of the foods collected in eight market basket surveys from 

different regions of the United States during the period of April 1982 to April 1984 (Gunderson 1988). 

Foods representative of the diets of eight different age/gender population groups were prepared for 

consumption prior to analysis in a revision to FDA's Total Diet Study methodology. Estimated mean 
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6. POTENTIAL FOR HUMAN EXPOSURE 

daily intakes (ng/kg/day) of pentachlorophenol for these groups in 1982–1984 were as follows: 

(1) 6–11-month-old infants, 59.0; (2) 2-year-old children, 48.5; (3) 14–16-year-old females, 16.2; 

(4) 14–16-year-old males, 20.7; (5) 25–30-year-old females, 15.9; (6) 25–30-year-old males, 18.2; 

(7) 60–65-year-old females, 13.9; and (8) 60–65-year-old males, 15.5. In a later survey of the Total Diet 

Study, Gunderson (1995a) estimated mean daily intakes (ng/kg/day) of pentachlorophenol for these same 

eight age/gender population groups during a 1986–1991 study as follows: (1) 6–11-month-old infants, 

0.9; (2) 2-year-old children, 1.4; (3) 14–16-year-old females, 0.5; (4) 14–16-year-old males, 0.5; 

(5) 25–30-year-old females, 0.8; (6) 25–30-year-old males, 0.7; (7) 60–65-year-old females, 0.8; and 

(8) 60–65-year-old males, 0.8. A substantial reduction in the amount of pentachlorophenol in the 

estimated mean daily intake has been observed since the 1982–1984 study. In a monitoring program 

conducted by the Danish National Pesticide Monitoring Program from 1995 to 1996, no pentachlorophenol was detected in the samples of fruits, vegetables, cereals, bran, fish, or animal products such as 

meats, butter, cheese, fat, and eggs. 

In earlier surveys of pentachlorophenol exposure, food was found to be the most important source of 

intake for members of the general population (Coad and Newhook 1992; Wild and Jones 1992). In a 

multimedia analysis of pentachlorophenol exposure for the general population of Canada, food sources 

(mostly dairy products, grains, and cereals) accounted for an estimated 74–89% of the total daily intake of 

pentachlorophenol. Inhalation exposure, especially of indoor air, accounted for an estimated 10–25% of 

total daily intake, whereas water and soil/household dust were found to be negligible sources. Daily 

exposure of recreational fishermen consuming about twice as much fish as members of the general 

population was estimated to be only about 2% higher than that of the general population. However, 

lifetime dietary intakes of pentachlorophenol for aboriginal subsistence fishermen, relying on traditional 

diets of fish and fish products were estimated to be about twice those of members of the general Canadian 

population (Coad and Newhook 1992). In the United Kingdom, dietary sources are believed to account 

for greater than 90% of the estimated total daily intake of 5.7 μg pentachlorophenol/day by members of 

the general population. This value is considerably smaller than the 39 μg/day estimate for 

occupationally-exposed individuals. Inhalation is believed to be the most important route of exposure in 

workplace settings (Wild and Jones 1992). In a study that used the clearance concept to estimate net daily 

intake (i.e., net daily intake=clearance times average steady state concentration in plasma), the net daily 

intake of pentachlorophenol for members of the general U.S. population not specifically exposed to the 

compound was estimated to be 12.3–135.9 μg/day. For members of the general U.S. population residing 

in log homes, net intake was estimated to be 140–157 μg/day. Daily intake estimates for occupationally­
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6. POTENTIAL FOR HUMAN EXPOSURE 

exposed individuals varied widely depending on the type of work involved; estimates ranged from 35 to 

24,000 μg/day (Reigner et al. 1992a). 

The National Organic Monitoring Survey conducted in 1976 found pentachlorophenol residues in 

86 of 108 drinking water samples, with a mean of 0.07 μg/L and a maximum of 0.7 μg/L (EPA 1978a); 

however, the median concentration was less than 0.01 μg/L, the minimum detectable limit. In another 

survey, pentachlorophenol was detected at 1.3–12.0 μg/L in 8 out of 135 systems surveyed (EPA 1980a, 

1980c). Assuming an intake of 2 L of drinking water/day, exposure for most people would be less than 

0.02 μg/day, while the maximum exposure would be 24 μg/day. 

Inhalation of estimated ambient levels of pentachlorophenol in the atmosphere has an associated exposure 

level of 6 μg/day for the general population (EPA 1980f). Subpopulations in the vicinity of pentachlorophenol sources and workers may be exposed to significantly higher levels. For example, workers in the 

vicinity of a cooling tower may have been exposed to 14.4 mg pentachlorophenol/day, and those in woodtreatment plants may have been exposed to 0.9–14 mg pentachlorophenol/day (EPA 1980f). Pentachlorophenol levels in the air of an experimentally treated room varied greatly (1–160 μg/m3

) with temperature 

and ventilation (Gebefugi et al. 1976). 

Pentachlorophenol was detected at a geometric mean concentration of 0.080 ng/L in 62 of 63 air samples 

taken in 21 log homes treated with the compound. The homes, all located in Kentucky, were categorized 

into six treatment types: (1) "never treated"; (2) external treatment; (3) manufacturer treated; (4) treated 

and sealed; (5) treated, sealed, and neutralized; and (6) treated and neutralized. Concentrations in "never 

treated" homes, which were lower than those in treated homes, were believed to be the result of the 

application of pentachlorophenol to logs during storage to prevent fungal growth. Treated logs were 

found to be the source of pentachlorophenol in indoor air; air concentrations were highly correlated with 

pentachlorophenol concentrations in wood cores (geometric mean, 15,900 ng/g wood) and log surface 

wipes (geometric means, 89.6 and 187 ng/100 cm2

) (Hosenfeld et al. 1986). Concentrations of 

pentachlorophenol in older structures built with pressure-treated wood brushed with pentachlorophenol 

were reported to range from 0.5 to 10 μg/m3

 (EPA 1984b). Use of sealers decreased this concentration by 

85%. Indoor air interiors of structures built with industrially dipped nonpressure-treated wood were 

reported to contain levels of pentachlorophenol that ranged from 34 to 104 μg/m3

 (EPA 1984b). Logs 

used for home construction are no longer treated with pentachlorophenol. Pentachlorophenol in air 

samples taken from 75 rooms in 30 buildings with suspected use of pentachlorophenol-containing wood 
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6. POTENTIAL FOR HUMAN EXPOSURE 

preservatives in Germany ranged from <0.03 to 576 ng/m3. Pentachlorophenol in the dust samples taken 

from the same sites ranged from 0.083 to 79 ng/kg (Schnelle-Kreis et al. 2000). 

Dermal absorption is another potential exposure pathway. Pentachlorophenol is readily absorbed through 

skin (Qiao et al. 1997; Wester et al. 1993). EPA (1984) has assumed a dermal absorption efficiency in 

humans of 50% for pentachlorophenol in organic solvents and 10% for an aqueous solution of sodium 

pentachlorophenate. Dermal exposure is potentially an occupational problem; the general public is not 

expected to be exposed to pentachlorophenol via dermal contact. Santodonato (1986) suggested that 

dermal contact is the most important route of occupational exposure to pentachlorophenol because of the 

manner in which the compound is used (i.e., manual handling of solutions and treated materials) and its 

low vapor pressure. Workers such as carpenters, lumberyard workers, and loading-dock laborers who 

handle treated materials could be exposed continually via this route as well as by inhalation. The 

potential for dermal exposure to pentachlorophenol at hazardous waste sites is unknown. 

The National Occupational Hazard Survey (NOHS), conducted by the National Institute for Occupational 

Safety and Health (NIOSH), estimated that 179,243 workers in 22,347 plants were potentially exposed to 

pentachlorophenol in the workplace in 1970 (NIOSH 1976). The largest numbers of exposed workers 

were employed in the following fields: general building contractors; special trade contractors; chemicals 

and allied products industries; electric, gas, and sanitary services; and medical and other health services 

industries. 

Preliminary data from a second workplace survey, the National Occupational Exposure Survey (NOES) 

conducted by NIOSH from 1980 to 1983 indicated that 26,463 workers (including 3,916 women) in 

1,490 plants employed in lumber and wood products, business services, wholesale trade, general building 

contractors, and chemicals and allied products industries were potentially exposed to pentachlorophenol 

in the workplace in 1980 (NIOSH 1984a). Most of these workers were pest controllers, electrical power 

installers and repairers, laborers, assemblers, carpenters, miscellaneous precision workers, janitors, 

engineers, and engineering technicians. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in 3.7 Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Children are likely to be exposed to pentachlorophenol via the same routes that affect adults, such as 

inhalation of contaminated air, ingestion of contaminated groundwater used as a source of drinking water, 

ingestion of contaminated food, and dermal contact with contaminated soils or products treated with the 

compound. In addition, small children are more likely than adults to come into intimate contact with yard 

dirt, lawns, and house (carpet) dust. Dislodgeable pesticide residues in carpets or on uncovered floors 

may present a relatively important exposure route for infants and toddlers through dermal contact and oral 

ingestion. The tendency of young children to ingest soil, either intentionally through pica or 

unintentionally through hand-to-mouth activity, is well documented. These behavioral traits can result in 

ingestion of pentachlorophenol present in soil and dust. Though pentachlorophenol is known to: 

(1) adsorb to soil, especially at lower pH (Chang and Choi 1974; Choi and Aomine 1974; Kuwatsuka and 

Igarashi 1975); (2) have an insignificant rate of volatilization from soil (Kilzer et al. 1979); and 

(3) biodegrade at a moderately rapid rate, very little data are available on the actual measurements of 

pentachlorophenol in soil. No studies are available that describe the dermal absorption of 

pentachlorophenol in children. Two studies are available, however, that show that absorption of 

pentachlorophenol occurs in both Rhesus monkeys and swine when dermally exposed to soil amended 

with pentachlorophenol (see Section 3.4.1.3). Therefore, it is possible that children may absorb 

pentachlorophenol dermally when exposed to soil contaminated with pentachlorophenol. 

Hill et al. (1989) compared the amounts of chlorinated phenols and phenoxy acids found in the urine of 

97 children living in the vicinity of a herbicide manufacturing plant to those found in the urine of a 
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6. POTENTIAL FOR HUMAN EXPOSURE 

control group of 100 children living away from the herbicide plant. There was no significant difference 

in the amounts of pentachlorophenol or other herbicide residues detected in the two groups with the 

median pentachlorophenol concentration of 14 μg/L. This insignificant difference in the amounts of 

pentachlorophenol between the two groups indicated that the children living in the vicinity of the 

herbicide plant were not at a greater risk of exposure. Cline et al. (1989) measured the pentachlorophenol 

in the serum and urine of adults and children living in pentachlorophenol-treated log houses. The 

pentachlorophenol serum levels of children were found to average 1.8 times those of their parents. The 

mean concentrations were: (1) 2–5-year-old children, 600 μg/L; (2) 6–10-year-olds, 490 μg/L; 

(3) 11–15-year-olds, 370 μg/L; and (4) adults, 310 μg/L. The higher concentration of pentachlorophenol 

detected in children was attributed to their greater body surface-to-weight ratio and a higher respiratory 

rate as compared to adults. An East German study (Rehwagen et al. 1999), comparing urban versus rural 

exposure, detected a lower concentration of pentachlorophenol in the urine of children from the city of 

Leipzig than in the urine of children from the towns of Hettsdedt, Wippra, Roitzsch, and Greppin. 

Although the inhalation of house dust was a possible source of exposure to pentachlorophenol, no 

correlation could be established between the amount of pentachlorophenol detected in the urine and the 

amount of pentachlorophenol in the house dust. 

Pentachlorophenol was used extensively in treating wood. Today, though no longer used in treatment of 

wood products in residences and agricultural buildings, pentachlorophenol is still widely used in the 

treatment of utility poles and railroad ties. Playing near a utility pole such as a telephone or an electrical 

pole may pose a risk of dermal exposure. Pentachlorophenol is also known to volatilize from treated 

wood (Bunce and Nakai 1989) with emissions expected to be highest in the hottest months of the summer 

(Ingram et al. 1986). Therefore, low-level inhalation exposure may occur for children playing nearby. 

The soil samples, within a distance of 8 inches from the utility poles, were found to have a higher 

concentration of pentachlorophenol relative to those further away, indicating that leaching is occurring 

from their bases (Weinberg 1997). This indicated a downward migration of pentachlorophenol down the 

poles, which would result in a higher concentration in the lower sections. Higher than expected dermal 

exposure of children may, therefore, also occur since children may touch the lowest sections of utility 

poles while playing. Old and unpainted playground equipment constructed with pentachlorophenoltreated wood may be another mode of dermal exposure for children. 

Lewis et al. (1994) conducted a nine-home pilot study to monitor the potential exposure of small children 

to pesticides in the residential environment. Pentachlorophenol was found to be one of the most 

frequently occurring pesticides and was detected in all of the samples in all nine houses irrespective of the 
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6. POTENTIAL FOR HUMAN EXPOSURE 

age of the house (year of construction ranged from 1930 to 1989). The mean concentration of 

pentachlorophenol reported by the authors at various sites around a house is as follows: entryway soil, 

0.03 μg/g; walkway soil, 0.02 μg/g; and play area soil, 0.02 μg/g. It was also detected in house dust, 

0.83 μg/g; child hand rinse, 0.02 μg; and air, 0.05 μg/m3

. No attempts were made by the authors to 

estimate the amounts of carpet dust or soil that the children who participated in the study may have 

ingested. The authors concluded that dust ingestion could constitute a substantial portion of a child’s 

exposure to pesticides along with dermal absorption from house dust or yard soil. 

A potential source of exposure in infants is the presence of pentachlorophenol in breast milk or formula. 

No data were located on the presence of pentachlorophenol in breast milk in the United States. However, 

in a study from Upper Bavaria, Gebefugi and Korte (1983) detected pentachlorophenol in 100% of the 

samples of breast milk, with a median concentration of 1.43 μg/kg. No significant sources of 

pentachlorophenol exposure were identified. In a more recent study from Bratislava, Slovakia (a city 

with a highly concentrated chemical industry and intensive agriculture), human milk obtained from 

50 mothers was analyzed for the presence of chlorophenols (Veningerova et al. 1996). The median 

concentration of pentachlorophenol was found to be 2.21 μg/kg. The main source of pentachlorophenol 

exposure was through the ingestion of contaminated foods. No pesticide residues (including 

pentachlorophenol) were detected in ready to serve milk-based infant formula, with and without iron 

(Gunderson 1995b; Yess et al. 1993). 

Van Langeveld (1975) reported levels of pentachlorophenol ranging from 10 to 270 μg/L in 9 out 

of 65 samples of children's paints in the Netherlands. It is not known whether these paints are imported 

into the United States. No data were available about the presence of pentachlorophenol in children’s 

paints made in the United States. 

Percutaneous pentachlorophenol absorption from the pentachlorophenol used in the laundry can be a 

significant source of pentachlorophenol exposure in infants. Smith et al. (1996) reported an occurrence of 

pentachlorophenol poisoning in newborn infants in St. Louis, Missouri during April–August 1967. The 

infants were exposed to pentachlorophenol through the diapers, which were rinsed in the hospital laundry 

room with an anti-mildew agent containing 22.9% sodium pentachlorophenate. Pentachlorophenol has, 

since then, been regulated as a restricted-use pesticide. It is not likely to be used in the laundry today. 

Foods representative of the diets of eight different age/gender population groups, including children 

(6–11-month-old infants, 2-year-old children, and 14–16-year-old males and females), were prepared for 
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6. POTENTIAL FOR HUMAN EXPOSURE 

consumption prior to analysis in a revision to the FDA's Total Diet Study methodology (Gunderson 

1988). Estimated mean daily intakes (ng/kg/day) of pentachlorophenol for children in 1982–1984 were 

as follows: (1) 6–11-month-old infants, 59.0; (2) 2-year-old children, 48.5; (3) 14–16-year-old females, 

16.2; and (4) 14–16-year-old males, 20.7. In comparison, the intake for adults ranged from 15.5 to 

18.2 ng/kg/day. In a later survey of the Total Diet Study during 1986–1991, Gunderson (1995a) 

estimated mean daily intakes (ng/kg/day) of pentachlorophenol for these population groups as follows: 

(1) 6–11-month-old infants, 0.9; (2) 2-year-old children, 1.4; (3) 14–16-year-old females, 0.5; 

(4) 14–16-year-old males, 0.5; and (5) 25–30-year-old females, 0.8. In comparison, the intake for adults 

ranged from 0.7 to 0.8 ng/kg/day. A substantial reduction in the amount of pentachlorophenol in the 

estimated mean daily intake has been observed since the 1982–1984 study. No data are available for the 

exposure to and the effect of pentachlorophenol through specific food sources such as fish, animal 

products, cereals, etc. FDA also tested the presence of pesticide residues in a variety of infant and adult 

foods eaten by infants and children (Yess et al. 1993). Since whole and unpeeled fruits and vegetables 

were tested, the results were not indicative of pesticide residues in foods as consumed. Pentachlorophenol was found in plain milk (6.5% of the samples, maximum residue of 100 ppb), vitamin D milk (3% 

of the samples, maximum residue of 20 ppb), pork (7% of the samples, maximum residue of 6 ppb), grape 

jelly (4% of the samples, maximum residue of 4 ppb), raw pears (4% of the samples, maximum residue 

of 7 ppb), and in canned, evaporated milk (7% of the samples, maximum residue of 7 ppb). No data are 

available on children and their weight-adjusted intake of pentachlorophenol. 

The children of pesticide applicators who use pentachlorophenol may potentially be exposed to elevated 

levels from contact with their parents’ skin, hair, work clothes, and/or other workplace objects. In 

addition, pentachlorophenol adsorbed onto the parent or the parent’s clothing may contaminate household 

objects when they come in contact with them, potentially exposing children to pentachlorophenol. 

Although pentachlorophenol is a restricted-use pesticide and is only supposed to be used by an EPAcertified applicator for specified uses, there have been instances in which children were exposed to 

pesticides (methyl parathion) from the illegal application of pesticides. No monitoring data are available 

on this route of exposure to pentachlorophenol. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Pentachlorophenol levels in human tissues are much higher in occupationally exposed groups than in the 

general public. Populations with potentially high exposure include individuals involved in the 

manufacture and use of the compound. Residents near pentachlorophenol manufacturing plants and waste 

water treatment sludge disposal sites may also be exposed to the chemical at higher concentrations than 

the general public. Residents around the 313 NPL sites known to have pentachlorophenol contamination 

may also be exposed to the chemical at higher levels (>1,000 μg/kg) in contaminated environmental 

media. 

Pentachlorophenol is found as a residue in treated wood that has been preserved with this chemical. 

Examples of consumer items containing pentachlorophenol-treated wood have included boats, furniture, 

and log homes. In fact, some families living in homes historically treated with pentachlorophenol have 

been reported to have symptoms of chronic exposure (Jagels 1985). Since the compound is no longer 

used in the treatment of wood products for log homes, outdoor furniture, or playground equipment, 

human exposure from these sources is probably limited to contact with materials treated in the past. 

6.8 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 pentachlorophenol is available. Where adequate 

information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is 

required to assure the initiation of a program of research designed to determine the health effects (and 

techniques for developing methods to determine such health effects) of pentachlorophenol. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health 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. 
 

 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. The physical/chemical properties of pentachlorophenol are
 

well characterized and allow the prediction of the environmental fate of the compound (see Chapter 4). 

Estimates of the distribution of pentachlorophenol in the environment based on available constants (e.g.,
 

water solubility, Log Kow, Log Koc, vapor pressure) are generally in good agreement with experimentally
 

determined values. No additional studies are required at this time.
 

Production, Import/Export, Use, Release, and Disposal. Pentachlorophenol is currently being
 

produced by only one manufacturer (SRI 1998). Current production volume data are not available;
 

however, it is known that production volumes steadily decreased from 45 million pounds in
 

1983 (Mannsville 1987) to 9.1 million pounds in 1996 (IARC 1999). No recent data are available on the
 

production, export, and use volumes of pentachlorophenol. In the past, pentachlorophenol was one of the
 

most heavily used pesticides in the United States but is now regulated as a restricted use pesticide
 

(CELDS 1992; EPA 1984b). The compound is found in all environmental media (air, soil, and water) as
 

a result of its past widespread use. The only disposal method located in the literature is incineration,
 

which releases polychlorinated dibenzo-p-dioxins and dibenzofurans at unspecified levels (Karasek and
 

Dickson 1987). Disposal of pentachlorophenol is subject to EPA restrictions (EPA 1991, 1992). 

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C.
 

Section 11023, industries are required to submit chemical release and off-site transfer information to the
 

EPA. The TRI, which contains this information for 1999, became available in 2001. This database will
 

be updated yearly and should provide a list of industrial production facilities and emissions.
 

Environmental Fate. Information on environmental fate of pentachlorophenol is sufficient to permit
 

a general idea of transport and transformation of the chemical in the environment. Atmospheric or vaporphase pentachlorophenol is expected to photolyze at an estimated (midday in summer at 40 EN) maximum
 

rate of 6.2% per hour, and to degrade through reactions with hydroxyl radicals at an estimated (midday in
 

summer) loss rate of 1.5% per hour (Bunce and Nakai 1989). Meylan and Howard (1993) estimated a
 

half-life of 58 days for the vapor-phase reaction of pentachlorophenol with hydroxyl radicals. However,
 

the data need still exists for actual rates of vapor-phase photolysis and atmospheric degradation due to
 

hydroxyl radical attack. Volatilized pentachlorophenol may also be lost from the atmosphere through
 

deposition. The compound is expected to partition to soils and sediment (Kuwatsuka and Igarashi 1975),
 

and to be transported in surface water and groundwater (Davis et al. 1994; Mohammed et al. 1998). 
PENTACHLOROPHENOL 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

Pentachlorophenol is transformed by photolysis in water, with half-lives of 3.5 hours (pH 7.3) to 

100 hours (pH 3.3) under UV light and a half-life of 48 hours (pH 7.3) in sunlight (Wong and Crosby 

1981). Aqueous photolysis of the compound occurs more rapidly at the water surface (half-life of 

0.7 hours at 0.5-cm depth), with attenuated rates occurring at greater depths in the water column (half-life 

of 9.6 hours at 13.8-cm depth; Pignatello et al. 1983). Pentachlorophenol does not photolyze to a 

significant extent in soils, but may be photolyzed at the soil surface (top 0.5 mm) when near-saturated 

conditions exist; total degradation in near-saturated irradiated soils was 55% greater than in the dark 

controls (Donaldson and Miller 1997). Additional information on soil photolysis rates at various soil 

moisture contents may be helpful in determining the potential for degradation of the compound at sites 

with pentachlorophenol-contaminated areas which are flooded intermittently. A more important 

mechanism for the transformation of pentachlorophenol in soils is the adsorption of the compound to soil 

mineral particles and soil organic matter. Pentachlorophenol is a weakly acidic compound (pKa of 4.74) 

that is adsorbed to the largest extent under acidic soil conditions (where it is present in the unionized form 

which it is less soluble in water), and has greater mobility in neutral or alkaline soils where it is present as 

the phenolate anion (Kuwatsuka and Igarashi 1975). Maximum adsorption has been reported at soil pH 

values of 4.6–5.1, with no adsorption above pH 6.8; at a given pH, adsorption increases with increasing 

organic matter content (Choi and Aomine 1974). In aquifers, the retardation or decreased mobility of the 

compound has been observed to be greater in areas of lower pentachlorophenol concentrations 

(<0.04 mg/L) than in areas of high concentrations (>1 or 10 mg/L; Davis et al. 1994). Although it was 

determined in previously conducted studies of natural sediments and aquifer materials that the adsorption 

of pentachlorophenol was highly dependent on the organic matter content of the adsorbent, with an 

average Koc of 32,900 measured (Schellenberg et al. 1984), the use of normalized partition coefficients 

(Koc) do not accurately predict the adsorption of ionizable compounds such as pentachlorophenol since 

the adsorption of such does not increase linearly with the increasing concentration of the compound 

(Christodoulatos et al. 1994). For this reason, the need exists for a more accurate means of measuring 

and/or interpreting the potential mobility of pentachlorophenol in aquifers and in surface soils which are 

either intermittently subjected to flooding or are in contact with overland runoff. Because the presence of 

alcohols and petroleum compounds such as oils and kerosene (all of which are utilized as cosolvents in 

the application of pentachlorophenol) may decrease the adsorption of pentachlorophenol in soils 

(Christodoulatos et al. 1994; Jackson and Bisson 1990), and because pentachlorophenol has also been 

observed to desorb more readily from contaminated soils in the presence of compounds such as methanol 

(You and Liu 1996), there is a need for data that indicate the potential mobility of pentachlorophenol 

when it is present in the soil or water in combination with such cosolvents. Additionally, data are 

necessary on the adsorption of pentachlorophenol when it is present in combination with other 
 

PENTACHLOROPHENOL 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

contaminants expected to occur in the same environment. Biodegradation is another major mechanism 

for the transformation of pentachlorophenol in the environment (Englehardt et al. 1986; McAllister et al. 

1996; Pignatello et al. 1983). In water, pentachlorophenol may be biodegraded with observed first halflives of less than 1 month following acclimation periods of 5–7 weeks; the presence of sediment generally 

decreases the acclimation period (Ingerslev et al. 1998; Pignatello et al. 1985). The biotransformation of 

pentachlorophenol in groundwater, and possibly in surface water may not be significant in the absence of 

nonacclimated microbial populations. Decreases in the observed aqueous concentration of the compound 

may be attributed to adsorption to sediment or particulate material rather than to degradation of the 

compound (Mohammed et al. 1998). Additional information, such as biodegradation half-lives in both 

surface water and groundwater, is necessary to evaluate the potential for the degradation of the compound 

in water that is not in contact with sediment, rock, or macrophyte surfaces and where acclimated 

microbial populations do not exist. In soils, biodegradation of pentachlorophenol is generally rapid, with 

half-lives of 2–4 weeks. The metabolism of the compound is more rapid in soils with acclimated 

microbial populations (Kaufman 1978). Biodegradation of pentachlorophenol and aged residues of the 

compound occurs in both aerobic and anaerobic soils, usually following an acclimation period, but may 

occur more completely and rapidly in aerobic soils (Frisbie and Nies 1997). In other studies, 

biodegradation of the compound was observed to be more rapid in anaerobic environments (Ide et al. 

1972; Kuwatsuka and Igarashi 1975). McAllister et al. (1996) reported that there are multiple pathways 

for the biodegradation of pentachlorophenol, which differ according to the microbial populations present 

in the soil. While the biodegradation of pentachlorophenol has been studied extensively, there may still 

be a need for data that elucidate the effect of anaerobic environments (and alternating aerobic/anaerobic 

environments) on the rate and extent of the degradation of the compound and its metabolites. 

Additionally, information on the uptake and transformation of the compound in plants is necessary to 

improve the current understanding of pentachlorophenol's environmental fate; currently existing data on 

plant uptake and transformation are inconsistent between studies and are inconclusive with regard to the 

ability of specific plants to remove the compound from the soil (McAllister et al. 1996). 

Bioavailability from Environmental Media. Pentachlorophenol is readily and completely 

absorbed following inhalation (Casarett et al. 1969; Cline et al. 1989; Hosenfeld et al. 1986; Jones et al. 

1986), oral (Braun et al. 1979; Uhl et al. 1986), and dermal exposure (Hosenfeld et al. 1986; Qiao et al. 

1997; Wester et al. 1993). Using Rhesus monkeys, Wester et al. (1993) demonstrated the dermal 

absorption from pentachlorophenol-treated soil. It was also shown that when [14C-UL]-pentachlorophenol 

in a soil-based mixture was applied occlusively or nonocclusively to a clipped 7.5-cm2

 abdominal site of 

8 to 10-week-old female pigs, total radiolabel absorption was 29.08% under nonocclusive conditions and 
 

 

PENTACHLOROPHENOL 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

100.72% under occlusive conditions 408 hours after dosing (Qiao et al. 1997). Additional information on 

the bioavailability of pentachlorophenol adsorbed to soils would be helpful in assessing the relative 

importance of ingestion of contaminated soils as a potential route of human exposure. Additional 

information is also necessary on the desorption of the compound from soils when the soil pH is altered or 

when pentachlorophenol-contaminated soil comes into contact with cosolvents (such as alcohols or 

petroleum compounds), which may enhance desorption and/or increase the solubility of 

pentachlorophenol. Cline et al. (1989) detected elevated levels of pentachlorophenol in the urine of loghome residents. They believed inhalation to be the most likely route of exposure. Additional information 

is required to correlate the presence of pentachlorophenol in contaminated air and the exposure via 

inhalation. 

Food Chain Bioaccumulation. The log Kow of pentachlorophenol presented in Chapter 4 is 5.01, 

suggesting that pentachlorophenol is likely to bioaccumulate. However, the extent of bioaccumulation 

will depend on the pH of the medium since pentachlorophenol converts at higher pH levels to the more 

water-soluble pentachlorophenate anion. Pentachlorophenol is bioconcentrated by terrestrial and aquatic 

organisms (EPA 1986c; Makela et al. 1991; Smith et al. 1990). However, biomagnification of the 

compound in terrestrial and aquatic food chains has not been demonstrated as a result of the fairly rapid 

metabolism of the compound by exposed organisms (Niimi and Cho 1983). BCF values of 218 (whole 

fish) to 1,633 (fish lipid basis) for juvenile American flagfish were demonstrated by Smith et al. (1990). 

The half-life of pentachlorophenol in the tissues was reported to be about 16 hours. The food chain 

bioaccumulation potential of pentachlorophenol can currently be characterized without generating 

additional data. 

Exposure Levels in Environmental Media. Pentachlorophenol has been detected in ambient air, 

surface water, drinking water, soils, and foods. Estimates of dietary intake of the compound have been 

made by the World Health Organization (WHO 1987), EPA (EPA 1978a), and FDA (FDA 1989; 

Gunderson 1988). In a comparison of the 1986–1991 study to the 1982–1984 study, Gunderson (1995a) 

observed a substantial reduction in the amount of pentachlorophenol in the estimated mean daily intake. 

Lewis et al. (1994) detected low levels of pentachlorophenol in air, dust and soil in a nine-home (year of 

construction ranged from 1930 to 1989) pilot study to monitor the potential exposure of small children to 

pesticides in the residential environment. Further monitoring is required to be able to evaluate the risk of 

exposure from pentachlorophenol-treated wood in homes. Limited information is available regarding the 

levels of pentachlorophenol in air in the United States. More ambient monitoring data of air is required to 

estimate the exposure of the general population via inhalation of pentachlorophenol in the 1990s. 
 

 

PENTACHLOROPHENOL 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

Contemporary monitoring studies demonstrating the presence or absence of pentachlorophenol in various 

sources of surface and drinking water are also needed. 

Reliable monitoring data for the levels of pentachlorophenol in contaminated media at hazardous waste 

sites are needed so that the information obtained on levels of pentachlorophenol in the environment can 

be used in combination with the known body burden of pentachlorophenol to assess the potential risk of 

adverse health effects in populations living in the vicinity of hazardous waste sites. 

Exposure Levels in Humans. Pentachlorophenol has been measured in blood (NHANES III) 

(Ferreira et al. 1997; NHANES II), urine (Barbieri et al. 1995; Bevenue et al. 1967; Colosio et al. 1993a; 

Ferreira et al. 1997; Hill et al. 1989, 1995; Thompson et al. 1994, 1996; Treble and Thompson 1996), 

cerebrospinal fluid (Jorens et al. 1991), and tissues of humans (Bevenue et al. 1967). Quantitative data 

that correlate varying levels in the environment with levels in body fluids and health effects are not 

available. One study exists for residents of log homes treated with pentachlorophenol; levels in blood and 

urine were highly correlated with levels in indoor air ( Lewis et al. 1994). Additional information on 

exposure levels for populations living near hazardous waste sites would be helpful. Information 

regarding the exposure levels for populations near pentachlorophenol-treated utility poles would be 

useful. This information is necessary for assessing the need to conduct health studies on these 

populations. 

Exposures of Children. No monitoring studies have been performed to investigate the exposure to 

and the body burden of pentachlorophenol in children. No studies are available on the dermal absorption 

of pentachlorophenol in infants and toddlers due to activities such as crawling, which will result in 

contact with the floor (carpet) and soil. Since pentachlorophenol is likely to be adsorbed to these 

materials, more information would allow the estimation of a child’s exposure to pentachlorophenol to be 

more rigorously determined. A pilot study measured the amounts of pentachlorophenol in dust and soils 

that are found in areas where children may play, such as carpets and playgrounds (Lewis et al. 1994). As 

part of the FDA total diet study, mean daily intake of pentachlorophenol by 6–11-month-old infants, 

2-year-old children, and 14–16-year-old males and females were determined (Gunderson 1995a). Studies 

dealing with the weight-adjusted intake of pentachlorophenol by children would help in assessing the 

effects of pentachlorophenol in children. No studies are available on the amounts of pentachlorophenol 

present in the breast milk of women in the United States. The estimation of the amounts of soil and house 

dust that are ingested by children needs to be determined. No information is available on the exposure of 
 

PENTACHLOROPHENOL 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

children to pentachlorophenol from the parent’s body, work clothes, and other objects from work. 

Studies are required to identify childhood-specific means of decreasing exposure to pentachlorophenol. 

Child health data needs relating to susceptibility are discussed in 3.12.2 Identification of Data Needs: 

Children’s Susceptibility. 

Exposure Registries. No exposure registries for pentachlorophenol were located. This substance is 

not currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for 

subregistries to be established. The information that is amassed in the National Exposure Registry 

facilitates the epidemiological research needed to assess adverse health outcomes that may be related to 

exposure to this substance. 

6.8.2 Ongoing Studies 

As part of the Third National Health and Nutrition Evaluation Survey (NHANES III), the Environment 

Health Laboratory Sciences Division of the National Center for Environmental Health, Centers for 

Disease Control and Prevention, will be analyzing human urine samples for pentachlorophenol and other 

phenolic compounds. These data will give an indication of the frequency of occurrence and background 

levels of these compounds in the general population. 

The U.S. Department of Agriculture is sponsoring several studies on the degradation, adsorption, and 

uptake of pentachlorophenol. At the Agricultural Research Service, Fargo, North Dakota, research is 

being conducted to identify and quantitate residues of chlorinated organics (congeners of dioxins, furans, 

and polychlorinated biphenyls) in beef, milk, and animal feeds, particularly forages. In another study at 

Ohio Agricultural Research and Development Center, Wooster, Ohio, models for the transport of dioxins 

that are contained in feed and in other environmental matrices to beef that is intended for human 

consumption are being developed. At Xenometrix, Inc., research is being focused on the microbial 

dehalogenation of pentachlorophenol by Flavobacterium. Researchers at University of Florida, 

Gainesville, Florida, are studying the soil processes that regulate the fate of chlorophenols in wetlands. 

Research is underway at Forest and Wildlife Research Center, Mississippi, to develop a rapid biological 

technique for cleanup of organic wood preservatives in groundwater using oxygen, surfactants, cofactors, 

and micronutrients; and to evaluate different commercial surfactants for enhancing the biodegradation of 

wood-preserving process water containing high concentrations of pentachlorophenol, polyaromatic 
PENTACHLOROPHENOL 183 

6. POTENTIAL FOR HUMAN EXPOSURE 

hydrocarbons, oil, and grease. At Texas A&M University, College Station, Texas, research is being 

conducted to develop a method for dechlorinating pentachlorophenol from contaminated water and soil, 

and to refine the use of bioassays as monitoring tools to assess the changes in toxicity occurring as a 

result of remedial activities at Superfund waste sites. At Oregon State University, Corvallis, Oregon, 

researchers are working on determining the effects of estrogenic environmental pollutants on chemical 

carcinogenesis using rainbow trout as a model system. 

In a study sponsored by the National Institute of General Medical Sciences, at University of Colorado, 

Boulder, Colorado, research is being performed to determine the mechanism of the enzyme, tetrachlorohydroquinone dehalogenase, that plays a critical role in biodegradation of pentachlorophenol. A similar 

study, sponsored by National Science Foundation, investigating the role of tetrachloro-1,4-hydroquinone 

dehalogenase in the degradation of pentachlorophenol is underway at University of Colorado, Boulder, 

Colorado. The biochemistry of 2,4,5-trichlorophenoxyacetate and pentachlorophenol is being 

investigated in a National Science Foundation sponsored study at Washington State University, Richland, 

Washington. 

In addition, ongoing remedial investigations and feasibility studies at NPL sites known to be 

contaminated with pentachlorophenol should add to the available database for environmental levels, 

environmental fate, and human exposure. 

PENTACHLOROPHENOL 185 

7. ANALYTICAL METHODS
 

The purpose of this chapter is to describe the analytical methods that are available for detecting, and/or 

measuring, and/or monitoring pentachlorophenol, its metabolites, and other biomarkers of exposure and 

effect to pentachlorophenol. The intent is not to provide an exhaustive list of analytical methods. Rather, 

the intention is to identify well-established methods that are used as the standard methods of analysis. 

Many of the analytical methods used for environmental samples are the methods approved by federal 

agencies and organizations such as EPA and the National Institute for Occupational Safety and Health 

(NIOSH). Other methods presented in this chapter are those that are approved by groups such as the 

Association of Official Analytical Chemists (AOAC) and the American Public Health Association 

(APHA). Additionally, analytical methods are included that modify previously used methods to obtain 

lower detection limits, and/or to improve accuracy and precision. 

7.1 BIOLOGICAL MATERIALS 

Exposure to pentachlorophenol is most commonly evaluated by analysis of urine, blood, feces, or adipose 

or other tissues, using gas chromatography (GC) combined with electron capture detection (ECD) or 

high-performance liquid chromatography (HPLC) combined with ultraviolet (UV) detection. Recovery is 

generally high and sensitivity using GC/ECD and HPLC/UV is in the parts per billion (ppb) range. Some 

efforts are currently in development to detect pentachlorophenol metabolites in urine as a biological 

marker. 

Many purification schemes take advantage of the fact that pentachlorophenol is a weak organic acid. 

These methods involve extracting the compound into the organic phase under acidic conditions, and/or 

extracting into alkaline solution as phenolate salts (Chou and Bailey 1986; EPA 1986b). Thus, the 

standard methods involve multiple extractions, with potential for sample loss; some of these methods 

derivatize pentachlorophenol prior to analysis (EPA 1980b; NIOSH 1984b). Derivatization often 

involves diazomethane or diazoethane, which are toxic substances (Bevenue et al. 1968; Holler et al. 

1989; Morgade et al. 1980; Shafik 1973; Wagner et al. 1991). Recent methods have tried to simplify the 

purification scheme and avoid using toxic chemicals for derivatization (Maris et al. 1988). 

In an effort to use less toxic materials, blood and urine samples were derivatized with acetic anhydride 

(Needham et al. 1981). The detection limit was 1–2 ppb using GC/ECD. Penta- and tetrachlorophenols 

were analyzed simultaneously in urine using HPLC (Pekari and Aito 1982). This method was used for 
PENTACHLOROPHENOL 186 

7. ANALYTICAL METHODS 

3 years in Finland in the biological monitoring of workers exposed to chlorophenols. It is more rapid 

than GC and does not involve the use of chemicals such as benzene, diazomethane, or pyridine, which 

pose health risks to the analyst. A rapid extraction method followed by GC/ECD had a detection limit of 

0.5 ppb (Kalman 1984). 

Because pentachlorophenol exists in urine as both free pentachlorophenol and conjugated pentachlorophenol (glucuronide and sulfate), hydrolysis of urine is necessary to determine total pentachlorophenol 

(Edgerton and Moseman 1979; Pekari et al. 1991). Acid hydrolysis is preferable to enzymatic hydrolysis 

because the pentachlorophenol metabolite TCHQ is an inhibitor of β-glucuronidase (Drummond et al. 

1982). Although pentachlorophenol and other chlorinated phenols are stable in frozen urine samples, 

they are degraded by repeated thawing and refreezing (Edgerton 1981). Acid hydrolysis followed by 

reverse phase HPLC/UV and GC/ECD have been used to measure total pentachlorophenol in urine of 

people occupationally exposed to pentachlorophenol (Drummond et al. 1982; Pekari et al. 1991). The 

detection limits for HPLC/UV and GC/ECD were 0.20 and 0.01 ppm, respectively, which are sufficiently 

sensitive to detect occupational exposure. Using a simplified method without derivatization, total pentachlorophenol and free pentachlorophenol were measured in plasma and urine, with a detection limit of 

1.5 pg (Rick et al. 1982). This modification shortens analysis time and allows the use of GC/ECD, which 

increases sensitivity. 

The pentachlorophenol metabolites, TCHQ and tetrachloropyrocatechol, were identified in human urine 

samples using GC/MS (Edgerton et al. 1979). The detection limit was 1 ppb and recovery was about 

95%. Pentachlorophenol and TCHQ were also detected using a cheaper GC/ECD method following a 

simple extraction (Reigner et al. 1990), but the detection limit was at least 50 ppb. 

Negative chemical ionization (NCI) mass spectrometry (MS) was used to detect pentachlorophenol in 

human serum (Kuehl and Dougherty 1980). The NCI mass spectrometer was reported to be uniquely 

suited for screening partially purified samples. High sensitivity was obtained by dansylating purified 

compound and using HPLC/UV detection (de Ruiter et al. 1990). 

Hexane extraction, cleanup on thin layer chromatography (TLC) plates, and HPLC/UV detection were 

used to isolate and characterize pentachlorophenol in human fat, demonstrating that pentachlorophenol is 

present in human adipose tissue as an ester of palmitic acid (Ansari et al. 1985). Fatty acid conjugates of 

pentachlorophenol and other chlorinated phenols could be separated by reverse-phase HPLC (Kaphalia 

1991). TLC followed by GC/ECD was used to analyze pentachlorophenol in adipose tissue (Ohe 1979). 
PENTACHLOROPHENOL 187 

7. ANALYTICAL METHODS 

GC/ECD has been used to quantify pentachlorophenol residues in tissues (Wagner et al. 1991). The 

sensitivity of this method is in the sub-ppm range; >100% recoveries were obtained. GC/MS (NCI) was 

then used to confirm the identity of the pentachlorophenol residues in the samples. Precision data were 

not reported. 

Analytical methods for determining pentachlorophenol in biological fluids and tissues are shown in 

Table 7-1. 

7.2 ENVIRONMENTAL SAMPLES 

Concerns about contamination of environmental media, plants, and animals with pentachlorophenol have 

led to the need for more rapid, sensitive, and selective methods of analysis. As with biological samples, 

the most common methods of analysis are GC/ECD, high resolution gas chromatography (HRGC)/ECD, 

and HPLC/UV detection. Under EPA's Contract Laboratory Program for semivolatiles such as pentachlorophenol, the Contract Required Quantitation Levels (CRQL) for water and low soil sediments are 

50 mg/L (50 ppm) and 160 mg/kg (160 ppm), respectively (EPA 1986a). Methods are available that 

detect pentachlorophenol in water or sediment at the 1–10-ppb range. 

Pentachlorophenol could be detected in marine water at concentrations ranging from 0.2 to 200 ppb in 

volumes as small as 5 mL using a simplified monitoring procedure with HPLC/UV detection (Giam et al. 

1980). This method reduces costs and analysis time, and can also be used in other aquatic toxicity 

studies. Differential pulse polarography was used for direct determination of trace amounts of pentachlorophenol (Wade et al. 1979). It was demonstrated that pentachlorophenol is electrochemically 

reduced and direct determinations are possible at levels as low as 0.27 ppm. HPLC/UV was used to 

distinguish among 10 different phenolic compounds at mg/L levels in water (Realini 1981). HPLC/UV 

was also used to measure chlorinated phenols in surface-treated lumber and to distinguish between tetraand pentachlorophenol (Daniels and Swan 1979). Automated HPLC is 10 times faster than wet chemical 

techniques. Once the method for analysis has been established and tested thoroughly, the HPLC method 

requires neither extensive pretreatment nor highly trained laboratory personnel (Ervin and McGinnis 

1980). 

For relatively clean water samples, HPLC offers a rapid and sensitive method, but its advantages are lost 

when a complex matrix such as municipal waste water has to be analyzed (Buisson et al. 1984). The 

resolution possible with capillary gas chromatography and the selectivity of the ECD towards halogenated 
Table 7-1. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Biological Samples

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Blood Add sulfuric acid. Extract with 

hexane, derivatize with diazomethane, elute pentachloroanisole from alumina with benzene/hexane 

Blood Extract with benzene and convert 

PCP to its methyl ether derivative 

Blood Add H2SO4 and benzene to the 

sample and stir while heating; centrifuge; collect benzene layer, evaporate and add diazomethane to make methyl ether derivative 

Blood Add benzene and conc H2SO4 to the 

sample and rotate. Transfer benzene layer and add methylating agent and vortex. Dilute with isooctane or hexane. 

Serum Acidify with phosphoric acid; elute 

from reverse phase column with dichloromethane; dansylate; concentrate 

Serum Acidify sample to pH 1 with 

hydrochloric acid; extract with dichloromethane; concentrate; derivatize with diazoethane; cleanup using silica gel 

GC/ECD 1 μg/LGC/ECD 10 μg/LGC/ECD 20 μg/LGC/ECD No dataLC/UV 0.4 ppbGC/ECD 30.0 μg/L

90% 

92% 

87–100% 

No data 

85% 

99% 
Table 7-1. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Biological Samples (continued)

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Serum, urine Acidify to pH 2 with HCl, digest at 

100EC, extract with toluene 

Plasma, urine Sample collected into tubes 

containing EDTA and ascorbic acid; plasma mixed with citrate buffer, pH 3, extracted with diethyl ether, and concentrated. Urine was buffered with phosphate buffer pH 7.4 and processed as above 

Urine ADD HCl and NaHSO4, extract with 

benzene, derivatize with diazomethane, add hexane; elute pentachloroanisole from alumina with benzene/hexane 

Urine Acidify urine; hydrolyze; extract with 

benzene; methylate phenolic group 

Urine Add HCl to sample; boil; extract with 

hexane/isopropanol; centrifuge; dry; collect residue in methanol/water 

Urine Add HCl to sample; boil; extract with 

hexane/isopropanol; centrifuge; back extract to basic borate buffer; derivatize with acetic acid anhydride and pyridine 

Urine Acidify with HCl; boil; add Na 

bisulfite; centrifuge; extract with benzene 

GC/ECD 0.5 μg/L 

GC/ECD 100 μg/L (urine); 

50 μg/L (plasma) 

GC/ECD 1 μg/L GC/ECD 5 μg/L 

HPLC/UV 26 ppb GC/ECD 10 μg/L GC/ECD <1 μg/L 

105% 

(urine); 80% (serum) 89-93% 

94.7% 

90% 

84% 

No data 

91–97% 
Table 7-1. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Biological Samples (continued)

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Urine Urine Urine Urine Urine Urine Body fluids Human semen and adipose tissue 

Add H2SO4; collect distillate and add 

NaCl and NaOH; acidify aqueous layer; extract with methylene chloride 

Add HCl to sample; extract twice with 

benzene; add hexane 

Add internal standard to sample; mix 

Acidify with H2SO4; extract with 

hexane 

Acid hydrolysis; extract with 

benzene; derivatize with diazoethane; column cleanup 

Add NaHSO4, acidify with HCl, boil, 

add more NaHSO4, extract with 

benzene, concentrate, column cleanup 

Acidify sample and extract with 

hexane; add acetic anhydride; wash with boric acid / NaOH Macerate sample/tissue with sulfuric acid, complete steam distillation into 2,2,4-trimethylpentane; concentrate organic layer 

RPHPLC/UV GC/ECD

HPLC/UV

GC/ECDMS (NCI)GC/ECD GC/ECD MS (NCI) 

200 ppb 

<10 pg 

250 μg/L 

1.5 pg 

1 μg/L 

No data 

1–2 μg/L 

low ng 

>85% 88% 

89–96% 

102% 

-100% 

No data 

No data 

>90% 
Table 7-1. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Biological Samples (continued)

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Adipose tissue Grind tissue; add hexane; add 

NaOH; extract with hexane; add concentrated HCl; extract with diethyl ether; mix; add diazoethane; concentrate; add hexane and anhydrous sodium sulfate; analyze hexane layer 

Adipose tissue Homogenize sample; rehomogenize 

in hexane; combine supernatants; separate extracted fat on TLC; scrape appropriate area and suspend in hexane; evaporate 

Adipose t issue Add hexane; homogenize; add 

aqueous sodium hydroxide; extract with hexane; add diethyl ether; extract; derivatize with diazoethane 

Feces Collect sample into tubes containing 

EDTA and ascorbic acid; acidify in warm sulfuric acid, extract with diethyl ether; concentrate 

Liver Homogenize, incubate with sulfuric 

acid at 100EC; extract with 

hexane/toluene 

GC/ECD 5 ppb 75% GC/ECD 5 ppb 85–98% GC/ECD 140 ppb 91% 

GC/ECD 100 ppb No data LC/ECD 1.5 ppb 60–70% 
Table 7-1. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Biological Samples (continued)

Analytical Sample detection Percent 

Sample matrix Preparation method method limit recovery 

Fat, liver muscle, Fat: homogenize with HCl; extract serum with ethyl acetate-hexane; elute from 

florisil chlorophenol with methanolchloroform Other tissues: homogenize; reflux with Na2SO4 and NaOH; add TBAH 

and ether extract; concentrate extract; elute from silica column with methanol chloroform 

Tissues (testes, Homogenize tissue sample, extract kidney, prostate, liver with hexane/propanol and centrifuge; and omentum fat) remove hexane layer; repeat 

extraction twice; partition into potassium hydroxide; acidify aqueous layer; extract with hexane; derivatize with diazomethane; cleanup on Florisil column; elute with hexane; additional clean up on activated silica gel column; elute with benzene in hexane 

RPHPLC/UV <100 ppb 73–108% 

maximum 

GC/ECD; GCMS 4 ppb 115% (NCI) 

ECD = electron capture detection; EDTA = ethylendiaminetetraacetic acid; GC = gas chromatography; HCl = hydrochloric acid; HPLC = 

chromatography; H2SO4 = sulfuric acid; LC = liquid Chromatography; MS = mass spectrometry; Na = sodium; NaCl = sodium chloride; N

NaOH = sodium hydroxide; Na2SO4 = sodium sulphate; NCl = negative chemical ionization; PCP = pentachlorophenol; RPHPLC = rever

performance liquid chromatography; TBAH = tetrabutylammonium hydroxide; TLC = thin layer chromatography 
PENTACHLOROPHENOL 193 

7. ANALYTICAL METHODS 

compounds make HRGC/ECD the method of choice for the detection and quantification of chlorinated 

phenols at trace levels in complex matrices. Derivatization with a halogen-containing reagent enhances 

the ECD response. For measuring pentachlorophenol in waste water using HRGC/ECD, sensitivity is in 

the ppt range. Recoveries are adequate and precision is good. 

Similar results were obtained in a comparison of HPLC and GC techniques for determination of pentachlorophenol in animal materials (Mundy and Machin 1981). Pentachlorophenol could be separated from 

acidic pesticides and other organic acids possibly present in a mill effluent by extraction with an 

acetylating agent (Rudling 1970). A similar single step extraction and acetylation procedure was used to 

determine several chlorinated phenolic compounds in paper mill effluent without interference (Lee et al. 

1989). GC/MS has been used to measure pentachlorophenol in honey (Muiño and Lozano 1991). This 

method is simple, accurate, and rapid. Sensitivity is in the low-ppb range. Good recoveries (84–102%) 

and precision (2.8–6.3% relative standard deviation ([RSD]) were obtained. 

A study comparing several methods for rapidly extracting pentachlorophenol from water or soil reported 

high recovery from all methods using HPLC/UV (Wall and Stratton 1991). A method combining 

extraction with derivatization by acetic anhydride had a detection limit of about 0.1 ppb for GC/ECD (Xie 

1983). 

Immunochemical personal exposure monitors (PEMs) are currently being developed for assaying pentachlorophenol sampled from ambient air (Hall et al. 1992). This method is highly selective and involves 

direct, antibody-based sampling of analytes from air with subsequent quantitation of the analyte by 

enzyme immunoassay. The lower limit of detection for measuring pentachlorophenol in the assay is 

approximately 0.5 ng/mL. Recovery and precision data were not reported. 

Methods for analyzing pentachlorophenol in environmental samples are shown in Table 7-2. 

7.3 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 pentachlorophenol is available. Where adequate 

information is not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a 
Table 7-2. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Environmental Samples

Sample matrix Preparation method Analytical method 

Sample detection limit 

Percent recovery 

Stack samples Extract sample with hexane; 

derivatize with acetic anhydride, collect organic layer; concentrate 

GC/MS No data 80–104% 

Air Air samples collected in PEMs; 

analyte diffuses across semipermeable membrane into antibody reservoir; analyte is bound by antibody in PEM; antibody is removed from PEM device and 

ELISA 0.5 ng/mL No data 

quantified by enzyme immunoassay 

Air Air samples collected in ethylene 

glycol contained in bubbler using sampler pump, add methanol 

GC/UV 8 μg/sample No data 

Waste water Acidify waste water sample with 

H2SO4; extract with chloroform 

HPLC/UV 11 μg/L No data 

Water Acidify sample with HCl extract with 

methylene chloride 

HPLC/UV 1 μg/L 90% 

Water, mill effluent Acidify sample with H2SO4; extract 

with hexane; extract organic phase with borax; add hexane, acetylate, and analyze the organic phase 

GC/ECD 0.1 μg/L 84–93% 

Pulp mill effluent Extract onto solid phase sorbents; 

elute with acetonitrile 

LC-ED No data >100% 
Table 7-2. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Environmental Samples (continued)

Sample Percent 

Sample matrix Preparation method Analytical method detection limit recovery 

Marine water Drinking water Waste water Water and waste water Effluent Sludge/soil 

Take 5 mL water and acidify with 

H2SO4; extract with petroleum 

ether/diethyl ether; evaporate solvent; dissolve residue in CH3CN; 

measure at 254 nm 

Acidify water sample; extract with 

dichloromethane and hexane; derivatize with diazoethane; cleanup on silica gel 

Acidify to pH <2; extract with 

methylene chloride; exchange into 2-propanol. For ECD, derivatize with pentafluorobenzyl bromide Homogenize with dichloromethane; cleanup by sample concentration; back extract with alkali; derivatize by extractive alkylation with pentafluorobenzoyl chloride 

Mix sample with potassium 

carbonate, acetic anhydride, and petroleum ether; dry organic layer and concentrate 

Add Na2SO4; soxhlet extract using 

toluene/methanol or acetone/hexane; acid-base partition cleanup. For ECD derivatize with pentafluorobenzylbromide 

HPLC/UV 0.2 μg/L GC/ECD 300 ng/L GC/FID 7.4 μg/LGC/ECD 0.59 μg/LHRGC/ECD 5 ng/L GC/ECD #0.6 μg/L

GC/FID 7.4 μg/L

GC/ECD 0.59 μg/L

84% 

64% 36–134% 36–134% 

64–80% 

92–104% 

36–134% 36–134% 
Table 7-2. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Environmental Samples (continued)

Sample matrix Preparation method Analytical method 

Sample detection limit 

Percent recovery 

Sediment Mix with sodium carbonate with or 

without hexane (“pretreatment”); discard organic phase if present; derivatize by adding acetic anhydride in hexane; centrifuge 

GC/ECD -0.1 ng/g 96–99% 

(without pretreatment); 89% (with pretreatment) 

Soil (1) Soxhlet extract in 

ethanol/toluene; (2) extract with hexane/acetone acidified to pH 2 with HCl centrifuge; (3) add water to sample and acidify with HCl ultrasonically extract with hexane/acetone; centrifuge; (4) vortex extract with acetonitrile; centrifuge; dry extracts and dissolve in acetonitrile 

HPLC/UV No data (1) 94.3–98% 

(2) 94.8–97.8% (3) 94.4–98.5% (4) 96.1–100% 

Soil/sediment Add Na2SO4 and methanol, 

centrifuge. To 2 mL of extract, add pentafluorobenzyl bromide, hexacyclooctadecane, Na2SO4 

GC/ECD No data No data 

Soil Add acidified water, MTBE, and 

centrifuge. Derivatize with N-nitrosomethyl urea, concentrate 

GC/ECD No data No data 

Surface-treated lumber 

Grind dried lumber sample; extract with acetonitrile containing pbromophenacyl derivative of ßßdimethylahyic acid 

HPLC/UV 0.1 mg/cm3 No data 
Table 7-2. Analytical Methods for Determining Pentachlorophenol and 

Metabolites in Environmental Samples (continued)

Sample matrix Preparation method Analytical method 

Sample detection limit 

Percent recovery 

Egg Homogenize sample; extract with 

ethyl acetate-hexane; elute chlorophenol with methanol chloroform 

RPHPLC/ UV <100 μg/kg 73–108% 

maximum 

Fish tissue Homogenize in water; acidify to pH 

2 with HCl extract with methylene chloride; extract with 0.1 N NaOH; acidify; extract with toluene, dry 

GC/ECD 0.5 ppb 86% 

Honey Dissolve sample in acidified water; 

extract onto Sep-Pak C18 cartridge; 

elute with hexane/diethyl ether 

GC/MS 7.6 μg/kg 84–102% 

Gelatin Add 12 N H2SO4, extract with 

hexane-isopropanol, partition into 1 N KOH, acidify with 12 NH2SO4, extract with hexane 

GC/ECD 10 ppb No data 

General Add internal standard, sonnicate 

and separate 

HPLC/UV No data No data 

General Add internal standard and acetone GC/FID-IS No data No data 

CH3CN = acetonitrile; ECD = electron capture detection; FID = flame ionization; GC = gas chromatography; HCl = hydrochloric acid; HPL

liquid chromatography; H2SO4 = sulfuric acid; MS = mass spectrometry; MTBE = methyl-tertiary-butyl ether; NaOH = sodium hydroxide; N

RPHPLC = reverse phase high performance liquid chromatography; UV = ultra-violet detection 
 

PENTACHLOROPHENOL 198 

7. ANALYTICAL METHODS 

program of research designed to determine the health effects (and techniques for developing methods to 

determine such health effects) of pentachlorophenol. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health 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. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Methods are available to 

detect and quantify pentachlorophenol in blood (Bevenue et al. 1968; EMMI 1997; EPA 1980b; NIOSH 

1984b), serum (Kalman 1984; Morgade et al. 1980), urine (Chou and Bailey 1986; Edgerton et al. 1979; 

EMMI 1997; EPA 1980b; Holler et al. 1989; Kalman 1984; NIOSH 1984b; Rick et al. 1982; Siqueina 

and Fernicola 1981), adipose tissue (Kuehl and Dougherty 1980; Morgade et al. 1980; Ohe 1979; Shafik 

1973), feces (Reigner et al. 1990), liver (Maris et al. 1988) and tissue including the liver, muscle, testes, 

prostrate, and omentum fat (Wagner et al. 1991). Chromatographic techniques, such as GC and HPLC 

were used to isolate the pentachlorophenol, its derivatives, and its degradation products. ECD and MS 

were coupled with the separation techniques to detect these compounds. Sensitivity was high (blood: 

1–20 ppb; serum: 0.4–30 ppb; urine: 0.5–250 ppb; adipose tissue: low ng–140 ppb; feces: 100 ppb; and 

other tissues: 1.5–<100 ppb) and recovery was good (blood: 87–100%; serum: 80–99%; urine: 84–105%; 

adipose tissue: 75–98%; and other tissues: 60–115%). These methods can accurately detect pentachlorophenol at background concentrations in blood, urine, and adipose tissue. Only limited data exist on 

methods for metabolite characterization. TCHQ, tetrachloropyrocatechol, and palmitoyl-pentachlorophenol are the known metabolites of pentachlorophenol. These compounds can be monitored using 

GC/ECD (Reigner et al. 1990) or MS (Edgerton et al. 1979). GC/ECD is more economical than MS, but 

using GC/ECD for metabolite detection has been reported in only one study (Reigner et al. 1990). 

However, since the majority of pentachlorophenol is excreted unchanged, monitoring of metabolites 

might not provide useful additional information on exposure concentrations. In general, no attempts have 

been made to correlate levels of pentachlorophenol in the body with levels absorbed through skin or via 

inhalation. However, data from a study in log homes demonstrate a positive correlation between serum 

and urine concentrations of pentachlorophenol and indoor air concentrations of this compound (Hosenfeld 

et al. 1986; Hill et al. 1989). 
 

PENTACHLOROPHENOL 199 

7. ANALYTICAL METHODS 

No identified biomarkers of effect (e.g., increased SGOT or SGPT enzyme levels in serum, increased 

blood urea nitrogen, or neurological symptoms) are specific for pentachlorophenol. The identification of 

specific biomarkers of effect may be useful. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods are available to measure pentachlorophenol in stack samples (Cuiu et al. 1986), air 

(Cuiu et al. 1986; Hall et al. 1992; NIOSH 1994), water (Giam et al. 1980; Morgade et al. 1980; Realini 

1981), waste water and effluent (Buisson et al. 1984; Butler and Dal Pont 1992; EPA 1986b; Ervin and 

McGinnis 1980; Lee et al. 1989; Rudling 1970), soil, sludge and sediment (EMMI 1997; EPA 1986b; 

Wall and Stratton 1991; Xie 1983), surface-treated lumber (Daniels and Swan 1979), fish tissue (Kalman 

1984), honey (Muiño and Lozano 1991), and gelatin (Helrich 1990). Sensitivity of detection is as 

follows: air: 5 ppb; water: 0.1–30 ppb; waste water: 0.1 ppb–7.4 ppm; soil/sludge: 0.1 ppb–7.4 ppm; and 

foods: 0.5–100 ppb. The recovery of pentachlorophenol varies depending on the method of isolation and 

detection, and the source of the sample (water: 64–102%; waste water: 36–134%; and soil/sludge: 

36–134%). The available methods are, in general, sensitive enough to measure both the background 

levels and the higher levels of acute exposure. However, even though inhalation is considered to be a 

major route of human exposure, only limited data concerning methods for determining pentachlorophenol 

in air were located (Cuiu et al. 1986; Hall et al. 1992), and recovery data were not reported for these 

methods. Although both occupational exposure and exposure from sources such as log cabins are known 

to occur, methods for measuring ambient concentrations of pentachlorophenol in air are lacking. An 

additional source of pentachlorophenol exposure is food; methods are available for analyzing pentachlorophenol in animal tissue and honey (Kalman 1984; Muiño and Lozano 1991), though the recovery is 

not very good. More methods are required to accurately measure the levels of pentachlorophenol (low 

ppb levels or lower) in foods. 

7.3.2 Ongoing Studies 

L.L. Ingram, Jr., of the Forest Products Utilization Laboratory at Mississippi State University, is 

conducting research on the development of mass spectrometric methods for analysis of creosote and 

pentachlorophenol (CRISP 1992). 

The Environmental Health Laboratory Sciences Division of the National Center for Environmental Health 

and Injury Control, Centers for Disease Control, is developing methods for the analysis of pentachlorophenol and other phenolic compounds in urine. These methods use high resolution gas chromatography 
PENTACHLOROPHENOL 200 

7. ANALYTICAL METHODS 

and magnetic sector mass spectrometry, which gives detection limits in the low parts per trillion (ppt) 

range. 
PENTACHLOROPHENOL 201 

8. REGULATIONS AND ADVISORIES
 

The international, national, and state regulations and guidelines regarding pentachlorophenol in air, water, 

and other media are summarized in Table 8-1. 

An acute-duration oral MRL of 0.005 mg/kg/day has been derived for pentachlorophenol. This MRL is 

based on a LOAEL of 5 mg/kg/day for developmental effects (increased occurrence of delayed 

ossification of the skull) in the offspring of rats (Schwetz et al. 1974). The MRL was derived by dividing 

the LOAEL by an uncertainty factor of 1,000 (10 to account for the use of a LOAEL, 10 for interspecies 

extrapolation, and 10 for human variability). 

An intermediate-duration oral MRL of 0.001 mg/kg/day has been derived for pentachlorophenol. This 

MRL is based on a LOAEL of 1 mg/kg/day for reproductive effects (increased severity of cystic uterine 

glands and decreased proportions of mink accepting a second mating and number of mink whelping) in 

mink (Beard et al. 1997). The MRL was derived by dividing the LOAEL by an uncertainty factor of 

1,000 (10 to account for the use of a LOAEL, 10 for interspecies extrapolation, and 10 for human 

variability). 

An MRL of 0.001 mg/kg/day has been derived for chronic-duration oral exposure to pentachlorophenol. 

The MRL is based on a LOAEL of 1 mg/kg/day for decreased serum thyroxine concentrations and 

decreased relative thyroid weight in mink (Beard and Rawlings 1998). The LOAEL was divided by an 

uncertainty factor of 1,000 (10 to account for the use of a LOAEL, 10 for interspecies extrapolation, and 

10 for human variability) to derive the MRL. 

EPA (IRIS 2001) derived an oral reference dose (RfD) of 0.03 mg/kg/day for pentachlorophenol. The 

RfD was based on a NOAEL of 3 mg/kg/day for liver and kidney pathology in rats (Schwetz et al. 1978). 

The MRL was derived by dividing the NOAEL by an uncertainty factor of 100 (10 for interspecies 

extrapolation and 10 for human variability). 

EPA (IRIS 2001) has assigned pentachlorophenol a weight-of-evidence classification of B2, probable 

human carcinogen. 

The International Agency for Research on Cancer (IARC 2001) assigned pentachlorophenol a group 2B 

cancer classification, possibly carcinogenic to humans. 
PENTACHLOROPHENOL 202 

8. REGULATIONS AND ADVISORIES 

EPA has restricted the sale and use of pesticide products containing pentachlorophenol (EPA 1987d). 

This was effective July 13, 1984 (EPA 1984a). 
PENTACHLOROPHENOL 203 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

Agency Description	 Information References 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification Group 2Ba IARC 2001 

WHO Drinking water quality 9 μg/L WHO 2001 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV–TWAb 0.5 mg/m3	 ACGIH 2000 

EPA RAC 30 μg/m3	 EPA 2001k
 

40CFR266
 

Appendix IV
 

NIOSH REL (TWA)b 0.5 mg/m3	 NIOSH 2001a 

IDLH	 2.5 mg/m3 NIOSH 2001b 

OSHA PEL (8-hour TWA)b OSHA 2001b 

General industry 0.5 mg/m3 29CFR1910.1000 

Table Z-1 

PEL (8-hour TWA)b OSHA 2001c 

Construction industry 0.5 mg/m3 29CFR1926.55 

Appendix A 

PEL (8-hour TWA)b OSHA 2001a 

Shipyard construction 0.5 mg/m3 29CFR1915.100 

Table Z 

USC	 HAP USC 2001
 

42USC7412
 

b. Water 

DOT	 Marine pollutant— DOT 2001b 

pentachlorophenol and sodium 49CFR172.101 

pentachlorophenate Appendix B 

EPA Drinking water standard 1x10-3 ppm	 EPA 2001j 

40CFR141.32 

Groundwater monitoring	 EPA 2001l 

list—standards for TSD	 40CFR264 

Suggested method 8040 8270 Appendix IX 

PQL 5 μg/L 50 μg/L 
PENTACHLOROPHENOL 204 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description	 Information References 

NATIONAL (cont.) 

EPA 

c. Food 

FDA 

MCL—applies to community and 

non-transient, non-community 

water systems 

MCLG 

Effluent guidelines—toxic pollutant 

1-Day health advisory (10-kg child) 

10-Day health advisory 

(10-kg child) 

DWEL 

Concentration at cancer risk of 10-4 

Organoleptic effect criteria 

Toxic criteria for those states not 

complying with Clean Water Act 

section 303(c)(2)(B) 

Freshwater 

Maximum concentration 

Continuous concentration 

Saltwater 

Maximum concentration 

Continuous concentration 

Water pollution—designation of 

hazardous substance 

Water programs—determination of 

reportable quantities of hazardous 

substances 

Bottled water—allowable level 

Indirect food additives— adhesives 

and components of coatings 

Indirect food additives—animal glue 

Sodium pentachlorophenate 

1x10-3 mg/L	 EPA 2001h 

40CFR141.61 

0 mg/L	 EPA 2001i 

40CFR141.50 

EPA 2001a 

40CFR401.15 

1.0 mg/L	 EPA 2000d 

0.3 mg/L 

1.0 mg/L 

0.03 mg/L 

30 μg/L	 EPA 1999b 

EPA 2001o 

40CFR131.36 

20 μg/L 

13 μg/L 

13 μg/L 

7 μg/L 

EPA 2001p 

40CFR116.4 

10 pounds	 EPA 2001q 

40CFR177.3 

1x10-3 mg/L	 FDA 2000a 

21CFR165.110 

FDA 2000b 

21CFR175.105 

FDA 2000c 

21CFR178.3120 

(d)(3) 
PENTACHLOROPHENOL 205 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description	 Information References 

NATIONAL (cont.) 

FDA Indirect food additives—rubber 

articles intended for repeated use 

Sodium pentachlorophenate 

Indirect food additives—textiles and 

textile fibers 

Sodium pentachlorophenate 

Indirect food additives— 

preservatives for wood 

Pentachlorophenol and sodium 

pentachlorophenate 

d. Other 

ACGIH BEI 

Total pentachlorophenol in urine 

Free pentachlorophenol in 

plasma 

Carcinogenicity classification 

DOT	 Hazardous material— 

pentachlorophenol and sodium 

pentachlorophenate 

Use of tank cars—hazardous 

substance 

EPA	 Carcinogenicity classification 

Oral slope factor 

RfD 

General pretreatment regulations 

for existing and new sources of 

pollution—pollutants eligible for a 

removal credit (land application) 

Identification and listing of 

hazardous waste—comparable/ 

Syngas fuel exclusion 

Minimum required detection limit 

for comparable fuel specification 

Not to exceed 

50 ppm in the 

treated wood 

2 mg/g creatinine 

5 mg/L 

A3c 

B2d 

12 (mg/kg/day)-1 

3x10-2 mg/kg/day 

30 mg/kg 

2,400 mg/kg 

FDA 2000e 

21CFR177.2600 

(c)(4) 

FDA 2000f 

21CFR177.2800 

(d)(5) 

FDA 2000d 

21CFR177.3800 

(b) 

ACGIH 2000 

DOT 2001a 

49CFR172.101 

DOT 2001c 

49CFR173.31 

(f)(2) 

IRIS 2001 

EPA 2001b 

40CFR403 

Appendix G 

EPA 2001f 

40CFR261.38 
PENTACHLOROPHENOL 206 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description	 Information References 

NATIONAL (cont.) 

EPA	 Identification and listing of
 

hazardous waste—hazardous
 

constituent
 

Identification and listing of 

hazardous waste—maximum 

concentration of contaminant for 

the toxicity characteristic 

Hazardous waste—concentration 

limits for health based limits for 

exclusion of waste-derived residues 

Health and environmental 

protection standards for uranium 

and thorium mill tailings 

Superfund—reportable quantity 

Toxic chemical release reporting; 

Community Right-to-Know 

—effective date 

STATE 

Regulations and 

Guidelines: 

a. Air: 

Arkansas	 RAC 

California	 RAC 

Toxic air contaminant 

Colorado Hazardous air pollutant
 

8 hour
 

30 minute
 

Delaware	 RAC 

Idaho Toxic air pollutant
 

OEL
 

EL
 

AAC
 

Illinois	 RAC 

Toxic air contaminant 

EPA 2001e 

40CFR261 

Appendix VIII 

100 mg/L	 EPA 2001g 

40CFR261.24 

1 mg/kg	 EPA 2001c 

40CFR266 

Appendix VII 

Listed constituent	 EPA 2001d 

40CFR192 

Appendix I 

10 pounds	 EPA 2001m 

40CFR302.4 

01/01/87	 EPA 2001n 

40CRF372.65 

30 μg/m3	 BNA 2001 

30 μg/m3	 BNA 2001 

BNA 2001 

10 μg/m3 

50 μg/m3 

30 μg/m3	 BNA 2001 

BNA 2001 

0.5 mg/m3 

0.033 pounds/hour 

0.025 mg/m3 

30 μg/m3	 BNA 2001 
PENTACHLOROPHENOL 207 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description	 Information References 

STATE (cont.)
 

Kansas HAP BNA 2001
 

Maximum air emissions allowed 0.7 tons/year CDC 1999a
 

Kentucky RAC 30 μg/m3 BNA 2001
 

Minnesota HAP threshold 0.7 tons/year BNA 2001
 

New Hampshire Regulated toxic air pollutant BNA 2001
 

OEL 0.5 mg/m3
 

North Carolina Emission rates requiring a permit BNA 2001
 

Chronic toxicants 0.063 pounds/day
 

Acute systemic toxicants 0.0064 pounds/day
 

Chronic toxicants (24 hour) 0.003 mg/m3
 

Acute systemic toxicants 0.025 mg/m3
 

(1 hour)
 

allowable concentration
 

Annual average 1.19 μg/m3
 

Action level 0.10 μg/m3
 

Wisconsin Proposed thresholds Wisconsin DNR
 

24 hour $25 ft <75 ft 0.104 pounds/hour
 

24 hour $75 ft 0.811 pounds/hour
 

Toxic air pollutants BNA 2001
 

Rhode Island HAP BNA 2001
 

South Carolina RAC 30 μg/m3 BNA 2001
 

Toxic air emissions—maximum 5 μg/m3 BNA 2001
 

Tennessee RAC 30 μg/m3 BNA 2001
 

Vermont Hazardous ambient air standard BNA 2001
 

Washington Threshold for HAPs 0.35 tons/year BNA 2001
 

24 hour <25 ft 0.0269 pounds/hour 2001
 

Proposed standard—AAC 12 μg/m3
 

Wyoming RAC 30 μg/m3 BNA 2001
 

b. Water: 

Alabama MCL	 1 ppb BNA 2001
 

Toxic pollutant criteria	 BNA 2001
 

Marine acute 13 μg/L
 

Marine chronic 7.9 μg/L
 
PENTACHLOROPHENOL 208 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description Information References 

STATE (cont.) 

Alaska MCL 0.001 mg/L BNA 2001
 

Freshwater 2.1 μg/L
 

Costal and marine estuarine 7.9 μg/L
 

waters
 

Hawaii MCL—community, non-transient, 1x10-3 mg/L CDC 1999b
 

and non-community water systems
 

groundwater monitoring
 

concentrations
 

Michigan MCL 0.001 mg/L BNA 2001
 

Minnesota Drinking water guideline 3 μg/L HSDB 2001
 

Groundwater clean-up level 0.001 mg/L BNA 2001
 

Arizona MCL 0.001 mg/L BNA 2001
 

Aquifer water quality standard 0.001 mg/L BNA 2001
 

Drinking water guideline 220 μg/L HSDB 2001
 

Arkansas Groundwater monitoring (PQL) 5 mg/L BNA 2001
 

Colorado MCL 0.001 mg/L BNA 2001
 

Florida MCL 0.001 mg/L BNA 2001
 

Georgia MCL 0.001 mg/L BNA 2001
 

Instream concentrations BNA 2001
 

Idaho Groundwater quality standard 0.001 mg/L BNA 2001
 

Illinois MCL 0.001 mg/L BNA 2001
 

Groundwater monitoring 5 μg/L BNA 2001
 

Indiana MCL 0.001 mg/L BNA 2001
 

Iowa MCL 0.001 mg/L BNA 2001
 

Kansas MCL 0.001 mg/L BNA 2001
 

Kentucky MCL 0.001 mg/L BNA 2001
 

Hazardous constituent for BNA 2001
 

Maximum allowable instream 0.28 mg/L BNA 2001
 

Maine Drinking water guideline 1 μg/L HSDB 2001
 

Maryland MCL 0.001 mg/L BNA 2001
 

Massachusetts Groundwater monitoring (PQL) 5 μg/L BNA 2001
 
PENTACHLOROPHENOL 209 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description	 Information References 

STATE (cont.) 

Mississippi Groundwater standard
 

Freshwater
 

Acute
 

Chronic
 

Salt water
 

Acute
 

Chronic
 

Missouri MCL
 

Montana MCL
 

Nebraska MCL
 

Drinking water standard 

Nevada Standards for toxic materials 

applicable to municipal or domestic 

supply 

New Hampshire	 MCL
 

MCLG
 

Ambient groundwater quality
 

standard 

New Hampshire Water quality criteria 

Fresh acute 

Fresh chronic 

Marine acute 

Marine chronic 

Water and fish ingestion 

Fish consumption only 

New Jersey Groundwater quality criteria 

PQL 

New Mexico MCL 

Groundwater parameters (PQL) 

New York MCL 

Groundwater monitoring (PQL) 

North Dakota MCL
 

Ohio MCL
 

Oklahoma MCL
 

Water column criteria to protect for 

the consumption of fish flesh 

1 ppb	 BNA 2001 

BNA 2001 

3.32 μg/L 

2.1 μg/L 

13 μg/L 

7.9 μg/L 

0.001 mg/L	 BNA 2001 

0.001 mg/L	 BNA 2001 

0.001 mg/L	 BNA 2001 

0.001 mg/L BNA 2001 

1,010 μg/L BNA 2001 

0.001 mg/L BNA 2001 

0 

1 μg/L	 BNA 2001 

BNA 2001 

5.28 μg/L 

4.05 μg/L 

13.0 μg/L 

7.9 μg/L 

0.28 μg/L 

8.2 μg/L 

0.3 μg/L BNA 2001 

1.0 μg/L 

0.001 mg/L	 BNA 2001 

0.005 mg/L	 BNA 2001 

0.001 mg/L BNA 2001 

5 μg/L BNA 2001 

0.001 mg/L	 BNA 2001 

0.001 mg/L	 BNA 2001 

0.001 mg/L BNA 2001 

29,370 μg/L BNA 2001 
PENTACHLOROPHENOL 210 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description Information References 

STATE (cont.) 

Oklahoma Hazardous constituent (PQL) 5 μg/L BNA 2001 

Rhode Island MCLG 0 BNA 2001 

MCL 0.001 mg/L 

Groundwater quality standard 

Preventive action limit 

0.001 mg/L 

0.0005 mg/L 

BNA 2001 

South Carolina Groundwater monitoring (PQL) 5 μg/L BNA 2001 

Water quality criteria 

MCL 

Organism consumption 

1.0 μg/L 

82 μg/L 

BNA 2001 

South Dakota MCL 0.001 mg/L BNA 2001 

Groundwater standard 1x10-3 mg/L FSTRAC 1999b 

Tennessee Toxic substance criteria 

Maximum concentration 

Continuous concentration 

Water and organism 

Organism only 

1.0 μg/L 

20 μg/L 

13 μg/L 

2.8 μg/L 

82 μg/L 

BNA 2001 

Texas MCL 0.001 mg/L BNA 2001 

Utah MCL 0.001 mg/L BNA 2001 

Groundwater quality standard 0.001 mg/L BNA 2001 

Vermont MCL 0.001 mg/L BNA 2001 

MCLG 0 BNA 2001 

Vermont Consumption of water and 

organism 

Consumption of organism only 

0.28 μg/L 

8.2 μg/L 

BNA 2001 

Enforcement standard 

Preventive action level 

1.0 μg/L 

0.3 μg/L 

BNA 2001 

Virginia Hazardous constituent (PQL) 5 μg/L BNA 2001 

Public water supplies 

All other surface waters 

2.8 μg/L 

82 μg/L 

BNA 2001 

Washington MCL 0.001 mg/L BNA 2001 

West Virginia Groundwater standard 0.001 mg/L BNA 2001 

Wisconsin MCLG 0.003 mg/L BNA 2001 

c. Food 

Nebraska Standards for bottled water 0.001 mg/L BNA 2001 
PENTACHLOROPHENOL 211 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pentachlorophenol 

(continued) 

Agency Description Information References 

STATE (cont.) 

d. Other 

Arizona Soil remedial level BNA 2001 

Residential 

Non-residential 

25.0 mg/kg 

79.0 mg/kg 

Connecticut Direct exposure criteria for soil 

Residential 

Industrial/commercial 

5.1 ppm 

48 ppm 

BNA 2001 

Hawaii Restricted use pesticide Restricted 

concentration 

BNA 2001 

above 5% 

Massachusetts RfD 

Oral slope factor 

3x10-2 mg/kg/day 

12 (mg/kg/day)-1 

BNA 2001 

Toxic pollutant 

Minnesota Slope factor 

Health risk limit 

0.12 (mg/kg/day)-1 

3 μg/L 

BNA 2001 

Missouri Hazardous constituent BNA 2001 

New Hampshire Restricted use pesticide All concentrations BNA 2001 

New Jersey Restricted use pesticide All concentrations 

above 5% 

BNA 2001 

New York Restricted use pesticide All concentrations 

above 5% 

BNA 2001 

a

Group2B: possibly carcinogenic to humans

b

Skin notation: danger of cutaneous absorption 

c

A3: confirmed animal carcinogen with unknown relevance to humans

d

Group B2: probable human carcinogen
 

AAC = acceptable ambient concentrations; ACGIH = American Conference of Governmental Industrial Hygienists;
 

BEI = biological exposure index; BNA = Bureau of National Affairs; CDC = Center for Disease Control; CFR = Code of
 

Federal Regulations; DNR = Department of Natural Resources; DOT = Department of Transportation;
 

DWEL = drinking water equivalent level; EL = emissions level; EPA = Environmental Protection Agency; FDA = Food
 

and Drug Administration; FSTRAC = Federal–State Toxicology Risk Analysis Committee; HAP = hazardous air
 

pollutant; HSDB = Hazardous Substances Data Bank; IARC = International Agency for Research on Cancer;
 

IDLH = immediately dangerous to life and health; IRIS = Integrated Risk Information System; MCL = maximum
 

contaminant level; MCLG = maximum contaminant level goal; NIOSH = National Institute of Occupational Safety and
 

Health; OEL = occupational exposure level; OSHA = Occupational Safety and Health Administration;
 

PEL = permissible exposure limit; PQL = practical quantitation limit; RAC = reference air concentration;
 

REL = recommended exposure release; RfD = reference dose; TLV = threshold limit value; TSD = treatment, storage,
 

and disposal; TWA = time-weighted average; USC = United States Code; WHO = World Health Organization
 

_______________ 

PENTACHLOROPHENOL 213 

9. REFERENCES
 

ACGIH. 1986a. Documentation of the threshold limit values and biological exposure indices. 5th ed. 

Cincinnati, OH: American Conference of Governmental Industrial Hygienists. 

ACGIH. 1986b. Recommended BEI. Cincinnati, OH: American Conference of Governmental 

Industrial Hygienists. 

*ACGIH. 1991. Threshold limit values and biological exposure indices for 1990-1991. Cincinnati, OH: 

American Conference of Governmental Industrial Hygienists. 

ACGIH. 1998. Documentation of the threshold limit values and biological exposure indices. 6th ed. 

Cincinnati, OH: American Conference of Governmental Industrial Hygienists. 

*ACGIH. 2000. Pentachlorophenol. Threshold limit values for chemical substances and physical agents 

and biological exposure indices. Cincinnati, OH: American Conference of Governmental Industrial 

Hygienists. 

*Adinolfi M. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 

27:532-537. 

*Adlercreutz H. 1995. Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ 

Health Perspect Suppl 103(7):103-112. 

*Ahlborg UG, Larsson K, Thunberg T. 1978. Metabolism of pentachlorophenol in vivo and in vitro. 

Arch Toxicol 40:45-53. 

*Ahlborg UG, Lindgren JE, Mercier M. 1974. Metabolism of pentachlorophenol. Arch Toxicol 

32:271-281. 

Ahmad W, Ali MN. 1996. A comprehensive assessment of potential hazards of chlorinated phenoxy 

compounds (2,4-D, PCP and 2,4,5-T) in catfish (heteropneustes fossilis): Chromosomal and molecular 

genotoxicity. Chem Environ Res 5:267-281. 

Ahmed FE, Hattis D, Wolke RE, et al. 1993. Risk assessment and management of chemical 

contaminants in fishery products consumed in the USA. J Appl Toxicol 13:395-410. 

Alabanis TA, Danis TG, Jourgia MG. 1998. Adsorption-desorption studies of selected chlorophenols 

and herbicides and metal release in soil mixtures with fly ash. Environ Technol 19:25-34. 

Allard AS, Neilson AH. 1997. Bioremediation of organic waste sites: A critical review of 

microbiological aspects. Int Biodeterior Biodegrad 39:253-285. 

Alm H, Tiemann U, Torner H. 1996. Influence of organochlorine pesticides on development of mouse 

embryos in vitro. Reprod Toxicol 10:321-326. 

*Cited in text 
PENTACHLOROPHENOL 214 

9. REFERENCES 

Alm H, Torner H, Tiemann U, et al. 1998. Influence of organochlorine pesticides on maturation and 

postfertilization development of bovine oocytes in vitro. Reprod Toxicol 12:559-563. 

*Altman PK, Dittmer DS. 1974. In: Biological handbooks: Biology data book. Vol. III, 2nd ed. 

Bethesda, MD: Federation of American Societies for Experimental Biology, 1987-2008, 2041. 

Amer SM, Ali EM. 1969. Cytological effects of pesticides--IV. Mitotic effects of some phenols. 

Cytologic 34:533-539. 

*Andersen KJ, Leighty EG, Takahashi MT. 1972. Evaluation of herbicides for possible mutagenic 

properties. J Agric Food Chem 20:649-656. 

*Andersen ME, Krishnan K. 1994. Relating in vitro to in vivo exposures with physiologically based 

tissue dosimetry and tissue response models. In: Salem H, ed. Animal test alternatives: Refinement, 

reduction, replacement. New York: Marcel Dekker, Inc., 9-25. 

*Andersen ME, Clewell HJ 3rd, Gargas ML, et al. 1987. Physiologically based pharmacokinetics and 

the risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87:185-205. 

Anderson RS, Brubacher LL. 1993. Inhibition by pentachlorophenol of production of reactive-oxygen 

intermediates by medaka phagocytic blood cells. Mar Environ Res 35:125-129. 

Anderson SL, Hose JE, Knezovich JP. 1994. Genotoxic and developmental effects in sea urchins are 

sensitive indicators of effects of genotoxic chemicals. Environ Toxicol Chem 13:1033-1041. 

Angelova MB, Genova LK, Pashova SB, et al. 1996. Induction of superoxide dismutase synthesis in 

humicola lutea 110 by pentachlorophenol. Can J Microbiol 42:1197-1202. 

Angerer J, Goen T, Lehnert G. 1993. Internal exposure to predioxins and other organic substances in 

waste incineration plants. In: Organohalogen compounds. Erlangen: Institute of Occupational and 

Social Medicine. 163-167. 

Angerer J, Goen T, Schaller K, et al. 1996. [Prenatal exposure to polychlorinated biphenyls and 

hexachlorobenzene- a comparison of the results from 1984/85 and 1994/95.] Umweltmed Forsch Prax 

1:78-82. (German) 

Angerer J, Heinzow B, Reimann DO, et al. 1992. Waste incineration: Estimation of the workers internal 

exposure to PCB, PAH chlorophenols and other relevant agents. In: Vo-Dinht, Cammann K, eds. 

International conference on monitoring of toxic chemicals and biomarkers, Berlin, FRG, June 23-36, 

1992. Berlin: SPIE, 418-426. 

Anonymous. 1966. Recommendation of occupational exposure limits (1996-1997). J Occup Health 

38:134-147. 

*Anonymous. 1999. Public health assessment for Camilla Wood Preserving Company, Camilla, 

Mitchell County, Georgia, region 4. CERCLIS No. GAD008212409. NTIS/PB2000-103266. Govt 

Reports Announcements & Index (GRA&I), No. 13. 

*Ansari GAS, Britt SG, Reynolds ES. 1985. Isolation and characterization of palmitoylpentachlorophenol from human fat. Bull Environ Contam Toxicol 34:661-667. 
PENTACHLOROPHENOL 215 

9. REFERENCES 

Ansari GAS, Kaphalia BS, Boor P J. 1987. Selective pancreatic toxicity of palmitoylpentachlorophenol. 

Toxicology 46:57-63. 

Appel KE. 1994. [On the carcinogenicity of pentachlorophenol.] Bundesgesundheitsgblatt 37:334-341. 

(German) 

Argese E, Bettiol C, Ghelli A, et al. 1995. Submitochondrial particles as toxicity biosensors of 

chlorophenols. Environ Toxicol Chem 14:363-368. 

Argus. 1993a. Developmental toxicity (embryo-fetal toxicity and teratogenic potential) study of 

pentachlorophenol administered orally via stomach tube to New Zealand rabbits. Horsham, PA: Argus 

Research Laboratories, Inc. (Unpublished study - see Bernard et al. 2001a) 

Argus. 1993b. Developmental toxicity (embryo-fetal toxicity and teratogenic potential) study of 

pentachlorophenol administered orally via gavage to Crl:CD BR VAF/Plus presumed pregnant rats. 

Horsham, PA: Argus Research Laboratories, Inc. (Unpublished study - see Bernard et al. 2001b) 

Argus. 1997. Oral (gavage) two-generation (one litter per generation) reproduction study of 

pentachlorophenol in rats. Horsham, PA: Argus Research Laboratories, Inc. (Unpublished study - see 

Bernard et al. 2001c) 

*Armstrong RW, Eichner ER, Klein DE, et al. 1969. Pentachlorophenol poisoning in a nursery for 

newborn infants: II. Epidemiologic and toxicologic studies. J Pediatr 75:317-325. 

Arnold SF, Collins BM, Robinson MK, et al. 1996. Differential interaction of natural and synthetic 

estrogens with extracellular binding proteins in a yeast estrogen screen. Steroids 61:642-646. 

*Arrhenius E, Renberg L, Johansson L. 1977. Subcellular distribution, a factor in risk evaluation of 

pentachlorophenol. Chem Biol Interact 18:23-34. 

*Arsenault RD. 1976. Pentachlorophenol and contained chlorinated dibenzodioxins in the environment: 

A study of environmental fate, stability, and significance when used in wood preservation. Alexandria, 

VA: American Wood-Preservers Assoc. 122-147. 

ATSDR. 1989. Decision guide for identifying substance-specific data needs related to toxicological 

profiles; Notice. Agency for Toxic Substances and Disease Registry. Federal Register 54(174):37617­

37634. 

*ATSDR. 1993a. Public health assessment for Koppers Company/Charleston, Charleston County, South 

Carolina, region 4. CERCLIS No. SCD980310239. Government Reports Announcements & Index 

(GRA&I), No. 20. 

*ATSDR. 1993b. Public health assessment for Munisport Landfill, North Miami, Dade County, Florida, 

region 4. CERCLIS No. FLD084535442. Government Reports Announcements & Index (GRA&I) Issue 

09. 

*ATSDR. 1995. Health assessment for American Creosote Works, Incorporated, (Winnfield Plant), 

Winnfield, Winn Parish, Louisiana, region 6. CERCLIS No. LAD000239814. Government Reports 

Announcements & Index (GRA&I) No. 13. 
PENTACHLOROPHENOL 216 

9. REFERENCES 

*Baader EW, Bauer HJ. 1951. Industrial intoxication due to pentachlorophenol. Ind Med Surg 

20:286-290. 

*Baker MD, Mayfield CI, Inniss WE. 1980. Degradation of chlorophenols in soil, sediment and water at 

low temperature. Water Res 14:1765-1771. 

*Ballhorn L, Rozman T, Rozman K, et al. 1981. Cholestryamine enhances fecal elimination of 

pentachlorophenol in Rhesus monkeys. Chemosphere 10:877-888. 

Banerji SK, Wei SM, Bajpai RK. 1993. Pentachlorophenol interactions with soil. Water Air Soil Pollut 

69:149-163. 

Barbeau C, Deschenes L, Karamanev D, et al. 1997. Bioremediation of pentachlorophenol-contaminated 

soil by bioaugmentation using activated soil. Appl Microbiol Biotechnol 48:745-752. 

*Barbieri F, Colosio C, Schlitt H, et al. 1995. Urine excretion of pentachlorophenol (PCP) in 

occupational exposure. Pestic Sci 43:259-262. 

*Bargagna S, Chiovato L, Dinetti D, et al. 1997. Neuropsychological development in a child with earlytreated congenital hypothyroidism as compared with her unaffected identical twin. Eur J Endocrinol 

136:100-104. 

Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments. 

Regul Toxicol Pharmacol 8:471-486. 

Barry TC. 1967. Toxicity of pentachlorophenol. Can Med Assoc J 96:228. 

Barthel W, Curley A, Thrasher C, et al. 1969. Determination of pentachlorophenol in blood, urine, 

tissue, and clothing. J Assoc Off Agric Chem 52:294-298. 

Battershill JM, Fielder RJ. 1998. Mouse-specific carcinogens: An assessment of hazard and significance 

for validation of short-term carcinogenicity bioassays in transgenic mice. Hum Exp Toxicol 17:193-205. 

*Bauchinger M, Dresp J, Schmid E, et al. 1982. Chromosome exchanges in lymphocytes after 

occupational exposure to pentachlorophenol (PCP). Mutat Res 102:83-88. 

*Beard AP, Rawlings NC. 1998. Reproductive effects in mink (mustela vison) exposed to the pesticides 

lindane, carbofuran and pentachlorophenol in a multigeneration study. J Reprod Fertil 113:95-104. 

*Beard AP, Rawlings NC. 1999. Thyroid function and effects of reproduction in ewes exposed to the 

organochlorine pesticides lindane or pentachlorophenol (PCP) from conception. J Toxicol Environ 

Health 58:509-530. 

*Beard AP, Bartlewski PM, Chandolia RK. 1999a. Reproductive and endocrine function in rams 

exposed to the organochlorine pesticides lindane and pentachlorophenol. J Reprod Fertil 115:303-314. 

*Beard AP, Bartlewski PM, Rawlings NC. 1999b. Endocrine and reproductive function in ewes exposed 

to the organochlorine pesticides lindane or pentachlorophenol. J Toxicol Environ Health 56:23-46. 

Beard AP, Bartlewski PM, Rawlings NC. 1996. Endocrine and reproductive function in ewes exposed to 

the organochlorine pesticides lindane or pentachlorophenol (PCP) [Abstract]. J Reprod Fertil 18:23-24. 
PENTACHLOROPHENOL 217 

9. REFERENCES 

*Beard AP, McRae AC, Rawlings NC. 1997. Reproductive efficiency in mink (mustela vison) treated 

with the pesticides lindane, carbofuran and pentachlorophenol. J Reprod Fertil 111:21-28. 

Beaudet R, McSween G, Lepine F, et al. 1997. Anaerobic biodegradation of pentachlorophenol in a 

liquor obtained after extraction of contaminated chips and wood powder. J Appl Microbiol 82:186-190. 

*Begley J, Reichert EL, Siesmen AW, et al. 1977. Association between renal function tests and 

pentachlorophenol exposure. Clin Toxicol 11:97-106. 

Belfroid AC, Sijm DTHM, Van Gestel CAM. 1996. Bioavailability and toxicokinetics of hydrophobic 

aromatic compounds in benthic and terrestrial invertebrates. Environ Res 4:276-299. 

Berg UT, Nyholm N. 1996. Biodegradability simulation studies in semicontinuous activated sludge 

reactors with low (μg/L range) and standard (ppm range) chemical concentrations. Chemosphere 33:711­

735. 

*Berger GS. 1994. Epidemiology of endometriosis. In: Modern surgical management of endometriosis. 

New York, NY: Springer-Verlag. 

*Bergner H, Constantinidis P, Martin JH. 1965. Industrial pentachlorophenol poisoning in Winnipeg. 

Can Med Assoc J 92:448-451. 

*Bernard BK, Ranpuria AK, Hoberman AM. 2001a. Developmental toxicity (embryo-fetal toxicity and 

teratogenic potential) study of pentachlorophenol in the rabbit. (Submitted for publication in the 

International Journal of Toxicology - see Argus 1993a) 

*Bernard BK, Ranpuria AK, Hoberman AM. 2001b. Developmental toxicity (embryo-fetal toxicity and 

teratogenic potential) study of pentachlorophenol in the rats. (Submitted for publication in the 

International Journal of Toxicology - see Argus 1993b) 

*Bernard BK, Ranpuria AK, Hoberman AM, et al. 2001c. Oral (gavage) two-generation (one litter per 

generation) reproduction study of pentachlorophenol in rats. (Submitted for publication in the 

International Journal of Toxicology - see Argus 1997) 

Besombes JL, Cosnier S, Labe P, et al. 1995. Determination of phenol and chlorinated phenolic 

compounds based on a PPO-bioelectrode and its inhibition. Anal Lett 28:405-424. 

Bevenue A. 1972. Organochlorine pesticides in rainwater, Ohau, Hawaii 1971-1972. Bull Environ 

Contam Toxicol 8:238-241. 

*Bevenue A, Beckman H. 1967. Pentachlorophenol: A discussion of its properties and its occurrence as 

a residue in human and animal tissues. Residue Rev 19:83-134. 

*Bevenue A, Emerson ML, Casarett LJ, et al. 1968. A sensitive gas chromatographic method for the 

determination of pentachlorophenol in human blood. J Chromatogr 38:467-472. 

*Bevenue A, Wilson J, Casarett LJ, et al. 1967. A survey of pentachlorophenol content in human urine. 

Bull Environ Contam Toxicol 2:319-332. 

Bhattacharya SK, Yuan Q, Jin PL. 1996. Removal of pentachlorophenol from wastewater by combined 

anaerobic-aerobic treatment. J Hazard Mater 49:143-154. 
PENTACHLOROPHENOL 218 

9. REFERENCES 

Bidstrup PL, Gauvain S, Spalding JMK, et al. 1969. Toxic chemicals and peripheral neuropathy. Proc R 

Soc Med 62:208-210. 

Bierkens J, Maes J, Plaetse FV. 1998. Dose-dependent induction of heat shock protein 70 synthesis in 

raphidocelis subcapitata following exposure to different classes of environmental pollutants. Environ 

Pollut 101:91-97. 

*Birrell J, Frost GJ, Parkin JM. 1983. The development of children with congenital hypothyroidism. 

Dev Med Child Neurol 25:512-519. 

Blair DM. 1961. Dangers in using and handling sodium pentachlorophenate as a molluscicide. Bull 

World Health Organ 25:597-601. 

*Blankenship A, Chang DPY, Jones AD, et al. 1994. Toxic combustion by-products form the 

incineration of chlorinated hydrocarbons and plastics. Chemosphere 28:183-196. 

*Blakley BR, Yole MJ, Brousseau P, et al. 1998. Effect of pentachlorophenol on immune function. 

Toxicology 125:141-148. 

*BNA. 2001. Environment and safety: States and territories. Bureau of National Affairs. 

Http://www.bna.com/. February 13, 2001. 

*Borzelleca JF, Hayes JR, Condi LW, et al. 1985. Acute toxicity of monochlorophenols, 

dichlorophenols and pentachlorophenol in the mouse. Toxicol Lett 29:39-42. 

*Boutwell RK, Bosch DK. 1959. The tumor-promoting action of phenol and related compounds for 

mouse skin. Cancer Res 19:413-424. 

Bowes RC, Ramos KS. 1994. Assessment of cell-specific cytotoxic responses of the kidney to selected 

aromatic hydrocarbons. Toxicol in Vitro 8:1151-1160. 

*Boylan J, Egle J, Guzelian R. 1977. Cholestyramine: Use as a new therapeutic approach for 

chlordecone (Kepone) poisoning. Science 199:893-895. 

*Boyle TP, Robinson-Wilson EF, Petty JD, et al. 1980. Degradation of pentachlorophenol in simulated 

lentic environment. Bull Environ Contam Toxicol 24:177-184. 

*Braun WH, Sauerhoff MW. 1976. The pharmacokinetic profile of pentachlorophenol in monkeys. 

Toxicol Appl Pharmacol 38:525-533. 

*Braun WH, Blau GE, Chenoweth MB. 1979. The metabolism/pharmacokinetics of pentachlorophenol 

in man, and a comparison with the rat and monkey. In: Deichmann WE, ed. Toxicology and 

occupational medicine. New York, NY: Elsevier, 289-296. 

*Braun WH, Young JD, Blau GE, et al. 1977. The pharmacokinetics and metabolism of pentachlorophenol in rats. Toxicol Appl Pharmacol 41:395-406. 

Brisset JL. 1998. Removal of pentachlorophenol from water by AC corona discharge treatment in air. J 

Trace Microprobe Tech 16:363-370. 
PENTACHLOROPHENOL 219 

9. REFERENCES 

Brouwer A, Morse DC, Lans MC, et al. 1998. Interactions of persistent environmental organohalogens 

with the thyroid hormone system: Mechanisms and possible consequences for animal and human health. 

Toxicol Ind Health 14:59-84. 

Bryant DE, Schultz TW. 1994. Toxicological assessment of biotransformation products of 

pentachlorophenol: Tetrahymena population growth impairment. Arch Environ Contam Toxicol 26:299­

303. 

*Bryant FO, Hale DD, Rogers JE. 1991. Region specific dechlorination of pentachlorophenol by 

dichlorophenol-adapted microorganisms in freshwater, anaerobic sediment slurries. Appl Environ 

Microbiol 57:2293-2301. 

Buckley TJ, Liddle J, Ashley DL, et al. 1997. Environmental and biomarker measurements in nine 

homes in the lower Rio Grande valley: Multimedia results for pesticides, metals, PAHs, and VOCs. 

Environ Int 23:705-732. 

*Budavari S, O'Neil MJ, Smith A, et al. 1989. The Merck index: An encyclopedia of chemicals, drugs, 

and biologicals. 11th ed. Rahway, NJ: Merck and Co., Inc., 1126. 

*Buhler DR, Rasmussen ME, Nakane HS. 1973. Occurrence of hexachlorophene and pentachlorophenol 

in sewage and water. Environ Sci Technol 7:929-934. 

*Buisson RSK, Kirk PWW, Lester JN. 1984. Determination of chlorinated phenols in water, wastewater, 

and wastewater sludge by capillary GC/ECD. J Chromatogr Sci 22:339-342. 

*Bunce NJ, Nakai JS. 1989. Atmospheric chemistry of chlorinated phenols. J Air Pollut Control Assoc 

39:820-823. 

Burton BT. 1993. Hazardous materials. In: Kravis TC, Warner CG, Jacobs LMJ, eds. Emergency 

medicine. New York, NY: Raven Press, Ltd, 747-759. 

*Buselmaier W, Rohrborn G, Propping P. 1973. Comparative investigations on the mutagenicity of 

pesticides in mammalian test systems. Mutat Res 21:25-26. 

*Butler ECV, Dal Pont G. 1992. Liquid chromatography-electrochemistry procedure for the 

determination of chlorophenolic compounds in pulp mill effluents and receiving waters. J Chromatogr 

609:113-123. 

Butte W. 1985. Pentachlorophenol concentrations in serum and urine of persons that have used wood 

preserving agents. J Clin Chem Clin Biochem 23:599. 

Carr RS, Thomas P, Neff JM. 1982. A simple spectrophotometric technique for the determination of 

pentachlorophenol in water. Bull Environ Contam Toxicol 28:477-479. 

Carstens CP, Blum JK, Witte I. 1990. The role of hydroxyl radicals in tetrachlorohydroquinone induced 

DNA strand break formation in PM2 DNA and human fibroblasts. Chem Biol Interact 74:305-314. 

*Casarett LJ, Benevue WL, Yauger WL, et al. 1969. Observations on pentachlorophenol in human blood 

and urine. Am Ind Hyg Assoc J 30:360-366. 
PENTACHLOROPHENOL 220 

9. REFERENCES 

CDC. 1996. Pentachlorophenol poisoning in newborn infants- St. Louis, Missouri, April-August 1967. 

MMWR Morb Mortal Wkly Rep 45:545-551. 

*CDC. 1999a. Hawaii. Center for Disease Control & Prevention. 

Http://search.cdc.gov/shd/search2.html. May 25, 1999. 

*CDC. 1999b. Kansas. Center for Disease Control & Prevention. 

Http://search.cdc.gov/shd/search2.html. May 25, 1999. 

*CELDS. 1992. Computer-Environmental Legislative Data Systems. Urbana, IL: University of Illinois, 

March 1992. 

Cerda F, Godoy F, Garcia A, et al. 1997. Effects of pentachlorophenol upon the expression of outer 

membrane proteins, and role of exopolysaccharide and lipopolysaccharide in the tolerance of 

pseudomonas fluorescens to this compound. Microbios 90:79-85. 

*Cessna AJ, Waite DT, Constable M. 1997. Concentrations of pentachlorophenol in atmospheric 

samples from three Canadian locations, 1994. Bull Environ Contam Toxicol 58:651-658. 

*Chadwick RW, George SE, Chang J, et al. 1993. Effects of age, species difference, antibiotics and 

toxicants on intestinal enzyme activity and genotoxicity. Environ Toxicol Chem 12:1339-1352. 

*Chang NI, Choi J. 1974. Studies on the adsorption of pentachlorophenol (PCP) in soil. Hanguk 

Touang Bilyo Hakkhoe Chi 7:197-20. 

Chapman JB. 1970. Poisoning with PCP. Br Med J 2:480. 

*Chapman JB, Robson P. 1965. Pentachlorophenol poisoning from bath water. Lancet 1:1266-1267. 

*Cheng WN, Coenraads PJ, Hao ZH, et al. 1993. A health survey of workers in the pentachlorophenol 

section of a chemical manufacturing plant. Am J Ind Med 24:81-92. 

*Chhabra RS, Maronpot RM, Bucher JR, et al. 1999. Toxicology and carcinogenesis studies of 

pentachlorophenol in rats. Toxicol Sci 48:14-20. 

*Choi J, Aomine S. 1974. Adsorption of pentachlorophenol by soils. Soil Sci Plant Nutr 20:135-144. 

*Chou PP, Bailey JL. 1986. Liquid chromatographic determination of urinary pentachlorophenol. Clin 

Chem 32:1026-1028. 

*Christodoulatos C, Korfiatis GP, Talimcioglu NM, et al. 1994. Adsorption of pentachlorophenol by 

natural soils. J Environ Sci Health A29:883-898. 

Chu JP, Kirsch EJ. 1972. Metabolism of pentachlorophenol by an axenic bacterial culture. Appl 

Microbiol 23:1033-1035. 

*Cirelli DP. 1978a. Patterns of pentachlorophenol usage in the United States of America—an overview. 

In: Rao KR, ed. Pentachlorophenol, chemistry, pharmacology, and environmental toxicology. New 

York, NY: Plenum Press, 13-18. 
PENTACHLOROPHENOL 221 

9. REFERENCES 

Cirelli DP. 1978b. Pentachlorophenol: Position document 1. U.S. Environmental Protection Agency. 

Federal Register 40:48446-48477. 

Clausen CA. 1996. Bacterial associations with decaying wood: A review. Int Biodeterior Biodegrad 

101-107. 

*Clewell HJ III, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling. 

Toxicol Ind Health 1:111-131. 

*Cline RE, Hill RH Jr, Phillips DL, et al. 1989. Pentachlorophenol measurements in body fluids of 

people in log homes and workplaces. Arch Environ Contam Toxicol 18:475-481. 

*CMR. 1987. Biocide ranks thin as costs multiply. Chemical Marketing Reporter. New York, NY: 

Schnell Publishing Company. 

*Coad S, Newhook RC. 1992. PCP exposure for the Canadian general population: A multimedia 

analysis. J Exp Anal Environ Epidemiol 2:391-413. 

Coenraads PJ, Brouwer A, Olie K, et al. 1994. Chloracne: Some recent issues. Dermatol Clin 12:569­

576. 

*Colosio C, Barberi F, Bersani M, et al. 1993a. Markers of occupational exposure to pentachlorophenol. 

Bull Environ Contam Toxicol 51:820-826. 

*Colosio C, Maroni M, Barcellini W, et al. 1993b. Toxicological and immune findings in workers 

exposed to pentachlorophenol (PCP). Arch Environ Health 48:81-88. 

Comstock EG. 1974. Urinary excretion of pentachlorophenol in an occupationally exposed population. 

Clin Tox 7:208. 

Copeland TL, Raustenbach DJ, Harris MA, et al. 1993. Comparing the results of a Monte Carlo analysis 

with EPA's reasonable maximum exposed individual (RMEI): A case study of a former wood treatment 

site. Regul Toxicol Pharmacol 18:275-312. 

Cornwall R, Toomey BH, Bard S, et al. 1995. Characterization of multixenobiotic/multidrug transport in 

the gills of the mussel mytilus californianus and identification of environmental substrates. Aquat 

Toxicol 31:277-296. 

*Courtney KD, Copeland MF, Robbins A. 1976. The effects of pentachloronitrobenzene, 

hexachlorobenzene, and related compounds on fetal development. Toxicol Appl Pharmacol 35:239-256. 

*Cranmer M, Freal J. 1970. Gas chromatographic analysis of pentachlorophenol in human urine by 

formation of alkyl ethers. Life Sci 9:121-128. 

*Cretney MJ. 1976. Pentachlorophenol death. Bull TIAFT 12:10. 

*CRISP. 1992. Computer Retrieval of Information on Scientific Projects. National Library of Medicine. 

Medlars Toxline File. 

*Crosby DG. 1981. Environmental chemistry of pentachlorophenol: A special report on pentachlorophenol in the environment. Pure Appl Chem 53:1051-1080. 
PENTACHLOROPHENOL 222 

9. REFERENCES 

*Crosby DG, Hamadad N. 1971. The photoreduction of pentachlorobenzenes. Food Chem 

19:1171-1174. 

Crosby DG, Wong AS. 1976. Photochemical generation of chlorinated dioxins. Chemosphere 

5:327-332. 

Cserjesi J. 1967. The adaptation of fungi to pentachlorophenol and its biodegradation. Can J Microbiol 

13:1234-1249. 

Cserjesi AJ, Johnson EL. 1972. Methylation of pentachlorophenol by trichoderma virgatum. Can J 

Microbiol 18:45-49. 

*Cuiu C, Halman R, Li K, et al. 1986. Analytical procedures to assay environmental samples for 

PCDD/PCDF, PAH, PCB, chlorobenzenes (CB), and chlorophenols. Chemosphere 15:1091-1098. 

*Dahlhaus M, Almstadt E, Appel KE. 1994. The pentachlorophenol metabolite tetrachloro-phydroquinone induces the formation of 8-hydroxy-2-deoxyguanosine in liver DNA of male B6C3F1 

mice. Toxicol Lett 74:265-274. 

*Dahlhaus M, Almstadt E, Henschke P, et al. 1996. Oxidative DNA lesions in V79 cells mediated by 

pentachlorophenol metabolites. Arch Toxicol 70:457-460. 

Daimon H, Sawada S, Asakura S, et al. 1997/1998. Inhibition of sulfotransferase affecting in vivo 

genotoxicity and DNA adducts induced by safrole in rat liver. Teratog Carcinog Mutagen 17:327-337. 

*Daniel V, Huber W, Bauer K, et al. 1995. Impaired in-vitro lymphocyte responses in patients with 

elevated pentachlorophenol (PCP) blood levels. Arch Environ Health 50:287-292. 

*Daniels CR, Swan EP. 1979. Determination of chlorinated phenols in surface-related lumber by HPLC. 

J Chromatogr Sci 17:628-630. 

*Davis A, Campbell J, Gilbert C, et al. 1994. Attenuation and biodegradation of chlorophenols in 

ground water at a former wood treating facility. Ground Water 32:248-257. 

Deichmann W, Keplinger ML. 1981. Patty's industrial hygiene and toxicology. 3rd ed. Toxicology 

2A:2610. 

*Deichmann W, Machle W, Kitzmiller KV, et al. 1942. Acute and chronic effects of pentachlorophenol 

and sodium pentachlorophenate upon experimental animals. J Pharmacol Exp Ther 76:104-117. 

De Maeyer J, Schepens PJC, Jorens PG, et al. 1995. Exposure to pentachlorophenol as a possible cause 

of miscarriages. Br J Obstet Gynaecol 102:1010-1011. 

*den Besten C, Vet JJRM, Besselink HT, et al. 1991. The liver, kidney, and thyroid toxicity of 

chlorinated benzenes. Toxicol Appl Pharmacol 111:69-81. 

*den Besten C, Bennik MHJ, Bruggeman I, et al. 1993. The role of oxidative metabolism in 

hexachlorobenzene-induced porphyria and thyroid hormone homeostatsis: A comparison with 

pentachlorobenzene in a 13-week feeding study. Toxicol Appl Pharmacol 119:181-194. 
PENTACHLOROPHENOL 223 

9. REFERENCES 

Derner M, Gerhard I, Monga B, et al. 1995. [Immunological, endocrine and chemical changes in women 

with hormonal disorders due to exposure to pentachlorophenol and lindane.] Zentralbl Arbeitsmed 

Arbeitsschutz Prophyl 45:312-328. (German) 

*de Ruiter C, Brinkman J-HW, Frei RW, et al. 1990. Liquid chromatographic determination of 

pentachlorophenol in serum, using pre-column phase-transfer catalyzed dansylation and post-column 

photolysis and fluorescence detection. Analyst 115:1033-1036. 

*Detrick RS. 1977. Pentachlorophenol, possible sources of human exposure. Forest Proc J 27:13-16. 

Dich J, Zahm SH, Hanberg A, et al. 1997. Pesticides and cancer. Cancer Causes Control 8:420-443. 

*Dimich-Ward H, Hertzman C, Teschke K, et al. 1996. Reproductive effects of paternal exposure to 

chlorophenate wood preservatives in the sawmill industry. Scand J Work Environ Health 22:267-273. 

Dolan DG. 1995. A cohort study of the effects of pentachlorophenol on male reproductive function. 

Doctor of Philosophy Thesis, University of Illinois at Chicago. 

*Donaldson S, Miller G. 1997. Transport and photolysis of pentachlorophenol in soils subject to 

evaporating water. J Environ Qual 26:402-409. 

*Donnelly KC, Claxton LD, Huebner HJ, et al. 1998. Mutagenic interactions of model chemical 

mixtures. Chemosphere 37:1253-1261. 

*DOT. 2001a. Hazardous materials tables and hazardous materials communications regulations. U.S. 

Department of Transportation. Code of Federal Regulations. 49 CFR 172.101. 

Http://www.dot.gov/safety.html. April 04, 2001. 

*DOT. 2001b. List of marine pollutants. U.S. Department of Transportation. Code of Federal 

Regulations. 49 CFR 172.101, Appendix B. Http://www.dot.gov/safety.html. April 04, 2001. 

*DOT. 2001c. Use of tank cars. List of hazardous substances. U.S. Department of Transportation. 

Code of Federal Regulations. 49 CFR 173.31 (f)(2). Http://www.dot.gov/safety.html. April 04, 2001. 

*Dougherty RC. 1978. Human exposure to pentachlorophenol. In: Rao KR, ed. Pentachlorophenol, 

chemistry, pharmacology, and environmental toxicology. New York, NY: Plenum Press, 351-361. 

*Dougherty RC, Piotrowska K. 1976. Screening by negative chemical ionization mass spectrometry for 

environmental contamination with toxic residues: Application to human urine. Proc Natl Acad Sci USA 

73:1777-1781. 

*Dreisbach RH. 1980. Handbook of poisonings: Prevention, diagnosis, and treatment. 10th ed. Los 

Altos, CA: Lange Medical Publications, 364. 

*Drummond I, Van Roosmalen PB, Kornicki M. 1982. Determination of total pentachlorophenol in the 

urine of workers. Int Arch Occup Environ Health 50:321-327. 

*Dubois M, Plaisance H, Thome JP, et al. 1996. Hierarchical cluster analysis of environmental 

pollutants through P450 induction in cultured hepatic cells. Ecotoxicol Environ Saf 34:205-215. 

Duncan CG, Deverall FJ. 1964. Degradation of wood preservatives by fungi. Appl Microbiol 12:57-62. 
PENTACHLOROPHENOL 224 

9. REFERENCES 

*Dust JV, Thompson WS. 1972. Pollution control in the wood preserving industry: Part 3. Chemical 

and physical methods of treating wastewater. Forest Prod J 22:25-30. 

*Duxbury CL, Thompson JE. 1987. Pentachlorophenol alters the molecular organization of membranes 

in mammalian cells. Arch Environ Contam Toxicol 16:367-373. 

*Edgehill RV, Finn RK. 1983. Microbial treatment of soil to remove pentachlorophenol. Appl Environ 

Microbiol 45:1122-1125. 

Edgerton TR. 1981. Storage stability of chlorinated phenols in urine. J Agric Food Chem 29:415-416. 

*Edgerton TR, Moseman RF. 1979. Determination of pentachlorophenol in urine: The importance of 

hydrolysis. J Agric Food Chem 27:197-199. 

*Edgerton TR, Moseman RF, Linder RE, et al. 1979. Multi-residue method for the determination of 

chlorinated phenol metabolites in urine. J Chromatogr 170:331-342. 

*Ehrlich W. 1990. The effect of pentachlorophenol and its metabolite tetrachlorohydroquinone on cell 

growth and the induction of DNA damage in Chinese hamster ovary cells. Mutat Res 244:299-302. 

*Ellinger C, Seffner W, Schiller F. 1991. Investigations on the sensitivity of several biochemical and 

histological methods after liver intoxication induced by pentachlorophenol and carbon tetrachloride. 

Arch Toxicol Suppl 14:63-67. 

*EMMI. 1997. Environmental Monitoring Methods Index, Ver 1.1 Environ Dynamics, Inc. McLean, 

VA. 

Enarson DA, Chan-Yeung M, Embree V, et al. 1986. Occupational exposure to chlorophenates. Scand J 

Work Environ Health 12:144-148. 

*Engelhardt G, Wallnofer PR, Mucke W, et al. 1986. Transformations of pentachlorophenol. Toxicol 

Environ Chem 11:233-252. 

EPA. 1975. Identification of organic compounds in effluents from industrial sources. Washington, DC: 

U.S. Environmental Protection Agency, Office of Toxic Substances. EPA 560/3-75-002. 

*EPA. 1978a. National organic monitoring survey. Washington, DC: U.S. Environmental Protection 

Agency. 

EPA. 1978b. Designation of hazardous substances. U.S. Environmental Protection Agency. Code of 

Federal Regulations. 40 CFR 116.4. 

EPA. 1978c. Designation of hazardous substances. U.S. Environmental Protection Agency. Federal 

Register 43(49):10474-10488. 

EPA. 1978d. Notice of rebuttable presumption against registration and continued registration of 

pesticide products containing pentachlorophenol. Position document 1. U.S. Environmental Protection 

Agency. Federal Register 43:48443-48477. 

EPA. 1978e. Wood preservative pesticides, initiation of schedule for review and notices. U.S. 

Environmental Protection Agency. Federal Register 43:48446-48447. 
PENTACHLOROPHENOL 225 

9. REFERENCES 

*EPA. 1979a. Criteria and standards for the national pollutant discharge elimination system. U.S. 

Environmental Protection Agency. Federal Register 44:32948-32956. 40 CFR 125. 

*EPA. 1979b. STORET data base. Washington, DC: U.S. Environmental Protection Agency. 

EPA. 1979c. Toxic pollutants. U.S. Environmental Protection Agency. Code of Federal Regulations. 

40 CFR 401.15.
 

EPA. 1979d. Toxic pollutants. U.S. Environmental Protection Agency. Federal Register
 

44(147):44502-44503.
 

*EPA 1979e. Water-related environmental fate of 129 priority pollutants. Vol. 2. Washington, DC: 

U.S. Environmental Protection Agency, Office of Water and Waste Management. EPA 440/4-79-029B. 

*EPA. 1980a. Identification and listing of hazardous waste, discarded commercial chemical products, 

off-specification species, container residues, and spill residues thereof. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 261.33(f). 

*EPA. 1980b. Manual of analytical methods for the analysis of pesticides in humans and environmental 

samples section 5.4.a. Research Triangle Park, NC: U.S. Environmental Protection Agency, Health 

Effects Research Laboratory, Environmental Toxicology Division. EPA 600/8-80-038. 

*EPA. 1980c. Hazardous waste management system: Identification and listing of hazardous waste. 

Appendix VIII. Hazardous constituents. U.S. Environmental Protection Agency. Federal Register 

45:33133. 40 CFR 261.33(f). 

EPA. 1980d. Ambient water quality criteria for pentachlorophenol. Cincinnati, OH: U.S. 

Environmental Protection Agency, Environmental Criteria and Assessment Office. NTIS PB 81-117764. 

EPA 400/4-80-065. 

EPA. 1980e. Guidelines and methodology used in the preparation of health effect assessment chapters of 

the consent decree water criteria documents. U.S. Environmental Protection Agency. Federal Register 

45:79347-79357. 

*EPA. 1980f. Exposure and risk assessment for pentachlorophenol. Washington, DC: U.S. 

Environmental Protection Agency. NTIS PB85-211944. EPA 440/4-81-021. 

*EPA. 1980g. Timber products. U.S. Environmental Protection Agency. Federal Register 

45:62810-62846. 

EPA. 1981a. Hazardous wastes from non-specific sources. U.S. Environmental Protection Agency. 

Code of Federal Regulations. 40 CFR 261.31/261.32. 

EPA. 1981b. Hazardous wastes from non-specific sources. U.S. Environmental Protection Agency. 

Federal Register 46(11):4615-4620. 

EPA. 1982. Wood preservative pesticides creosote, pentachlorophenol and the inorganic arsenicals 

(wood uses). Position document 2/3. Washington, DC: U.S. Environmental Protection Agency, Office 

of Pesticides and Toxic Substances. EPA 540/9-82-004. 
PENTACHLOROPHENOL 226 

9. REFERENCES 

EPA. 1983. EPA administered permit programs: The national pollutant discharge elimination system: 

General permits. U.S. Environmental Protection Agency. Federal Register 49:14153-14178. 40 CFR 

122.28. 

*EPA. 1984a. Notice of intent to cancel registration of pesticide products containing creosote, 

pentachlorophenol (including its salts), and the inorganic arsenical. 49 CAR 28666. July 13, 1984. 

*EPA. 1984b. Wood preservative pesticides: Creosote, pentachlorophenol, inorganic arsenicals. 

Position document 4. Washington, DC: U.S. Environmental Protection Agency, Office of Pesticides and 

Toxic Substances. 

EPA. 1985. Designation, reportable quantities, and notification: Designation of hazardous substances. 

U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4. 

*EPA. 1986a. Water pollution: General pretreatment regulations for existing and new sources; Final 

rule. U.S. Environmental Protection Agency. Federal Register 51:20429. 

EPA. 1986b. Test methods for evaluating solid waste: Volume II: Field manual physical/chemical 

methods. Vol. 2, 3rd ed. Washington, DC: U.S. Environmental Protection Agency, Office of Solid Waste 

and Emergency Response. 

*EPA. 1986c. Ambient water quality criteria for pentachlorophenol. Washington, DC: U.S. 

Environmental Protection Agency, Office of Water Regulations and Standards, Criteria and Standards 

Division. EPA 440/5-86-009. 

EPA. 1987a. Emergency planning and notification: The list of extremely hazardous substances and their 

threshold planning quantities. U.S. Environmental Protection Agency. Federal Register 52:13395-13410. 

EPA. 1987b. Emergency planning and notification: The list of extremely hazardous substances and their 

threshold planning quantities. U.S. Environmental Protection Agency. Code of Federal Regulations. 

40 CFR 355. 

EPA. 1987c. List (phase 1) of hazardous constituents for ground-water monitoring. U.S. Environmental 

Protection Agency. Federal Register 52(131):25942-25953. 

EPA. 1987d. Final determination and intent to cancel and deny applications for registrations of pesticide 

products containing pentachlorophenol (including but not limited to its salts and esters) for non-wood 

uses. U.S. Environmental Protection Agency. Federal Register 52:2282-2293. 

*EPA. 1987e. Pentachlorophenol: Health advisory. Washington, DC: U.S. Environmental Protection 

Agency, Office of Drinking Water. 

EPA. 1987f. Maximum concentration of constituents for ground-water protection. U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 264.94. 

EPA. 1988a. Hazardous waste management system: Identification and listing of hazardous waste. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261. 

EPA. 1988b. Hazardous waste management system: Identification and listing of hazardous waste. U.S. 

Environmental Protection Agency. Federal Register 53(78):13382-13393. 
PENTACHLOROPHENOL 227 

9. REFERENCES 

EPA. 1988c. Contract Laboratory Program Statistical Database (CLPD). U.S. Environmental Protection
 

Agency.
 

EPA. 1988d. Toxic chemical release reporting: Community right-to-know. U.S. Environmental
 

Protection Agency. Code of Federal Regulations. 40 CFR 372.
 

EPA. 1988e. Toxic chemical release reporting: Community right-to-know. U.S. Environmental
 

Protection Agency. Federal Register 53(30):4500-4554.
 

EPA. 1988f. General pretreatment regulations for existing and new sources of pollution. U.S.
 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 403 Appendix B.
 

EPA. 1988g. General pretreatment regulations for existing and new sources of pollution. U.S.
 

Environmental Protection Agency. Federal Register 53(200):40610-40616.
 

EPA. 1989a. List of hazardous substances and reportable quantities. U.S. Environmental Protection
 

Agency. Federal Register 54(155):33426-33484.
 

*EPA. 1989b. Recognition and management of pesticide poisonings. 4th ed. Washington, DC: U.S. 

Environmental Protection Agency. EPA-540/9-88-001.
 

EPA. 1990a. Interim methods for development of inhalation reference concentrations. Research
 

Triangle Park, NC: U.S. Environmental Protection Agency. EPA/600/8-90/066A.
 

EPA. 1990b. Toxicity characteristics. U.S. Environmental Protection Agency. Code of Federal
 

Regulations. 40 CFR 261.24.
 

EPA. 1990c. Toxicity characteristics. U.S. Environmental Protection Agency. Federal Regulations
 

55(61):11863.
 

*EPA. 1991. Land disposal restrictions. U.S. Environmental Protection Agency. Federal Register
 

55(21):3864-3928.
 

*EPA. 1992. Land disposal restrictions. U.S. Environmental Protection Agency. Code of Federal
 

Regulations. 40 CFR 268.
 

EPA. 1996. Drinking Water Regulations and Health Advisories. Washington DC: U.S. Environmental
 

Protection Agency, Office of Water. EPA 822-B-96-002.
 

*EPA. 1997. Special report on environmental endocrine disruption: An effects assessment and analysis.
 

Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum. EPA/630/R-96/012.
 

EPA. 1998a. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.61. 

EPA. 1998b. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.50. 

EPA. 1998c. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.32. 

EPA. 1998d. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4. 

EPA. 1998e. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 116.4. 
PENTACHLOROPHENOL 228 

9. REFERENCES 

EPA. 1998f. U. S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 401.15.
 

EPA. 1998g. Rainbow Report. Washington, DC: U. S. Environmental Protection Agency, Office of
 

Pesticide Programs. EPA-738/R-98-002.
 

*EPA. 1998h. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4.
 

*EPA. 1999a. National Recommended Water Quality Criteria- Correction. U.S. Environmental
 

Protection Agency, Office of Water. EPA822-Z-99-001.
 

*EPA. 1999b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.61.
 

*EPA. 1999c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 372.65.
 

*EPA. 2000a. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.50.
 

*EPA. 2000b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.32.
 

*EPA. 2000c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 401.15.
 

*EPA. 2000d. Drinking Water Standards and Health Advisories. U.S. Environmental Protection
 

Agency, Office of Water. EPA-822-B-00-001.
 

*EPA. 2000e. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 116.4
 

*EPA. 2000f. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261.24.
 

*EPA. 2001a. Effluent guidelines and standards. Toxic pollutants. U.S. Environmental Protection
 

Agency. Code of Federal Regulations. 40 CFR 401.15. 

Http://ecfrback.access.gpo.gov/otcg...=BSECCT&SUBSET=SUBSET&FROM=1& ITEM=1. 

April 04, 2001.
 

*EPA. 2001b. General pretreatment regulations for existing and new sources of pollution. Pollutants
 

eligible for a removal credit. U.S. Environmental Protection Agency. Code of Federal Regulations. 40
 

CFR 403, Appendix G. Http://ecfrback.access.gpo.gov/otcgi/cfr/otfilter.... April 04, 2001.
 

*EPA. 2001c. Hazardous waste. Health based limits for exclusion of waste-derived-residue. U.S.
 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 266, Appendix VII. 

Http://ecfrback.access.gpo.gov/otcgi/cf...=BAPPCT&SUBSET =SUBSET& FROM=1&ITEM=1. 

April 04, 2001.
 

*EPA. 2001d. Health and environmental protection standards for uranium and thorium mill tailings. 

Listed constituents. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 192,
 

Appendix I. 

Http://ecfrback.access.gpo.gov/otcgi/cf...=BAPPCT&SUBSET=SUBSET&FROM=1&ITEM=1. 

April 04, 2001.
 

*EPA. 2001e. Identification and listing of hazardous waste. Hazardous constituent. U.S. Environmental
 

Protection Agency. Code of Federal Regulations. 40 CFR 261, Appendix VIII. 

Http://ecfrback.access.gpo.gov/otcgi/cfr/otfilter.... April 06, 2001.
 
PENTACHLOROPHENOL 229 

9. REFERENCES 

*EPA. 2001f. Identification and listing of hazardous waste. Comparable/Singes fuel exclusion. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261.38. 

Http://ecfrback.access.gpo.gov/otcgi/cfr/otfilter.... April 06, 2001. 

*EPA. 2001g. Identification and listing of hazardous waste. Toxicity characteristics. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261.24. 

Http://ecfrback.access.gpo.gov/otcg...=BSECCT&SUBSET=SUBSET& FROM=1&ITEM=1. 

April 06, 2001. 

*EPA. 2001h. National primary drinking water regulations. Maximum contaminant levels for organic
 

contaminants. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.61. 

Http://ecfrback.access.gpo.gov/otcg...=BSECCT&SUBSET=SUBSET& FROM=1&ITEM=1. 

April 06, 2001.
 

*EPA. 2001i. National primary drinking water regulations. Maximum contaminant level goals for 

organic contaminants. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 

141.50. Http://ecfrback.access.gpo.gov/otcg...=BSECCT&SUBSET=SUBSET& FROM=1&ITEM=1. 

April 06, 2001. 

*EPA. 2001j. National primary drinking water regulations. Public notification. U.S. Environmental
 

Protection Agency. Code of Federal Regulations. 40 CFR 141.32. 

Http://ecfrback.access.gpo.gov/otcg...=BSECCT&SUBSET=SUBSET& FROM=1&ITEM=1. 

April 06, 2001.
 

*EPA. 2001k. Reference air concentrations. U.S. Environmental Protection Agency. Code of Federal
 

Regulations. 40 CFR 266, Appendix IV. 

Http://ecfrback.access.gpo.gov/otcgi...=BAPPCT&SUBSET=SUBSET& FROM=1&ITEM=1. 

April 04, 2001.
 

*EPA. 2001l. Standards for owners and operators of hazardous waste treatment, storage, and disposal
 

facilities. Groundwater monitoring list. U.S. Environmental Protection Agency. Code of Federal
 

Regulations. 40 CFR 264, Appendix IX. Http://ecfrback.access.gpo.gov/otcgi/cfr/otfilter.... 

April 04, 2001.
 

*EPA. 2001m. Superfund. Designation of hazardous substance. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 302.4. Http://ecfrback.access.gpo.gov/otcgi/cfr/otfil.... 

April 04, 2001. 

*EPA. 2001n. Toxic chemical release reporting: Community right-to-know. Chemicals and chemical 

categories to which this part applies. U.S. Environmental Protection Agency. Code of Federal 

Regulations. 40 CFR 372.65. Http://ecfrback.access.gpo.gov/otcgi...=BSECCT&SUBSET=SUBSET& 

FROM=1&ITEM=1. April 06, 2001. 

*EPA. 2001o. Toxic criteria for those states not complying with Clean Water Act section 303(c)(2)(B). 

U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 131.36. 

Http://ecfrback.access.gpo.gov/otcgi/cfr/otfil.... April 06, 2001. 

*EPA. 2001p. Water programs. Designation of hazardous substances. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 116.4. Http://ecfrback.access.gpo.gov/otcgi/cf...= 

BAPPCT&SUBSET =SUBSET& FROM=1&ITEM=1. April 04, 2001. 
PENTACHLOROPHENOL 230 

9. REFERENCES 

*EPA. 2001q. Water programs. Determination of reportable quantities of hazardous substances. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 117.3. 

Http://ecfrback.access.gpo.gov/otcgi/cf...= BSECCT&SUBSET =SUBSET& FROM=1&ITEM=1. 

April 04, 2001. 

*Eriksson M, Hardell L, Adami HO. 1990. Exposure to dioxins as a risk factor for soft tissue sarcoma: 

A population-based case-control study. J Natl Cancer Inst 82:486-490. 

*Eriksson M, Hardell L, Berg NO, et al. 1981. Soft-tissue sarcomas and exposure to chemical 

substances: A case-referent study. Br J Ind Med 38:27-33. 

*Ervin HE, McGinnis GD. 1980. Analysis of pentachlorophenol in waste water using high-performance 

liquid chromatography. J Chromatogr 190:203-207. 

Exon JH. 1984. A review of chlorinated phenols. Vet Hum Toxicol 26:508-520. 

*Exon JM, Koller LD. 1982. Effects of transplacental exposure to chlorinated phenols. Environ Health 

Perspect 46:137-140. 

Exon JM, Koller LD. 1983. Effects of chlorinated phenols on immunity in rats. Int J Immunopharmacol 

5:131-136. 

Faber F, Egli T, Harder W. 1993. Transient repression of the synthesis of Hmpf and aspartame 

transcarbamoylase in escherichia coli K12 as a response to pollutant stress. FEMS Microbiol Lett 

111:189-196. 

*Fahrig R. 1974. Comparative mutagenicity studies with pesticides. IARC Sci Publ 10:161-181. 

*Fahrig R, Steinkamp-Zucht A. 1996. Co-recombinogenic and anti-mutagenic effects of 

diethylhexylphthalate, inactiveness of pentachlorophenol in the spot test with mice. Mutat Res 354:59­

67. 

*Fahrig R, Nilsson C, Rappe C. 1978. Genetic activity of chlorophenols and chlorophenol impurities. 

In: Rao KR, ed. Pentachlorophenol: Chemistry, pharmacology and environmental toxicology. Vol. 

325-338. New York, NY: Plenum Press. 

*Farrington DS, Munday JW. 1976. Determination of trace amounts of chlorophenols by gas-liquid 

chromatography. Analyst 101:639-643. 

FDA. 1977a. Compliance program evaluation TY 9174 total diet studies. Washington, DC: U.S. Food 

and Drug Administration, Bureau of Foods. 

FDA. 1977b. Indirect food additives: Adhesive coatings and components; adhesives. U.S. Food and 

Drug Administration. Code of Federal Regulations. 21 CFR 175.105. Federal Register 42:14539. 

FDA. 1977c. Indirect food additives: Adhesives coatings and components. Food and Drug 

Administration. Federal Register 42(50):14434-14554. 

*FDA. 1989. Food and Drug Administration program residues in foods - 1988. J Assoc Off Anal Chem 

72:133A-152A. 
PENTACHLOROPHENOL 231 

9. REFERENCES 

FDA. 1998a. Food and Drug Administration. Code of Federal Regulations. 21 CFR 176.200. 

*FDA. 1998b. Food and Drug Administration. Code of Federal Regulations. 21 CFR 181.30. 

FDA. 1998c. Food and Drug Administration. Code of Federal Regulations. 21 CFR 178.3120. 

FDA. 1998d. Food and Drug Administration. Code of Federal Regulations. 21 CFR 177.1210. 

FDA. 1998e. Food and Drug Administration. Code of Federal Regulations. 21 CFR 165.110. 

FDA. 1998f. Food and Drug Administration. Code of Federal Regulations. 21 CFR 175.105. 

FDA. 1998g. Food and Drug Administration. Code of Federal Regulations. 21 CFR 176.210. 

*FDA. 2000a. Food and Drug Administration. Code of Federal Regulations. 21 CFR 165.110. 

*FDA. 2000b. Food and Drug Administration. Code of Federal Regulations. 21 CFR 175.105. 

*FDA. 2000c. Indirect food additives: Adjuvants, production aids, and sanitizers. Animal glue. U.S.
 

Food and Drug Administration. Code of Federal Regulations. 21 CFR 178.3120 (d)(3). 

Http://frwebgate.access.gpo.gov/ cgi...78&SECTION=3120&YEAR=2000&TYPE=TEXT. 

April 04, 2001.
 

*FDA. 2000d. Indirect food additives: Adjuvants, production aids, and sanitizers. Preservatives in
 

wood. U.S. Food and Drug Administration. Code of Federal Regulations. 21 CFR 178.3800 (b). 

Http://frwebgate.access.gpo.gov/ cgi...78&SECTION=3800&YEAR=2000&TYPE=TEXT. 

April 04, 2001.
 

*FDA. 2000e. Indirect food additives: Polymers. Rubber articles intended for repeated use. U.S. Food
 

and Drug Administration. Code of Federal Regulations. 21 CFR 177.2600 (c)(4). 

Http://frwebgate.access.gpo.gov/ cgi...77&SECTION=2600&YEAR=2000&TYPE=TEXT. 

April 04, 2001.
 

*FDA. 2000f. Indirect food additives: Polymers. Textiles and textile fibers. U.S. Food and Drug
 

Administration. Code of Federal Regulations. 21 CFR 177.2800 (d)(5). 

Http://frwebgate.access.gpo.gov/ cgi...77&SECTION=2800&YEAR=2000&TYPE=TEXT. 

April 04, 2001.
 

FEDRIP. 1992. Federal Research in Progress: Pentachlorophenol. Dialog Information Services, Inc. 

Palo Alto, CA. February 1992.
 

*FEDRIP. 1999. Federal Research in Progress: Pentachlorophenol. Dialog Information Services, Inc. 

Palo Alto, CA. May 1999.
 

Fent K, Hunn J. 1996. Cytotoxicity of organic environmental chemicals to fish liver cells (PLHC-1). 

Mar Environ Res 42:377-382.
 

*Ferreira AG, Vieira DN, Marques EP, et al. 1997. Occupational exposure to pentachlorophenol: The
 

Portugese situation. Ann NY Acad Sci 837:291-299.
 
PENTACHLOROPHENOL 232 

9. REFERENCES 

Ferro AM, Sims RC, Bugbee B. 1994. Hycrest crested wheatgrass accelerates the degradation of 

pentachlorophenol in soil. J Environ Qual 23:272-279. 

Fijalkowska S, Lisowska K, Dlugonski J. 1998. Bacterial elimination of polycyclic aromatic 

hydrocarbons and heavy metals. J Basic Microbiol 38:361-369. 

*Fingerhut MA, Halperin WE, Honchar PA, et al. 1984. An evaluation of reports of dioxin exposure and 

soft tissue sarcoma pathology among chemical workers in the United States. Scand J Work Environ 

Health 10:299-303. 

*Fleischer M, Meiss R, Robenek H, et al. 1980. Ultrastructural morphometric investigations on rat liver 

of young and adult rats after treatment with technical pentachlorophenol (PCP). Arch Toxicol 

44:243-257. 

Flouriot G, Pakdel F, Ducouret B, et al. 1995. Influence of xenobiotics on rainbow trout liver estrogen 

receptor and vitellogenin gene expression. J Mol Endocrinol 15:143-151. 

*Fomon SJ. 1966. Body composition of the infant. Part I: The male “reference infant”. In: Falkner F, 

ed. Human Development. Philadelphia, PA: WB Saunders, 239-246. 

*Fomon SJ, Haschke F, Ziegler EE, et al. 1982. Body composition of reference children from birth to 

age 10 years. Am J Clin Nutr 35:1169-1175. 

Forsell JH, Shull LR, Kateley JR. 1981. Subchronic administration of technical pentachlorophenol in 

lactating dairy cattle: Immunologic evaluation. J Toxicol Environ Health 8:543-558. 

*Fort DJ, Stover EL. 1997. Development of short-term, whole-embryo assays to evaluation detrimental 

effects on amphibian limb development and metamorphosis using xenopus laevis. In: Dwyer FJ, Doane 

TR, Hinman M, eds. Environmental toxicology and risk assessment: Modeling and risk assessment. 

Philadelphia, PA: ASTM, 376-390. 

Fossi MC. 1998. Biomarkers as diagnostic and prognostic tools for wildlife risk assessment: Integrating 

endocrine-disrupting chemicals. Toxicol Ind Health 14:291-309. 

*Fountaine JE, Joshipura PB, Keliher PN. 1975. Some observations regarding pentachlorophenol levels 

in Haverford Township, Pennsylvania. Water Res 10:185-188. 

*Franco G, Fonte R, Tempini G, et al. 1986. Serum bile acid concentrations as a liver function test in 

workers occupationally exposed to organic solvents. Int Arch Occup Environ Health 58:157-164. 

Frankovic L, Khan MAQ, Ghais SMA. 1995. Metabolism of hexachlorobenzene in the fry of Steelhead 

trout, Salmo gairdneri (oncorhynchus mykiss). Arch Environ Contam Toxicol 28:209-214. 

Fries GF, Feil VJ, Davison KL. 1996. Evidence that pentachlorophenol-treated wood is an important 

source of dioxin residues in beef. J Anim Sci 74(Suppl. 1):209. 

*Frisbie AAJ, Nies L. 1997. Aerobic and anaerobic biodegradation of aged pentachlorophenol by 

indigenous microorganisms. Biorem J 1:65-75. 

FSTRAC. 1988. Summary of state and federal drinking water standards and guidelines. Federal-State 

Toxicology and Regulatory Alliance Committee. 
PENTACHLOROPHENOL 233 

9. REFERENCES 

*FSTRAC. 1999. Federal-State Toxicology and Risk Analysis Committee. Office of Water. U. S. 

Environmental Protection Agency. Http://www.epa.gov/ostwater/fstrac/states.html. May 20, 1999. 

Fullerton PM. Toxic chemicals and peripheral neuropathy: Clinical and epidemiological features. Proc 

R Soc Med 62:201-204. 

*Gab S, Nitz H, Korte F. 1975. Photomineralisation of certain aromatic xenobiotica. Chemosphere 

4:251-257. 

*Galil NI, Novak JT. 1995. Pentachlorophenol-induced release of soil organics and colloids. Water Res 

29:1533-1540. 

Gandy J, Millner GC, Bates HK, et al. 1990. Effects of selected chemicals on the glutathione status in 

the male reproductive system of rats. J Toxicol Environ Health 29:45-57. 

Ganjidouse H, Tatsumi K, Wada S, et al. 1996. Role of peroxidase and chitosan in removing 

chlorophenols from aqueous solution. Water Sci Technol 34:151-159. 

Gates M, Fredrickson H, Gunnison D, et al. 1997. Bioremediation of high pH soil from a wood 

treatment facility from El Dorado, AR. Abstr Annu Meet Am Soc Microbiol 97:477. 

Gates VL, Tjeerdema RS. 1993. Disposition and biotransformation of pentachlorophenol in the striped 

bass (morone saxatilis). Pestic Biochem Physiol 46:161-170. 

*Gebefugi I, Korte F. 1983. Pentachlorophenol contamination of human milk samples. Chemosphere 

12:1055-1060. 

*Gebefugi I, Parlar H, Korte F. 1976. [Contribution of ecological chemistry CXXVI: Short note on the 

analytical determination of pentachlorophenol in closed areas]. Chemosphere 5:227-230. (German) 

Gebefugi I, Parlar H, Korte F. 1979. Occurrence of PCP in enclosed environments. Ecotoxicol Environ 

Safety 3:269-300. 

Gerhard I. 1993. Reproductive risks of heavy metals and pesticide in women. In: Reproduction 

Toxicology, 167-183. 

Gerhard I. 1995. [Environment and reproduction.] Arch Gynecol Obstet 257:239-246. (German) 

*Gerhard I, Daniel V, Link S, et al. 1998. Chlorinated hydrocarbons in women with repeated 

miscarriages. Environ Health Perspect 106:675-681. 

*Gerhard I, Derner M, Runnebaum B. 1991. Prolonged exposure to wood preservatives induces 

endocrine and immunologic disorders in women [Letter]. Am J Obstet Gynecol 165:487-488. 

Gerhard I, Eckrich W, Runnebaum B. 1993. [Toxic substances and infertility: Organic solvents, 

pesticides.] Geburtshilfe Frauenheilkd 53:147-160. (German) 

*Gerhard I, Frick A Monga B, et al. 1999. Pentachlorophenol exposure in women with gynecological 

and endocrine dysfunction. Environ Res 80(Section A):383-388. 
PENTACHLOROPHENOL 234 

9. REFERENCES 

*Geyer HJ, Scheunert I, Korte F. 1987. Distribution and bioconcentration potential of the environmental 

chemical pentachlorophenol (PCP) in different tissue of humans. Chemosphere 16:887-899. 

*Giam CS, Trujillo DA, Kira S, et al. 1980. Simplified monitoring procedures for benzo(a)pyrene, 

hexachlorobenzene and pentachlorophenol in water. Bull Environ Contam Toxicol 25:824-827. 

*Gilbert FI Jr, Minn CE, Duncan RC, et al. 1990. Effects of pentachlorophenol and other chemical 

preservatives on the health of wood-treating workers in Hawaii. Arch Environ Contam Toxicol 19:603­

609. 

*Giwercman A, Carlsen E, Keiding N, et al. 1993. Evidence for increasing incidence of abnormalities of 

the human testis: A review. Environ Health Perspect Suppl 101:65-71. 

*Gluth G, Freitage D, Hanke W, et al. 1985. Accumulation of pollutants in fish. Comp Biochem Physiol 

81:273-277. 

Goldstein JA, Friesen M, Linder RE, et al. 1977. Effects of pentachlorophenol on hepatic 

drug-metabolizing enzymes and porphyria related to contamination with chlorinated dibenzo-p-dioxins 

and dibenzofurans. Biochem Pharmacol 26:1549-1577. 

*Gómez-Catalán J, To-Figueras J, Planas J, et al. 1987. Pentachlorophenol and hexachlorobenzene in 

serum and urine of the population of Barcelona. Human Toxicol 6:397-400. 

*Gómez-Catalán J, To-Figueras J, Rodamilans M, et al. 1991. Transport of organochlorine residues in 

the rat and human blood. Arch Environ Contam Toxicol 20:61-66. 

*Goodman AG, Rall TW, Nies AS, et al. 1990. Goodman & Gilman’s the pharmacological basis of 

therapeutics. 8th ed. New York, NY: Pergamon Press, 1635. 

Goodrich-Mahoney JW, Murarka IP, Holcombe LJ, et al. 1993. Pentachlorophenol-treated wood poles 

and crossarms: Toxicity characteristics leaching procedure (TCLP) results. Environ Int 19:535-542. 

*Gordon D. 1956. How dangerous is pentachlorophenol? Med J Austr 43:485-488. 

*Gould E, Franfurt M, Westlind-Danielsson A, et al. 1990. Developing forebrain astrocytes are sensitive 

to thyroid hormone. Glia 3:283-292.

 *Gray RE, Gilliland RD, Smith EE, et al. 1985. Pentachlorophenol intoxication: Report of a fatal case, 

with comments on the clinical course and pathologic anatomy. Arch Environ Health 40:161-164. 

*Greene MH, Brinton LA, Fraumeni JF, et al. 1978. Familial and sporadic Hodgkin's disease associated 

with occupational wood exposure. Lancet 2:626-627. 

*Greichus YA, Libal GW, Johnson DD. 1979. Diagnosis and physiologic effects of pentachlorophenols 

on young pigs: Part I. Effects of purified pentachlorophenol. Bull Environ Contam Toxicol 23:418-422. 

*Grimm H-G, Schellman B, Schaller K-H, et al. 1981. [Pentachlorophenol concentrations in tissues and 

bodyfluids of normal persons.] Zentrabl Bakteriol Mikrobiol Hyg [B] 174:77-90. (German) 

Gschwendt G, Huber W. 1996. [Therapeutic approaches to the detoxification of selected environmental 

toxins]. Forum Staedte Hyg 47:225-230. (German) 
PENTACHLOROPHENOL 235 

9. REFERENCES 

Gu Y, Korus RA. 1995. Effects of p-cresol and chlorophenols on pentachlorophenol biodegradation. 

Biotechnol Bioeng 47:470-475. 

Gulden M. 1993. In vitro toxicity screening using cultured rat skeletal muscle cells. I. Surfactants and 

mitochondrial poisons. Toxicol in Vitro 7:25-34. 

Gulden M, Seibert H. 1996. Cytotoxic and non-cytotoxic effects of the MEIC reference chemicals on 

spontaneously contracting primary cultured rat skeletal muscle cells. Toxicol in Vitro 10:395-406. 

*Gunderson EL. 1988. FDA total diet study, April 1982–April 1984: Dietary intakes of pesticides, 

selected elements, and other chemicals. J Assoc Off Anal Chem 71:1200-1209. 

*Gunderson EL. 1995a. FDA total diet study, July 1986-August 1991, dietary intake on pesticides, 

selected elements, and other chemicals. J AOAC Int 78:1353-1363. 

*Gunderson EL. 1995b. Dietary intakes of pesticides, selected elements, and other chemicals: FDA total 

diet study, June 1984-April 1986. J AOAC Int 78:910-921. 

Gunter EW. 1997. Biological and environmental specimen banking at the Centers for Disease Control 

and Prevention. Chemosphere 34:1945-1953. 

*Guzelian PS, Henry CJ, Olin SS. 1992. Similarities and differences between children and adults: 

Implications for risk assessment. Washington, DC: International Life Sciences Institute Press. 

*Haley TJ. 1977. Human poisoning with pentachlorophenol and its treatment. Ecotoxicol Environ Saf 

1:343-347. 

*Hall LT, Van Emon J, Lopez-Avila V. 1992. Development of immunochemical personal exposure 

monitors for pentachlorophenol. Proc SPIE-Int Soc Opt Eng, Environ Process Monit Technol 1637:189­

195. 

*Haque A, Ebing W. 1988. Uptake and accumulation of pentachlorophenol and sodium pentachlorophenate by earthworms from water and soil. Sci Total Environ 68:113-125. 

*Hardell L, Sandstrom A. 1979. Case-control study: Soft tissue sarcomas and exposure to 

phenoxyacetic acids or chlorphenols. Br J Cancer 39:711-717. 

*Hardell L, Eriksson M, Degerman A. 1994. Exposure to phenoxyacetic acids, chlorphenols, or organic 

solvents in relation to histopathology, stage, and anatomical localization of non-Hodgkin's lymphoma. 

Cancer Res 54:2386-2389. 

*Hardell L, Erikksson M, Degereman A. 1995. Meta-analysis of four Swedish case-control studies on 

exposure to pesticides as risk-factor for soft-tissue sarcoma including the relation to tumour localization 

and histopathological type. Int J Oncol 6:847-851. 

*Hassan AB, Hiseligmann H, Bassan HM. 1985. Intravascular haemolysis induced by 

pentachlorophenol. Br Med J 291:21-22. 

*Hattemen-Frey HA, Travis CC. 1989. Pentachlorophenol: Environmental partitioning and human 

exposure. Arch Environ Contam Toxicol 18:482-489. 
PENTACHLOROPHENOL 236 

9. REFERENCES 

Hautala E, Rekila R, Tarhanen J, et al. 1995. Deposition of motor vehicle emissions and winter
 

maintenance along roadside assessed by snow analysis. Environ Pollut 87:45-49.
 

*Hayes WJ. 1982. Pesticides studied in man. Baltimore, MD: Waverly Press, 477.
 

HazDat. 1993. Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA. 

HazDat. 1999. Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA. 

*HazDat. 2001. Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA. 

Http://www.atsdr.cdc.gov/gsql/sitecontam.script. February 07, 2001.
 

*Hebert VR, Miller GC. 1990. Depth dependence of direct and indirect photolysis on soil surfaces. J
 

Agric Food Chem 38:913-918.
 

*Heeb NV, Dolezal TB, Mattrel P, et al. 1995. Distribution of halogenated phenols including mixed
 

brominated and chlorinated phenols in municipal waste incineration flue gas. Chemosphere 31:3033­

3041.
 

Heida H, Van Der Berg M, Olie K. 1995. Risk assessment approach to evaluating potential remedial 

actions at the Diemerzeedijk hazardous waste site. Haz Waste Haz Mater 12:1-14. 

Heikes DL. 1979. FDA finds PCP in peanut butter in market basket study. Food Chem News 21:14. 

Helmstetter MF, Alden RW. 1995. Toxic responses of Japanese medaka (oryzias latipes) eggs following 

topical and immersion exposures to pentachlorophenol. Aquat Toxicol 32:15-29. 

*Helrich, K. 1990. Official methods of analysis of the Association of Official Analytical Chemists. 

Arlington, VA: Association of Official Analytical Chemists, Inc., 308-309.
 

*Hendriksen HV, Larsen S, Ahring BK. 1991. Anaerobic degradation of PCP and phenol in fixed-film
 

reactors: The influence of an additional substrate. Water Sci Technol 24:431-436.
 

Herr C, Harpel S, Petereit-Wolf G, et al. 1997. [Pentachlorophenol in a weekend cottage.] Zentralbl
 

Hyg Umweltmed 199:435. (German)
 

*Hertzman C, Teschke K, Ostry A, et al. 1997. Mortality and cancer incidence among sawmill workers
 

exposed to chlorophenate wood preservatives. Am J Public Health 87:71-79.
 

Heussen GAH, Schefferlie GJ, Talsma MJG, et al. 1993. Effects on thyroid hormone metabolism and
 

depletion of lung vitamin A in rats by airborne particulate matter. J Toxicol Environ Health 38:419-434.
 

Hiatt CW. 1960. The action of sunlight on sodium pentachlorophenate. Am J Tropical Med Hyg
 

19:527-531.
 

*Hill RH Jr, Head SL, Baker S, et al. 1995. Pesticide residues in urine of adults living in United States: 

Reference range concentrations. Environ Res 71:99-108.
 

*Hill RH Jr, To T, Holler JS, et al. 1989. Residues of chlorinated phenols and phenoxy acid herbicides
 

in the urine of Arkansas children. Arch Environ Contam Toxicol 18:469-474.
 
PENTACHLOROPHENOL 237 

9. REFERENCES 

Hiraku Y, Oikawa S, Kawanishi S. 1995. [Oxidative DNA damage induced by interaction of metals and 

carcinogenic organic compounds.] Kankyo Hen'igen Kenkyu 17:75-85. (Japanese) 

*Hoak RD. 1957. The causes of tastes and odors in drinking water. Water Sewage W:104, 243-247. 

*Hoben HJ, Ching SA, Casarett LJ. 1976a. A study of the inhalation of pentachlorophenol by rat: Part 

II. A new inhalation exposure system for high doses in short exposure time. Bull Environ Contam 

Toxicol 15:86-92. 

*Hoben HJ, Ching SA, Casarett LJ. 1976b. A study of inhalation of pentachlorophenol by rats: Part III. 

Inhalation toxicity study. Bull Environ Contam Toxicol 15:463-465. 

*Hoben HJ, Ching SA, Casarett LJ. 1976c. A study of inhalation of pentachlorophenol by rats: Part IV. 

Distribution and excretion of inhaled pentachlorophenol. Bull Environ Contam Toxicol 15:466-474. 

*Hoben HJ, Ching SA, Young RA, et al. 1976d. A study of the inhalation of pentachlorophenol by rats: 

Part V. A protein binding study of pentachlorophenol. Bull Environ Contam Toxicol 16:225-232. 

*Hoel DG, Davis DL, Miller AB, et al. 1992. Trends in cancer mortality in 15 industrialized countries, 

1969-1986. J Natl Cancer Inst 84:313-320. 

*Holler JS, Fast DM, Hill RH Jr, et al. 1989. Qualification of selected herbicides and chlorinated 

phenols in urine by using gas chromatography/mass spectrometry/mass spectrometry. J Anal Toxicol 

13:152-157. 

*Holsapple MP, McNerney PJ, McCay JA. 1987. Effects of pentachlorophenol on the in vitro and in 

vivo antibody response. J Toxicol Environ Health 20:229-239. 

*Hoppin JA, Tolbert PE, Herrick RF, et al. 1998. Occupational chlorophenol exposure and soft tissue 

sarcoma risk among men aged 30-60 years. Am J Epidemiol 148:693-703. 

*Horstman SW, Rossner A, Kalman DA, et al. 1989. Penetration of pentachlorophenol and 

tetrachlorophenol through human skin. J Environ Sci Health A24:229-242. 

*Hosenfeld JM, Moody LA, Gabriel MJ, et al. 1986. Pentachlorophenol in log homes: A study of 

environmental and clinical aspects. U.S. Environmental Protection Agency Report. Washington, DC: 

Office of Toxic Substances. EPA-560/5-87-001. 

Houx NWH, Aben WJM. 1993. Bioavailability of pollutants to soil organisms via the soil solution. Sci 

Total Environ (Suppl 1993):387-395. 

*Hryhorczuk DO, Wallace WH, Persky V, et al. 1998. A morbidity study of former pentachlorophenolproduction workers. Environ Health Perspect 107:401-408. 

*HSDB. 1992. Hazardous Substances Data Bank. Bethesda, MD: National Library of Medicine, 

National Toxicology Information Program. January 23, 1992. 

HSDB. 1999a. Pentachlorophenol, Sodium Salt. Hazardous Substances Data Bank. Bethesda, MD: 

National Library of Medicine, National Toxicology Information Program. April 20, 1999. 
PENTACHLOROPHENOL 238 

9. REFERENCES 

*HSDB. 1999b. Pentachlorophenol. Hazardous Substances Data Bank. Bethesda, MD: National 

Library of Medicine, National Toxicology Information Program. 

Http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. April 16, 1999. 

*HSDB. 2001. Pentachlorophenol. Hazardous Substance Data Bank. Bethesda, MD: National Library 

of Medicine, National Toxicology Information Program. 

Http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. February 2, 2001. 

Hughes BJ, Forsell JH, Sleight SD, et al. 1985. Assessment of pentachlorophenol toxicity in newborn 

calves: Clinicopathology and tissue residues. J Anim Sci 61:1587-1603. 

*IARC. 1979. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: 

Some halogenated hydrocarbons. Lyon, France: World Health Organization, International Agency for 

Research on Cancer. Vol. 20:303-325. 

IARC. 1982. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: 

Chemical, industrial processes and industries associated with cancer in humans. Supplement 4. Lyon, 

France: World Health Organization, International Agency for Research on Cancer, 205-206. 

IARC. 1991. IARC monographs for the evaluation of the carcinogenic risk of chemicals to humans. 

Lyon, France: World Health Organization, International Agency for Research on Cancer. 

*IARC. 1999. IARC monographs for the evaluation of the carcinogenic risk of chemicals to humans: 

Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. Vol. 71. Lyon, France: 

World Health Organization, International Agency for Research on Cancer. 

Http://193.51.164.11/ntdocs/monographs/Vol71/028-polychloroph.html. May 05, 1999. 

*IARC. 2001. IARC monographs for the evaluation of the carcinogenic risk of chemicals to humans: 

Polychlorophenols and their sodium salts. (Group 2B). Vol. 71. Lyon, France: World Health 

Organization, International Agency for Research on Cancer. 

Http://193.51.164.11/htdocs/Monographs/Vol71/028-polychloroph.html. February 07, 2001. 

*Ide A, Niki Y, Watanabe I, et al. 1972. Decomposition of pentachlorophenol in paddy soil. Agric Biol 

Chem 36:1937-1944. 

Igisu H. 1993a. [Binding of toxic substances and suppression of their toxicities by albumin—studies on 

psychosine and pentachlorophenol.] J Uoeh 15:217-225. (Japanese) 

Igisu H. 1993b. Haemolysis of human erythrocytes by pentachlorophenol and its suppression by 

albumin. Br J Ind Med 50:378-379. 

Igisu H, Matsumura H, Matsuoka M. 1994. [Acetylcholinesterase in the erythrocyte membrane.] J Uoeh 

16:253-262. (Japanese) 

*Ingerslev F, Baun A, Nyholm N. 1998. Aquatic biodegradation behavior of pentachlorophenol assessed 

through a battery of shake flask die-away tests. Environ Toxicol Chem 17:1712-1719. 

*Ingram LLJ, McGinnis GD, Gjovik LR. 1986. Studies on the vaporization of pentachlorophenol from 

treated wood. Arch Environ Contam Toxicol 15:669-676. 
PENTACHLOROPHENOL 239 

9. REFERENCES 

*Innes J, Ulland B, Valerio M, et al. 1969. Bioassay of pesticides and industrial chemicals for 

tumorigenicity in mice: A preliminary note. J Natl Cancer Inst 42:1101-1114. 

IRIS. 1992. Integrated Risk Information Systems. Cincinnati, OH: U.S. Environmental Protection 

Agency, Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office. 

*IRIS. 1999. Integrated Risk Information Systems. Cincinnati, OH: U.S. Environmental Protection 

Agency, Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office. 

*IRIS. 2001. Integrated Risk Information Systems. Cincinnati, OH: U.S. Environmental Protection 

Agency, Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office. 

*Jackson DR, Bisson DL. 1990. Mobility of polychlorinated aromatic compounds in soils contaminated 

with wood-preserving oil. J Air Waste Manage Assoc 40:1129-1133. 

*Jagels R. 1985. Health hazards of natural and introduced chemical compounds of boat building woods. 

Am J Ind Med 8:241-251. 

*Jakobson K, Yllner S. 1971. Metabolism of 14C-pentachlorophenol in the mouse. Acta Pharmacol 

Toxicol 19:513-524. 

Jansson K, Jansson V. 1986. Inability of chlorophenols to induce 6-thioguanine-resistant mutants in 

V79 Chinese hamster cells. Mutat Res 171:165-168. 

*Jansson K, Jansson V. 1991. Induction of mutation in V79 Chinese hamster cells by tetrachlorohydroquinone, a metabolite of pentachlorophenol. Mutat Res 260:83-87. 

Jansson K, Jansson V. 1992. Induction of micronuclei in V79 Chinese hamster cells by 

tetrachlorohydroquinone, a metabolite of pentachlorophenol. Mutat Res 279:205-208. 

Jansson K, Jansson V. 1993. The toxicity of chlorophenols in V79 Chinese hamster cells. Toxicol Lett 

69:289-294. 

*Jäppinen P, Pukkala E, Tola S. 1989. Cancer incidence of workers in a Finnish sawmill. Scand J Work 

Environ Health 15:18-23. 

*Jekat FW, Meisel ML, Eckard R, et al. 1994. Effects of pentachlorophenol (PCP) on the pituitary and 

thyroidal hormone regulation in the rat. Toxicol Lett 71:9-25. 

Jeong YC, Yoon BS, Lee YS, et al. 1997. [Covalent interactions of reactive pentachlorophenol 

metabolites with cellular macromolecules.] Korean Journal of Toxicology 13:257-263. (Korean) 

*Johanson CE. 1980. Permeability and vascularity of the developing brain: Cerebellum vs cerebral 

cortex. Brain Res 190:3-16. 

*Johnson CC, Feingold M, Tilley B. 1990. A meta-analysis of exposure to phenoxy acid herbicides and 

chlorophenols in relation to risk of soft tissue sarcoma. Int Arch Occup Environ Health 62:513-520. 

*Johnson RD, Manske DD. 1977. Pesticides in food and feed: Pesticide and other chemical residues in 

total diet samples (XI). Pest Monit J 11:116-131. 
PENTACHLOROPHENOL 240 

9. REFERENCES 

*Johnson RL, Gehring PJ, Kociba RJ, et al. 1973. Chlorinated dibenzodioxins and pentachlorophenol. 

Environ Health Perspect 5:171-175. 

*Jones RD, Winter DP, Cooper AJ. 1986. Absorption study of pentachlorophenol in persons working 

with wood preservatives. Hum Toxicol 5:189-194. 

Jorens PG, Schepens PJC. 1993. Human pentachlorophenol poisoning. Hum Exp Toxicol 12:479-495. 

*Jorens PG, Janssens JJ, van Tichelen WI, et al. 1991. Pentachlorophenol concentrations in human 

cerebrospinal fluid. Neurotoxicology 12:1-7. 

*Juhl U, Witte I, Butte W. 1985. Metabolism of pentachlorophenol to tetrachlorohydroquinone by 

human liver homogenate. Bull Environ Contam Toxicol 35:596-601. 

Juhler RK, Lauriidsen MG, Christensen MR, et al. 1999. Pesticides residues in selected food 

commodities. Results from the Danish National Pesticide Monitoring Program 1995-1996. J AOAC Intl 

82:337. 

Kadry AM, Skowronski GA, Abdel-Rahman MS. 1995. Evaluation of the use of uncertainty factors in 

deriving RfDs for some chlorinated compounds. J Toxicol Environ Health 45:83-95. 

*Kalman DA. 1984. Determination of pentachlorophenol and 2,3,4,6-tetrachlorophenol in human urine 

by high resolution gas chromatography. J Chromatogr Sci 22:452-455. 

Kalman DA, Horstman SW. 1983. Persistence of tetrachlorophenol and pentachlorophenol in exposed 

woodworkers. J Toxicol Clin Toxicol 20:343-352. 

Kammenga JE, Van Koert PHG, Koeman JH, et al. 1997. Fitness consequences of toxic stress evaluated 

within the context of phenotypic plasticity. Ecol Appl 7:726-734. 

*Kaphalia BS. 1991. Fatty acid conjugates of chlorinated phenols and their high-performance liquid 

chromatographic analysis. J Chromatogr 537:85-92. 

*Karasek FW, Dickson LC. 1987. Model studies of polychlorinated dibenzo-p-dioxin formation during 

municipal refuse incineration. Science 237:754-756. 

Karmaus W, Wolf N. 1995. Reduced birthweight and length in the offspring of females exposed to 

PCDFs, PCP, and lindane. Environ Health Perspect 103:1120-1125. 

*Kaufman DD. 1978. Degradation of pentachlorophenol in soil, and by soil organisms. In: Rao KR, ed. 

Pentachlorophenol: Chemistry, pharmacology, and environmental toxicology. New York, NY: Plenum 

Press, 27-39. 

Kelce WR, Gray LE, Wilson EM. 1998. Antiandrogens as environmental endocrine disruptors. Reprod 

Fertil Develop 10:105-111. 

*Kerkvliet NI, Baecher-Steppan L, Schmitz JA. 1982. Immunotoxicity of pentachlorophenol (PCP): 

Increased susceptibility to tumor growth in adult mice fed technical PCP-contaminated diets. Toxicol 

Appl Pharmacol 62:55-64. 
PENTACHLOROPHENOL 241 

9. REFERENCES 

*Kerkvliet NI, Brauner JA, Baecher-Steppan L. 1985b. Effects of dietary technical pentachlorophenol 

exposure on T-cell, macrophage and natural killer cell activity in C57BL/6 mice. Int J Immunopharmacol 

7:239-247. 

*Kerkvliet NI, Brauner JA, Matlock JP. 1985a. Humoral immunotoxicity of polychlorinated diphenyl 

ethers, phenoxyphenols, dioxins and furans present as contaminants of technical grade pentachlorophenol. 

Toxicology 36:307-324. 

*Kilzer L, Scheunert I, Geyer H, et al. 1979. Laboratory screening of the volatilization rates of organic 

chemical from water and soil. Chemosphere 10:751-761. 

*Kimbrough RD, Linder RE. 1978. The effect of technical and purified pentachlorophenol on the rat 

liver. Toxicol Appl Pharmacol 46:151-162. 

Kimura T, Kuroki K, Doi K. 1998. Dermatotoxicity of agricultural chemicals in the dorsal skin of 

hairless dogs. Toxicol Pathol 26:442-447. 

Kinzell JH, Ames NK, Sleight SD, et al. 1981. Subchronic administration of technical pentachlorophenol to lactating dairy cattle: Performance, general health, and pathologic changes. J Dairy Sci 

64:42-51. 

Kirsch EJ, Etzel JE. 1973. Microbial decomposition of pentachlorophenol. J Water Pollut Control Fed 

45:359-364. 

*Klemmer HW. 1972. Human health and pesticides: Community pesticide studies. Res Rev 41:55-63. 

*Klemmer HW, Wong L, Sato MM, et al. 1980. Clinical findings in workers exposed to pentachlorophenol. Arch Environ Contam Toxicol 9:715-725. 

Klotz DM, Arnold SF, McLachlan JA. 1997. Inhibition of 17 beta-estradiol and progesterone activity in 

human breast and endometrial cancer cells by carbamate insecticides. Life Sci 60:1467-1475. 

*Knudsen I, Verschuuren HG, den Tonkellar EM, et al. 1974. Short-term toxicity of pentachlorophenol 

in rats. Toxicology 2:141-152. 

*Komori M, Nishio K, Kitada M, et al. 1990. Fetus-specific expression of a form of cytochrome P-450 

in human liver. Biochemistry 29:4430-4433. 

Konishi-Imamura L, Kim DH, Koizumi M, et al. 1995. Regulation of arylsulfate sulfotransferase from a 

human intestinal bacterium by nucleotides and magnesium ion. J Enzym Inhib 8:233-241. 

Konopka L. 1994. [Environmental pollution with organochlorine compounds and their effect on human 

health: Human and environmental risks of chloro-organic substances]. Acta Haematol Pol 25:77-90. 

(Polish) 

*Kooistra L, Laane C, Vulsma T, et al. 1994. Motor and cognitive development in children with 

congenital hypothyroidism: A long-term evaluation of the effects of neonatal treatment. J Pediatr 

124:903-909. 

*Krishnan K, Andersen ME. 1994. Physiologically-based pharmacokinetic modeling in toxicology. In: 

Hayes AW, ed. Principles and methods of toxicology. New York, NY: Raven Press, Ltd., 149-188. 
PENTACHLOROPHENOL 242 

9. REFERENCES 

*Krishnan K, Andersen ME, Clewell H 3rd, et al. 1994. Physiologically based pharmacokinetic 

modeling of chemical mixtures. In: Yang R, ed. Toxicology of chemical mixtures. New York, NY: 

Academic Press, 399-437. 

*Kuehl DW, Dougherty RC. 1980. Pentachlorophenol in the environment. Evidence for its origin from 

commercial pentachlorophenol by negative chemical ionization mass spectrometry. Environ Sci Tech 

14:447-449. 

*Kutz FW, Cook BT, Carter-Pokras OD, et al. 1992. Selected pesticide residues and metabolites in urine 

from a survey of the U.S. general population. J Toxicol Environ Health 37:277-291. 

*Kutz FW, Murphy RS, Strassman SC. 1978. Survey of pesticide residues and their metabolites in urine 

from the general population. In: Rao KR, ed. Pentachlorophenol: Chemistry, pharmacology, and 

environmental toxicology. New York, NY: Plenum Press, 363-369. 

*Kuwatsuka S, Igarashi M. 1975. Degradation of PCP in soil: II. The relationship between the 

degradation of PCP and the properties of soils and the identification of the degradation products of PCP. 

Soil Sci Plant Nutr 21:405-414. 

Lamar RT, Glaser JA, Kirk TK. 1990. Fate of pentachlorophenol (PCP) in sterile soils inoculated with 

the white-rot basidiomycete phanerochaete chrysosporium: Mineralization, volatilization and depletion 

of PCP. Soil Biol Biochem 22:433-440. 

*Lambert J, Schepens P, Janssens J, et al. 1986. Skin lesions as a sign of subacute pentachlorophenol 

intoxication. Acta Derm Venreol 66:170-172. 

Lamparski LL, Stehl RH, Johnson RL. 1980. Photolysis of pentachlorophenol-treated wood. Chlorinated 

dibenzo-p-dioxin formation. Environ Sci Technol 14:196-200. 

*Lampi P, Hakulinen T, Luostarinen T, et al. 1992. Cancer incidence following chlorophenol exposure 

in a community in Southern Finland. Arch Environ Health 47:167-175. 

Lang D, Mueller-Ruchholtz W. 1991. Human lymphocyte reactivity after in vitro exposure to technical 

and analytical grade pentachlorophenol. Toxicology 70:271-282. 

Langwaldr JH, Mannisto MK, Wichmann R, et al. 1998. Simulation of in situ subsurface biodegradation 

of polychlorophenols in air-lift percolators. Appl Microbiol Biotechnol 49:663-668. 

Larsen RV. 1976. The placental transfer and teratology of pentachlorophenol in rats [Abstract]. Diss 

Abstr Int B37:1184-1185. 

*Larsen RV, Born GS, Kessler WV, et al. 1975. Placental transfer and teratology of pentachlorophenol 

in rats. Environ Lett 10:121-128. 

*Larsen RV, Kirsch LE, Shaw SM, et al. 1972. Excretion and tissue distribution of uniformly labeled 

[14C]- pentachlorophenol in rats. J Pharmacol Sci 61:2004-2006. 

Lee HB, Hong-You RL, Fowlie PJA. 1989. Chemical derivatization analysis of phenols: Part VI. 

Determination of chlorinated phenolics in pulp and paper effluents. J Assoc Off Anal Chem 72:979-984. 
PENTACHLOROPHENOL 243 

9. REFERENCES 

*Leeder JS, Kearns GL. 1997. Pharmacogenetics in pediatrics: Implications for practice. Pediatr Clin 

North Am 44:55-77. 

*Leighty EG, Fentiman AF. 1982. Conjugation of pentachlorophenol to palmitic acid by liver 

microsomes. Bull Environ Contam Toxicol 28:329-333. 

*Lemma A, Ames BN. 1975. Screening for mutagenic activity of some molluscicides. Transcripts of the 

Royal Society of Tropical Medicine and Hygiene 69:167-168. 

*Leung H-W. 1993. Physiologically-based pharmacokinetic modelling. In: Ballentine B, Marro T, 

Turner P, eds. General and applied toxicology. New York, NY: Stockton Press, 153-164. 

*Lewis RG, Fortmann RC, Camann DE. 1994. Evaluation of methods for monitoring the potential 

exposure of small children to pesticides in the residential environment. Arch Environ Contam Toxicol 

26:37-46. 

*Lilienblum W. 1985. Formation of pentachlorophenol glucuronide in rat and human liver microsomes. 

Biochem Pharmacol 34:893-894. 

*Lin PH, Waidyanatha S, Pollack GM, et al. 1997. Dosimetry of chlorinated quinone metabolites of 

pentachlorophenol in the livers of rats and mice based upon measurement of protein adducts. Toxicol 

Appl Pharmacol 145:399-408. 

Lin P-H, Waidyanatha S, Pollack GM, et al. 1999. Dose-specific production of chlorinated quinone and 

semiquinone adducts in rodent livers following administration of pentachlorophenol. Toxicol Sci 47:126­

133. 

Lin P-H, Waidyanatha S, Rappaport SM. 1996. Investigation of liver binding of pentachlorophenol 

based upon measurement of protein adducts. Biomarkers 1:237-243. 

Linko PC, Goldstein JA. 1979. Hepatic effects of technical pentachlorophenol after cutaneous 

administration. Environ Health Perspect 33:383. 

Lippens R, Claeys M, Wildemauwe C, et al. 1983. Mutagenicity studies on 10 pesticides, on 

trichloroethane and on diaminobenzidine [Abstract]. Mutat Res 113:277-278. 

Liu D, Thomson K, Strachan WMJ. 1981. Biodegradation of pentachlorophenol in a simulated aquatic 

environment. Bull Environ Contam Toxicol 26:85-90. 

Liu P-Y, Metcalf RL, Cole LK. 1978. The environmental fate of 14C-pentachlorophenol in laboratory 

model ecosystems. In: Rao KR, ed. Pentachlorophenol: Chemistry, pharmacology, and environmental 

toxicology. New York, NY: Plenum Press, 53-63. 

*Livingston, AL. 1978. Forage plant estrogens. J Toxicol Environ Health 4:301-324. 

*Lyman WJ, Reehl WF, Rosenblatt DH. 1982. Handbook of chemical property estimation methods, 

environmental behavior of organic compounds. New York, NY: McGraw-Hill Book Co. 

*Makela TP, Petanan T, Kukkonen J, et al. 1991. Accumulation and depuration of chlorinated phenolics 

in the freshwater mussel (anodonta anatina L.). Ecotoxicol Environ Safety 22:153-163. 
PENTACHLOROPHENOL 244 

9. REFERENCES 

*Makishima M, Okamoto AY, Repa JJ, et al. 1999. Identification of a nuclear receptor for bile acids. 

Science 284:1362-1365. 

Malfatti MA, Buonarati MH, Turteltaub KW, et al. 1994. The role of sulfation and/or acetylation in the 

metabolism of the cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in salmonella 

typhimurium and isolated rat hepatocytes. Chem Res Toxicol 7:139-147. 

Manns A, Flauss A, Zastrow D. 1997. Determination of PCP in air by immunoassay. In: Field 

analytical methods hazardous wastes toxic chemicals: Proceedings of the special conference. Lubeck: 

Dragerwerk AG - Safety Division, 870-874. 

*Mannsville. 1987. Pentachlorophenol. Asbury Park, NF: Mannsville Chemical Products Synopsis. 

*Manske DD, Corneliussen PE. 1976. Pesticide residues in total diet samples (VII). Pestic Monit J 

8:110-124. 

*Maris FA, de Jong GJ, Somsen GW, et al. 1988. Determination of pentachlorophenol in rabbit and 

human liver using liquid chromatography and gas chromatography with electron-capture detection. 

Chemosphere 17:1301-1308. 

*Markiewicz KV, Howie LE, Safe SH, et al. 1996. Mutagenic potential of binary and complex mixtures 

using different enzyme induction systems. J Toxicol Environ Health 47:443-451. 

*Martins JM, Montrozier LJ, Bardin ACR. 1997. Microbial response to repeated applications of low 

concentrations of pentachlorophenol in an alfisol under pasture. Chemosphere 35:1637-1650. 

Mason MF, Wallace SM, Foerster E, et al. 1965. Pentachlorophenol poisoning: Report of two cases. J 

Forensic Sci 10:136-147. 

Masurekar PS, Kahgan MP, Demain AL. 1972. Mutagenesis and enrichment of auxotrophs in 

penicillium chrysogenum. Appl Microbiol 24:995-996. 

Matsumura H, Matsuoka M, Igisu H, et al. 1997. Cooperative inhibition of acetylcholinesterase 

activities by hexachlorophene in human erythrocytes. Arch Toxicol 71:151-156. 

Maurice DM, Brooks D. 1995. The permeability of the mouse cornea as a test for acute ocular toxicity. 

In Vitro Toxicol 8:113-120. 

*Mayr U, Butsch A and Schneider S. 1992. Validation of two in vitro test systems for estrogenic 

activities with zearalenone, phytoestrogens and cereal extracts. Toxicology 74:135-149. 

*McAllister KA, Lee H, Trevore JT. 1996. Microbial degradation of pentachlorophenol. Biodegradation 

7:1-40. 

McBain ADK, Salkinoja-Salonen MS, Senior E, et al. 1997. Pentachlorophenol-contaminated soil 

bioremediation: Survival and efficacy of monoculture inoculants and enrichment of indigenous catabolic 

populations. South African Journal of Plant Soil 14:81-88. 

McCarthy DL, Claude AA, Copley SD. 1997. In vivo levels of chlorinated hydroquinones in a 

pentachlorophenol-degrading bacterium. Appl Environ Microbiol 63:1883-1888. 
PENTACHLOROPHENOL 245 

9. REFERENCES 

*McChesney TC. 1988. Unpublished letter and enclosures to B. L. Johnson. Agency for Toxic 

Substances and Disease Registry. September 16, 1988. Arkansas: Department of Health. 

*McConnachie PR, Zahalsky AC. 1991. Immunological consequences of exposure to 

pentachlorophenol. Arch Environ Health 46:249-253. 

McConnell EE, Moore JA, Gupta BN, et al. 1980. The chronic toxicity of technical and analytical 

pentachlorophenol in cattle: I. Clinicopathology. Toxicol Appl Pharmacol 52:468-490. 

McGavack TH, Boyd FV, Piccione FV, et al. 1941. Acute and chronic intoxications with sodium 

pentachlorophenate in rabbits. J Ind Hyg Toxicol 23:239-251. 

*Meerman JHN, Sterenborg HMJ, Mulder GJ. 1983. Use of pentachlorophenol as long-term inhibitor of 

sulfation of phenols and hydroxamic acids in the rat in vivo. Biochem Pharmacol 32:1587-1593. 

*Meerman JHN, Vandoorn BD, Mulder GJ. 1980. Inhibition of sulfate conjugation of N-hydroxy-2­

acetylaminofluorene in isolated perfused rat liver and in the rat in vivo by pentachlorophenol and low 

sulfate. Cancer Res 40:3772-3779. 

*Mehmood Z, Williamson MP, Kelly DE, et al. 1996. Metabolism of organochlorine pesticides: The 

role of human cytochrome P450 3A4. Chemosphere 33:759-769. 

Meissner T, Schweinsberg F. 1996. Pentachlorophenol in the indoor environment: Evidence for a 

correlation between pentachlorophenol in passively deposited suspended particulate and in urine of 

exposed persons. Toxicol Lett 88:237-242. 

Melin ES, Ferguson JF, Puhakka JA. 1997. Pentachlorophenol biodegradation kinetics of an 

oligotrophic fluidized-bed enrichment culture. Appl Microbiol Biotechnol 47:675-682. 

Melin ES, Jarvinen KT, Puhakka JA. 1998. Effects of temperature on chlorophenol biodegradation 

kinetics in fluidized-bed reactors with different biomass carriers. Water Res 32:81-90. 

*Menon JA. 1958. Tropical hazards associated with the use of pentachlorophenol. Br Med J 

1:1156-1158. 

*Meylan WM, Howard P. 1993. Computer estimation of the atmospheric gas-phase reaction rate of 

organic compounds with hydroxyl radicals and ozone. Chemosphere 26:2293-2299. 

Middeldorp PJ, Briglia M, Salkinoja-Salonen MS. 1990. Biodegradation of pentachlorophenol in natural 

soil by inoculated rhodococcus chlorophenolicus. Microbiol Ecol 20:123-139. 

Miller GC, Hebert VR, Miille MJ, et al. 1989. Photolysis of octachlorodibenzo-p-dioxin on soils: 

Production of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemosphere 18:1265-1274. 

*Mohammed SA, Sorensen DL, Sims RC, et al. 1998. Pentachlorophenol and phenanthrene 

biodegradation in creosote contaminated aquifer material. Chemosphere 37:103-111. 

Mohtashamipur E, Norpoth K. 1984. Non-mutagenicity of some wood related compounds in the 

bacterial/microsome plate incorporation and microsuspension assays. Int Arch Occup Environ Health 

54:83-90. 
PENTACHLOROPHENOL 246 

9. REFERENCES 

*Monteith DK. 1992. Inhibition of sulfotransferase affecting unscheduled DNA synthesis induced by 2­

acetylaminofluorene: An in vivo and in vitro comparison. Mutat Res 282:253-258. 

Montoya GA, Roa J, Cruz F, et al. 1988. The actions of phenol and pentachlorophenol (PCP) on axonal 

conduction, ganglionic synaptic transmission, and the effect of pH changes. Comp Biochem Physiol 

89C:377-382. 

Moorthy B, Randerath K. 1996. Pentachlorophenol enhances 9-hydroxybenzo[a]pyrene-induced hepatic 

DNA adduct formation in vivo and inhibits microsomal epoxide hydrolase and glutathione S-transferase 

activities in vitro: Likely inhibition of epoxide detoxification by pentachlorophenol. Arch Toxicol 

70:696-703. 

Morgade C, Barquet A, Pfaffenber CD. 1980. Determination of polyhalogenated phenolic compounds in 

drinking water, human blood serum, and adipose tissue. Bull Environ Contam Toxicol 24:257-264. 

Morgan DP. 1989. Recognition and management of pesticide poisonings. 4th Ed. U.S. Environmental 

Protection Agency. 

*Moriya M, Ohta T, Watanabe K, et al. 1983. Further mutagenicity studies on pesticides in bacterial 

reversion assay systems. Mutat Res 116:185-216. 

Morselli PL, Franco-Morselli R, Bossi L. 1980. Clinical pharmacokinetics in newborns and infants. 

Clin Pharmacokin 5:485-527. 

Mueller JG, Middaugh DP, Lantz SE, et al. 1991. Biodegradation of creosote and pentachlorophenol in 

contaminated groundwater: Chemical and biological assessment. Appl Environ Microbiol 57:1277-1285. 

*Muiño FMA, Lozano SJ. 1991. Mass spectrometric determination of pentachlorophenol in honey. 

Anal Chim Acta 247:121-123. 

*Mulder G, Scholtens E. 1977. Phenol sulphotransferase and uridine diphosphate glucuronyltransferase 

from rat liver in vivo and in vitro. Biochem J 165:553-559. 

*Mundy DE, Machin AF. 1981. Determination of pentachlorophenol and related compounds in animal 

materials by high-performance liquid chromatography and gas chromatography. J Chromatogr 

216:229-238. 

*Murphy RS, Kutz FW, Strassman SC. 1983. Selected pesticide residues or metabolites in blood and 

urine specimens from a general population survey. Environ Health Perspect 48:81-86. 

Murthy NBK. 1979. Degradation of pentachlorophenol (PCP) in aerobic and anaerobic soil. J Environ 

Sci Health B14:1-14. 

NAS. 1977. Organic solutions. In: Drinking water and health. Vol. 1. Washington, DC: National 

Academy of Sciences, Washington, DC, 750-753. 

NAS. 1986. Drinking water and health. Vol. 6. Washington, DC: National Academy of Sciences. 

NAS/NRC. 1989. Report of the oversight committee. In: Biologic markers in reproductive toxicology. 

Washington, DC: National Academy of Sciences, National Research Council, National Academy Press, 

15-35. 
PENTACHLOROPHENOL 247 

9. REFERENCES 

NATICH. 1992. Data base report on state, local, and EPA air toxics activities. National Air Toxics 

Information Clearinghouse. Washington, DC: U.S. Environmental Protection Agency, Office of Air 

Quality Planning and Standards. March 23, 1992. 

*NCI. 1968. Evaluation of carcinogenic, teratogenic, and mutagenic activities of selected pesticides and 

industrial chemicals. Volume I: Carcinogenic study. Bethesda, MD: National Cancer Institute. NTIS 

PB-223-159. 

*NCI/NTP. 1980. Bioassay of a mixture of 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin and 

1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (gavage) for possible carcinogenicity. Research Triangle Park, 

NC: National Cancer Institute/National Toxicology Program. NTP no. 80-12. NCI carcinogenesis 

technical report series No. 198. 

*Needham LL, Cline RE, Head SL, et al. 1981. Determining pentachlorophenol in body fluids by gas 

chromatography after acetylation. J Anal Toxicol 5:283-286. 

Needham LL, Hill RHJ, Ashley DL, et al. 1995. The priority toxicant reference range study: Interim 

report. Environ Health Perspect Suppl 103:89-94. 

Nelson DR, Kamataki T, Waxman DJ, et al. 1993. The P450 superfamily: Update on new sequences, 

gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 

12:1-51. 

*Neveu I, Arenas E. 1996. Neurotrophins promote the survival and development of neurons in the 

cerebellum of the hypothyroid rats in vivo. J Cell Biol 133:631-646. 

*Niimi AJ, Cho CY. 1983. Laboratory and field analysis of pentachlorophenol (PCP) accumulation by 

salmonids. Water Res 17:1791-1795. 

*NIOSH. 1976. National occupational hazard survey 1970 (1972-1974). Cincinnati, OH: U.S. 

Department of Health and Human Services, National Institute for Occupational Safety and Health. 

NIOSH. 1978. NIOSH/OSHA pocket guide to chemical hazards. Washington, DC: U.S. Department of 

Health and Human Services, National Institute for Occupational Safety and Health. DHEW (NIOSH) 

publication no. 78-210., 74. 

NIOSH. 1984a. National occupational exposure survey (1980-1983). Cincinnati, OH: National Institute 

for Occupational Safety and Health, U.S. Department of Health and Human Services. 

*NIOSH. 1984b. NIOSH manual of analytical methods. Vol. 1, 3rd ed. Cincinnati, OH: U.S. 

Department of Human Health Services, National Institute for Occupational Safety and Health, Division of 

Physical Sciences and Engineering. 

NIOSH. 1992. NIOSH pocket guide to chemicals hazards. Washington, DC: U.S. Department of 

Health and Human Service, Centers for Disease Control, National Institute for Occupational Safety and 

Health, Division of Standard Development and Technology Transfer. NIOSH publication no. 90-117. 

NIOSH. 1994. NIOSH manual of analytical methods. 4th ed. Cincinnati, OH: U.S. Department of 

Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National 

Institute for Occupational Safety and Health. 
PENTACHLOROPHENOL 248 

9. REFERENCES 

NIOSH. 1999. Pentachlorophenol. Pocket guide to chemical hazards. Washington D.C.: National 

Institute for Occupational Safety and Health, U.S. Department of Health and Human Services. 

*NIOSH. 2001a. Pentachlorophenol. National Institute for Occupational Safety and Health, U.S. 

Department of Health and Human Services. Http://www.cdc.gov/niosh/npg/npgd0484.html. 

February 07, 2001. 

*NIOSH. 2001b. Pentachlorophenol. Documentation for immediately dangerous to life or health 

concentrations (IDLHs). National Institute for Occupational Safety and Health, U.S. Department of 

Health and Human Services. Http://www.cdc.gov/niosh/idlh/87865.html. February 07, 2001. 

*Nishimura H, Nishimura N, Oshima H. 1980. Experimental studies on the toxicity of 

pentachlorophenol. J Aichi Med Univ Assoc 8:203-209. 

*Nishimura H, Nishimura N, Oshima H. 1982. Effects of pentachlorophenol on the levels of hepatic 

glycogen. Sangyo Igaku 24:398-399. 

Norris B, Quevedo L. 1993. Pentachlorophenol (PCP) inhibits ion transport in the isolated toad cornea. 

Gen Pharmacol 24:867-872. 

*NRC. 1993. Pesticides in the diets of infants and children. National Research Council. Washington, 

DC: National Academy Press. 

NREPC. 1986. Natural Resources and Environmental Protection Cabinet. Department for 

Environmental Protection, Division of Air Pollution, Frankfort, KY. 401 KAR 63:022. 

*NTP. 1989. NTP technical report on the toxicology and carcinogenesis studies of two 

pentachlorophenol technical grade mixtures (CAS no 87-86-5) in B6C3F1 mice (feed studies). National 

Toxicology Program, Research Triangle Park, NC. NTP TR 349. NIH publication No. 89-2804. 

NTP. 1997. NTP technical report on the toxicology and carcinogenesis studies of pentachlorophenol 

(CAS no 87-86-5) in F344/N rats (feed studies): Scheduled peer review date: 9-10 December 1997. 

Draft. National Toxicology Program. Research Triangle Park, NC: NTP TR 483. NIH publication No. 

97-3973. 

*NTP. 1999. Toxicology and carcinogenesis studies of pentachlorophenol (CAS no 87-86-5) in F344/N 

rats (feed studies). Research Triangle Park, NC: National Institutes of Health, Public Health Service, 

U.S. Department of Health and Human Services, National Toxicology Program. NIH publication no. 

99-3973. NTP TR 483. 

*Ohe T. 1979. Pentachlorophenol residues in human adipose tissue. Bull Environ Contam Toxicol 

22:287-292. 

*O'Malley MA, Carpenter AV, Sweeney MH, et al. 1990. Chloracne associated with employment in the 

production of pentachlorophenol. Am J Ind Med 17:411-421. 

OSHA. 1974. Occupational Safety and Health Standards. U.S. Department of Labor, Occupational 

Safety and Health Administration. Federal Register 39:23542. 

OSHA. 1989a. Toxic and hazardous substances. U.S. Department of Labor, Occupational Safety and 

Health Administration. Code of Federal Regulations. 29 CFR 1910.1000. 
PENTACHLOROPHENOL 249 

9. REFERENCES 

OSHA. 1989b. Toxic and hazardous substances. U.S. Department of Labor, Occupational Safety and 

Health Administration. Federal Register 54(12):2920-2960. 

OSHA. 1998a. U.S. Department of Labor, Occupational Safety and Health Administration. Code of, 

Federal Regulations. 29 CFR 1926.55. 

OSHA. 1998b. U.S. Department of Labor. Occupational Safety and Health Administration. Code of 

Federal Regulations. 29 CFR 1915.1000. 

*OSHA. 1998c. U.S. Department of Labor. Occupational Safety and Health Administration. Code of 

Federal Regulations. 29 CFR 1910.1000. 

*OSHA. 1999a. U.S. Department of Labor. Occupational Safety and Health Administration. Code of 

Federal Regulations. 29 CFR 1926.55. 

*OSHA. 2000a. U.S. Department of Labor. Occupational Safety and Health Administration. Code of 

Federal Regulations. 29 CFR 1910, 1000. 

*OSHA. 2000b. U.S. Department of Labor. Occupational Safety and Health Administration. Code of 

Federal Regulations. 29 CFR 1915. 1000. 

*OSHA. 2001a. Air contaminants. Shipyards. Occupational Safety and Health Administration. U.S. 

Department of Labor. Code of Federal Regulations. 29 CFR 1915.1000, Table Z. Http://www.oshaslc.gov/OshStd_data/1915_1000.html. March 26, 2001. 

*OSHA. 2001b. Limits for air contaminants. U.S. Department of Labor. Occupational Safety and 

Health Administration. Code of Federal Regulations. 29 CFR 1910.1000, Table Z-1. Http://www.oshaslc.gov/OshStd_data/1910_1000_Table Z-1.html. March 26, 2001. 

*OSHA. 2001c. Threshold limit values of airborne contaminants for construction. U.S. Department of 

Labor, Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR 1926.55, 

Appendix A. Http://www.osha-slc.gov/OshStd_data/1926_0055_APP_A.html. March 26, 2001. 

*Owen GM, Brozek J. 1966. Influence of age, sex, and nutrition on body composition during childhood 

and adolescence. In: Falkner F, ed. Human Development. Philadelphia, PA: WB Saunders, 222-238. 

*Parks DJ, Blanchard SG, Bledsoe RK, et al. 1999. Bile acids: Natural ligands for an orphan nuclear 

receptor. Science 284:1365-1368. 

Parks LG, Leblanc GA. 1996. Reductions in steroid hormone biotransformation/elimination as a 

biomarker of pentachlorophenol chronic toxicity. Aquat Toxicol 34:291-303. 

*Pekari K, Aitio A. 1982. A simple liquid chromatographic method for the analysis of penta- and 

tetrachlorophenols in urine of exposed workers. J Chromatogr 232:129-136. 

*Pekari K, Luotamo M, Järvisalo J, et al. 1991. Urinary excretion of chlorinated phenols in saw-mill 

workers. Int Arch Occup Environ Health 63:57-62. 

*Peper M, Ertl M Gerhard I. 1999. Long-term exposure to wood-preserving chemicals containing 

pentachlorophenol and lindane is related to neurobehavioral performance in women. Am J Ind Med 

35:632-641. 
PENTACHLOROPHENOL 250 

9. REFERENCES 

*Pierce RH, Jr, Victor DM. 1978. The fate of pentachlorophenol in an aquatic ecosystem. In: Rao KR, 

ed. Pentachlorophenol: Chemistry, pharmacology, and environmental toxicology. New York, NY: 

Plenum Press, 41-52. 

*Pignatello JJ, Johnson LK, Martinson MM, et al. 1985. Response of the microflor in outdoor 

experimental streams to pentachlorophenol: Compartmental contributions. Appl Environ Microbiol 

50:127-132. 

*Pignatello JJ, Martinson MM, Steiert JG, et al. 1983. Biodegradation and photolysis of 

pentachlorophenol in artificial freshwater streams. Appl Environ Microbiol 46:1024-1031. 

Pohl HR, Smith-Simon C, Hicks H. 1998. Health effects classification and its role in the derivation of 

minimal risk levels: Developmental effects. Regul Toxicol Pharmacol 28:55-60. 

Pohland FG, Karadagli F, Kim JC, et al. 1998. Landfill codisposal of pentachlorophenol (PCP)-treated 

waste wood with municipal solid waste. Water Sci Technol 38:169-175. 

Prescott CA, Wilkie BN, Hunter B, et al. 1982. Influence of a purified grade of pentachlorophenol on 

the immune response of chickens. Am J Vet Res 42:481-487. 

*Pruitt GW, Grantham BJ, Pierce RH. 1977. Accumulation and elimination of pentachlorophenol by the 

bluegill, lepomis macrochirus. Transactions of the American Fisheries Society 106:462-465. 

*Qiao GL, Brooks JD, Riviere JE. 1997. Pentachlorophenol dermal absorption and disposition from soil 

in swine: Effects of occlusion and skin microorganism inhibition. Toxicol Appl Pharmacol 147:234-246. 

*Ramlow JM, Spadacene NW, Hoag SR, et al. 1996. Mortality in a cohort of pentachlorophenol 

manufacturing workers, 1940-1989. Am J Ind Med 30:180-194. 

Randerath E, Zhou GD, Donnelly KC, et al. 1996. DNA damage induced in mouse tissues by organic 

wood preserving waste extracts as assayed by 32P-postlabeling. Arch Toxicol 70:683-695. 

Randerath K, Zhou GD, Randerath E, et al. 1997. Comparative 32P-postlabeling analysis of exogenous 

and endogenous DNA adducts in mouse skin exposed to a wood-preserving waste extract, a complex 

mixture of polycyclic and polychlorinated chemicals. Environ Mol Mutagen 29:372-378. 

*Rawlings NC, Cook SJ, Waldbillig D. 1998. Effects of the pesticides carbofuran, chlorpyrifos, 

dimethoate, lindane, triallate, trifluralin, 2,4-D, and pentachlorophenol on the metabolic endocrine and 

reproductive endocrine system in ewes. J Toxicol Environ Health Part A 54:21-36. 

*Realini PA. 1981. Determination of priority pollutant phenols in water by HPLC. J Chromatogr Sci 

19:124-129. 

*Rehwagen M, Rolle-Kampczyk U, Herbarth O, et al. 1999. [Pentachlorophenol in house dusts and 

urine of Eastern German children.] Geharstoffe Reinhalt Luft 59:43-47. (German) 

*Reigner BG, Bois FY, Tozer TN. 1992a. Assessment of pentachlorophenol exposure in humans using 

the clearance concept. Hum Exp Toxicol 11:17-26. 

*Reigner BG, Bois FY, Tozer TN. 1993. Pentachlorophenol carcinogenicity: Extrapolation of risk from 

mice to humans. Hum Exp Toxicol 12:215-225. 
PENTACHLOROPHENOL 251 

9. REFERENCES 

*Reigner BG, Gungon RA, Hoag MK, et al. 1991. Pentachlorophenol toxicokinetics after intravenous 

and oral administration to rat. Xenobiotica 21:1547-1558. 

Reigner BG, Rigod JF, Tozer TN. 1990. Simultaneous assay of pentachlorophenol and its metabolite, 

tetrachlorohydroquinone, by gas chromatography without derivatization. J Chromatogr Biomed Appl 

98:111-124. 

*Reigner BG, Rigod JF, Tozer TN. 1992b. Disposition, bioavailability, and serum protein binding of 

pentachlorophenol in the B6C3F1 mouse. Pharm Res 9:1053-1057. 

*Reiman W, Walton H. 1970. Ion exchange in analytical chemistry. New York, NY: Pergamon Press, 

168. 

*Reiner EA, Chu J, Kirsch EJ. 1978. Microbial metabolism of pentachlorophenol. In: Rao, KR, ed. 

Pentachlorophenol: Chemistry, pharmacology, and environmental toxicology. New York, NY: Plenum 

Press, 67-81. 

*Renner G. 1989. Urinary excretion of pentachlorophenol (PCP) and its metabolite tetrachlorohydroquinone (TCH) in rats. Toxicol Environ Chem 25:29-32. 

*Renner G, Hopfer C. 1990. Metabolic studies on pentachlorophenol (PCP) in rats. Xenobiotica 

20:573-582. 

Renner G, Hopfer C, Gokel JM. 1986. Acute toxicities of pentachlorophenol, pentachloroanisole, 

tetrachlorohydroquinone, tetrachlorocatechol, tetrachlororesorcinol, tetrachlorodimethoxybenzenes and 

tetrachlorodibenzenediol diacetates administered to mice. Toxicol Environ Chem 11:37-50. 

*Rick DL, Licht CF, McCarty LP. 1982. Determination of phenol and pentachlorophenol in plasma and 

urine samples by gas liquid chromatography. J Anal Toxicol 6:297-300. 

Rivera MD, Haggblom MM, Young LY. 1993. Anaerobic degradation of mixtures of pentachlorophenol 

and cresols [Abstract]. Abstr Annu Meet Am Soc Microbiol 93:414. 

*Roberts HJ. 1963. Aplastic anemia due to pentachlorophenol and tetrachlorophenol. South Med J 

56:632-635. 

*Roberts HJ. 1981. Aplastic anemia due to pentachlorophenol [Letter]. N Eng J Med 305:1605-1651. 

*Roberts HJ. 1983. Aplastic anemia and cell aplasia due to pentachlorophenol. South Med J 76:45-48. 

*Roberts HJ. 1990. Pentachlorophenol-associated aplastic anemia, red cell aplasia, leukemia and other 

blood disorders. J Fla Med Assoc 77:86-90. 

*Robinson C, Fowler D, Brown D, et al. 1985. Plywood Mill workers' mortality 1945-1977. Menlo 

Park, CA: Stanford Research Institute. 

*Robson AM, Kissane JM, Elvick HN, et al. 1969. Pentachlorophenol poisoning in a nursery for 

newborn infants: I. Clinical features and treatment. J Pediatr 75:309-316. 

Roszell LE, Anderson RS. 1996. Effect of chronic in vivo exposure to pentachlorophenol on nonspecific immune functions in fundulus heteroclitus. Mar Environ Res 42:191-194. 
PENTACHLOROPHENOL 252 

9. REFERENCES 

*Rozman T, Ballhorn L, Rozman K, et al. 1982. Effect of cholestyramine on the disposition of 

pentachlorophenol in Rhesus monkeys. J Toxicol Environ Health 10:277-283. 

*RTECS. 1991. Registry of Toxic Effects of Chemical Substances. Washington, DC: U.S. Department 

of Health and Human Services, National Institute for Occupational Safety and Health. December 24, 

1991. 

RTECS. 1999. Pentachlorophenol. Registry of Toxic Effects of Chemical Substances. National 

Institute for Occupational Safety and Health. April 19, 1999. 

*Rudling L. 1970. Determination of pentachlorophenol in organic tissues and water. Water Res 4:533­

537. 

*Rugman FP, Cosstick R. 1990. Aplastic anemia associated with organochlorine pesticide: Case reports 

and review of evidence. J Clin Pathol 43:98-101. 

Rumack BH. 1999. POISONDEC DATABASE. Micromedex. 

Rutgers M, Gooch DD, Breure AM, et al. 1996. Assessment of inhibition kinetics of the growth of strain 

P5 on pentachlorophenol under steady-state conditions in a nutristat. Arch Microbiol 165:194-200. 

*Sai-Kato K, Umemura T, Takagi A, et al. 1995. Pentachlorophenol-induced oxidative DNA damage in 

mouse liver and protective effect of antioxidants. Food Chem Toxicol 33:877-882. 

*Samokyszyn VM, Freeman JP, Maddipati KR, et al. 1995. Peroxidase-catalyzed oxidation of 

pentachlorophenol. Chem Res Toxicol 8:349-355. 

*Santodonato J. 1986. Monograph on human exposure to chemicals in the workplace: Pentachlorophenol. NTIS/PB86-155116. 

Saracci R, Kogevinas M, Bertazzi PA, et al. 1991. Cancer mortality in workers exposed to 

chlorophenoxy herbicides and chlorophenols. Lancet 338:1027-1032. 

*Savolainen H, Pekari K. 1979. Neurochemical effects of peroral administration of technical 

pentachlorophenol. Res Commun Chem Pathol Pharmacol 23:97-105. 

Sax NI. 1984. Dangerous properties of industrial materials. New York, NY: Van Nostrand Reinhold, 

2127. 

*Schellenberg K, Leuenberger C, Schwarzenbach RP. 1984. Sorption of chlorinated phenols by natural 

sediments and aquifer materials. Environ Sci Technol 18:652-657. 

Schmid K, Lederer P, Goen T, et al. 1997. Internal exposure to hazardous substances of persons from 

various continents: Investigations on exposure to different organochlorine compounds. Int Arch Occup 

Environ Health 69:399-406. 

Schnelle-Kreis J, Scherb H, Gebefugi I, et al. 2000. Pentachlorophenol in indoor environments. 

Correlation of PCP concentrations in air and settled dust from floors. Sci Total Environ 256:125. 
PENTACHLOROPHENOL 253 

9. REFERENCES 

Schuur Ag, Bergman A, Brouwer A, et al. 1999. Effects of pentachlorophenol and hydroxylated 

polychlorinated biphenyls on thyroid hormone conjugation in a rat and a human hepatoma cell line. 

Toxicol In Vitro 13:417-425. 

*Schwetz BA, Keeler PA, Gehring PJ. 1974. The effect of purified and commercial grade 

pentachlorophenol on rat embryonal and fetal development. Toxicol Appl Pharmacol 28:151-161. 

*Schwetz BA, Quast JF, Keeler PA, et al. 1978. Results of two-year toxicity and reproduction studies on 

pentachlorophenol in rats. In: Rao KR, ed. Pentachlorophenol: Chemistry, pharmacology and 

environmental toxicology. New York, NY: Plenum Press, 301-309. 

Seech AG, Trevors JT, Bulman TL. 1991. Biodegradation of pentachlorophenol in soil: The response to 

physical, chemical, and biological treatments. Can J Micobiol 37:440-444. 

*Sehgal VN, Ghorpade A. 1983. Fume inhalation chloracne. Dermatologica 167:33-36. 

*Seidler A, Hellenbrand W, Robra BP, et al. 1996. Possible environmental, occupational, and other 

etiologic factors for Parkinson's disease. Neurology 46:1275-1284. 

Seidler JJ, Landau M, Dierberg FE, et al. 1986. Persistence of pentachlorophenol in a wastewaterestuarine aquaculture system. Bull Environ Contam Toxicol 36:101-108. 

*Setchell BP, Waites GMH. 1975. The blood testis barrier. In: Creep RO, Astwood EB, Geiger SR, 

eds. Handbook of physiology: Endocrinology V. Washington, DC: American Physiological Society. 

*Shafik TM. 1973. The determination of pentachlorophenol and hexachlorophene in human adipose 

tissue. Bull Environ Contam Toxicol 10:57-63. 

Shealy DB, Bonin MA, Wooten JV, et al. 1996. Application of an improved method for the analysis of 

pesticides and their metabolites in the urine of farmer applicators and their families. Environ Int 22:661­

675. 

Shofer SL, Tjeerdema RS. 1993. Comparative disposition and biotransformation of pentachlorophenol 

in the oyster (crassostrea gigas) and abalone (haliotis fulgens). Pestic Biochem Physiol 46:85-95. 

Shofer SL, Willis JA, Tjeerdema RS. 1996. Sublethal effects of pentachlorophenol and hypoxia on rates 

of arginine kinase flux in Red Abalone (haliotis rufescens) as measured by 31P magnetization saturation 

transfer NMR. Mar Environ Res 42:363-367. 

Shoji R, Sakoda A, Sakai Y, et al. 1998. Rapid bioassay of toxicity in environmental water by LDLuptaking activity of human cell. Water Sci Technol 38:271-278. 

Sikka K, Sharma AK. 1976. The effects of some herbicides on plant chromosomes. Proceedings of the 

Indian National Science Academy 46 Pt B:299-307. 

*Simmon VF, Mitchell AD, Jorgenson TA. 1977. Evaluation of selected pesticides as chemical 

mutagens: In vitro and in vivo studies. Washington, DC: U.S. Environmental Protection Agency. EPA 

600/1-77-028. 

*Siqueina MEPB, Fernicola NAGG. 1981. Determination of pentachlorophenol in urine. Bull Environ 

Contam Toxicol 27:380-385. 
PENTACHLOROPHENOL 254 

9. REFERENCES 

*Smejtek P. 1987. The physicochemical basis of the membrane toxicity of pentachlorophenol: An 

overview. J Membr Sci 33:249-268. 

*Smith AD, Bharath A, Mallard C, et al. 1990. Bioconcentration kinetic of some chlorinated benzene 

and chlorinated phenols in American flagfish, jordanella floridae (Goode and Bean). Chemosphere 

20:379-386. 

*Smith GB, Lee SF, Netzer A. 1976. Model studies in aqueous chlorination: The chlorination of 

phenols in dilute aqueous solutions. Water Res 10:985-990. 

Smith J, Loveless L, Belden E. 1967. Pentachlorophenol poisoning in newborn infants. MMWR Morb 

Mortal Wkly Rep 16:124-133. 

*Smith JE, Loveless LE, Belden EA. 1996. Pentachlorophenol poisoning in newborn infants—St. Louis, 

Missouri, April-August 1967. MMWR Morb Mortal Wkly Rep 45:545-548. 

Smith JG, Christophers AJ. 1992. Penoxy herbicides and chlorophenols: A case control study on soft 

tissue sarcoma and malignant lymphoma. Arch Environ Health 47:167-175. 

Sodum RS, Sohn OS, Nie G, et al. 1994. Activation of the liver carcinogen 2-nitropropane by aryl 

sulfotransferase. Chem Res Toxicol 7:344-351. 

Soimasuo R, Jokinen I, Kukkonen J, et al. 1995. Biomarker responses along a pollution gradient: 

Effects of pulp and paper mill effluents on caged whitefish. Aquat Toxicol 31:329-345. 

Spencer EY. 1982. Guide to the chemicals used in crop protection. Ottawa, Canada: Research Institute, 

Agriculture Canada, Information Canada. Publication 1093, 443. 

SRI. 1991. Directory of chemical producers: United States of America. Menlo Park, CA: Stanford 

Research Institute International, 849. 

SRI. 1996. Directory of chemical producers: United States of America. Menlo Park, CA: Stanford 

Research Institute International, 409-410. 

*SRI. 1998. Directory of chemical producers: United States of America. Menlo Park, CA: Stanford 

Research Institute International, 797. 

Stangroom SJ, Collins CD, Lester JN. 1998. Sources of organic micropollutants to lowland rivers. 

Environ Technol 19:643-666. 

STAPPA/ALAPCO. 1999. State and Territorial Air Pollution Program Administrators/Association of 

Local Air Pollution Control Officials. Washington, DC. Http://www.4cleanair.org/states.html#NorthC. 

June 16, 1999. 

Stehl RH, Papenfus RR, Bredeweg RA, et al. 1973. Stability of pentachlorophenol and chlorophenol and 

chlorinated dioxins to sunlight, heat, and combustion. Adv Chem Ser 120:119-125. 

Stein K, Ohlenbusch G. 1997. Inhibition of the enzyme phosphoenolpyruvate-carboxylase (PEPC) by 

different pollutants. Talanta 44:475-481. 
PENTACHLOROPHENOL 255 

9. REFERENCES 

*Stein SA, Kirkpatrick LL, Shanklin DR, et al. 1991. Hypothyroidism reduces the rate of slow 

component A (Sca) axonal transport and the amount of transported tubulin in the hyt/hyt mouse optic 

nerve. J Neurosci Res 28:121-133. 

*St. Omer VEV, Gadusek F. 1987. The acute oral LD50 of technical pentachlorophenol in developing 

rats. Environ Toxicol Chem 6:147-149. 

*Thompson TS, Treble RG. 1994. Preliminary results of a survey of pentachlorophenol levels in human 

urine. Bull Environ Contam Toxicol 53:274-279. 

*Thompson TS, Treble RG. 1996. Pentachlorophenol levels in human urine. Bull Environ Contam 

Toxicol 56:520-526. 

*Thompson TS, Treble RG, Mariasegaram M. 1997. Determination of atmospheric contamination by 

pentachlorophenol using pine needles located near treated utility pole storage sites. Bull Environ Contam 

Toxicol 59:548-555. 

Tjeerdema RS, Kauten RJ, Crosby DG. 1993. Interactive effects of pentachlorophenol and temperature 

in the abalone (haliotis rufescens) as measured by in vivo 32p-NMR spectroscopy. Aquat Toxicol 

26:117-132. 

Tjeerdema RS, Lukrich KL, Stevens EM. 1994. Toxicokinetics and biotransformation of 

pentachlorophenol in the sea urchin (strongylocentrotus purpuratus). Xenobiotica 24:749-757. 

*Tran DQ, Klotz DM, Ladlie BL, et al. 1996. Inhibition of progesterone receptor activity in yeast by 

synthetic chemicals. Biochem Biophys Res Commun 229:518-523. 

Trapido M, Hirvonen A, Veressinina Y, et al. 1997. Ozonation, ozone/UV and UV/H2O2 degradation of 

chlorophenols. Ozone Sci Eng 19:75-96. 

*Treble RG, Thompson TS. 1996. Normal values for pentachlorophenol in urine samples collected from 

a general population. J Anal Toxicol 20:313-317. 

Trenti T, Ventura E, Ceccarelli D, et al. 1986. Porphyrins and pentachlorophenol in rat-liver 

mitochondria in hexachlorobenzene-induced porphyria. IARC Sci Publ:457-459. 

Trevors JT, Mayfield CI, Inniss WE, et al. 1981. Effects of phenolic antioxidants on the toxicity of 

pentachlorophenol in short-term bacterial bioassays. Bull Environ Contam Toxicol 27:433-439. 

Trevors JT, Mayfield CI, Inniss WE. 1982. Effect of sequence of exposure to chlorophenols in 

short-term bacterial bioassays. Arch Environ Contam Toxicol 11:203-207. 

TRI90. 1992. Toxic Chemical Release Inventory. Bethesda, MD: National Library of Medicine, 

National Toxicology Information Program. 

TRI92. 1996. Toxic Substances Release Inventory. Bethesda, MD: National Library of Medicine, 

National Toxicology Information Program. 

TRI96. 1999. Toxic Substances Release Inventory. Bethesda, MD: National Library of Medicine, 

National Toxicology Information Program. 
PENTACHLOROPHENOL 256 

9. REFERENCES 

TRI98. 2000. TRI explorer: Providing access to EPA’s toxics release inventory data. Washington, DC: 

Office of Information Analysis and Access. Offices of Environmental Information. U.S. Environmental 

Protection Agency. Toxic Release Inventory. Http://www.epa.gov/triexplorer/. November 09, 2000. 

*TR199. 2001. TRI explorer. Providing access to EPA’s toxics release inventory data. Washington, 

DC: Office of Information Analysis and Access. Offices of Environmental Information. U.S. 

Environmental Protection Agency. Toxic Release Inventory. Http://www.epa.gov/triexplorer/. May 15, 

2001. 

*Triebig G, Csuzda I, Krekeler HJ, et al. 1987. Pentachlorophenol and the peripheral nervous system: A 

longitudinal study in exposed workers. Br J Ind Med 44:638-641. 

UATW. 1999. Unified air toxics website. Office of Air Quality Planning and Standards, U.S. 

Environmental Protection Agency. Http://www.epa.gov/ttnuatw1/uatwn.html. May 6, 1999. 

*Uhl S, Schmid P, Schlatter C. 1986. Pharmacokinetics of pentachlorophenol in man. Arch Toxicol 

58:182-186. 

Umegaki K, Ikegami S, Ichikawa T. 1993. [Hepatic DNA damage in mice given organochlorine 

chemicals.] J Food Hyg Soc Jpn 34:68-73. (Japanese) 

*Umemura T, Kai S, Hasegawa R, et al. 1999. Pentachlorophenol (PCP) produces liver oxidative stress 

and promotes but does not initiate hepatocarcinogenesis in B6C3F1 mice. Carcinogenesis 20(6):1115­

1120. 

*Umemura T, Sai-Kato K, Takagi A, et al. 1996. Oxidative DNA damage and cell proliferation in the 

livers of B6C3F1 mice exposed to pentachlorophenol in their diet. Fundam Appl Toxicol 30:285-289. 

*USC. 1998. United States Code. 42 USC 7412. 

*USC. 2001. United States Code. 42 USC Section 7412. 

*van Gestel C, Ma V. 1988. Toxicity and bioaccumulation of chlorophenols in earthworms, in relation 

to bioavailability in soil. Ecotoxicol Environ Safety 15:289-297. 

Van Gestel CAM, Adema DMM, Dirven-Van Breemen EM. 1996. Phytoxicity of some chloroanilines 

and chlorophenols in relation to bioavailability in soil. Water Air Soil Pollut 88:119-132. 

*Van Langeveld HEAM. 1975. Determination of pentachlorophenol in toy paints. J Off Anal Chem 

58:19-22. 

*van Raaij JA, van den Berg KJ, Engel R, et al. 1991a. Effects of hexachlorobenzene and its metabolites 

pentachlorophenol and tetrachlorohydroquinone on serum thyroid hormone levels in rats. Toxicology 

67:107-116. 

*van Raaij JA, van den Berg KJ, Notten WR. 1991b. Hexachlorobenzene and its metabolites 

pentachlorophenol and tetrachlorohydroquinone: Interaction with thyroxine binding sites of rat thyroid 

hormone carriers ex vivo and in vitro. Toxicol Lett 59:101-107. 

*van Raaij JAGM, Frijters CMG, Kong LWY, et al. 1994. Reduction of thyroxine uptake into 

cerebrospinal fluid and rat brain by hexachlorobenzene and pentachlorophenol. Toxicology 94:197-208. 
PENTACHLOROPHENOL 257 

9. REFERENCES 

Vasarhelyi B, Balzovics A, Feher J. 1993. [The place of pentachlorophenol in general medicinal 

practice]. [Hungarian] Orv Hetil 134:2649-2652. 

*Vega-Nunez E, Menedez-Hurtado A, Garesse R, et al. 1995. Thyroid hormone-regulated brain 

mitrochondrial genes revealed by differential cDNA cloning. J Clin Invest 96:893-899. 

Veith GD, Defoe D, Knuth M. 1985. Structure-activity relationships for screening organic chemicals for 

potential ecotoxicity effects. Drug Metab Rev 15:1295-1303. 

Venegas W, Hermosilla I, Quevedo L, et al. 1993. Genotoxic and teratogenic effect of 

pentachlorophenol, pollutant present in continental water bodies in the south of Chile. Bull Environ 

Contam Toxicol 51:107-114. 

Venegas W, Zapata I, Carbonell E, et al. 1998. Micronuclei analysis in lymphocytes of pesticide 

sprayers from Concepcion, Chile. Teratog Carcinog Mutagen 18:123-129. 

*Veningerova M, Uhnak J, Prachar V, et al. 1996. Chlorinated phenols in human milk. Z Lebensm 

Unters Forsch 203:309-310. 

*Verschueren K. 1983. Handbook of environmental data on organic chemicals. 2nd ed. New York, NY: 

Van Nostrand Reinhold Co., 953-954. 

*Vieira I, Sonnier M, Cresteil T. 1996. Developmental expression of CYP2E1 in the human liver: 

hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238:476-483. 

*Villena F, Montoya G, Klaasen R, et al. 1992. Morphological changes on nerves and histopathological 

effects on liver and kidney of rats by pentachlorophenol (PCP). Comp Biochem Physiol, C: Comp 

Pharmacol Toxicol 101C:353-363. 

*Vizethum W, Goerz G. 1979. Induction of the hepatic microsomal and nuclear cytochrome 

P-450 system by hexachlorobenzene, pentachlorophenol, and trichlorophenol. Chem Biol Interact 

28:291-299. 

*Vogel E, Chandler JLR. 1974. Mutagenicity testing of cyclamate and some pesticides in drosophila 

melanogaster. Experientia 30:621-623. 

Vonier PM, Crain DA, McLachlan JA, et al. 1996. Interaction of environmental chemicals with the 

estrogen and progesterone receptors from the oviduct of the American alligator. Environ Health Perspect 

104:1318-1322. 

*Vulcan Chemicals. 1989. Vulcan Chemicals. Written communication May 15, 1989 to ATSDR. 

Public comment on toxicological profile for pentachlorophenol. Birmingham, AL. 

*Wade AL, Hawkridge FM, Williams HP. 1979. Direct determination of pentachlorophenol by 

differential pulse polarography. Anal Chem Acta 105:91-97. 

*Wagner SL, Durand LR, Inman RD, et al. 1991. Residues of pentachlorophenol and other chlorinated 

contaminants in human tissues: Analysis by electron capture gas chromatography and electron capture 

negative ion mass spectrometry. Arch Environ Contam Toxicol 21:596-606. 
PENTACHLOROPHENOL 258 

9. REFERENCES 

*Waidyanatha S, Lin PH, Rappaport SM. 1996. Characterization of chlorinated adducts of hemoglobin 

and albumin following administration of pentachlorophenol to rats. Chem Res Toxicol 9:647-653. 

*Waidyanatha S, McDonald TA, Lin PH, et al. 1994. Measurement of hemoglobin and albumin adducts 

of tetrachlorobenzquinone. Chem Res Toxicol 7:463-468. 

*Wall AJ, Stratton GW. 1991. Comparison of methods for the extraction of pentachlorophenol from 

aqueous and soil systems. Chemosphere 22:99-106. 

Waltner-Toews D, McEwen SA. 1994. Residues of industrial chemicals and metallic compounds in 

foods of animal origin: A risk assessment. Prev Vet Med 20:201-218. 

Wang WX, Widdows J. 1993. Interactive effects of pentachlorophenol (PCP) and hypoxia on the energy 

metabolism of the mussel, mytilus edulis. Mar Environ Res 35:109-113. 

*Wang YJ, Lin JK. 1995. Estimation of selected phenols in drinking water with in situ acetylation and 

study on the DNA damaging properties of polychlorinated phenols. Bull Environ Contam Toxicol 

28:537-542. 

Wassom JS, Huff JE, Loprieno N. 1977/1978. A review of the genetic toxicology of chlorinated 

dibenzo-p-dioxins. Mutat Res 47:141-160. 

Watanabe I. 1973. Isolation of pentachlorophenol decomposing bacteria from soil. Soil Sci Plant Nutr 

19:109-116. 

Watanabe S, Kato Y, Miyasaka K, et al. 1994. Inhibitory effect of riboflavin tetrabutyrate on the lipid 

peroxidation by pentachlorophenol. Jpn J Toxicol Environ Health (Eisei Kagaku) 40:433-439. 

Watanabe S, Miyasaka K, Yamamoto K, et al. 1993. [Production of active oxygen species and lipid 

peroxidation by the metabolism of pentachlorophenol.] Jpn J Toxicol Environ Health (Eisei Kagaku) 

39:534-542. (Japanese) 

*Waters MD, Sandhu SS, Simmon VF. 1982. Study of pesticide genotoxicity. Basic Life Sci 

21:275-326. 

WDNR. 1987. Surface water quality criteria for toxic substances. Wisconsin Department of Natural 

Resources, 1987. Order of the State of Wisconsin Natural Resources Board Repealing, Renumbering, 

Renumbering and Amending, Amending, Repealing and Recreating, and Creating Rules. Section 27, 

Chapter NR 105. 

*Weinbach EC. 1954. The effect of pentachlorophenol on oxidative phosphorylation. J Biol Chem 

210:545-550. 

*Weinbach EC, Garbus J. 1965. The interaction of uncoupling phenols with mitochondria and 

mitochondrial proteins. J Biol Chem 240:1811-1819. 

*Weinberg. 1997. Draft: Preliminary risk assessment of microcontaminant leaching from 

pentachlorophenol-treated wood poles in Canada. Washington, DC: The Weinberg Group Inc. 

*Welsh JJ, Collins TFX, Black TN, et al. 1987. Teratogenic potential of purified pentachlorophenol and 

pentachloroanisole in subchronically exposed Sprague-Dawley rats. Food Cosmet Toxicol 25:163-172. 
 

PENTACHLOROPHENOL 259 

9. REFERENCES 

*West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and 

maximal tubular excretory capacity in infancy. J Pediatr 32:10-18. 

*Wester RC, Maibach HI, Sedik L, et al. 1993. Percutaneous absorption of pentachlorophenol from soil. 

Fundam Appl Toxicol 20:68-71. 

*White KL, Jr, Anderson AC. 1985. Suppression of mouse complement activity by contaminants of 

technical grade pentachlorophenol. Agents Actions 16:385-392. 

White R, Jobling S, Hoare SA, et al. 1994. Environmentally persistent alkylphenolic compounds are 

estrogenic. Endocrinology 135:175-182. 

WHO. 1984. Guidelines for drinking water quality: Recommendations. Vol. 1. Lyon, France: World 

Health Organization, 8. 

*WHO. 1987. Environmental health criteria 71: Pentachlorophenol. International Programme on 

Chemical Safety, World Health Organization, Geneva, Switzerland, CH-1211. 

*WHO. 2001. Water, sanitation and health. Guidelines for drinking water quality. Geneva, 

Switzerland; World Health Organization. 

Http://www.who.int/water_sanitation..Chemicals/pentachlorophenolfull.htm. February 07, 2001. 

*Widdowson EM, Dickerson JWT. 1964. Chapter 17: Chemical composition of the body. In: Comar 

CL, Bronner F, eds. Mineral metabolism: An advanced treatise. Volume II: The elements Part A. New 

York, NY: Academic Press. 

*Wild SR, Jones KC. 1992. Pentachlorophenol in the UK environment: II. Human exposure and an 

assessment of pathways. Chemosphere 24:847-855. 

Williams PL. 1982. Pentachlorophenol, an assessment of the occupational hazard. Am Ind Hyg Assoc J 

43:799-810. 

Willis KJ, Ling N, Chapman MA. 1995. Effects of temperature and chemical formulation on the acute 

toxicity of pentachlorophenol to simocephalus vetulus (Schoedler, 1858) (Crustacea: Cladocera). N Z J 

Mar Freshwater Res 29:289-294. 

Windolz M, ed. 1983. The Merck index. 10th ed. Rahway, NJ: Merck & Co. 

*Wisconsin DNR. 2001. Draft NR 445 chemical list final tag Sept 2001. Wisconsin Department of 

Natural Resources. 

Witte I, Juhl U, Butte W. 1985. DNA-damaging properties and cytotoxicity in human fibroblasts of 

tetrachlorohydroquinone, a pentachlorophenol metabolite. Mutat Res 145:71-75. 

Wolf J, Fengel D, Klein RG, et al. 1998. [Etiology of nose cancer in the wood working industry.] 

Geharstoffe Reinhalt Luft 58:455-461. (German) 

Wong AS, Crosby DG. 1978. Photolysis of pentachlorophenol in water. In: Rao KR, ed. 

Pentachlorophenol: Chemistry, pharmacology, and environmental toxicology. New York, NY: Plenum 

Press, 19-25. 
PENTACHLOROPHENOL 260 

9. REFERENCES 

*Wong AS, Crosby DG. 1981. Photodecomposition of pentachlorophenol in water. J Agric Food Chem 

29:125-130. 

*Wood S, Rom WN, White GL, et al. 1983. Pentachlorophenol poisoning. J Occup Med 25:527-530. 

*Wyllie JA, Gabica J, Benson WW, et al. 1975. Exposure and contamination of the air and employees of 

a pentachlorophenol plant, Idaho-1972. Pestic Monit J 9:150-153. 

*Xie TM. 1983. Determination of trace amounts of chlorophenols and chloroguaiacols in sediment. 

Chemosphere 12:1183-1191. 

Xing B, Mcgill WB, Dudas MJ. 1993. Thermodynamic parameters for pentachlorophenol sorption on 

montmorillonite in aqueous suspensions. Chemosphere 26:1311-1324. 

*Yess NJ, Genderson EL, Roy RR. 1993. U.S. Food and Drug Administration monitoring of pesticide 

residues in infant foods and adult foods eaten by infants/children. J AOAC Int 76:492-507. 

Yoon B, Cho M, Kim I, et al. 1997. [Mutant frequency at the HPRT locus in human T-cell exposed to 

pentachlorophenol.] Korean Journal of Toxicology 13:71-78. (Korean) 

*You CN, Liu JC. 1996. Desorptive behavior of chlorophenols in contaminated soils. Water Sci 

Technol 33:263-270. 

*Young HC, Carroll JC. 1951. The decomposition of pentachlorophenol when applied as a residual preemergence herbicide. Agron J 43:504-507. 

*Young RHF, Lau LS, Konno SK, et al. 1976. Water quality monitoring: Kaneohe bay and selected 

watersheds, July to December 1975. Water Resources Research Center, University of Hawaii, Honolulu, 

Hawaii. Technical Report No. 98. 

Yu Z, Iryo Y, Matsuoka M, et al. 1998. Effects of pentachlorophenol, pentylenetetrazol and carnitine on 

mitochondria. J Uoeh 20:315-322. 

Yuan JH, Goehl TJ, Murrill E, et al. 1993. Toxicokinetics of pentachloroanisole in F344 rats and 

B6C3F1 mice. Xenobiotica 23:427-438. 

*Yuan JH, Goehl TJ, Murrill E, et al. 1994. Toxicokinetics of pentachlorophenol in the F344 rat. 

Gavage and dosed feed studies. Xenobiotica 24:553-560. 

Zamorano-Ponce E, Fernandez JR, Vega LR, et al. 1994. [Pentachlorophenol inhibits the mutagenic 

effect of benzidine.] Rev Toxicol 11:32-35. (Spanish) 

Zhao F, Mayura K, Hutchinson RW, et al. 1995. Developmental toxicity and structure-activity 

relationships of chlorophenols using human embryonic palatal mesenchymal cells. Toxicol Lett 78:35­

42. 

Zhao W, Ramos KS. 1998. Cytotoxic response profiles of cultured rat hepatocytes to selected aromatic 

hydrocarbons. Toxicol in Vitro 12:175-182. 
PENTACHLOROPHENOL 261 

9. REFERENCES 

*Zhu B-Z, Kirotsky N, Chevion M. 2000. Evidence for production of hydroxyl radicals by 

pentachlorophenol metabolites and hydrogen peroxide: A metal-dependent organic fenton reaction. 

Biochem Biphys Res Commun 270:942-946. 

*Ziegler EE, Edwards BB, Jensen RL et al. 1978. Absorption and retention of lead by infants. Pediatr 

Res 12:29-34. 

*Ziemsen B, Angerer J, Lehnart G. 1987. Sister chromatid exchange and chromosomal breakage in PCP 

exposed workers. Int Arch Occup Environ Health 59:413-417. 

PENTACHLOROPHENOL 263 

10. GLOSSARY 

Absorption—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 or less, 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 a 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)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

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—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of 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 which examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research but are not actual research studies. 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research but are not actual research studies. 
PENTACHLOROPHENOL 264 

10. GLOSSARY 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Clastogenic–An agent capable of causing breakage of chromosomes. 

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. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups which examines the 

relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health 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 adverse effects. 

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 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Endocrine System–A system of ductless hormone-secreting glands that includes the hypothalamus, 

pituitary gland, adrenal glands, thyroid glands, parathyroid glands, and pancreatic islets. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance 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. 

Epidemiology—Refers to 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. 

FEFR25–75—Forced expiratory flowrate between 25 and 75%. 

FEV1.0—Forced expiratory volume in 1.0 seconds. 

FVC—Forced vital capacity. 

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. 
PENTACHLOROPHENOL 265 

10. GLOSSARY 

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. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

Immune System–A cellular complex that forms the basis of the body’s defenses to both biological and 

chemical exogenous substances. 

Incidence—The ratio 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. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

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 which 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 which 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. 
PENTACHLOROPHENOL 266 

10. GLOSSARY 

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. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

Mortality—Death; 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. A mutation is a change 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 

chemical. 

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. Effects may be produced at this dose, but 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) which 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 of greater than 1 is considered to indicate greater risk 

of disease in the exposed group compared to the unexposed. 

Organophosphate or Organophosphorus Compound—A phosphorus containing organic compound and 

especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour 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. 

Pharmacokinetics—The science of quantitatively predicting 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. 
PENTACHLOROPHENOL 267 

10. GLOSSARY 

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 whereby the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically-based doseresponse model which quantitatively describes the relationship between target tissue dose and toxic end 

points. 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. 

Physiologically Based Pharmacokinetic (PBPK) Model—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: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information 

such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called 

biologically based tissue dosimetry models. 

ppbv—Parts per billion by volume. 

ppmv—Parts per million by volume. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Proportionate Mortality Ratio (PMR)—The ratio of a cause-specific mortality proportion in an exposed 

group to the mortality proportion in an unexposed group; mortality proportions may be adjusted for 

confounding variables such as age. Cause-specific mortality proportions can be calculated when the 

cohort (the population at risk) cannot be defined due to inadequate records, but the number of deaths and 

the causes of deaths are known. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1

*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentrations 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 

reference concentration is for continuous inhalation exposures and is appropriately expressed in units of 

mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 
PENTACHLOROPHENOL 268 

10. GLOSSARY 

effects during a lifetime. The RfD is operationally derived from the No-Observed-Adverse-Effect Level 

(NOAEL- from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Relative Risk (RR)—The risk expressed as a ratio of the incidence of diseased subjects exposed to a 

particular risk factor to the incidence of diseased subjects in a non-exposed referent group. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under the 

Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater 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 chemical. 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 chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic, that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial Hygienists 

(ACGIH) maximum concentration to which workers can be exposed for up to 15 min continually. No 

more than four excursions are allowed per day, and there must be at least 60 min between exposure 

periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may not be exceeded. 

Standardized Mortality Ratio (SMR)—The ratio of a cause-specific mortality rate in an exposed cohort 

during a given period to the mortality rate of an unexposed cohort; mortality rates are often adjusted for 

age or other confounding variables. 

Standardized Proportionate Incidence Ratio (SPIR)—Similar to a Proportionate Mortality Ratio (PMR) 

in that it is a ratio of a proportion of a specific disease in an exposed group compared with the proportion 

in an unexposed group. 
PENTACHLOROPHENOL 269 

10. GLOSSARY 

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 most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The study of the absorption, distribution and elimination of toxic compounds in the 

living organism. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

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 one can be 

used; however a reduced UF of three may be used on a case-by-case basis, three being the approximate 

logarithmic average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 

PENTACHLOROPHENOL A-1 

APPENDIX A
 

ATSDR MINIMAL RISK LEVELS AND WORKSHEETS
 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 

99–499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly 

with the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances 

most commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (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 duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. 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 no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) 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 chemical-induced end 

point 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. 
PENTACHLOROPHENOL A-2 

APPENDIX A 

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 a hundredfold below levels 

that have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, 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 levels. For additional information 

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333. 
 

PENTACHLOROPHENOL A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Pentachlorophenol 

CAS Number: 87-86-5 

Date: June 22, 2001 

Profile Status: Final 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Key to Figure: 14 

Species: Rats 

Minimal Risk Level: 0.005 [X] mg/kg/day [ ] mg/m3 

Reference: Schwetz BA, Keeler PA, Gehring PJ. 1974. The effect of purified and commercial grade 

pentachlorophenol on rat embryonal and fetal development. Toxicol Appl Pharmacol 28:151-161. 

Experimental design (human study details or strain, number of animals per exposure/control groups, sex, 

dose administration details): Purified (98%+) and commercial-grade (88.4%) pentachlorophenol were 

administered by gavage in corn oil to groups of 20–40 pregnant Sprague-Dawley rats on days 6–15 of 

gestation at doses of 0 (corn oil control), 5, 15, 30, and 50 mg/kg/day. At the 5 and 30 mg/kg/day dose 

levels, the actual amount of pentachlorophenol administered was 5.8 and 34.7 mg/kg/day, which was 

equivalent to 5 and 30 mg/kg/day pure pentachlorophenol. 

Effects noted in study and corresponding concentrations: Maternal body weight gain was significantly 

decreased at 30 and 50 mg/kg/day with both pure and commercial-grade pentachlorophenol. Otherwise, 

no signs of maternal toxicity were noted. Significant increases in incidences of resorptions were seen at 

15, 30, and 50 mg/kg/day commercial-grade pentachlorophenol and at 30 and 50 mg/kg/day with the pure 

pentachlorophenol. There was 100% resorption of implantations at the 50 mg/kg/day pure 

pentachlorophenol dose level. The sex ratio was significantly altered at 30 mg/kg/day pure 

pentachlorophenol and 50 mg/kg/day of the commercial-grade pentachlorophenol, with the majority of 

the survivors being male offspring. 

Significant decreases in fetal body weight were observed at 30 and 50 mg/kg/day of commercial-grade 

pentachlorophenol and significant decreases in fetal body weight and crown-rump length were seen with 

30 mg/kg/day of pure pentachlorophenol. Fetal malformations and/or variations were observed at 

15 mg/kg/day and higher for the commercial-grade pentachlorophenol and 5 mg/kg/day and higher for the 

pure pentachlorophenol. The observed effects for the commercial-grade groups included subcutaneous 

edema and lumbar spurs at $15 mg/kg/day, rib, sternebrae, and vertebrae anomalies at $30 mg/kg/day. In 

the pure pentachlorophenol offspring, the incidence of delayed ossification of the skull was significantly 

increased at $5 mg/kg/day, and significant increases in the occurrence of subcutaneous edema, lumbar 

spurs, and skeletal anomalies in the ribs, sternebrae, and vertebrae were observed at $15 mg/kg/day. 

Concentration and end point used for MRL derivation: This MRL is based on a LOAEL of 5 mg/kg/day 

for delayed ossification of the skull in rat pups when the dams were given pure pentachlorophenol by 

corn oil gavage on gestation days 6 through 15. 

[ ] NOAEL [X] LOAEL 
PENTACHLOROPHENOL A-4 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No 

If an inhalation study in animals, list conversion factors used in determining human equivalent 

concentration: NA 

Was a conversion used from intermittent to continuous exposure? NA 

Other additional studies or pertinent information that lend support to this MRL: Similar developmental 

effects have been observed in another developmental toxicity study (Argus 1993b/Bernard et al. 2001b). 

In this study, significant increases in the occurrence of resorptions, soft tissue and skeletal malformations 

and variations and decreases in fetal body weight were observed in the offspring of rats were administered 

by gavage 80 mg/kg/day technical grade (89% pure) pentachlorophenol on gestational days 6–15. This 

study identified a NOAEL of 30 mg/kg/day. Intermediate-duration oral developmental toxicity studies in 

rats have also reported increased fetal/neonatal mortality, malformations, and/or variations, and decreased 

growth (Argus 1997/Bernard et al. 2001c; Courtney et al. 1976; Exon and Koller 1982; Schwetz et al. 

1978; Welsh et al. 1987). 

Agency Contact (Chemical Manager): Lori L. Miller, M.P.H. 
PENTACHLOROPHENOL A-5 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Pentachlorophenol 

CAS Number: 87-86-5 

Date: June 22, 2001 

Profile Status: Final 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Key to Figure: 47 

Species: Mink 

Minimal Risk Level: 0.001 [X] mg/kg/day [ ] mg/m3 

Reference: Beard AP, McRae AC, Rawlings NC. 1997. Reproductive efficiency in mink (Mustela 

vison) treated with the pesticides lindane, carbofuran, and pentachlorophenol. J Reprod Fertil 111:21-28. 

Experimental design (human study details or strain, number of animals per exposure/control groups, sex, 

dose administration details): Groups of 10 female mink were exposed to 1 mg/kg/day pentachlorophenol 

in the diet for 3 weeks prior to mating with unexposed males and throughout pregnancy and lactation. 

The females were mated twice at 7–8 day intervals. The purity of the pentachlorophenol was not 

reported. 

Effects noted in study and corresponding concentrations: A decrease in the proportion of mated females 

accepting a second mating and the proportion of mink that whelped were observed. No effect on the 

proportion of mink accepting the first mating or the proportion of mink with visible implantation sites 

were found. An increase in the severity cystic uterine glands was also observed in the pentachlorophenolexposed mink. 

Concentration and end point used for MRL derivation: This MRL is based on a LOAEL of 1 mg/kg/day 

for reproductive effects in mink exposed to pentachlorophenol (purity not reported) in the diet. 

[ ] NOAEL [X] LOAEL 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Dose was calculated 

by the study authors. 

If an inhalation study in animals, list conversion factors used in determining human equivalent 

concentration: NA 

Was a conversion used from intermittent to continuous exposure? NA 

Other additional studies or pertinent information that lend support to this MRL: Several other studies 

have examined the reproductive toxicity of pentachlorophenol. Decreased fertility has been observed in 
PENTACHLOROPHENOL A-6 

APPENDIX A 

the first generation of rats exposed to 60 mg/kg/day, but not in the parental or second generations; the 

NOAEL for this effect is 30 mg/kg/day (Argus 1997/Bernard et al. 2001c). A significant decrease in 

testicular spermatid count, decreases in absolute testes weight and the ratio of testes weight to brain 

weight, and focal/multifocal mononuclear cell infiltrate in the epididymis were observed in the F1 rats 

administered 30 or 60 mg/kg/day. However, no alterations in the average number of motile or nonmotile 

sperm, epididymal or testicular sperm counts, or sperm morphology were observed in either generation 

(Argus 1997/Bernard et al. 2001c). No alterations in reproductive tissues were observed in the female 

rats. Significant increases in the average day of preputial separation and vaginal patency were observed 

in the F1 generation, suggesting that in utero exposure to pentachlorophenol disrupted the normal 

development of the reproductive system. No adverse reproductive effects were observed in another mink 

study in which the animals were also fed a diet containing 1 mg/kg/day pentachlorophenol (purity not 

reported) (Beard and Rawlings 1998). Additionally, no significant alterations in mating response, 

ovulation rate, follicle and corpus luteum size, gestation length, pregnancy rate, lambing rate, and lamb 

birth rate were observed in sheep exposed to 1 mg/kg/day pentachlorophenol in the diet for 5 weeks 

premating and throughout the gestation and lactation periods (Beard et al. 1999b). No effect on fertility 

was observed in the offspring of these sheep, later mated to unexposed males (Beard and Rawlings 1999). 

Several reproductive toxicity and nonreproductive toxicity studies have reported histological alterations 

in reproductive tissues. The observed effects include focal degeneration of the seminiferous tubules and 

decreased sperm density in the epididymis body (but not in caput or cauda epididymis) in sheep exposed 

to 1 mg/kg/day pentachlorophenol (purity not reported) in the diet during gestation, lactation, and for 

20 weeks postnatally (Beard et al. 1999a), minimal to marked germinal epithelial degeneration and lack 

of spermatozoa in the seminiferous tubules of rats exposed to 270 mg/kg/day pure pentachlorophenol in 

the diet for 28 days (effects may have been secondary to poor condition of animals) (Chhabra et al. 1999; 

NTP 1999), increased severity of oviductal intraepithelial cysts in sheep administered 2 mg/kg/day pure 

pentachlorophenol by gavage twice weekly for 43 days (Rawlings et al. 1998), and lymphocyte 

infiltration into the endometrium in sheep exposed to 1 mg/kg/day pentachlorophenol (purity not 

reported) in the diet for 5 weeks premating and during the gestation and lactation periods (Beard et al. 

1999b). No histological alterations in reproductive tissues were observed in male or female rats 

chronically exposed to 30 mg/kg/day pure pentachlorophenol in the diet for 2 years (Chhabra et al. 1999; 

NTP 1999). Additionally, no alterations in reproductive hormones (estradiol, testosterone, progesterone, 

follicle stimulating hormone, and/or luteinizing hormone levels) have been observed in mink (Beard et al. 

1997) or sheep (Beard et al. 1999a). 

Liver and developmental effects also appear to be sensitive end points of pentachlorophenol following 

intermediate-duration oral exposure; the lowest adverse effect levels for these effects are 10-fold higher 

than the reproductive effects reported in mink. Significant increases in relative liver weight and the 

occurrence of centrilobular hepatocellular hypertrophy have been reported in rats and mice exposed to 

<10 mg/kg/day pure or technical-grade pentachlorophenol (Blakley et al. 1998; Kerkvliet et al. 1982; 

Kimbrough and Linder 1978; Knudsen et al. 1974). At higher doses, hepatocyte degeneration and 

necrosis have been observed (Kerkvliet et al. 1982; NTP 1989, 1999). Developmental effects (decreased 

pup body weight) have also been observed in rat offspring at 10–15 mg/kg/day (Argus 1997/Bernard et 

al. 2001c; Welsh et al. 1987). 

Agency Contact (Chemical Manager): Lori L. Miller, M.P.H. 
PENTACHLOROPHENOL A-7 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Pentachlorophenol 

CAS Number: 87-86-5 

Date: June 22, 2001 

Profile Status: Final 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Key to Figure: 54 

Species: Mink 

Minimal Risk Level: 0.001 [X] mg/kg/day [ ] mg/m3 

Reference: Beard AP, Rawlings NC. 1998. Reproductive effects in mink (mustela vison) exposed to the 

pesticides lindane, carbofuran and pentachlorophenol in a multigeneration study. J Reprod Fertil 113:95­

104. 

Experimental design (human study details or strain, number of animals per exposure/control groups, sex, 

dose administration details): Pentachlorophenol (Sigma, St. Louis, Missouri; purity not indicated) was 

administered at a dose of 1 mg/kg/day in the diet to parental-generation female mink from 3 weeks prior 

to mating (with untreated males) until weaning of first-generation offspring. Male and female offspring 

in the first and second generations were continued on the pentachlorophenol diet effectively from 

conception until sexual maturity. As with the parental generation, females of the first generation were 

mated with untreated males. The number of control and treated females in the parental generation was 

not indicated. Ten control and 8 pentachlorophenol-treated females of the first generation, continued on 

the pentachlorophenol diet throughout growth, mating, pregnancy, lactation, and for 3 months after the 

end of lactation, were mated to produce the second generation. Ten control and 6 pentachlorophenol 

males of the first generation were killed when their testis development was maximal at about 42 weeks of 

age. The study group in the second generation consisted of 8 males and 10 females given control diet and 

8 males and 10 females continued on the pentachlorophenol diet. At necropsy of the first-generation 

males, weights of the testes, epididymides, and penis were recorded, and these organs and samples of the 

pancreas, liver, and pituitary gland were fixed for microscopic examination; dimensions of the testes and 

penis were also recorded. At necropsy of the first-generation females, weights of the ovaries, oviduct, 

uterus, pituitary, thyroid, parathyroid, and adrenals were recorded, and samples of these and the pancreas 

were fixed for microscopic examination. Weights of the heart, brain, liver, and kidney were also 

recorded. In the second-generation animals, the same tissues were weighed and measured, but no tissues 

were examined histologically in the females and only endocrine and reproductive tissues were examined 

histologically in the males. Serum from blood samples collected at necropsy of first and second 

generation males and females was analyzed for estradiol and thyroxine. Serum cortisol was also 

measured in first-generation females and serum testosterone was measured in first- and second-generation 

males. 

Effects noted in study and corresponding concentrations: No overt signs of toxicity were seen and no 

reproductive effect end points were altered in the pentachlorophenol-treated groups compared with 

controls. The only effects noted in the pentachlorophenol-treated groups were significantly-decreased 

serum thyroxine concentrations in males of the first generation and in males and females of the second 

generation, and significantly-decreased relative thyroid weight in females of the second generation. 
PENTACHLOROPHENOL A-8 

APPENDIX A 

Concentration and end point used for MRL derivation: This MRL is based on a LOAEL of 1 mg/kg/day 

(only dose tested) for significantly-decreased serum thyroxine concentrations in males of the first 

generation and males and females of the second generation and decreased relative thyroid weight in 

females of the second generation when mink were administered pentachlorophenol of unspecified purity 

continuously in the diet in a multigeneration reproduction study. 

[ ] NOAEL [X] LOAEL 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No. The dose of 

1 mg/kg/day was estimated by the study authors. Details of the method of dose estimation were not 

provided. 

If an inhalation study in animals, list conversion factors used in determining human equivalent 

concentration: NA 

Was a conversion used from intermittent to continuous exposure? NA 

Other additional studies or pertinent information that lend support to this MRL: Single intraperitoneal 

injections of pentachlorophenol of unspecified purity at doses up to 28 mg/kg caused marked, statistically 

significant, dose-related decreases in the serum total thyroxine level in male rats (van Raaij et al. 1991a). 

The decreases were maximal at 6–24 hours after administration, and thyroxine levels slowly returned to 

control values within 96 hours after administration. Further in vitro studies by these investigators 

revealed that the likely mechanism of action for this anti-thyroid effect was competition for serum protein 

thyroxine binding sites (van Raaij et al. 1991b). A decrease in maternal serum thyroxine (T4) 

concentration throughout pregnancy and lactation and a significant increase in maternal thyroid gland 

follicle size were found in female sheep administered 1 mg/kg/day pentachlorophenol (purity not 

indicated) in the diet 5 weeks prior to mating and throughout pregnancy and lactation until 2 weeks after 

weaning of the lambs (Beard et al. 1999b). Additionally, increased thyroxine levels were observed in 

their ewe and ram lambs that also received postnatal exposure to pentachlorophenol (Beard and Rawling 

1999; Beard et al. 1999a). Oral gavage administration of pure pentachlorophenol to young adult female 

rats over a 28-day period at doses of 3 or 30 mg/kg produced decreases in circulating and free 

concentrations of the thyroid hormones triiodothyronine (T3) and T4 in serum, a decrease in serum 

thyroid stimulating hormone, decreases in intrathyroidal levels of T3 and T4, a decrease in the T4:T3 

ratio in serum, and a reduction in thyroidal hormone stores. Technical-grade pentachlorophenol, tested 

only at a dose of 3 mg/kg, produced the same effects except the reduction in free T3 in serum (data for 

free serum T4 were not reported) (Jekat et al. 1994). Single intraperitoneal injections of pentachlorophenol of unspecified purity into adult male rats at doses of 7, 14, or 28 mg/kg also caused marked, 

statistically significant, dose-related decreases in the uptake of radiolabeled T4 into cerebrospinal fluid 

compared with control (van Raaij et al. 1994). 

Agency Contact (Chemical Manager): Lori L. Miller, M.P.H. 
PENTACHLOROPHENOL B-1 

APPENDIX B 

USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, 

weight-of-evidence discussions for human health end points 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? 

The chapter covers end points in the same order they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are 

presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered 

in this chapter. If data are located in the scientific literature, a table of genotoxicity information is 

included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 
PENTACHLOROPHENOL B-2 

APPENDIX B 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (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. They should help physicians 

and public health officials determine the safety of a community living near a chemical 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. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" 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 the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

To derive an MRL, ATSDR generally selects the most sensitive end point 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 end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest 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 (UF) 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 substance-specific MRL 

are provided in the footnotes of the LSE Tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) 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, minimal risk levels 

(MRLs) to humans for noncancer end points, and EPA's estimated range associated with an upper- bound 

individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures 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 No-Observed-Adverse-Effect Levels 

(NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs). 
PENTACHLOROPHENOL B-3 

APPENDIX B 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 3-1 

(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. When sufficient 

data exists, 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 

Table 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation (LSE Figure 3-1) 

and oral (LSE Figure 3-2) routes. Not all substances will have data on each route of exposure and 

will not therefore have all five of the tables and figures. 

(2)	 Exposure Period Three exposure periods - acute (less than 15 days), intermediate (15–364 days), 

and chronic (365 days or more) are presented within each relevant route of exposure. In this 

example, an inhalation study of intermediate exposure duration is 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)	 Health Effect The major categories of health effects included in LSE tables and figures are death, 

systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and 

LOAELs can be reported in the tables and figures for all effects but cancer. Systemic effects are 

further defined in the "System" column of the LSE table (see key number 18). 

(4)	 Key to Figure 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 18 has been used to derive a NOAEL and a Less Serious LOAEL (also see the 

2 "18r" data points in Figure 3-1). 

(5)	 Species The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "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. 

(6)	 Exposure Frequency/Duration The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to 1,1,2,2-tetrachloroethane via 

inhalation for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the 

dosing regimen refer to the appropriate sections of the text or the original reference paper, i.e., 

Nitschke et al. 1981. 

(7)	 System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. 

"Other" refers to any systemic effect (e.g., a decrease in body weight) not covered in these systems. 

In the example of key number 18, 1 systemic effect (respiratory) was investigated. 
PENTACHLOROPHENOL B-4 

APPENDIX B 

(8)	 NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which no 

harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 3 ppm 

for the respiratory system which was used to derive an intermediate exposure, inhalation MRL of 

0.005 ppm (see footnote "b"). 

(9)	 LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study 

that caused a harmful 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 end point used to quantify the adverse effect accompanies the LOAEL. The respiratory 

effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 ppm. MRLs are not 

derived from Serious LOAELs. 

(10)	 Reference The complete reference citation is given in Chapter 9 of the profile. 

(11)	 CEL 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. 

(12)	 Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found in 

the footnotes. Footnote "b" indicates the NOAEL of 3 ppm in key number 18 was used to derive an 

MRL of 0.005 ppm. 

LEGEND 

See Figure 3-1 

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 intermediate and chronic exposure periods are illustrated. 

(14)	 Health Effect These are the categories of health effects for which reliable quantitative data exists. 

The same health effects 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)	 NOAEL In this example, 18r NOAEL is the critical end point for which an intermediate inhalation 

exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol indicates 

to a NOAEL for the test species-rat. The key number 18 corresponds to the entry in the LSE table. 

The dashed descending arrow indicates the extrapolation from the exposure level of 3 ppm (see 

entry 18 in the Table) to the MRL of 0.005 ppm (see footnote "b" in the LSE table). 

(17)	 CEL Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The diamond 

symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to 

the entry in the LSE table. 
PENTACHLOROPHENOL B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the 

upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are 

derived from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of 

the cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 
2 

SAMPLE 

6 Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 1 

3 4 

Key to figurea Species 

Exposure frequency/ duration System 

NOAEL (ppm) 

6 INTERMEDIATE EXPOSURE 

5 6 7 8 

6 Systemic 9 9 9 96 18 Rat 13 wk 

5 d/wk 6 hr/d 

Resp 3b 

CHRONIC EXPOSURE Cancer 38 Rat 18 mo 

5 d/wk 7 hr/d 

39 Rat 89–104 wk 

5 d/wk 6 hr/d 

40 Mouse 79–103 wk 

5 d/wk 6 hr/d 

a The number corresponds to entries in Figure 3-1. 

LOAEL (effect) 

Less serious (ppm) Serious (ppm) 

9 

9 

10 (hyperplasia) 

11 

9

20 (CEL, multiple 

organs) 

10 (CEL, lung tumors

nasal tumors) 

10 (CEL, lung tumors

hemangiosarcom

b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10-3 ppm; dose adjusted for intermittent ex

an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 12 6


PENTACHLOROPHENOL C-1 

APPENDIX C 

ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ADI Acceptable Daily Intake 

ADME Absorption, Distribution, Metabolism, and Excretion 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT Best Available Technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BSC Board of Scientific Counselors 

C Centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL Cancer Effect Level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CNS central nervous system 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

d day 

Derm dermal 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

DWEL Drinking Water Exposure Level 

ECD electron capture detection 

ECG/EKG electrocardiogram 
 

PENTACHLOROPHENOL C-2 

APPENDIX C 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

ft foot 

FR Federal Register 

g gram 

GC gas chromatography 

Gd gestational day 

gen generation 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

hr hour 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IDLH Immediately Dangerous to Life and Health 

IARC International Agency for Research on Cancer 

ILO International Labor Organization 

in inch 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LCLo lethal concentration, low 

LC50 lethal concentration, 50% kill 

LDLo lethal dose, low 

LD50 lethal dose, 50% kill 

LT50 lethal time, 50% kill 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

m meter 

MA trans,trans-muconic acid 

MAL Maximum Allowable Level 

mCi millicurie 

MCL Maximum Contaminant Level 

MCLG Maximum Contaminant Level Goal 

mg milligram 

min minute 

mL milliliter 
PENTACHLOROPHENOL C-3 

APPENDIX C 

mm millimeter 

mm Hg millimeters of mercury 

mmol millimole 

mo month 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCI National Cancer Institute 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NFPA National Fire Protection Association 

ng nanogram 

NLM National Library of Medicine 

nm nanometer 

NHANES National Health and Nutrition Examination Survey 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH Polycyclic Aromatic Hydrocarbon 

PBPD Physiologically Based Pharmacodynamic 

PBPK Physiologically Based Pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

PID photo ionization detector 
PENTACHLOROPHENOL C-4 

APPENDIX C 

pg picogram 

pmol picomole 

PHS Public Health Service 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS Pretreatment Standards for New Sources 

REL recommended exposure level/limit 

RfC Reference Concentration 

RfD Reference Dose 

RNA ribonucleic acid 

RTECS Registry of Toxic Effects of Chemical Substances 

RQ Reportable Quantity 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

sec second 

SIC Standard Industrial Classification 

SIM selected ion monitoring 

SMCL Secondary Maximum Contaminant Level 

SMR standard mortality ratio 

SNARL Suggested No Adverse Response Level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC Total Organic Compound 

TPQ Threshold Planning Quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TRI Toxics Release Inventory 

TWA time-weighted average 

U.S. United States 

UF uncertainty factor 

VOC Volatile Organic Compound 

yr year 

WHO World Health Organization 

wk week 

> 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 
PENTACHLOROPHENOL C-5 

APPENDIX C 

μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 

PENTACHLOROPHENOL D-1 

APPENDIX D
 

INDEX
 

adipose tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113, 130, 145, 147, 165, 166, 168, 186, 190, 191, 198
 

adsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145, 152-159, 178, 179, 182
 

aerobic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103, 152, 158-160, 179
 

Ah receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 
 

alanine aminotransferase (see ALT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 71 
 

ALT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71, 114, 131
 

ambient air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162, 180, 193, 207
 

aspartate aminotransferase (see AST) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 54 
 

AST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71, 114, 131
 

BCF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155, 156, 180
 

bioaccumulation ............................................................................. 155, 156, 180
 

bioavailability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83, 180 
 

bioconcentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145, 155, 156, 168
 

bioconcentration factor (see BCF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 
 

biodegradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155, 157-160, 179, 182, 183
 

biomagnification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145, 155, 180
 

biomarker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111-113, 130, 131
 

body weight effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 
 

breast milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 84, 85, 111, 132, 135, 172, 174, 181
 

cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4, 5, 22, 29-31, 65-68, 74, 109, 124-126, 130, 134, 138, 201, 204, 211
 

carcinogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 14, 15, 67, 126, 201, 211
 

carcinogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 14, 15, 21, 22, 29, 51, 67, 74, 125, 126, 130, 201, 211
 

carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65, 106, 125, 203, 205
 

carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 
 

cardiovascular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53, 122 
 

chloracne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24, 26, 122, 130
 

Clean Water Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 
 

dechlorination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80, 89, 91, 94, 132, 160, 161
 

dermal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26, 72 
 

DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31, 75-80, 105, 112, 113, 115, 119, 126, 134
 

endocrine effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25, 56, 74 
 

estrogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 
 

FDA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2, 3, 9, 165, 168, 175, 180, 181, 204, 205, 211
 

FEDRIP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 
 

fetus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89, 108, 110, 122, 124, 127, 135
 

fish consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65, 209 
 

Food and Drug Administration (see FDA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2, 9, 211 
 

fruits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 169, 175
 

garden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 23, 122, 129, 143
 

gastrointestinal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 
 

general population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3, 13, 111, 113, 145, 165-170, 180, 182
 

goiter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 
 

half-life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82, 83, 87, 95-99, 112, 152, 155-157, 159-161, 167, 177, 178, 180
 

hematological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24, 53, 70 
 

Henry’s law . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 
 

hepatic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 24, 53, 71, 124 
 

hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141, 145, 152, 157, 186, 190
 

hydroxyl radical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156, 157, 177
 

hyperthermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27, 31, 53, 60, 69-73, 103, 109, 114, 116, 117, 122, 123, 129
 

immune system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 6, 14, 31, 60, 124, 128, 134
 

immunological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17, 27, 57, 60, 73 
 

Integrated Risk Information System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 
 

kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30, 31, 51, 55, 75, 87, 98, 113, 114, 116, 117, 168, 192, 201
 

LD50 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31, 32, 109 
 
PENTACHLOROPHENOL D-2 

APPENDIX D 

leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 
 

liver . . . . . . . . . . . . . . . . . . . 5, 6, 14, 15, 19, 31, 51, 54, 66, 69, 71, 75, 80, 82, 84-89, 92-94, 102, 103, 105, 109, 112-117, 119,
 

122-125, 131, 132, 134, 168, 191, 192, 198, 201
 

lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82, 85, 87, 95, 112 
 

lymphoreticular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26, 57, 73 
 

menstrual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25, 28, 126 
 

mesothelioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 
 

milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 84, 85, 111, 132, 135, 147, 168, 172, 174, 175, 181, 182
 

miscarriages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 
 

MRL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15-19, 22, 56, 63, 122-125, 127, 201
 

NAS/NRC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111, 112
 

National Priorities List (see NPL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 14, 145 
 

neurobehavioral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27, 61, 106, 110, 128, 134
 

neurochemical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60, 61 
 

neurodevelopmental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 
 

NHATS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 
 

NIOSH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 112, 113, 130, 138, 171, 185, 188, 189, 194, 198, 199, 203, 211
 

NOAEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18, 21, 32, 60, 65, 201 
 

NOES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 
 

non-Hodgkin’s lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30, 125, 130
 

no-observed-adverse-effect level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 
 

NPL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 14, 145-147, 163, 176, 183
 

ocular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26, 32, 70 
 

oxidative phosphorylation . . . . . . . . . . . . . . . . . . . 14, 15, 27, 31, 53, 60, 69, 70, 73, 93, 103, 104, 109, 114, 116, 117, 122, 123,
 

129, 131, 134
 

partition coefficients .......................................................................... 139, 153, 178
 

PBPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 
 

PBPK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100-102, 110, 135
 

pharmacodynamic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 
 

pharmacokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81, 100-102, 106, 135
 

photolysis .................................................................. 139, 152, 156, 157, 159, 177, 178
 

playground equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 173, 176
 

precipitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 
 

public health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 4, 9, 13, 21, 22, 106, 119, 120, 176, 185, 193
 

reductive dechlorination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160, 161
 

reference dose (see RfD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201, 211
 

regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 10, 201, 203-206, 211
 

renal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24, 55, 56, 71 
 

reproductive system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 16, 31, 62, 65, 110, 123
 

Restricted-use pesticide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 141, 143, 145, 147, 162, 165, 174, 175
 

RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201, 205, 211
 

sediment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153, 158, 159, 161, 163, 177, 179, 187, 196, 199
 

selenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 
 

soil . . . . . . . . . . . . . . . . . . . . 2, 3, 6-9, 13, 84, 98, 131, 133, 145, 151-156, 158-160, 163, 169, 172-174, 177-183, 187, 193, 195,
 

196, 199, 211
 

solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 32, 96, 139, 154, 177, 180
 

Superfund . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 
 

surface water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2, 3, 151, 152, 158, 162, 163, 177, 179, 180
 

T3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 
 

T4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56, 88, 101, 104
 

TCHQ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75, 80, 89-93, 105, 110, 113, 115, 130-132, 186, 198
 

tetrachlorohydroquinone (see TCHQ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79, 80, 160, 183
 

thyroid . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 15, 19, 25, 31, 51, 56, 74, 80, 104, 107, 117, 124, 125, 127, 128, 130, 134, 135, 201
 

thyroid stimulating hormone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 25, 56, 107 
 

thyroxine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 19, 56, 61, 74, 80, 104, 107, 110, 117, 124, 125, 128, 131, 134, 201
 

time-weighted average . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 
 

toxicokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21, 101, 133
 

Toxics Release Inventory (see TRI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141, 147
 

tremors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 
 

TRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65, 90, 95, 141, 147, 148, 150-152, 177
 

triiodothyronine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 19, 25, 56, 107, 110
 
tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 51, 52, 58, 59, 66, 67, 74, 105, 130
 

TWA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203, 211
 

U.S. Department of Agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 
 

vapor pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139, 171, 177
 

volatilization .................................................................... 147, 148, 152, 153, 165, 172
 
PENTACHLOROPHENOL D-4 

APPENDIX D