TOXICOLOGICAL PROFILE FOR
 

MIREX AND CHLORDECONE
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

August 1995 
MIREX AND CHLORDECONE 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. 
MIREX AND CHLORDECONE 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
 

 

V 

FOREWORD 

This toxicological prolile is prepared in accordance with guidelines developed by ATSDR and 

EPA. The onginal guidelines were published in the Federal on April 17, 1987. Each protile will be revised 

and republished as necessary. 

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health 

effects information for the hazardous substance being described. Each profile identifies and reviews the key 

literature (that has been peer-reviewed) that describes a hazardous substance’s toxicologic properties. Other 

pertinent literature is also presented, but described in less detail than the key studies. The profile is not 

intended to be an exhaustive document; however, more comprehensive sources of specialty information are 

referenced. 

Each toxicological profile begins with a public health statement, that describes in nontechnical 

language, a substance’s relevant toxicological properties. Following the public health statement is 

information concerning levels of significant human exposure and, where known, significant health effects. 

The adequacy of information to determine a substance’s health effects is described in a health effects 

summary. Data needs that are of significance to protect public health will be identified by ATSDR and 

EPA. The focus of the protiles is on health and toxicologic 

information; therefore, we have included this information in the beginning of the document. 

Each profile must include the following: 

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

epidemiologic evaluations on a hazardous substance in order to ascertain the levels of significant 

human exposure for the substance and the associated acute, subacute, and chronic health effects. 

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

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

significant risk to human health of acute, subacute, and chronic health effects. 

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

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

The principal audiences for the toxicological profiles are health professionals at the federal, state, 

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

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 the Agency for Toxic Substances and Disease Registry (ATSDR) to prepare 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 

Environmental Protection Agency (EPA). The availability of the revised priority list of 275 hazardous 

substances was announced in the Federal on February 28, 1994 (59 FR 9486). For prior versions of the list 

of substances, see m notices dated April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); 

October 26, 1989 (54 FR 43619); October 17, 1990 (55 FR 42067); and October 17, 1991 (56 FR 52166); 

and October 28, 1992 (57 FR 48801). 

MIREX AND CHLORDECONE vii 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S):
 

Obaid Faroon, Ph.D.
 

ATSDR, Division of Toxicology, Atlanta, GA
 

Steven Kueberuwa, M.S.
 

Research Triangle Institute, Research Triangle Park, NC
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS:
 

1 . Green Border Review. Green Border review assures consistency with ATSDR policy. 

2 . 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. 

3 . 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. 

4. Quality Assurance Review. The Quality Assurance Branch assures that consistency across 

profiles is maintained, identifies any significant problems in forrnat or content, and establishes 

that Guidance has been followed. 

MIREX AND CHLORDECONE ix 

PEER REVIEW
 

A peer review panel was assembled for mirex and chlordecone. The panel consisted of the 

following members: 

1. Dr. Ihn Chu, Head, Environmental Contaminants Section, Environmental Health Center, 

Ottawa,Ontario; 

2. Dr. Syed Naqvi, Professor of Biology, Southern University, Baton Rouge, Louisiana. 

3. Dr. Harihara Mehendale, Professor of Toxicology, College of Pharmacy and Health 

Science, Northeast Louisiana University, Monroe, Louisiana. 

These experts collectively have knowledge of mirex and chlordecone’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. 









MIREX AND CHLORDECONE 1 

1. PUBLIC HEALTH STATEMENT 

This statement was prepared to give you information about mirex and chlordecone and to 

emphasize the human health effects that may result from exposure to them. The 

Environmental Protection Agency (EPA) has identified 1,408 hazardous waste sites as the 

most serious in the nation. These sites make up the National Priorities List (NPL) and are the 

sites targeted for long-term federal clean-up activities. Mirex has been found in at least 7 of 

the sites on the NPL. Chlordecone has been found at 2 of the sites on the NPL. However, 

neither mirex or chlordecone are on EPA’s list of target chemicals and the number of NPL 

sites evaluated for mirex and chlordecone is not known. As EPA evaluates more sites, the 

number of sites at which mirex and chlordecone are found may increase. This information is 

important because exposure to mirex and chlordecone may cause harmful health effects and 

because these sites are potential or actual sources of human exposure to mirex and 

chlordecone. 

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 can be exposed to a substance only when you come in contact with it. 

You may be exposed by breathing, eating, or drinking substances containing the substance or 

by skin contact with it. 

If you are exposed to substances such as mirex and chlordecone, many factors will determine 

whether harmful health effects will occur and what the type and severity of those health 

effects will be. These factors include the dose (how much), the duration (how long), the route 

or pathway (breathing, eating, drinking, or skin contact) by which you are exposed, the other 

chemicals to which you are exposed, and your individual characteristics such as age, sex, 

nutritional status, family traits, lifestyle, and state of health. 
MIREX AND CHLORDECONE 2 

1. PUBLIC HEALTH STATEMENT 

1.1 WHAT ARE MIREX AND CHLORDECONE? 

Mirex and chlordecone are two separate synthetic insecticides that have similar chemical 

structures. They do not occur naturally in the environment. Mirex is a snow-white 

crystalline solid and chlordecone is a tan-white crystalline solid. Both compounds are 

odorless and neither burns easily. 

Mirex and chlordecone are no longer made or used in the United States. Mirex and 

chlordecone were most commonly used in the 1960s and 1970s. Mirex was used as a 

pesticide to control fire ants mostly in the southeastern part of the United States. It was also 

used extensively as a flame retardant additive under the trade name Dechlorane® in plastics, 

rubber, paint, paper, and electrical goods from 1959 to 1972 because it does burn easily. 

Chlordecone was used to control insects that attacked bananas, citrus trees with no fruits, 

tobacco, and ornamental shrubs. It was also used in household products such as ant and roach 

traps. Chlordecone is also known by its trade name Kepone®. All registered products 

containing mirex and chlordecone were canceled in the United States between 1977 and 1978. 

Chapter 3 has more information on the physical and chemical properties of mirex and 

chlordecone. Chapter 4 has more information on the production and use of mirex and 

chlordecone. 

1.2 WHAT HAPPENS TO MIREX AND CHLORDECONE WHEN THEY ENTER

 THE ENVIRONMENT? 

Mirex and chlordecone contaminated water and soil while they were being manufactured and 

used in the 1960s and 1970s. These substances can still enter surface water through runoff of 

contaminated soil at facilities that once manufactured these chemicals or by seeping from 

waste disposal sites. Mirex and chlordecone do not evaporate to any great extent into the air. 

They also do not dissolve easily in water. Most of the mirex and chlordecone in water attaches 

to soil particles suspended in the water or to sediment. When they bind to soil particles in 

water, they can travel long distances. Both compounds bind strongly to soil. 
MIREX AND CHLORDECONE 3 

1. PUBLIC HEALTH STATEMENT 

Because they are not likely to move through the soil, very little will get into underground 

water. Mirex and chlordecone can stay in soil, water, and sediment for years. Both 

compounds are slowly broken down in soil, water, and sediment. Mirex is broken down more 

quickly than chlordecone. Mirex is broken down to photomirex, which can also cause 

harmful health effects. Photomirex is even more poisonous than mirex. It is produced when 

sunlight reacts with mirex in water or in the air. Fish or animals that live in waters that 

contain mirex or chlordecone, or that eat other animals contaminated with mirex or 

chlordecone, can build up these substances in their bodies. The amounts of mirex and 

chlordecone in their bodies may be several times greater than the amount in their prey or in 

the surrounding water. See Chapter 3 for more information on the chemical and physical 

properties of mirex and chlordecone. See Chapter 5 for more information on their occurrence 

and what happens to them in the environment. 

1.3 HOW MIGHT I BE EXPOSED TO MIREX AND CHLORDECONE? 

Most people are exposed to very low levels of mirex and chlordecone. The most likely way 

for people in the general population to be exposed to mirex or chlordecone is by eating food, 

particularly fish, taken from contaminated areas. Currently, three states (Ohio, New York, 

and Pennsylvania) have issued a warning to the public that fish may contain mirex. This 

warning applies mostly to fish caught in Lake Ontario. The state of Virginia has also issued 

a warning to the public about possible chlordecone contamination in fish and shellfish caught 

in the lower 113 miles of the James River. This contamination was caused when chlordecone 

was manufactured in one factory in Hopewell, Virginia, polluting the James River. People 

who live in areas where these compounds were used or made have higher levels in their 

tissues. Mirex was found in the milk of women who live in these areas, so nursing infants 

could be exposed. People who live near hazardous waste sites may be exposed to mirex or 

chlordecone by touching or eating contaminated soil that is on unwashed hands, food 

containers, or food itself, since these compounds bind to soil particles. Because mirex and 

chlordecone do not dissolve easily in water or evaporate easily in air, people are not likely to 

be exposed to them by drinking water or by inhaling air. Since mirex and chlordecone are no 
MIREX AND CHLORDECONE 4 

1. PUBLIC HEALTH STATEMENT 

longer produced, the only people likely to be exposed through their work are those involved 

in the clean-up and removal of contaminated soils and sediments. 

Mirex and chlordecone do not occur naturally in the environment. Although mirex is not 

usually found in the air, it was detected at very low levels of up to 10 parts of mirex per 

quadrillion (1,000,000,000,000,000) parts of air in air samples from southern Ontario, 

Canada. Surface water concentrations of mirex ranged from 0.06 to 2.6 parts mirex per one 

trillion (1,000,000,000,000) parts of water in the Niagara River between 1981 and 1983. More 

recent monitoring data from 1987 show that mirex concentrations are decreasing in the 

surface waters of the Great Lakes to about 0.022 parts per trillion (ppt). In the mid-1980s 

mirex was found in sediments of Lake Ontario at levels ranging from 6.4 parts per billion 

(ppb) to 38 ppb. Nationwide, the average level of mirex in fish was less than 4 ppb in 1986. 

However, fish from Lake Ontario had levels as high as 225 ppb. Chlordecone was found in 

surface water samples from the James River estuary at levels less than 10 ppt in 1977. More 

recent data were not available. In 1978, chlordecone was detected in sediments from the 

James River below its production site at concentrations of less than one part chlordecone in 

one million parts of sediment. In 1981, chlordecone was found in clams from the James River 

at levels ranging from 60 to 140 ppb. 

Chapter 5 has more information on how you may be exposed to mirex and chlordecone. 

1.4 HOW CAN MIREX AND CHLORDECONE ENTER AND LEAVE MY BODY? 

Studies in animals show that mirex can be taken into your bloodstream when you breathe in 

cigarette smoke containing mirex or eat food contaminated with mirex. We do not know if 

mirex can pass through your skin and enter your body after you touch it. Mirex passes from 

the stomach and intestines of animals into their blood. We do not know how much passes 

from the stomach and intestines of people into the bloodstream. Once in the bloodstream, 

mirex is carried to many parts of the body where it is stored, mainly in fat. Mirex is not 

broken down in the body. Mirex that is not stored leaves the body unchanged mainly in the 

feces. Very little leaves the body in the urine. Most of the mirex that is swallowed leaves 
MIREX AND CHLORDECONE 5 

1. PUBLIC HEALTH STATEMENT 

the body in feces within two days. However, the mirex that enters the bloodstream and is 

stored in fat leaves the body very slowly. This process can take from several weeks to 

months. Mirex can also enter breast milk from the bloodstream of nursing mothers who have 

been exposed. Refer to Chapter 2 for more information on this subject. 

Animal studies show that chlordecone can pass into your blood when you eat food 

contaminated with it. Animal data show that only a small amount of chlordecone can pass 

through the skin into the bloodstream. We do not know if or how much chlordecone can pass 

from your lungs into your blood when you breathe it in. Like mirex, once chlordecone is 

taken up by your body, it is carried by the blood throughout the body and is stored for a 

long time. Unlike mirex, chlordecone is found mainly in the liver. Chlordecone is broken 

down to chlordecone alcohol, which is a less harmful product. Chlordecone and its 

breakdown product slowly leave the body through the feces. This process can take from 

several weeks to months. Very little chlordecone leaves the body in the urine. Chlordecone 

has also been found in saliva and human milk. Refer to Chapter 2 for more information on 

this subject. 

1.5 HOW CAN MIREX AND CHLORDECONE AFFECT MY HEALTH? 

We do not know how mirex directly affects the health of people. However, animal studies 

have shown that eating mirex can cause harmful effects on the stomach, intestines, liver, and 

kidneys. Eating mirex can also cause harmful effects on the eyes, thyroid, nervous system, 

and reproductive system. Since these effects occur in animals, they may also occur in people. 

Animals that eat large amounts of mirex for a relatively short time can develop diarrhea. In 

animals, short-term exposure (14 days or less) to low and high levels of mirex and 

intermediate exposure (15-364 days) to low levels can harm the liver. Trembling, tiredness, 

and weakness can also occur after short-term exposure to large amounts of mirex. Younger 

animals are more sensitive to these effects on the nervous system. Intermediate exposures to 

low levels of mirex caused tiredness, and exposure to higher levels caused extreme 

excitability. Long-term (365 days or more) exposure to low levels of mirex caused harm to 
MIREX AND CHLORDECONE 6 

1. PUBLIC HEALTH STATEMENT 

the kidneys. Short-term and intermediate exposures to moderately low levels of mirex did 

not harm kidneys. Exposure to sufficient amounts of mirex may cause cataracts in animals if 

they are exposed before or soon after birth. We do not know whether human infants may 

also develop cataracts; it is not likely that mirex will cause cataracts in adults. Short-term, 

low-level exposure to mirex may harm reproduction and development in rodents. High-level 

exposures may result in miscarriage. 

Studies in workers exposed (intermediate- or long-term) to chlordecone have shown harmful 

effects on the liver, the nervous system, and reproductive systems. Workers exposed to high 

levels of chlordecone during its manufacture experienced trembling, irritability, blurry vision, 

and headaches. Studies in rats have shown that pretreatment with some anticonvulsants or 

antidepressants increases the seriousness of the tremors associated with chlordecone exposure. 

Therefore, people being treated with these drugs for epilepsy or depression may also 

experience more serious tremors if they are exposed to chlordecone. Male workers 

experienced some harmful reproductive effects. However, there was no evidence that the 

ability to father children was affected. Some workers exposed to high levels of chlordecone 

developed skin rashes and enlarged livers. Animal studies show effects similar to those seen 

in humans. In addition, long-term exposure to small amounts of chlordecone caused kidney 

effects in animals. It is possible exposure to high concentrations of chlordecone for a long 

time may also hurt people’s kidneys. Animal studies show harmful effects on the ability of 

female animals to reproduce. We do not know if similar effects occur in exposed women. 

Animal studies show that chlordecone harms the offspring of exposed animals. We do not 

know if similar harmful developmental effects will occur in people. However, it is possible 

that if parents are exposed to enough chlordecone, their children’s development may be 

harmed. Very young and very old people may be especially sensitive to chlordecone. 

We do not know for sure whether either mirex or chlordecone causes cancer in humans. The 

Department of Health and Human Services (DHHS) has determined that mirex and 

chlordecone may reasonably be expected to be carcinogens. The International Agency for 

Research on Cancer (IARC) has determined that mirex and chlordecone are possibly 

carcinogenic to humans. The EPA has not classified mirex or chlordecone as to 
MIREX AND CHLORDECONE 7 

1. PUBLIC HEALTH STATEMENT 

carcinogenicity. In rodents, mirex causes liver, adrenal, and blood cancer. Chlordecone also 

causes liver cancer in rodents, but because of problems with these animal studies, more 

information is necessary to be sure. 

Chapter 2 has information on the health effects of mirex and chlordecone. 

1.6 ARE THERE MEDICAL TESTS TO DETERMINE WHETHER I HAVE BEEN

 EXPOSED TO MIREX OR CHLORDECONE? 

There are medical tests to determine whether you have been exposed to mirex. Levels of 

mirex can be measured in blood, feces, fat, or milk. The tests are not done in routine medical 

examinations. However, doctors can collect tissue and body fluid samples and send them to 

university medical centers or medical laboratories where the tests can be performed. The 

tests are specific for mirex exposure. Since mirex is stored in your body for a long time and 

slowly excreted, the tests can detect mirex for a long time after exposure has stopped. 

However, the tests are unsatisfactory indicators of the amount of mirex to which you have 

been exposed. This is because a long time may have passed since you were exposed and you 

cannot be sure how much mirex may have left your body by the time the test is performed. 

The tests also cannot be used to predict whether you will experience any potential health 

effects or harmful changes following exposure. 

There are medical tests to determine whether you have been exposed to chlordecone and/or its 

breakdown product, chlordecone alcohol. Levels of chlordecone and/or chlordecone alcohol 

can be measured in blood, saliva, feces, or bile. Chlordecone levels in blood are the best 

indicator of exposure to chlordecone. Since chlordecone remains in the blood for a long time, 

the test is useful for a long time after exposure has stopped. Chlordecone can be detected in 

saliva only within the first 24 hours after exposure; therefore, this test has limited use. Blood 

levels of chlordecone are a good reflection of total body content of chlordecone. However, 

the test is an unsatisfactory indicator of the amount of chlordecone to which you have been 

exposed because you cannot be sure how much chlordecone left your body between the time 

you were exposed and the time the test is performed. These tests cannot predict how your 
MIREX AND CHLORDECONE 8 

1. PUBLIC HEALTH STATEMENT 

health may be affected after exposure. The tests are not done in routine medical 

examinations, but doctors can collect body fluid samples and send them to a university 

medical center or a medical laboratory for analysis. Refer to Chapters 2 and 6 for more 

information. 

1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO

 PROTECT HUMAN HEALTH? 

The federal government has made regulations to protect individuals from the possible health 

effects of mirex and chlordecone. The National Institute for Occupational Safety and Health 

(NIOSH) recommends that the average workroom air levels of chlordecone should not exceed 

50 parts per trillion (ppt) over an 8-hour period. EPA suggests that taking into your body 

each day an amount equal to 200 picograms (pg) of mirex per kilogram (kg) of your body 

weight is not likely to cause any significant (noncancer) harmful health effects. The Food 

and Drug Administration (FDA) has determined that concentrations of mirex below 100 ppt in 

fish and other foods are not likely to harm people who eat these foods. EPA has set a limit 

of 1 ppt in surface waters to protect aquatic life from the harmful effects of mirex. FDA has 

determined that concentrations of chlordecone below 400 ppt in fish, crabs, and shellfish are 

not likely to harm people who eat these foods. 

For more information on rules and standards for mirex and chlordecone, see Chapter 7. 

1.8 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, E-29
 

Atlanta, Georgia 30333
 

(404) 639-6000 
MIREX AND CHLORDECONE 9 

1. PUBLIC HEALTH STATEMENT 

This agency can also tell you where to find occupational and environmental health clinics. 

These clinics specialize in the recognition, evaluation, and treatment of illness resulting from 

exposure to hazardous substances. 

MIREX AND CHLORDECONE 11 

2. HEALTH EFFECTS 

2.1 INTRODUCTION 

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

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

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

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

data to public health. 

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

Mirex and chlordecone are structurally similar insecticides. The only structural difference is that 

mirex has two bridgehead chlorine atoms where chlordecone has a carbonyl oxygen atom. As 

suggested by this similarity in structure, these two chemicals produce similar toxicities in a number of 

organs. However, several aspects of the toxicity of mirex are distinctly different from those of 

chlordecone, and vice versa. Because the toxicity profiles of mirex and chlordecone differ 

significantly, each chemical will be discussed separately below. 

2.2 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-observedadverse-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 
MIREX AND CHLORDECONE 12 

2. HEALTH EFFECTS 

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 user of this profile to 

identify levels of exposure at which major health effects start to appear. LOAELs or NOAELs should 

also help in determining whether or not the effects vary with dose and/or duration, and place into 

perspective the possible significance of these effects to human health. 

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 mirex and 

chlordecone are indicated in Tables 2-l and 2-2 and Figures 2-l and 2-2. 

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

been made for mirex and chlordecone. 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. 
MIREX AND CHLORDECONE 13 

2. HEALTH EFFECTS 

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. 

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

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

2.2.1 Inhalation Exposure 

Information regarding health effects following inhalation exposure to mirex or chlordecone is limited. 

No data on health effects resulting from inhalation exposure to mirex were located. Health effects data 

on chlordecone resulting from inhalation exposure are limited to information on a single group of 133 

men exposed to chlordecone at a facility in Hopewell, Virginia, where chlordecone was manufactured 

over a period of 21-22 months (Cannon et al. 1978; Guzelian 1982a; Guzelian et al. 1980; Martinez et 

al. 1978; Sanbom et al. 1979; Taylor 1982, 1985; Taylor et al. 1978). Hygiene conditions at the plant 

were extremely poor, and substantial inhalation, dermal, and even oral exposures could have occurred. 

Because of uncertainties regarding exposure levels at the facility, possible contribution of exposure by 

the various routes, and concomitant exposure to the precursor used to manufacture chlordecone 

(hexachlorocyclopentadiene), no NOAELS or LOAELs could be established following inhalation 

exposure for the effects described below. 

2.2.1.1 Death 

No studies were located regarding death in humans following inhalation exposure to mirex. No deaths 

were reported to result from exposure to chlordecone (Cannon et al. 1978; Taylor et al. 1978). 

No studies were located regarding death in animals following inhalation exposure to mirex or 

chlordecone. 
 

MIREX AND CHLORDECONE 14 

2. HEALTH EFFECTS 

2.2.1.2 Systemic Effects 

No studies were located regarding gastrointestinal, hematological, renal or endocrine effects in humans 

or animals following inhalation exposure to mirex or chlordecone. The systemic effects observed after 

inhalation exposure are discussed below. 

Respiratory Effects. No studies were located regarding respiratory effects in humans following 

inhalation exposure to mirex. Thirty-two of 133 workers examined for toxicity following intermediateor 

chronic-duration inhalation exposures (exact duration periods unknown) at a chlordecone-manufacturing 

facility reported experiencing pleuritic chest pains (Cannon et al. 1978); among 23 workers with blood 

levels in excess of 2 μg/L, 18 reported pleuritic chest pains. Further examination of these workers did not 

reveal any dyspnea, and chest x-rays revealed no lung pathology (Taylor 1982, 1985). Therefore, the 

significance of the chest pains is unknown. No studies were located regarding respiratory effects in animals 

following inhalation exposure to mirex or chlordecone. 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans 

following inhalation exposure to mirex. Electrocardiography of 23 workers with active symptoms of 

chlordecone intoxication resulting from intermediate- or chronic-duration inhalation exposures to high 

blood concentrations (in excess of 2 μg/L) of chlordecone revealed no adverse effects on the heart 

(Taylor 1982, 1985). 

No studies were located regarding cardiovascular effects in animals following inhalation exposure to 

mirex or chlordecone. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans 

following inhalation exposure to mirex. Skeletal muscle biopsies obtained from six workers who had 

experienced tremors, muscle weakness, gait ataxia, and incoordination as a result of intermediate- or 

chronic-duration inhalation exposures to high concentrations of chlordecone revealed a predominance 

of fiber grouping characteristic of myopathic conditions, and a slight increase in lipochrome content 

(Martinez et al. 1978). The biological significance of the lipochrome is unknown. It is unclear 

whether the myopathy was a direct toxic effect of chlordecone on the muscle or whether the myopathy 
MIREX AND CHLORDECONE 15 

2. HEALTH EFFECTS 

was a consequence of neuronal dysfunction. In addition, arthralgia in the proximal joints was reported 

by 4 of 23 workers with active symptoms of chlordecone intoxication (Taylor 1982, 1985). No cause 

for the joint pain could be determined. 

No studies were located regarding musculoskeletal effects in animals following inhalation exposure to 

mirex or chlordecone. 

Hepatic Effects. No studies were located regarding hepatic effects in humans following inhalation 

exposure to mirex. Mild hepatomegaly (occasionally with splenomegaly) was noted in 9 of 23 

workers with blood levels in excess of 2 μg/L, but there were no observed changes in organ function 

and only slight increases in serum alkaline phosphatase in several of the men (Taylor 1982, 1985; 

Taylor et al. 1978). When liver function and structure in 32 men exposed to high concentrations of 

chlordecone while employed for l-22 months (5.6 months average) in the production of chlordecone 

were compared to those of healthy men of the same age, hepatomegaly had occurred in 20 of the 32 

exposed workers, with minimal splenomegaly in 10 of these 20 workers (Guzelian et al. 1980). In the 

exposed workers, urinary excretion of glucaric acid was significantly increased and the half-life of 

antipyrine in the blood was significantly decreased, indicating increased microsomal enzyme activity. 

Needle biopsies of hepatic tissue from 12 of the 32 workers showed marked proliferation of smooth 

endoplasmic reticulum in several samples. All of these are considered to be adaptive changes. 

Limited evidence of hepatic toxicity in these workers included small increases in serum alkaline 

phosphatase in 7 of the 32. In addition, liver biopsies showed lipofuscin accumulation in 11 of 12, 

mild inflammatory changes in 5 of 12, vacuolization of nuclei in 3 of 12, mild portal fibrosis in 3 of 

12, fatty infiltration in 3 of 12, and paracrystalline mitochondrial inclusions in 4 of 12 individuals 

tested. Retention of sulfobromophthalein was normal; serum levels of bilirubin, albumin, globulin, 

alanine and aspartate aminotransferase activity, and γ-glutamyl transferase activity were also normal. 

No studies were located regarding hepatic toxicity in animals following inhalation exposure to mirex 

or chlordecone. 

Dermal Effects. No studies were located regarding dermal effects in humans following inhalation 

exposure to mirex. Eighty-nine of the 133 workers interviewed as a result of intermediate- or chronicduration inhalation exposures to high concentrations of chlordecone during its manufacture experienced 

skin rashes of an erythematous, macropapular nature at some time during their exposure (Cannon et al. 
 

MIREX AND CHLORDECONE 16 

2. HEALTH EFFECTS 

1978). Among 23 workers with blood chlordecone levels in excess of 2 μg/L, 6 men had rashes 

following exposure (Taylor et al. 1978). It is likely that these rashes were the direct result of dermal 

exposure. However, insufficient information was given to eliminate a systemic effect resulting from 

inhalation exposure. 

No studies were located regarding dermal effects in animals following inhalation exposure to mirex or 

chlordecone. 

Ocular Effects. Vision was blurred in 15 of the 23 workers examined as a result of intermediateor 

chronic-duration inhalation exposures to high blood concentrations (in excess of 2 μg/L) of 

chlordecone during its production. The effects on vision were characterized by a disruption of ocular 

motility following a horizontal saccade by rapid random multidirectional eye movements. Visual 

acuity and smooth eye movements were unaffected (Taylor 1982, 1985). The rapid eye movements 

were probably due to disturbance of the brain stem. 

No studies were located regarding ocular effects in animals following inhalation exposure to mirex or 

chlordecone. 

Body Weight Effects. No studies were located regarding body weight effects in humans 

following inhalation exposure to mirex. Twenty-seven of 133 workers examined as a result of 

intermediate- or chronic-duration exposures to chlordecone experienced weight loss (Cannon et al. 

1978). Weight loss (up to 60 pounds in 4 months) was reported in 10 of 23 workers with blood 

chlordecone levels in excess of 2 μg/L (Taylor et al. 1978). 

2.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans or animals after inhalation 

exposure to mirex or chlordecone. 

2.2.1.4 Neurological Effects 

No studies were located regarding neurological effects in humans following inhalation exposure to 

mirex. Sixty-one of 133 workers examined as a result of intermediate- or chronic-duration inhalation 
MIREX AND CHLORDECONE 17 

2. HEALTH EFFECTS 

exposures to high concentrations of chlordecone during its production experienced tremors; 58 

experienced nervousness or unfounded anxiety; and 42 experienced visual difficulties (Cannon et al. 

1978). Tremors were observed in all 23 workers with blood chlordecone levels in excess of 2 μg/L 

(Taylor et al. 1978). The tremors were characterized as intention tremors or as occurring with a fixed 

posture against gravity (Taylor 1982, 1985). The tremors were most apparent in the upper extremities 

but were also detectable in the lower extremities. In the more severe cases, gait was affected. Mental 

disturbances consisting of irritability and poor recent memory were reported by 13 of the 23 workers. 

Standard tests of memory and intelligence showed clear evidence of an encephalopathy in 1 of the 

13 workers (Taylor 1982, 1985). The worker with encephalopathy reported auditory and visual 

hallucinations and demonstrated whole-body myoclonic jerks in response to loud noises. In 15 of the 

23 workers, vision was blurred (Taylor 1982, 1985). The effects on vision were characterized as a 

disruption of ocular motility following a horizontal saccade by rapid random multidirectional eye 

movements (Taylor 1982, 1985). Visual acuity and smooth eye movements were unaffected. 

Headaches of mild-to-moderate severity were reported by 9 of the 23 workers. Three of these 9 had 

increased cerebrospinal fluid pressure and papilledema (Sanborn et al. 1979; Taylor 1982, 1985). 

Nerve conduction velocity tests, electroencephalography, radioisotope brain scans, computerized 

tomography, and analyses of cerebral spinal fluid content were normal. Sural nerve biopsies obtained 

from 5 workers with detectable tremor, mental disturbances consisting of irritability and poor recent 

memory, rapid random eye movements, muscle weakness, gait ataxia, incoordination, or slurred speech 

revealed a greatly decreased number of small myelinated and unmyelinated axons (Martinez et al. 

1978). Ultrastructural analyses of the nerves showed increased interstitial collagen, redundant folds in 

the Schwann cell cytoplasm, and the presence of occasional crystalloid inclusions suggesting that the 

chlordecone had a direct toxic effect on the Schwann cell. Examination of 16 of the 23 affected 

individuals from 5 to 7 years after cessation of exposure and after body levels of chlordecone had been 

substantially reduced showed that 9 were asymptomatic, 5 had persistent tremor or nervousness, and 3 

had emotional problems (Taylor 1982, 1985). 

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

mirex or chlordecone. 
MIREX AND CHLORDECONE 18 

2. HEALTH EFFECTS 

2.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after inhalation exposure to mirex. 

The available human data on chlordecone provide qualitative evidence to support the conclusion that 

intermediate- or chronic-duration exposures to high concentrations of chlordecone in the workplace 

causes oligospermia and decreases sperm motility among male workers (Guzelian 1982a; Taylor 1982, 

1985; Taylor et al. 1978). The threshold for abnormally low sperm counts was =l ug chlordecone per 

liter of serum, and the number of motile sperm cells increased as the serum chlordecone concentration 

decreased (Guzelian 1982a). Despite loss of sperm motility in some of the workers, there were no 

reported difficulties with fertility (Taylor 1982, 1985). These studies, however, can only be used as 

suggestive evidence of chlordecone-induced male reproductive toxicity because the airborne 

concentrations of chlordecone and the frequency of exposure were not quantified, effects on sperm 

morphology were not examined, and possible chlordecone exposure via oral and dermal routes may 

have occurred. 

No studies were located regarding reproductive effects in animals after inhalation exposure to mirex or 

chlordecone. 

2.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans after inhalation exposure to mirex 

or chlordecone. Although impaired spermatogenesis among male workers exposed to chlordecone via 

inhalation did not affect their fertility (Guzelian 1982a; Taylor 1982, 1985; Taylor et al. 1978), it is 

unclear whether abnormalities in their sperm may have resulted in developmental effects in offspring. 

No increase in birth defects among offspring conceived after termination of exposure was mentioned 

(Taylor 1982, 1985). 

No studies were located regarding developmental effects in animals after inhalation exposure to mirex 

or chlordecone. 
 

MIREX AND CHLORDECONE 19 

2. HEALTH EFFECTS 

2.2.1.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans or animals following inhalation 

exposure to mirex or chlordecone. 

Genotoxicity studies are discussed in Section 2.4. 

2.2.1.8 Cancer 

No studies were located regarding cancer in humans following inhalation exposure to mirex. 

Extremely limited information was located regarding cancer in humans following inhalation exposure 

to chlordecone. Liver biopsy samples taken from 12 workers with hepatomegaly resulting from 

intermediate- or chronic-duration exposures to high concentrations of chlordecone showed no evidence 

of cancer (Guzelian et al. 1980). However, conclusions from this study are limited by the very small 

number of workers sampled. 

No studies were located regarding cancer in animals after inhalation exposure to mirex or chlordecone. 

2.2.2 Oral Exposure 

2.2.2.1 Death 

No studies were located regarding death in humans following oral exposure to mirex. No deaths were 

reported to have occurred from exposure to chlordecone (Cannon et al. 1978; Taylor et al. 1978). 

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

of mirex in corn oil resulted in an LD50 value in females of 365 mg/kg (Gaines and Kimbrough 1970), 

whereas in another study, the LD50 values in females and males were 600 and 740 mg/kg, respectively, 

after administration in corn oil but in excess of 3,000 mg/kg after administration in peanut oil (Gaines 

1969). No explanation for the vehicle effect was given. In male dogs, a single oral dose of 

1,250 mg/kg was lethal in 3 of 5 treated animals (Larson et al. 1979a). No deaths were observed in 

the dogs following a single oral dose of 1,000 mg/kg. When dosing occurs over several days, 

mortality is observed at substantially lower daily doses. Increased mortality in multiple-dose, acute­
 

 

 

MIREX AND CHLORDECONE 20 

2. HEALTH EFFECTS 

duration studies has been observed in female rats at doses as low as 50 mg/kg/day (Mehendale et al. 

1973). Pregnant rats appear to be somewhat more sensitive to the lethal effect of mirex. Although a 

single oral dose of 25 mg/kg resulted in no mortality in nonpregnant females (Mehendale et al. 1973), 

16-25% mortality in pregnant rats occurred at doses ranging from 6 to 10 mg/kg/day over a 

10-11-day period during gestation (Byrd et al. 1981; Chernoff et al. 1979b; Khera et al. 1976). 

Similarly, a 32-36% mortality was observed in rat and mouse pups exposed through the milk during 

the first 4 days of lactation at these doses (Chernoff et al. 1979b). Male rats showed approximately 

5% mortality at 6 mg/kg/day for 10 days (Khera et al. 1976). Male mice had slightly higher mortality 

with 80% mortality following 14 daily doses with 10 mg/kg/day (Fujimori et al. 1983). 

In intermediate-duration studies, mortality occurred at only slightly lower doses of mirex than in the 

multiple-dose, acute-duration studies in rats, but mice and dogs appeared more sensitive. In rats, 

mortality was increased in adult males at doses as low as 5 mg/kg/day for 30 days (Mehendale 1981b); 

in adult females at doses as low as 6.2 mg/kg/day for 90 days (Gaines and Kimbrough 1970; Larson et 

al. 1979a), and in rat pups at 1.8-2.8 mg/kg/day for the duration of lactation (Gaines and Kimbrough 

1970). In mice, 100% mortality occurred following 1.3 mg/kg/day for 60 days, and O-25% mortality 

occurred at 0.65 mg/kg/day for 120 days (Ware and Good 1967). In dogs, 50% mortality occurred at 

2.5 mg/kg/day for 13 weeks (Larson et al. 1979a), but this value may not be reliable because only 2 

dogs/sex/group were tested. In a 2-year study in rats, males exhibited increased mortality at 

1.8 mg/kg/day (63% mortality versus 15% mortality in controls), but females exhibited no decrease in 

survivol at as much as 7.7 mg/kg/day (NTP 1990). All mice ingesting 3.6 mg/kg/day for 18 months 

died prior to termination of the study (mortality in controls was 11%) (Innes et al. 1969), and 20% and 

92% mortality occurred in mice ingesting 0.24 and 2.4 mg/kg/day, respectively, for 15 months. 

Mortality among controls was less than 10% (Wolfe et al. 1979). 

Single-dose oral LD50 values in rats for chlordecone were reported to be 126 mg/kg in females (Larson 

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

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

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

single oral dose of 110 mg/kg resulted in 25% mortality in pregnant mice (Kavlock et al. 1985). No 

mortality was observed in male rats at approximately 10 mg/kg/day for 10 days (Simmons et al. 1987), 

but mortality in pregnant rats was 19% at 10 mg/kg/day during gestation (Chernoff and Rogers 1976). 

Ingestion of 24 mg/kg/day for 5 days during gestation resulted in 19% mortality in pregnant mice 
 

 

 

MIREX AND CHLORDECONE 21 

2. HEALTH EFFECTS 

(Seidenberg et al. 1986). Ingestion of milk from dams given 18 mg/kg/day during the first 4 days of 

lactation resulted in 64% mortality in mouse pups (Chernoff et al. 1979b). Ingestion of 25 mg/kg/day 

for 12 days resulted in 100% mortality in male mice (Desaiah et al. 1980a). 

In intermediate-duration studies in male rats, 40% mortality occurred at 5 mg/kg/day for 5 weeks 

(Mehendale 1981b), and 60% mortality occurred at 4.1 mg/kg/day for 15 weeks (Pryor et al. 1983). 

In mice of both sexes, at a dose of 7.8 mg/kg/day for up to 12 months, only 1 of 8 adult mice died 

whereas 4 of 4 juvenile mice died, indicating a greater sensitivity in immature mice (Huber 1965). All 

male mice at 10 mg/kg/day died by day 33 of dosing (Fujimori et al. 1983). Survivol was decreased 

in female rats at 1.25 mg/kg/day in a 2-year feeding study (Larson et al. 1979b) and in both male and 

female rats at 1.2-l .3 mg/kg/day in an 80-week feeding study (NCI 1976). Male mice showed 

decreased survivol at 2.6 mg/kg/day and above in an 80-week feeding study (NCI 1976). 

All LD50 and LOAEL values from each reliable study for death in rats and mice following acute-, 

intermediate-, and chronic-duration exposure are recorded for mirex in Table 2-l and for chlordecone 

in Table 2-2, and plotted for mirex in Figure 2-l and for chlordecone in Figure 2-2. 

2.2.2.2 Systemic Effects 

The systemic effects observed after oral exposure to mirex and chlordecone are discussed below. The 

highest NOAEL values and all LOAEL values from each reliable study for systemic effects in each 

species and duration category are recorded for mirex in Table 2-l and for chlordecone in Table 2-2, 

and plotted for mirex in Figure 2-l and for chlordecone in Figure 2-2. 

Respiratory Effects. No studies were located regarding respiratory effects in humans following 

oral exposure to mirex. Pleuritic chest pain was reported by 32 of 133 workers employed at a facility 

that manufactured chlordecone (Cannon et al. 1978). Among 23 workers with blood chlordecone 

levels in excess of 2 μg/L, 18 reported pleuritic chest pains. Further examination of these 18 workers 

revealed no dyspnea and chest x-rays were normal (Taylor 1982, 1985; Taylor et al. 1978); thus, the 

cause of the chest pains is unknown. Although oral exposures are not normally encountered in 

occupational situations, hygiene was particularly poor at this plant and oral exposures were likely. 

Therefore, intermediate- and chronic-duration oral exposure to chlordecone cannot be ruled out as a 

possible cause for the chest pains. 













































 

 

MIREX AND CHLORDECONE 67 

2. HEALTH EFFECTS 

No studies were located regarding respiratory effects in animals following oral exposure to mirex. 

Extremely lirnited information was located regarding respiratory effects in animals following oral 

exposure to chlordecone. Routine histopathological examination of the lungs of rats in both 90-day 

and 2-year feeding studies with doses as high as 4 mg/kg/day showed no adverse effects. Also, 

routine histopathological examination of the lungs of dogs exposed to doses as high as 

0.625 mg/kg/day in a 2-year feeding study showed no effects (Larson et al. 1979b). These studies are 

limited in that it is unclear how many lung tissue samples were actually examined, and the dog study 

is also limited in that the number of animals used (two/sex/dose) was low. These studies provide no 

possible explanation for the pleuritic chest pains experienced by workers exposed to chlordecone. 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans 

following oral exposure to mirex. Symptoms associated with the cardiovascular system were not 

commonly reported by 133 workers exposed for intermediate or chronic durations to unspecified levels 

of chlordecone at a chlordecone-manufacturing facility (Cannon et al. 1978; Taylor 1982, 1985; Taylor 

et al. 1978). Furthermore, results of .electrocardiography of 23 workers with active symptoms of 

chlordecone intoxication were normal. Although oral exposures are not normally encountered in 

occupational situations, hygiene was particularly poor at this plant and oral exposures were likely. 

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

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

periods during pregnancy. In this study, a single oral dose resulted in a decrease in blood flow to the 

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

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

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

weight of the maternal rats (Buelke-Sam et al. 1983). Another study showed that rats given mirex at 

100 mg/kg/day by gavage for 3 days experienced a slight inhibition of Na+

K+ATPase in myocardial 

membranes (Desaiah 1980). The biological significance of this effect is unknown. Routine gross and 

histopathological analyses of heart tissues obtained from rats at doses as high as 64 mg/kg/day for 

13 weeks showed no adverse compound-related effects on the heart (Larson et al. 1979a), but this 

study is limited in that the number of heart samples examined was not reported. An increase in 

chronic myocarditis at 2.5 and 5 mg/kg/day was reported by Reuber (1977) following a review of 

tissue slides from an 18-month rat cancer bioassay, but no control data were presented to support this 

conclusion. The conclusions of this independent review are disputed by the onginal authors; the 
 

MIREX AND CHLORDECONE 68 

2. HEALTH EFFECTS 

conclusions are considered a misrepresentation of the data by the onginal study author (Ulland et al. 

1977b). 

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

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

of chlordecone (10 mg/kg/day and greater for 3 days) resulted in inhibition of myocardial 

Na+

K+ATPase in rats (Desaiah 1980). At 25 mg/kg/day and above, inhibition of 

mitochondrial mg2+ATPase occurred, and at 50 mg/kg/day decreased norepinephrine and dopamine 

binding to myocardial membranes was observed. Similarly, inhibition of calcium uptake, Ca2+ATPase 

activity, and protein phosphorylation was observed in rat cardiac sarcoplasmic reticulum following 

gavage doses of 8.3 mg/kg/day for 3 days (Kodavanti et al. 1990a). Because of the importance of 

calcium regulation in all phases of the cardiac cycle, this could indicate a decrease in cardiac 

effectiveness. 

Vasodilation of tail vessels has been observed in rats following exposure to 4 mg/kg/day chlordecone 

for 90 days (Larson et al. 1979b). The cause of the vasodilation was not investigated but was 

suggested to have been associated with altered thermoregulatory mechanism (see Other Systemic 

Effects, below). 

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

exposure to 1.25 mg/kg/day chlordecone for 2 years or following exposure of dogs to 0.625 mg/kg/day 

for 124-128 weeks (Larson et al. 1979b). However, these studies are limited in that it is unclear how 

many heart samples were actually examined. Also, the dog study is limited in that too few dogs were 

used (two/sex/dose). Following an independent review of data from a rat cancer bioassay conducted 

by the NCI (1976), Reuber (1978a, 1979c) reported polyarteritis in male rats orally treated with 

chlordecone for 80 weeks. However, arteries were not routinely sectioned in this study so the ongin of 

data used by this reviewer to reach this conclusion is unclear. 

Gastrointestinal Effects. No studies were located regarding gastrointestinal effects in humans 

after oral exposure to mirex or chlordecone. 

Limited information was located regarding gastrointestinal effects in animals following oral exposure 

to mirex; however, the available data indicate that diarrhea is a relatively common result of high-dose 
MIREX AND CHLORDECONE 69 

2. HEALTH EFFECTS 

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

animals, but few of these studies presented sufficient information to derive a LOAEL for this effect. 

Diarrhea was identified as a predominant sign in female rats that died during a lo-day gavage study, 

but the mirex doses at which this was observed were not specified (6 or 12.5 mg/kg/day) (Khera et al. 

1976). Similarly, diarrhea was noted as one of the clinical signs seen in rats after a single gavage 

dose, but it was unclear whether this effect occurred at the lowest dose (100 mg/kg) at which clinical 

signs were observed (Gaines and Kimbrough 1970). Diarrhea was observed in a dietary study in 

which rats were fed a total of 365 mg/kg over 12 days, but the daily dose was not specified (Kendall 

1974a). Mild diarrhea was observed in treated rats (5 mg/kg/day) starting on the 8th day of exposure 

and continuing over the duration of a 30-day dietary study (Mehendale 1981b). Diarrhea was also 

observed in a 90-day gavage study in rats, but the dose (5, 12.5, or 25 mg/kg/day) at which it was 

observed was not reported (Dietz and McMillan 1979). Severe diarrhea was reported in mice 

following gastric intubation with mirex for up to 15 days, but the report did not state which of the 

doses (10, 25, or 50 mg/kg/day) caused this effect. Necropsy showed hemorrhagic intestines, 

indicating a gastrointestinal ongin for the diarrhea rather than a neurally mediated response (Fujimori 

et al. 1983). 

Mild diarrhea has also been observed in a 33-day gavage study in mice exposed to 10 mg/kg/day 

chlordecone. However, no effects on stomach or intestines at necropsy (Fujimori et al. 1983). 

Likewise, routine histopathological analyses of gastrointestinal tissues (described simply as “gut”) also 

showed no compound-related effects in rats after 2 years of exposure at 1.25 mg/kg/day or in dogs 

after 124-128 weeks of exposure at 0.625 mg/kg/day (Larson et al. 1979b). Both of these studies are 

limited in that it is unclear whether tissues from all exposed animals were examined and the number of 

dogs used was too low (two/sex/dose). 

Hematological Effects. No studies were located regarding hematological effects in humans after 

oral exposure to mirex or chlordecone. 

Adverse hematological effects have not been reported to be a prominent feature of mirex toxicity in 

animals. However, a few studies in which high doses of mirex were used have shown mild 

hematological effects. No effects on standard hematological parameters were observed after 14 days 

exposure of male rats to 10 mg/kg/day of mirex (Villeneuve et al. 1977). However, a single oral dose 

of 100 mg/kg mirex resulted in a 12% increase in hematocrit in treated rats (Ervin and Yarbrough 
 

 

MIREX AND CHLORDECONE 70 

2. HEALTH EFFECTS 

1983). The hematocrit was increased 26-27% in adrenalectomized rats. The significance of this effect 

is unclear. Most intermediate-duration studies have shown no effect of mirex on hematological 

parameters. No effect on routine hematological parameters occurred in rats at doses as high as 

3.75 mg/kg/day for 28 days (Chu et al. 1980a; Yarbrough et al. 1981). In addition, no effect on rats 

was seen in a 148-day feeding study at 2 mg/kg/day (Chu et al. 1981a). In contrast, hemoglobin of 

rats decreased at 16 mg/kg/day and leukocytes increased at 64 mg/kg/day exposure during a 13-week 

study (Larson et al. 1979a). Hematocrit increased at 2.5 mg/kg/day in a male dog that died during a 

13-week dietary study (Larson et al. 1979a). 

Studies examining the hematological effects of chlordecone in experimental animals have also given 

predominantly negative results. In intermediate-duration studies in rats, no effect on any 

hematological parameters occurred following 28 days of dietary exposure to 0.05 mg/kg/day (Chu et 

al. 1980a) or 90 days of dietary exposure to 4 mg/kg/day (Larson et al. 1979b). Similarly, in chronicduration studies, no effects were seen during routine hematology in rats exposed for 2 years at up to 

1.25 mg/kg/day or in dogs exposed for 124-128 weeks up to 0.625 mg/kg/day (Larson et al. 1979b). 

Although anemia was reported in rats during an 80-week dietary study (Reuber 1978a, 1979c) based 

on a review of the study conducted by NCI (1976), the onginal pathology review of the study did not 

include any incidence of anemia among the treated rats. Thus, the interpretation of data used by this 

reviewer for drawing a conclusion is unclear. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans 

following oral exposure to mirex. Skeletal muscle biopsies obtained from six workers who 

experienced tremors, muscle weakness, gait ataxia, and incoordination resulting from intermediate- or 

chronic-duration exposure to high levels of chlordecone revealed a predominance of fiber grouping, 

characteristic of myopathic conditions, and a slight increase in lipochrome content (Martinez et al. 

1978). The biological significance of the lipochrome is unknown. In addition, arthralgia in the 

proximal joints was experienced by 4 of 23 workers with active symptoms of chlordecone intoxication 

(Taylor 1982, 1985). No cause for the joint pain could be determined. Although oral exposure is not 

generally considered to be significant in occupational exposure situations, hygiene at the plant at which 

these men were employed was extremely poor and oral exposures were considered to be likely. 

No studies were located regarding musculoskeletal effects in animals after oral exposure to mirex. 

Studies examining the effects of acute-duration oral exposure to large amounts of chlordecone suggest 
MIREX AND CHLORDECONE 71 

2. HEALTH EFFECTS 

that direct toxic effects of chlordecone on muscle occur. However, chronic exposure of rats and dogs 

to chlordecone revealed no adverse effects on the skeletal muscles. A single gavage dose of between 

72 and 98 mg/kg of chlordecone resulted in increasing muscle weakness in treated rats (Egle et al. 

1979). Weakness was observed on the first day of treatment and continued to increase throughout a 

49-day observation period. Following 2-3 days of oral exposure (25 and 50 mg/kg/day), inhibition 

of mg2+ATPase was observed in sarcoplasmic reticulum of treated rats (Mishra et al. 1980). It is 

unclear whether this inhibition contributed to the muscle weakness observed by Egle et al. (1979). In 

longer duration, lower-dose studies, no effect was observed during routine histopathological analyses 

of skeletal muscle. For example, no compound-related effects were reported following routine 

histopathological analysis of skeletal muscle from rats exposed to doses of chlordecone as high as 

4 mg/kg/day for 90 days or 1.25 mg/kg/day for 2 years, or from dogs after 124-128 weeks of 

exposure to doses as high as 0.625 mg/kg/day (Larson et al. 1979b). 

Hepatic Effects. Hepatic changes were observed in one chronic human exposure to mirex, as well 

as in a number of workers exposed to chlordecone for intermediate or chronic durations. In the mirex 

study, human subjects (sex and number not specified) from a chronically exposed cohort from 

southeast Ohio (route of exposure not specified, assumed to be oral) were assessed for cytochrome 

P-4501A2 induction using a breath test that measures caffeine metabolism. The subjects exposed to 

mirex had elevated caffeine metabolism as compared to negative control individuals (subjects with no 

known exposure to polyhalogenated biphenyls or other related chemicals) in which the metabolism did 

not increase (Lambert et al. 1992). In the chlordecone study, liver function and structure in 32 men 

exposed to high levels of chlordecone while employed for l-22 months (5.6 months average) in the 

production of chlordecone were compared to those of healthy men of the same age. Although oral 

exposures are generally not considered to be significant in occupational situations, hygiene conditions 

at this plant were extremely poor and accidental ingestion of the chlordecone was considered to have 

been likely. Hepatomegaly occurred in 20 of the 32 exposed workers, with minimal splenomegaly in 

10 of these. Urinary excretion of glucaric acid was significantly increased, and the half-life of 

antipyrine in the blood was significantly decreased in exposed workers, indicating increased 

microsomal enzyme activity. Needle biopsies of hepatic tissues from 12 of the 32 workers showed 

marked proliferation of smooth endoplasmic reticulum in several samples. These are considered to be 

adaptive changes. Limited evidence of hepatic toxicity in these workers included small increases in 

serum alkaline phosphatase in 7 of the 32. In addition, liver biopsies showed lipofuscin accumulation 

in 11 of 12, mild inflammatory changes in 5 of 12, vacuolization of nuclei in 3 of 12, mild portal 
 

 

MIREX AND CHLORDECONE 72 

2. HEALTH EFFECTS 

fibrosis in 3 of 12, fatty infiltration in 3 of 12, and paracrystalline mitochondrial inclusions in 4 of 12. 

Retention of sulfobromophthalein was normal; serum levels of bilirubin, albumin, globulin, alanine and 

aspartate aminotransferase activity, and γ-glutamyl transferase activity were also normal (Guzelian et 

al. 1980). 

The hepatic effects of mirex have been well characterized in experimental animals. The changes 

observed in livers include both adaptive and toxic effects. The adaptive effects observed are those 

generally produced by halogenated hydrocarbons; these include increase in liver weight or size (Abston 

and Yarbrough 1976; Byard et al. 1975; Chadwick et al. 1977; Chambers and Trevethan 1983; Chu et 

al. 1980b, 1981a, 1981b; Curtis and Hoyt 1984; Davison et al. 1976; Elgin et al. 1990; Ervin and 

Yarbrough 1983; Fujimori et al. 1983; Fulfs et al. 1977; Gaines and Kimbrough 1970; Hewitt et al. 

1979; Jovanovich et al. 1987; Karl and Yarbrough 1984; Larson et al. 1979a; Mehendale 1981b; 

Mehendale et al. 1973; Pittz et al. 1979; Plaa et al. 1987; Purushotham et al. 1988; Ritchie and Ho 

1982; Robacker et al. 1981; Robinson and Yarbrough 1978a, 1978c; Teo and Vore 1991; Thottassery 

and Yarbrough 1991; Villeneuve et al. 1977; Warren et al. 1978; Williams and Yarbrough 1983; 

Wilson and Yarbrough 1988; Yarbrough et al. 1981, 1984, 1986a, 1986b, 1992). Other effects 

observed include hepatocellular hypertrophy (Davison et al. 1976; Fulfs et al. 1977; Gaines and 

Kimbrough 1970; Ulland et al. 1977a; Yarbrough et al. 1981), cytoplasmic eosinophilia with migration 

of basophilic granules (Chu et al. 1981a; NTP 1990; Yarbrough et al. 198 l), an increase in the smooth 

endoplasmic reticulum (Baker et al. 1972; Curtis et al. 1981; Davison et al. 1976; Fulfs et al. 1977; 

Gaines and Kimbrough 1970; Mehendale et al. 1989), an increase in microsomal protein (Chambers 

and Trevethan 1983; Davison et al. 1976; Elgin et al. 1990; Karl and Yarbrough 1984; Klingensmith 

and Mehendale 1983b; Pittz et al. 1979; Villeneuve et al. 1977; Yarbrough et al. 1981, 1986a), an 

increase in cytochrome P-450 content (Baker et al. 1972; Chambers and Trevethan 1983; Cianflone et 

al. 1980; Curtis et al. 1981; Davison et al. 1976; Fujimori et al. 1983; Iverson 1976; Klingensmith and 

Mehendale 1983b; Kocarek et al. 1991; Peppriell 1981; Robacker et al. 1981; Robinson and 

Yarbrough 1978a; Yarbrough et al. 1981, 1986a), and an increase in NADPH2-cytochrome c reductase 

(Chambers and Trevethan 1983; Fujimori et al. 1983; Robacker et al. 1981; Yarbrough et al. 1986a), 

accompanied or unaccompanied by an increase in microsomal enzyme activity (Byard et al. 1975; 

Chadwick et al. 1977; Chambers and Trevethan 1983; Chu et al. 1981a, 1981b; Cianflone et al. 1980; 

Curtis et al. 1981; Fabacher and Hodgson 1976; Iverson 1976; Mehendale et al. 1973; Robacker et al. 

1981; Stevens et al. 1979; Villeneuve et al. 1977; Warren et al. 1978; Yarbrough et al. 1981, 1986a). 
MIREX AND CHLORDECONE 73 

2. HEALTH EFFECTS 

In addition to the adaptive effects described above, marked hepatic toxicity has been observed after 

acute-duration oral exposure of animals to mirex. The primary form of hepatotoxicity observed in rats 

after acute-duration oral exposures is hepatobiliary toxicity (Berman et al. 1986; Davison et al. 1976; 

Hewitt et al. 1986a; Mehendale 1976, 1977c, 1979; Teo and Vore 1991). Administration of mirex by 

gavage at 50 mg/kg/day for 3-5 days resulted in inhibition of the excretion of morphine glucuronide 

(Berman et al. 1986), production of polar imipramine metabolites (Berman et al. 1986; Mehendale 

1977c), chlorinated biphenyl metabolites (Mehendale 1976). It also caused a decrease in taurocholate 

extraction from the blood and excretion in the bile (Teo and Vore 1991), and decreased 

sulfobromophthalein clearance (Mehendale 1977c). These decreases in hepatobiliary excretion 

generally occurred in the presence of increased bile flow (Berman et al. 1986; Curtis and Mehendale 

1979; Dahlstrbm-King et al. 1992; Hewitt et al. 1986a; Mehendale 1977c, 1979, 1981b; Teo and Vore 

1991), but the decrease in taurocholate transfer to the bile was observed in the presence of decreased 

bile flow (Teo and Vore 1991). Decreased uptake of substances into rat hepatocytes was observed 

after gavage dosing with 12.5 mg/kg/day and above for 3 days, suggesting that transport of substances 

into hepatocytes may contribute to the decrease in their biliary excretion (Teo and Vore 1990). If 

mirex was given to rats in the diet for 14 days, focal bile stasis was observed at 5 mg/kg/day (Davison 

et al. 1976). Other hepatic effects observed after 14 days of dietary exposure at 5 mg/kg/day included 

hepatocyte swelling, liver cord cell disruption, and necrosis of central or midzonal hepatocytes 

(Davison et al. 1976). Other evidence of generalized hepatic toxicity includes: (1) increases in serum 

alanine and/or aspartate aminotransferase in mice following gavage doses of 30 mg/kg/day for 2 days 

(Fouse and Hodgson 1987), and in rats after 2 doses of 120 mg/kg on a single day (Mitra et al. 1990); 

(2) periportal liposis and degeneration of the endoplasmic reticulum after a single oral dose of 

200 mg/kg in rats (Kendall 1979); (3) increased hepatic lipids or decreased hepatic glutathione or 

glucocorticoid receptors after single oral doses of 100 mg/kg in rats (Ervin and Yarbrough 1983; 

Sunahara and Chiesa 1992; Thottassery and Yarbrough 1991); (4) swollen hepatocytes after 3 days of 

exposure of rats to 10 mg/kg/day (Plaa et al. 1987); (5) increased hepatic lipid in rats after 7 days of 

exposure at 2 mg/kg/day; (6) increased serum tnglycerides after 4 days of exposure of rats to 

1,000 mg/kg/day (Jovanovich et al. 1987); and (7) increased vacuolization with a loss of basophilic 

staining in mice after a single oral dose of 50 mg/kg/day (Hewitt et al. 1979). 

Several investigators have observed hepatic glycogen depletion in rats (Ervin and Yarbrough 1983; 

Elgin et al. 1990; Jovanovich et al. 1987; Kendall 1974a, 1979) and in mice (Fujimori et al. 1983). In 

rats, glycogen depletion occurred after a single gavage dose as low as 100 mg/kg (Ervin and 
MIREX AND CHLORDECONE 74 

2. HEALTH EFFECTS 

Yarbrough 1983). In mice, glycogen depletion occurred following gavage doses of 25 mg/kg/day for 

4 days (Fujimori et al. 1983). 

Similar toxic effects were observed in laboratory animals after intermediate-duration oral exposure to 

mirex, but the doses at which these effects were observed were lower. Impaired biliary excretion was 

observed in rats following mirex or chlordecone doses as low as 0.5 mg/kg/day for 1.5 days or 

19 mg/kg/day for 3 days (Bell and Mehendale 1985; Curtis and Hoyt 1984; Curtis and Mehendale 

1979; Mehendale 1981b; Teo and Vore 1991). In dogs, impaired biliary excretion was observed at a 

dose of 2.5 mg/kg/day administered for 13 weeks (Larson et al. 1979a). The dog study is limited in 

that too few animals (two/sex/dose) were used, and it is unclear whether dogs at all doses were tested 

for hepatobiliary function. In a dietary study, histopathological analyses showed focal bile stasis, 

disruption of liver cord cells, and central or midzonal necrosis in rats at 0.5 mg/kg/day for 28 days 

(Davison et al. 1976). Decreased hepatic glycogen and bile canalicular degeneration were observed in 

this study at 5 mg/kg/day. Twenty-eight-day exposure of rats to mirex also resulted in cytoplasmic 

vacuolation, hepatocellular necrosis, and anisokaryosis at 0.25 mg/kg/day; pericentral fatty vacuolation 

at 2.5 mg/kg/day (Chu et al. 1981b); and panlobular ballooning of hepatocytes, anisokaryosis, and fatty 

vacuolation in males and moderate lobular pattern with perinuclear clear zone and perivenous 

cytoplasmic ballooning with anisokaryosis in females at 6.2 mg/kg/day (Chu et al. 1980b). 

Cytoplasmic vacuolation, moderately decreased aggregated basophilia, nuclear anisokaryosis, and 

hyperchromicity were found in the liver of both sexes of rats dosed at 0.25 mg/kg/day for 28 days 

(Chu et al. 1981b). A similar study found comparable effects after 21 months in both sexes of rats 

dosed at 0.07 mg/kg/day (Chu et al. 1981c). Hepatocellular vacuolation was also observed in rats 

following exposure to 4 mg/kg/day for 13 weeks (Larson et al. 1979a). Lipid accumulation was 

observed in livers of rats exposed to 0.65 mg/kg/day for up to 10 months (Fulfs et al. 1977). Bile 

stasis, decreased hepatic glycogen, and hepatocellular vacuolation were observed in rats after dietary 

exposure to 1.3-3.1 mg/kg/day for 166 days (Gaines and Kimbrough 1970). These effects were not 

observed at doses ranging from 0.21 to 0.48 mg/kg/day (Gaines and Kimbrough 1970). 

No data were located regarding the effects of mirex on hepatobiliary function following chronicduration 

oral exposure. However, other adverse liver effects have been reported in animals following 

chronic oral exposures. In an 18-month dietary study in rats, increased fatty degeneration, cystic 

degeneration, necrosis, biliary hyperplasia, and periportal fibrosis were observed at the lowest dose 

tested (2.4 mg/kg/day) (Ulland et al. 1977a). F344/N male and female rats fed mirex doses (males = 
MIREX AND CHLORDECONE 75 

2. HEALTH EFFECTS 

0.007, 0.07, 0.7, 1.8, 3.8 mg/kg/day; females = 0.007, 0.08, 0.7, 2.0, 3.9 mg/kg/day) for 2 years 

developed histopathological changes, which included hepatocytomegaly with eosinophilic cytoplasm 

were observed in males and females at >0.7 mg/kg/day. Fatty metamorphosis (cytoplasmic vacuoles 

consistent with intracellular fat accumulation) and necrosis of hepatocytes (focal and centrilobular) 

were increased in males and females at >0.7 mg/kg/day. Dilation of the sinusoids (by blood or 

proteinaceous material) was observed in males at >0.7 mg/kg/day and in females only at the highest 

dose tested (NTP 1990). An MRL of 0.0008 mg/kg/day, based on a LOAEL of 0.075 mg/kg/day for 

histopathological evidence of hepatic damage from this study, was derived for chronic-duration oral 

exposure to mirex. 

Like mirex, chlordecone causes both adaptive and toxic changes in the livers of experimental animals. 

Adaptive responses of the liver seen after oral exposure of rats, mice, or gerbils to chlordecone 

include: (1) increases in liver size or weight (Cannon and Kimbrough 1979; Chernoff and Rogers 

1976; Curtis and Mehendale 1979; EPA 1986c; Fabacher and Hodgson 1976; Fujimori et al. 1983; 

Huber 1965; Larson et al. 1979b; Mehendale 1981b; Mehendale et al. 1977b, 1978b; Purushotham et 

al. 1988; Simmons et al. 1987; Swartz and Schutzmann 1986, 1987); (2) increased hepatocellular 

hypertrophy (Cannon and Kimbrough 1979); (3) increased smooth endoplasmic reticulum (Curtis et al. 

1981; Lockard et al. 1983a, 1983b; Mehendale et al. 1989); (4) increased microsomal protein 

(Chambers and Trevethan 1983; Klingensmith and Mehendale 1982b, 1983b; Mehendale et al. 1977b, 

1978b); (5) increased cytochrome P-450 content (Agarwal and Mehendale 1984a; Britton et al. 1987; 

. Cai and Mehendale 1990; Chambers and Trevethan 1983; Chaudhury and Mehendale 1991; Fabacher 

and Hodgson 1976; Fujimori et al. 1983; Kitchin and Brown 1989; Klingensmith and Mehendale 

1982b, 1983b; Kocarek et al. 1991; Mehendale et al. 1977b, 1978b); (6) increased NADPH2­

cytochrome c reductase (Chambers and Trevethan 1983; Fujimori et al. 1983; Mehendale et al. 1977b, 

1978b); (7) and/or increased microsomal enzyme activity (Chaudhury and Mehendale 1991; Cianflone 

et al. 1980; Curtis et al. 1981; Fabacher and Hodgson 1976; Klingensmith and Mehendale 1982b; 

Mehendale et al. 1977b, 1978b). 

Impaired biliary excretion in the presence of increased bile flow has been observed in three acuteduration 

studies conducted with mirex or chlordecone in rats (Curtis and Mehendale 1979; Mehendale 

1977b; Teo and Vore 1991) as well as in two intermediate duration studies (Mehendale 1981b; Curtis 

and Mehendale 1979). Administration of 10 mg/kg/day of chlordecone to rats by gavage for 8 days 

resulted in decreased biliary excretion of imipramine metabolites and increased bile flow (Mehendale 
 

 

 

MIREX AND CHLORDECONE 76 

2. HEALTH EFFECTS 

1977b). Similarly, administration of 18.75 mg/kg/day to rats for 3 days resulted in decreased bile acid 

concentration, decreased bile acid secretion, and increased bile flow (Teo and Vore 1991). In the 

intermediate-duration studies, results of the analysis of hepatobiliary function and overt toxicity in 

Sprague-Dawley rats dosed with mirex or chlordecone doses of 5 mg/kg/day for 30 or 35 days, 

respectively, provided evidence of a correlation between hepatobiliary function (as indicated by 

increased bile flow) and overt toxicity (as measured by tremors and diarrhea). Starting on the 8th day 

of treatment, rats began showing overt toxicity (diarrhea, tremors, hyperactivity, and exaggerated 

startle response to touch and noise) as well as increased biliary flow. Biliary excretion of 

intravenously administered phenolphthalein glucuronide was significantly depressed at 10 days and 

continued to decrease until exposure was terminated at 30 days (approximately l/4 of normal at 

25 days). Biliary excretion returned to normal by 20 days post-exposure. Total bile flow was increased 

throughout the exposure and recovery period (Mehendale 1981b). A similar result was reported for 

chlordecone alone at a dose of 0.5 mg/kg/day for 15 days (Curtis and Mehendale 1979). No effects 

on hepatocyte uptake of 17β-estradiol glucuronide, taurocholate, or L-alanine were observed at this 

dose. Other indicators of hepatic toxicity observed after acute-duration oral exposure included: 

(1) increased serum alkaline phosphatase and alanine aminotransferase after exposure of rats to 

10 mg/kg/day for 10 days (EPA 1986c); (2) increased mannitol recovery (indicates decreased 

permeability of the canalicular membrane) (Hewitt et al. 1986a) or increased lysosomal fragility 

(Hewitt et al. 1990) after a single oral exposure of rats to 50 mg/kg; (3) increased cytoplasmic 

vacuolation and decreased basophilic staining of hepatocytes in mice after a single oral dose of 

50 mg/kg (Hewitt et al. 1979); and (4) decreased hepatic glycogen in mice after gavage dosing with 

25 mg/kg/day for 4 days (Fujimori et al. 1983). Single oral doses of 5 mg/kg in rats were without 

effect on hepatobiliary excretion (Davis and Mehendale 1980). Single oral doses of up to 50 mg/kg 

were without other adverse effects as determined by histopathological analyses and/or determination of 

serum alanine and aspartate aminotransferases (Glende and Lee 1985; Iijima et al. 1983; Klingensmith 

and Mehendale 1983b; Plaa et al. 1987). 

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

tnglycerides and LDL cholesterol were observed in Sprague-Dawley rats following 15 days dietary 

exposure to 5 mg/kg/day chlordecone (Chetty et al. 1993a, 1993b). In another study, impaired biliary 

function was also observed in intermediate-duration studies with chlordecone in experimental animals, 

although conflicting results were obtained regarding LOAELs and NOAELs for this effect. Although 

no effect on biliary excretion or flow was observed in several dietary studies in rats at 0.5 mg/kg/day 
 

 

 

 

MIREX AND CHLORDECONE 77 

2. HEALTH EFFECTS 

for 15 days (Agarwal and Mehendale 1982, 1983c; Agarwal et al. 1983; Bell and Mehendale 1985; 

Curtis and Mehendale 1980), inhibition of biliary excretion of phenolphthalein glucuronide was shown 

in a dietary study in rats at 0.5 mg/kg/day for 15 days (Curtis and Mehendale 1979; Curtis et al. 

1979b; Mehendale 1981b). In addition, inhibition of exogenous taurocholate excretion was shown in a 

dietary study in rats at 1 mg/kg/day for 1.5 days (Curtis and Hoyt 1984). Also, ultrastructural analysis 

showed that bile canaliculi from rats exposed at 0.5 mg/kg/day for 15 days appeared tortuous and 

contained deformed and swollen microvilli (Curtis et al. 1981). Inhibition of phenolphthalein 

glucuronide was observed in rats following ingestion of 2.5 mg/kg/day for 15 days (Mehendale 

1990a), 5 mg/kg/day for up to 35 days (Mehendale 1981b), and 7.5 mg/kg/day for 15 days (Curtis and 

Mehendale 1979). Increased bile flow was also observed by Mehendale (1981b) and Curtis and 

Mehendale (1979). Other evidence of hepatotoxicity seen in intermediate-duration studies in rats 

included increased incidences of swollen hepatocytes following ingestion of 1.25 mg/kg/day for 

90 days (Larson et al. 1979b); areas of focal necrosis at 1.17 mg/kg/day for 90 days (Cannon and 

Kimbrough 1979); depletion of hepatic glycogen (Curtis et al. 1979b); and fragmentation of and/or a 

decrease in rough endoplasmic reticulum (Curtis et al. 1981; Faroon et al. 1991), or minute 

vacuolation of the cytoplasm (Faroon and Mehendale 1990) in rats at 0.5 mg/kg/day for 15 days. 

However, similar ultrastructural effects have not been observed in the same strain of rats after 15 days 

exposure to 0.5 mg/kg/day chlordecone (Lockard et al. 1983a, 1983b). In mice, ingestion of 

5.2 mg/kg/day for up to 12 months resulted in increased incidences of areas of focal necrosis (Huber 

1965). Gerbils had no increase in serum alanine or aspartate aminotransferase and no increase in 

adverse histopathological findings following ingestion of 1 mg/kg/day for 15 days (Cai and Mehendale 

1991b). In another intermediate-duration rat study, 10 male weanling Sprague-Dawley rats were fed 

diets containing either corn oil or chlordecone dissolved in corn oil for 28 days, and then sacrificed. 

There were mild histological changes in the liver, consisting of multiple focal lymphoid aggregates, 

perivenous cytoplasmic ballooning, and perinuclear halos in the portal area in the treated rats. The 

livers from 5 rats contained average chlordecone levels of 6.1 ppm (Chu et al. 1980a). 

Limited information is available regarding hepatotoxicity of chlordecone following chronic-duration 

oral exposures. A 21-month study in Sprague-Dawley rats reported a decrease in hepatic microsomal 

aniline hydroxylase activity at a dose of 0.07 mg/kg/day. Histopathological findings in this study 

included panlobular cytoplasmic vacuolation with loss of basophilia, fatty infiltration, and 

anisokaryosis in liver (Chu et al. 1981c). A National Cancer Institute (NCI) cancer bioassay showed 

fatty infiltration and hepatocellular degeneration in rats at doses as low as 0.4 mg/kg/day for 80 weeks 
 

 

MIREX AND CHLORDECONE 78 

2. HEALTH EFFECTS 

(NCI 1976). In B6C3F1 mice, an 80-week exposure to 2.6 mg/kg/day of chlordecone resulted in 

hepatocellular hyperplasia (NCI 1976). Routine histopathological analyses of livers from rats exposed 

up to 1.25 mg/kg/day for 2 years or dogs exposed at up to 0.625 mg/kg/day for 2 years showed no 

increase in adverse compound-related effects (Larson et al. 1979b). Both of these studies are limited 

in that it is unclear whether all tissues were examined; in addition, the study in dogs is limited in that 

too few animals were tested (two/sex/dose). 

Renal Effects. No studies were located regarding renal effects in humans after oral exposure to 

mirex or chlordecone. 

Animal studies indicate that acute- and intermediate-duration exposures to mirex are without 

significant renal toxicity but that chronic-duration exposure to low levels of mirex may result in toxic 

effects on the kidneys. No effect on rat kidney weight or blood urea nitrogen and no adverse 

histopathological findings were reported following a single oral dose of 50 mg/kg or 3 daily doses of 

10 mg/kg/day (Plaa et al. 1987). Similarly, no effect on kidney weight, blood urea nitrogen, or ion 

exchange in the kidneys and no adverse histopathological findings were reported following a single 

oral dose of 50 mg/kg in mice (Hewitt et al. 1979). Thirteen-week exposures of rats to doses as high 

as 64 mg/kg/day and of dogs to doses as high as 2.5 mg/kg/day caused no increase in adverse 

histopathological findings or effects on urinalysis parameters (Larson et al. 1979a). At 

0.05 mg/kg/day, 2 of 10 rats were reported to have moderate focal lymphoid aggregates and multiple 

focal interstitial mononuclear infiltrates in the kidneys following 28 days of dietary exposure (Chu et 

al. 1980a). However, the significance of these findings is limited by the low number of animals with 

these findings and the use of only a single dose, precluding determination of the presence or absence 

of a dose-response relationship. As indicated above, chronic-duration studies have shown increased 

nephrotoxicity following exposure to mirex. Nephropathy was observed to increase in severity in both 

male and female rats following exposure in a 2-year dietary study (NTP 1990). In males, this effect 

was observed at 20.7 mg/kg/day. In females, this effect was observed at 2 mg/kg/day and above. 

Similarly, in an independent evaluation of an l&month rat carcinogenicity bioassay, Reuber (1977) 

reported an increased incidence of nephritis in both males and females at 2.5 mg/kg/day and an 

increased incidence of renal necrosis in females at >2.5 mg/kg/day. However, the onginal study 

author (Ulland et al. 1977b) disputed this interpretation and considers this conclusion a 

misrepresentation of the data since the conclusion is not supported by data produced in this study 

(Ulland et al. 1977b). 
 

MIREX AND CHLORDECONE 79 

2. HEALTH EFFECTS 

Like mirex, chlordecone produced observable renal effects following oral exposure primarily in 

chronic-duration studies. However, no adverse renal effects were observed after acute exposure. 

Although increases in blood urea nitrogen and kidney weight were observed following a lo-day 

exposure of rats to 10 mg/kg/day of chlordecone (EPA 1986c), no effect on rat kidney weight or blood 

urea nitrogen, and no adverse histopathological findings were reported following a single oral dose of 

50 mg/kg or 3 doses of 10 mg/kg/day (Plaa et al. 1987). Similarly, no effect on kidney weight, blood 

urea nitrogen, or ion exchange in the kidneys and no adverse histopathological findings were reported 

following a single oral dose of 50 mg/kg in mice (Hewitt et al. 1979). Exposure of rats to up to 

4 mg/kg/day for 90 days also resulted in no adverse histopathological findings in the kidneys or in 

urinalysis parameters (Agarwal et al. 1983; Larson et al. 1979b). An increase in eosinophilic 

inclusions in the proximal tubules was observed in 2 of 10 rats examined following exposure at 

0.05 mg/kg/day for 28 days (Chu et al. 1980a). However, the biological significance of this finding is 

unknown based on the small number of animals with this lesion and the use of only one dose, 

precluding the determination of a dose-response relationship. In contrast to the negative findings 

observed in acute-duration studies, renal pathology was observed in rats following intermediate- and 

chronic-duration exposures to small doses of chlordecone (Larson et al. 1979b). In a 2-year feeding 

study with rats, groups of Wistar rats of both sexes were administered 0, 0.05, 0.25, 0.5, 1.25, 2.5, or 

4.0 mg/kg/day for a period of 1 year. After 1 year, 5 rats/sex/dose group were sacrificed. 

Additionally, 3 to 5 rats of each sex receiving 0.25 or 0.5 mg/kg/day and 3 males receiving 

1.25 mg/kg/day were returned to the control diet for 4 weeks and then sacrificed. Proteinuria was 

noted in all treatment groups at all intervals after 3 months except in males at 21 and 24 months when 

control levels were elevated and in females at 24 months when the levels in only the 0.5 and 

1.25 mg/kg/day groups were elevated. The severity of observed glomerulosclerosis was increased in 

both males and females at ≥0.25 mg/kg/day as compared to undosed controls (Larson et al. 1979b). 

Intermediate- and chronic-duration MRLs of 0.0005 mg/kg/day were derived for oral exposure to 

chlordecone based on the NOAEL of 0.05 mg/kg/day for histopathological evidence of renal damage 

from this study. An independent review of an NTP (1990) mirex bioassay in rats, which reported 

nephrotoxicity in the treated animals, concluded that fibrosis of the kidney was more frequent in 

chlordecone-treated rats (Reuber 1978a, 1979c) but the doses at which this effect was observed were 

not reported. However, the onginal pathology review of the study did not include any significant 

incidence of renal fibrosis among the treated rats. Thus, the ongin of data used by this reviewer to 

reach this conclusion is unclear. Dogs appeared to be less sensitive to chlordecone than rats; no 
 

 

MIREX AND CHLORDECONE 80 

2. HEALTH EFFECTS 

increases in urinary protein or adverse histopathological changes were seen in the kidneys of dogs 

ingesting 0.625 mg/kg/day for 124-128 weeks (Larson et al. 1979b). 

Endocrine Effects. 

Thyroid. No studies were located regarding thyroid effects in humans after oral exposure to mirex or 

chlordecone. 

Studies in rats indicate that mirex is toxic to the thyroid (Chu et al. 1981a, 1981b; NTP 1990; Singh et 

al. 1982, 1985). Doses of 0.25 mg/kg/day for 28 days resulted in a reversible reduction in colloid, a 

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

of T3 or T4 (Chu et al. 1980b, 1981a, 1981b). Ultrastmctural analyses of thyroids from rats treated for 

28 days showed dilation of the rough endoplasmic reticulum at 0.25 mg/kg/day and increased 

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

vacuolization at 2.5 mg/kg/day (Singh et al. 1982, 1985). Similar effects were observed following 

dietary exposure to 0.25 mg/kg/day for 148 days (Chu et al. 1981a) and for 28 days (Chu et al. 

1981b). A similar study found comparable effects after 21 months in both sexes of rats dosed at 

0.07 mg/kg/day (Chu et al. 1981c). Dietary exposure to 0.7 mg/kg/day and above for 2 years also 

resulted in an increase in cystic follicles in male rats (NTP 1990). No studies were located regarding 

thyroid effects in animals following oral exposure to chlordecone. 

Adrenal. No studies were located regarding adrenal effects in humans after oral exposure to mirex or 

chlordecone. 

Studies in animals indicate that the adrenal gland hypertrophies and releases increased levels of 

corticosterone in response to mirex exposure (Ervin and Yarbrough 1985; Jovanovich et al. 1987; 

Williams and Yarbrough 1983). Single gavage doses of 20 mg/kg resulted in an increased level of 

serum corticosterone in rats (Williams and Yarbrough 1983); 100 mg/kg resulted in increased adrenal 

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

serum adrenocorticotropic hormone (Ervin and Yarbrough 1985). Seven days of exposure to 

1,000 mg/kg/day also increased adrenal weight in rats (Jovanovich et al. 1987). Consistent with the 

ability of corticosterone to mobilize fatty acids for energy, a decrease in body fats was observed in this 
 

 

MIREX AND CHLORDECONE 81 

2. HEALTH EFFECTS 

study. No effects on the adrenal medulla were observed following 8-day dietary exposure to 

17 mg/kg/day mirex in rats (Baggett et al. 1980). 

Less information is available regarding the effects of chlordecone on the adrenal glands of animals. 

Increased relative adrenal weight was observed following a single oral dose of 35 mg/kg in rats 

(Swanson and Wooley 1982). An enlarged adrenal with hyperplasia and hypertrophy of the cortical 

cells was observed in a 30-day dietary study in rats at 1.17 mg/kg/day (Cannon and Kimbrough 1979). 

Also, decreased adrenal lipid was observed at 1.25 mg/kg/day in a 90-day dietary study in rats (Larson 

et al. 1979b). Consistent with a corticosterone-induced increase in lipid utilization, decreased body fat 

was observed following a 16-day dietary exposure at 2.5 or 5 mg/kg/day in rats (Mehendale et al. 

1977b, 1978b), 15 or 20 days of dietary exposure at 5 mg/kg/day in rats (Klingensmith and Mehendale 

1982a), or 33 days of dietary exposure to 10 mg/kg/day in mice (Fujimori et al. 1983). In contrast to 

the absence of effects of mirex on the adrenal medulla, chlordecone at 17 mg/kg/day for 8 days 

resulted in a decrease in the medullary content of epinephrine in rats (Baggett et al. 1980). 

Dermal Effects. No studies were located regarding dermal effects in humans after oral exposure to 

mirex. Eighty-nine of 133 workers interviewed as a result of intermediate- or chronic-duration 

exposures to high levels of chlordecone during its manufacture reported skin rashes of an 

erythematous, macropapular nature that occurred at some time during their exposure (Cannon et al. 

1978). Among 23 workers with blood chlordecone levels above 2 μg/L, 16 reported exposure-related 

rashes (Taylor et al. 1978). While it is likely that these rashes were the direct result of dermal 

exposure, insufficient information was given to eliminate a systemic effect resulting from oral 

exposure. 

Hair loss in the very young is the primary dermal effect observed in animals as a result of oral 

exposure to mirex. Hair loss was reported in an acute-duration exposure study in which rats were 

given a total of 365 mg/kg over a 12-day period (Kendall 1974a), but a LOAEL could not be 

determined because the daily dose was not reported. Hair loss was also reported in a 90-day gavage 

study in rats (5, 12.5, 25 mg/kg/day) (Dietz and McMillan 1979), but the specific dose associated with 

this effect was not specified, precluding determination of LOAEL for this effect. 

No effects on the skin were observed during routine histopathological analyses of the skin of rats 

exposed to chlordecone for 90 days at doses as high as 4 mg/kg/day or for 2 years at doses as high as 
MIREX AND CHLORDECONE 82 

2. HEALTH EFFECTS 

1.25 mg/kg/day, or in dogs exposed for 124-128 weeks at doses as high as 0.625 mg/kg/day (Larson 

et al. 1979b). Increased dermatitis was reported in an 80-week dietary cancer bioassay in rats at doses 

as low as 0.4 mg/kg/day (NCI 1976). 

Ocular Effects. No studies were located regarding ocular effects in humans after oral exposure to 

mirex or chlordecone. 

Production of cataracts in the very young was observed in animals as a result of oral exposure to 

mirex in an acute-duration exposure study in which rats were given a total of 365 mg/kg over a 

12-day period (Kendall 1974a), but a LOAEL could not be determined because the daily dose was not 

reported. Cataracts were produced in other newborn rats and mice following early postnatal exposure 

(Chernoff et al. 197913; Rogers and Grabowski 1984; Scotti et al. 1981). Cataracts were characterized 

as diffuse anterior cornea1 opacities, and lenses were found to have increased water and sodium 

content relative to potassium content (Rogers and Grabowski 1984). Histopathological analyses 

showed increased vacuoles, pyknotic nuclei, swollen fibers, and/or degeneration. Cataracts were 

produced in newborn rodents that received doses of 5 mg/kg/day mirex by gavage directly (Scotti et 

al. 1981) and in those that received the mirex indirectly through the mother’s milk (Chernoff et al. 

1979b; Rogers and Grabowski 1984). Administration of mirex directly to the newborn by gavage at 

5 mg/kg/day starting on postpartum day 1 resulted in swelling of the lens fibers as early as postpartum 

day 7, with degeneration and necrosis of the lenses apparent with increasing duration of exposure 

(Scotti et al. 1981). Dietary exposure of maternal animals to doses as low as 1.25 mg/kg/day during 

postpartum days l-4 or to doses as low as 1.8-2.8 mg/kg/day throughout the period of lactation 

(Gaines and Kimbrough 1970) also resulted in the production of cataracts in rat pups. Exposure 

during the first few days of life appears to be critical to the development of cataracts. A single oral 

dose resulted in cataracts only if administered on or before postpartum day 6 and resulted in outlined 

lenses if administered on or before postpartum day 8 (Chernoff et al. 1979b). Thus, the very young 

represent a population especially susceptible to this effect (see also Section 2.7). Eye irritation was 

also reported in a 90-day gavage study in rats (5, 12.5, 25 mg/kg/day), but the specific dose associated 

with this effect was not specified, thus, precluding determination of LOAELs (Dietz and McMillan 

1979). 

In contrast to the results obtained with mirex, chlordecone was not found to be cataractogenic in the 

very young (Chernoff et al. 1979b). Exposure of maternal rats to doses as high as 10 mg/kg/day or 
 

 

 

MIREX AND CHLORDECONE 83 

2. HEALTH EFFECTS 

maternal mice to doses as high as 24 mg/kg/day during the first 4 days of lactation, and the resulting 

exposure of the young through the mother’s milk, resulted in no incidences of cataracts among the 

offspring of treated dams. 

Body Weight Effects. No studies were located regarding effects on body weight in humans after 

oral exposure to mirex. Twenty-seven of 133 workers examined as a result of intermediate or chronicduration exposures to chlordecone experienced weight loss (Cannon et al. 1978). Weight loss (up to 

60 pounds in 4 months) was reported in 10 of these workers (Taylor et al. 1978). 

Decreases greater than 10% in body weight or body weight gain have been observed in a number of 

acute-duration studies (Buelke-Sam et al. 1983; Byrd et al. 1981; Chadwick et al. 1977; Chernoff et al. 

1979a, 1979b; Elgin et al. 1990; Fujimori et al. 1983; Jovanovich et al. 1987; Khera et al. 1976; 

Mehendale et al. 1973; Ritchie and Ho 1982; Rogers and Grabowski 1984; Villeneuve et al. 1977), 

intermediate-duration studies (Chernoff et al. 1979b; Chu et al. 1981b; Curtis and Hoyt 1984; Davison 

et al. 1976; Fujimori et al. 1983; Larson et al. 1979a; NTP 1990), and chronic-duration studies (NTP 

1990) with mirex. 

Decreases greater than 10% in body weight or body weight gain have also been observed in several 

chlordecone acute-duration studies (Albertson et al. 1985; Chernoff and Kavlock 1982; Chernoff and 

Rogers 1976; EPA 1986c; Huang et al. 1980; Kavlock et al. 1987b; Seidenberg et al. 1986; Simmons 

et al. 1987; Smialowicz et al. 1985; Swanson and Wooley 1985), intermediate-duration studies 

(Cannon and Kimbrough 1979; Curtis and Hoyt 1984; Curtis and Mehendale 1979; Fabacher and 

Hodgson 1976; Klingensmith and Mehendale 1982a; Larson et al. 1979b; Mehendale et al. 1977b, 

1978b; Pryor et al. 1983), and chronic-duration studies (Larson et al. 1979b). In the report by Larson 

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

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

Other Systemic Effects 

Serum Glucose. No studies were located regarding effects on serum glucose in humans after oral 

exposure to mirex or chlordecone. 
MIREX AND CHLORDECONE 84 

2. HEALTH EFFECTS 

Serum glucose levels were decreased uniformly in all studies that examined this parameter following 

oral exposure of animals to high doses of mirex (Chu et al. 1981b; Ervin and Yarbrough 1983; 

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

1983; Yarbrough et al. 1981). Decreases were observed following single oral doses as low as 5 mg/kg 

in rats (Robinson and Yarbrough 1978a) and dietary doses as low as 0.25 mg/kg/day for 28 days in 

rats (Chu et al. 1981b). Reports of chlordecone-induced effects on serum glucose were limited to a 

single report of decreased serum glucose in mice exposed for 4 days at doses as low as 25 mg/kg/day 

or for 33 days at doses as low as 10 mg/kg/day (Fujimori et al. 1983). 

Thermoregulation. No studies were located regarding effects on thermoregulation in humans after 

oral exposure to mirex or chlordecone. 

Also, no studies were located regarding effects on thermoregulation in animals following oral exposure 

to mirex. Chlordecone was shown to cause a decrease in core temperature following ingestion of a 

single dose of 55 or 75 mg/kg in rats (Swanson and Wooley 1982). The core temperatures were 

depressed for up to 12 days after administration of 75 mg/kg of chlordecone. Slight hyperthermia 

occurred after the body temperature recovered. Slight hyperthermia was also observed in rats after 

12 weeks of exposure at 7.1 mg/kg/day (Pryor et al. 1983). 

2.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans after oral exposure to mirex or 

chlordecone. 

The only information about the immunological effects of mirex exposure in animals was provided by 

one acute oral study in rats in which decreased spleen weight was reported (Buelke-Sam et al. 1983). 

Two reports were located regarding effects of chlordecone on immunological end points in rats 

following acute exposure. Oral administration of chlordecone in corn oil to male Fischer 344 rats did 

not cause dose-related changes in lymphoproliferative responses of splenic lymphocytes to the T-cell 

mitogens, phytohemagglutinin or pokeweed mitogen; it did cause decreases in the proliferative 

response to the T-cell mitogen, concanavalin A, and the B-cell mitogen, Salmonella typhimurium 

mitogen, but only at a dose (10 mg/kg/day for 10 days) that also resulted in impaired overall health of 

the rats (EPA 1986c; Smialowicz et al. 1985). Similarly, statistically significant reductions in spleen 
 

MIREX AND CHLORDECONE 85 

2. HEALTH EFFECTS 

and thymus weights, and in natural killer cell activity of splenocytes against allogeneic (W/Fu-Gl rat 

lymphoma) and xenogeneic (YAK-l mouse lymphoma) tumor cell lines (EPA 1986c; Smialowicz et 

al. 1985), were observed only at a dose (10 mg/kg/day) producing generalized toxicity. Also, a slight 

decrease in total leukocyte count (EPA 1986c) and a 49% decrease in neutrophils (Smialowicz et al. 

198.5) were observed at toxic doses. The authors suggested that these effects were associated with the 

compromised health status of the animals and were not due to selective toxicity toward the immune 

system. The limitations of these studies include lack of information on cell-mediated functions, such 

as alloantigen reactivity and cytotoxicity, and on humoral immunity in the treated animals. However, 

as part of a study in male Sprague-Dawley rats on the effects of calcium deficiency on the toxicity of 

chlordecone, an increase in plaque-forming cells was observed at the lowest dose tested 

(0.5 mg/kg/day) (Chetty et al. 1993c). 

A significant reduction of thymus weight was also observed in Sprague-Dawley rats 3 weeks after a 

single oral dose of 75 mg/kg of chlordecone (Swanson and Wooley 1982). It is likely that this effect 

may also have been associated with generalized toxicity in the experimental animals. 

2.2.2.4 Neurological Effects 

No studies were located regarding neurological effects in humans after oral exposure to mirex. Sixty-one 

of 133 workers examined as a result of intermediate- or chronic-duration exposures to high levels 

of chlordecone during its production experienced tremors; 58 experienced nervousness or unfounded 

anxiety; and 42 experienced visual difficulties during exposure (Cannon et al. 1978). While oral 

exposures are generally not thought to contribute significantly in occupational exposure situations, 

hygiene at the facility was very poor and oral exposures (from food and water) were considered to 

have been likely. Tremors were observed in all 23 workers with blood levels >2 μg/L (Taylor et al. 

1978). The tremors were characterized as intention tremors or as occurring with a fixed posture 

against gravity (Taylor 1982, 1985). The tremors were most apparent in the upper extremities but 

were also detectable in the lower extremities. In the more severe cases, gait was affected. Mental 

disturbances consisting of irritability and poor recent memory were reported by 13 of the 23 workers. 

Standard tests of memory and intelligence showed clear evidence of an encephalopathy in 1 of the 13 

workers (Taylor 1982, 1985). The worker with encephalopathy reported auditory and visual 

hallucinations and demonstrated whole-body myoclonic jerks in response to loud noises. In 15 of the 

23 workers, vision was blurred (Taylor 1982, 1985). The effects on vision were characterized as a 
MIREX AND CHLORDECONE 86 

2. HEALTH EFFECTS 

disruption of ocular motility following a horizontal saccade by rapid random multidirectional eye 

movements (Taylor 1982, 1985). Visual acuity and smooth eye movements were unaffected. 

Headaches of mild-to-moderate severity were reported by 9 of the 23 workers. Three of these 9 had 

increased cerebrospinal fluid pressure and papilledema (Sanbom et al. 1979; Taylor 1982, 1985). 

Nerve conduction velocity tests, electroencephalography, radioisotope brain scans, computerized 

tomography, and analyses of cerebral spinal fluid content were normal. Sural nerve biopsies obtained 

from 5 workers with detectable tremor, mental disturbances consisting of irritability and poor recent 

memory, rapid random eye movements, muscle weakness, gait ataxia, incoordination, or slurred speech 

revealed a greatly decreased number of small myelinated and unmyelinated axons (Martinez et al. 

1978). Ultrastructural analyses of the nerves showed increased interstitial collagen, redundant folds in 

the Schwann cell cytoplasm, and the presence of occasional crystalloid inclusions suggesting that 

chlordecone had a direct toxic effect on the Schwann cell. Examination of 16 of the 23 affected 

individuals from 5 to 7 years after cessation of exposure and after body levels of chlordecone had been 

substantially reduced, showed that 9 were asymptomatic, 5 had persistent tremor or nervousness, and 3 

reported emotional problems (Taylor 1982, 1985). 

Clinical signs indicative of neurotoxicity were not widely reported in animals treated with mirex. 

However, a number of studies did note some abnormal behavior following oral administration of 

mirex. Following acute-duration exposures of rats to large doses (12.5 to >365 mg/kg) of mirex, 

lethargy, weakness, hyperexcitability, and/or tremors have been observed (Gaines and Kimbrough 

1970; Kendall 1974a). Although the precise doses associated with specific neurotoxic effects were not 

specified in these studies, single oral doses of 100 mg/kg or greater were necessary. Juvenile rats 

showed a high sensitivity to acute exposure to mirex immediately after birth. Ingestion of the milk of 

dams treated with 2.5 mg/kg/day on lactation days l-4 caused no behavioral abnormalities at the time 

of exposure but resulted in increased activity in the animals when they reached adulthood (Reiter 

1977). 

Intermediate-duration exposures to mirex generally resulted in lethargy as the predominant clinical sign 

at lower exposures and hyperexcitability at higher doses. Lethargy was observed at 5 mg/kg/day 

during both 15- and 30-day dietary studies in rats (Curtis and Hoyt 1984; Mehendale 1981b). 

Decreased operant responding was also observed in a 90-day gavage study in rats at 5 mg/kg/day 

(Dietz and McMillan 1979). At 10 mg/kg/day, mirex had no effect on motor coordination of mice, but 

some mice were observed to become too weak to balance on a glass rod during a 15-day gavage study 
MIREX AND CHLORDECONE 87 

2. HEALTH EFFECTS 

(Fujimori et al. 1983). Dietary exposure to 16 mg/kg/day was observed to have no effect on the 

behavior of rats over 13 weeks of exposure, but at 64 mg/kg/day for 13 weeks, rats were observed to 

become hyperexcitable and develop tremors and convulsions (Larson et al. 1979a). Similarly, longerduration exposures also resulted in increased excitability. Dietary exposure to 2 mg/kg/day for 

148 days resulted in hypoactivity, irritability, and tremors in treated rats (Chu et al. 1981a). 

In contrast to the limited information regarding the neurotoxicity of mirex, the neurotoxicity of 

chlordecone, which included tremoring and/or a time-dependent exaggerated startle response, was 

readily apparent in studies with experimental animals. Single oral doses of chlordecone resulted in 

increased tremoring and/or an exaggerated response to audio or tactile stimuli (Albertson et al. 1985; 

Aldous et al. 1984; Egle et al. 1979; End et al. 1981; Huang et al. 1980; Hwang and Van Woert 1979; 

Maier and Costa 1990; Swanson and Wooley 1982). Following single oral doses as low as 3.5 mg/kg 

in rats, increased tremoring during handling was observed for up to 1 week following dosing (Swanson 

and Wooley 1982). In mice, tremors, decreased motor coordination, and hyperexcitability were 

observed following a single oral dose of 10 mg/kg (Huang et al. 1980). In these studies, the tremors 

were apparent at earlier times when higher doses were used than when lower doses were used. 

Abnormal gait was also apparent after single oral doses of 72-98 mg/kg (Egle et al. 1979). Slightly 

lower multiple oral doses given over several days produced increased tremors, exaggerated startle 

responses, and/or abnormal gait (Aldous et al. 1984; Baggett et al. 1980; Chang-Tsui and Ho 1979; 

Desaiah et al. 1980a; Fujimori et al. 1982b; Hoskins and Ho 1982; Huang et al. 1980; Jordan et al. 

1981; Klingensmith and Mehendale 1982b; Mishra et al. 1980; Smialowicz et al. 1985). In rats, 

tremors and an exaggerated startle response were observed at doses as low as 5 mg/kg/day over 5 days 

(Klingensmith and Mehendale 1982b). An increased startle response without visible tremoring was 

observed at doses as low as 2.5 mg/kg/day over 10 days (EPA 1986c). This study was part of a 

toxicity screen performed at EPA in which male Fischer-344 rats received gavage doses of 1.25 or 

2.5 mg/kg/day chlordecone for 10 consecutive days. At 2.5 mg/kg/day and above, the amplitude of 

the acoustic startle response was significantly increased with all decibel stimuli used. Motor activity 

in a figure-8 maze was also decreased at the highest dose tested. At the other 2 doses, the amplitude 

was increased with all decibel stimuli. Motor activity in a figure-8 maze was decreased at the highest 

dose tested (EPA 1986c). An acute oral MRL of 0.01 has been developed for chlordecone based on 

the NOAEL of 1.25 mg/kg from this study. 
 

MIREX AND CHLORDECONE 88 

2. HEALTH EFFECTS 

Several acute-duration studies have attempted to correlate the tremoring with underlying neurochemical 

changes. However, in many cases it has been difficult to determine whether the effects observed were 

causative or the result of other underlying effects. Inhibition of brain Na+

K+ATPase and mg2+ATPases 

has been correlated with the onset and diminution of tremoring in both rats and mice (Bansal and 

Desaiah 1985; Desaiah et al. 1980a; Jordan et al. 1981). However, other studies have not produced 

similar results (Maier and Costa 1990; Mishra et al. 1980). In rats, mixed results have been obtained 

regarding changes in norepinephrine and dopamine levels in brains from treated animals. Although 

norepinephrine uptake and dopamine uptake and binding were decreased (Chang-Tsui and Ho 1980; 

Desaiah 1985) and striatal dopamine synthesis, uptake, and release were inhibited (Fujimori et al. 

1986) at tremongenic doses, no effect was observed on norepinephrine or on dopamine content 

(Aldous et al. 1984; End et al. 1981) or synthesis (End et al. 1981) at equally tremongenic doses. 

Effects on calcium have also been observed in treated rats and mice. Decreased calcium uptake 

occurred in rats following a single oral dose of 40 mg/kg (End et al. 1981), and decreased brain 

calcium content was observed in adult mice following a single oral dose of 25 mg/kg (Hoskins and Ho 

1982). Decreased brain calmodulin was observed in rats at 2.5 mg/kg/day for 10 days (Desaiah et al. 

1985). 

Tremoring, accompanied or unaccompanied by increased responsiveness to touch and noise, have also 

been observed in a number of intermediate-duration studies (Agarwal and Mehendale 1984c; Cannon 

and Kimbrough 1979; Curtis and Hoyt 1984; Curtis and Mehendale 1979; Dietz and McMillan 1979; 

Fujimori et al. 1983; Huber 1965; Klingensmith and Mehendale 1982a; Larson et al. 1979b; Linder et 

al. 1983; Mehendale 1981b; Mehendale et al. 1978; Pryor et al. 1983; Squibb and Tilson 1982b; 

Swartz and Schutzmann 1986, 1987). Mild tremors were observed in rats at doses as low as 

0.83 mg/kg/day for 90 days (Linder et al. 1983). At 0.5 mg/kg/day for 90 days, an increase in the 

startle response of rats was observed, but no tremoring or effects on reflexes such as the tail flick 

response or the negative geotaxis test were observed, indicating that the startle response may be a 

sensitive indicator of chlordecone-induced neuronal function (Squibb and Tilson 1982b). 

Chronic-duration studies in rats have also demonstrated increased tremoring. Tremoring was observed 

at 1.25 mg/kg/day but not at 0.5 mg/kg/day in a 2-year rat dietary study (Larson et al. 1979b). NCI 

(1976) bioassays in mice and rats reported tremoring at 3.0 and 0.4 mg/kg/day, respectively. No 

tremors or other behavioral abnormalities were observed in dogs ingesting 0.625 mg/kg/day in a 

companion 2-year dietary study (Larson et al. 1979b). 
MIREX AND CHLORDECONE 89 

2. HEALTH EFFECTS 

The highest NOAEL and all LOAEL values from each reliable study for neurological effects in each 

species and duration category are recorded for mirex in Table 2-l and for chlordecone in Table 2-2 

and plotted for mirex in Figure 2-l and for chlordecone in Figure 2-2. 

2.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after oral exposure to mirex. 

Occupational exposure to chlordecone for up to 1.5 years caused oligospermia and decreased sperm 

motility in male workers. However, no loss of fertility was reported by the workers (Guzelian 1982a; 

Taylor 1982, 1985; Taylor et al. 1978). Refer to Section 2.2.1.5 for further details. 

Studies in animals suggest that both male and female reproductive systems are adversely affected by 

mirex. Acute exposure of male rats to 6 mg/kg/day mirex daily for 10 days decreased their fertility 

significantly. Although residues of mirex were found in the testes of the 6 mg/kg/day dose-group 

males, this did not affect reproduction parameters in subsequent mating trials. The authors attributed 

the observed decrease in the incidence of pregnancy in females mated with males in this dose group in 

the first trial to a subclinical toxic effect as suggested by reduction in body weight gain in the dosed 

males (Khera et al. 1976). Gestational exposure of female rats with higher dosages (12.5 mg/kg/day; 

gestation days 6-15) of mirex resulted in increased resorptions and failure of pregnancy in 45% of 

dams (Grabowski and Payne 1980; Khera et al. 1976). Gestational exposure of female rats at 

10 mg/kg/day for 5 days resulted in decreased ovarian and uterine weights and reduced blood flow to 

the ovaries, uterus, and fetuses (Buelke-Sam et al. 1983). This effect was not observed if the duration 

of exposure during gestation was shortened to 1 day or lengthened to 10 days; thus, the significance of 

this effect is unknown. 

In a 28-day dietary study, decreased sperm count was noted in male rats at dosages as low as 

0.025 mg/kg/day; testicular degeneration was observed at dosage levels of 2.5 and 3.7 mg/kg/day 

(Yarbrough et al. 1981). However, mirex fed to male rats at 1.3-3.1 mg/kg/day for 2 generations 

resulted in no decrease in fertility (Gaines and Kimbrough 1970). In contrast, females given 

1.8-2.8 mg/kg/day for 2 generations produced a decreased number of litters (Gaines and Kimbrough 

1970). Administration of 0.25 mg/kg/day to male and female rats for 91 days prior to mating and then 

through lactation resulted in a decreased mating and litter size (Chu et al. 1981a). Male and female 
 

MIREX AND CHLORDECONE 90 

2. HEALTH EFFECTS 

mice at 0.65 mg/kg/day for 30 days prior to mating, and then for an additional 90 days, experienced 

reduced fecundity and had reduced litter size and number of offspring (Ware and Good 1967); 

however, only one dosage level was tested. Dietary exposure of wild mice to 2.4 mg/kg/day mirex for 

15 months inhibited reproduction (Wolfe et al. 1979). However, this study was limited in that few 

reproductive parameters were measured and mice of unknown genetic background were used. 

Chlordecone also produced reproductive toxicity in both male and female animals. Exposure of male 

rats to doses of chlordecone as low as 0.625 mg/kg/day for 10 days resulted in a decreased sperm 

count, although at the highest dose tested (10 mg/kg/day) decreased testes weight and an increase in 

sperm count was observed (EPA 1986c). A dominant lethal study, designed to test the effect of oral 

mirex doses on male fertility in Sprague-Dawley rats, showed no effect on the fertility of the male 

rats. The male rats were mated with naive, nulliparous females each week for 14 consecutive weeks 

two days after oral gavage dosing at 11.4 mg/kg/day for 5 days (Simon et al. 1986). Persistent 

vaginal estrus was reported in female mice receiving 2 mg/kg chlordecone daily for 2 weeks (Swartz 

et al. 1988). 

Effects observed after intermediate-duration exposure of male and female mice to chlordecone included 

decreased numbers of litters, litter size, and frequency of litter production (Good et al. 1965; Huber 

1965). These effects were observed at doses as low as 1.3 mg/kg/day for 130 days (Huber 1965) or 

0.65 mg/kg/day for 6 months (Good et al. 1965). 

Intermediate- and chronic-duration studies in rodents indicate that decreases in sperm count and 

testicular atrophy may result from exposure to chlordecone. Dietary exposure of male rats to 

0.83 mg/kg/day and above of chlordecone for 90 days decreased sperm motility and viability; at 

1.67 mg/kg/day and above, there was a decrease in the weight of seminal vesicles and prostate (Linder 

et al. 1983). Despite these effects, the fertility, litter size, sperm morphology, sperm count, and 

histopathology of male gonads were unaffected. Exposure of male rats to 1.17-1.58 mg/kg/day for 4.5 

months prior to mating also had no effect on fertility (Cannon and Kimbrough 1979). In mice at 

higher doses (5.2 mg/kg/day chlordecone for 160 days), no effect on spermatogenesis occurred, but a 

decrease in litter size was observed when treated males were mated with control females (Huber 1965). 

In contrast to the absence of adverse histopathological changes reported by Linder et al. (1983), 

testicular atrophy has been reported following dietary exposure of rats to 0.5 mg/kg/day of chlordecone 

for 90 days (Larson et al. 1979b). It was suggested that the difference in the two studies was due to 
MIREX AND CHLORDECONE 91 

2. HEALTH EFFECTS 

the use of younger males in the study by Larson et al. (1979b), suggesting that adolescent males may 

be more susceptible to adverse effects on the gonads. 

Intermediate-duration studies with treated females show that exposure to chlordecone may result in 

persistent vaginal estrus, decreased ovulation, and reproductive failure. Persistent vaginal estrus was 

observed in female mice at doses as low as 2 mg/kg/day for 3-6 weeks (Huber 1965; Swartz and Mall 

1989; Swartz et al. 1988). Increased atresia of follicles (Swartz and Mall 1989), decreased ovulation 

(Swartz et al. 1988), and small and medium-sized follicles (Swartz and Mall 1989) have been observed 

after 4 weeks of exposure to 8 mg/kg/day of chlordecone. Similarly, decreased corpora lutea have 

been observed following administration of 3.9 mg/kg/day for 130 days (Huber 1965). Decreased 

numbers of litters or complete reproductive failure have been observed after exposure of female rats to 

1.62-l .7 1 mg/kg/day for 4.5 months or female mice to 5.2 mg/kg/day for 160 days (Huber 1965). 

The highest NOAEL and all LOAEL values from each reliable study for reproductive effects in each 

species and duration category are recorded for mirex in Table 2-l and for chlordecone in Table 2-2 

and plotted for mirex in Figure 2-l and for chlordecone in Figure 2-2. 

2.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans after oral exposure to mirex or 

chlordecone. 

Exposure of maternal rats and mice to mirex during gestation resulted in increases in resorptions and 

stillbirths and decreases in postnatal viability (Buelke-Sam et al. 1983; Byrd et al. 1981; Chernoff and 

Kavlock 1982; Chernoff et al. 1979a; Grabowski 1983a; Grabowski and Payne 1980, 1983a, 1983b; 

Gray and Kavlock 1984; Gray et al. 1983; Khera et al. 1976; Rogers and Grabowski 1983) at doses as 

low as 1.25 mg/kg/day when administered from gestation days 4 through 22. Examination of fetuses 

at the end of gestation showed increases in the incidence of edematous fetuses and fetuses with cardiac 

arrhythmias (primarily first-degree heart block) (Buelke-Sam et al. 1983; Byrd et al. 1981; Chernoff et 

al. 1979a; Grabowski 1981, 1983a; Grabowski and Payne 1980, 1983a, 1983b; Kavlock et al. 1982; 

Khera et al. 1976; Rogers and Grabowski 1983). The final trimester appeared to be the most sensitive 

period for induction of cardiac dysrhythmias; the incidence was slightly increased at doses as low as 

0.1 mg/kg/day during gestation days 15.5-21.5 (Grabowski 1983a). These effects were generally seen 
MIREX AND CHLORDECONE 92 

2. HEALTH EFFECTS 

at lower doses than the increases in mortality. Other visceral anomalies were not widely reported, but 

instances of anomalies such as enlarged cerebral ventricles, undescended testes, ectopic gonads, 

hydrocephaly, scoliosis, cleft palate, fleshy heart, enlarged atrium, or short tail were reported in a few 

studies (Chernoff et al. 1979a; Kavlock et al. 1982; Khera et al. 1976). Additional effects observed in 

fetuses included decreased skeletal ossification (Chernoff et al. 1979a), fetal weight (Buelke-Sam et al. 

1983; Byrd et al. 1981; Chernoff and Kavlock 1982; Gray and Kavlock 1984; Gray et al. 1983; 

Kavlock et al. 1982; Khera et al. 1976), serum glucose and hematocrit (Rogers et al. 1984), serum 

plasma proteins (Grabowski 1981), fetal liver weight and glycogen content (Kavlock et al. 1982), renal 

protein and alkaline phosphatase (Kavlock et al. 1982), and kidney weights at postpartum day 250 

(Gray and Kavlock 1984; Gray et al. 1983), and increased dyspnea (Grabowski and Payne 1983a) and 

liver and thyroid lesions (Chu et al. 1981a). Cataracts were also observed in offspring in several 

studies (Chernoff et al. 1979a; Chu et al. 1981a; Gaines and Kimbrough 1970; Rogers and Grabowski 

1983; Rogers et al. 1984); however, cataracts also resulted from early postnatal exposure (Chernoff et 

al. 1979b; Rogers and Grabowski 1984; Scotti et al. 1981) (see Section 2.2.2.2) indicating that in 

utero exposure was not critical for their development. 

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

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

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

Seidenberg et al. 1986). The increase in fetal/pup mortality was observed at doses as low as 

10 mg/kg/day .when administered to rats during gestation days 7-16 (EPA 1986c) and at doses as low 

as 12 mg/kg/day when administered to mice during gestation days 7-16 (Chernoff and Rogers 1976). 

Edema was reported in rat fetuses at doses of 10 mg/kg/day during gestation days 7-16 (Chernoff and 

Rogers 1976), but this effect was not noted in other developmental toxicity studies with chlordecone. 

Other indicators of developmental toxicity included decreased fetal or neonatal weight and/or skeletal 

ossification (Chernoff and Kavlock 1982; Chernoff and Rogers 1976; EPA 1986c; Gray and Kavlock 

1984; Kavlock et al. 1985,. 1987b; Seidenberg et al. 1986) and a few instances of anomalies and 

malformations such as enlarged renal pelves, undescended testes, enlarged cerebral ventricles, clubfoot, 

fused vertebrae or ribs, and encephalocele (Chernoff and Rogers 1976; Kavlock et al. 1985). 

Anovulation and persistent vaginal estrus were observed in female offspring of maternal rats given 

15 mg/kg/day of chlordecone on gestation days 14-20 (Gellert and Wilson 1979). However, no 

effects on vaginal patency or fertility were observed in female offspring of maternal mice given 

20 mg/kg/day during gestation days 8-12 or 14-18 (Gray and Kavlock 1984). 
 

 

MIREX AND CHLORDECONE 93 

2. HEALTH EFFECTS 

Exposure of female rats to chlordecone for 60 days prior to mating through lactation day 12 showed 

subtle neurological changes in the offspring later in life (Rosecrans et al. 1982; Seth et al. 1981; 

Squibb and Tilson 1982a). Although major reflexes were unaltered, the offspring of dams exposed to 

0.3 mg/kg/day showed increased serotonin turnover and decreased dopamine in response to stress 

(Rosecrans et al. 1982) and increased striatal dopamine binding (Seth et al. 1981). Furthermore, 

offspring of mice exposed to 0.05 mg/kg/day in this exposure paradigm showed an increased reactivity 

to apomorphine (a dopamine agonist) (Squibb and Tilson 1982a). These studies suggest that perinatal 

exposure to low doses of chlordecone may affect dopaminergic function in adult offspring. 

The highest NOAEL values and all reliable LOAEL values from each reliable study for developmental 

effects in each species and duration category are recorded for mirex in Table 2-l and for chlordecone 

in Table 2-2 and plotted for mirex in Figure 2-l and for chlordecone in Figure 2-2. 

2.2.2.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans after oral exposure to mirex or 

chlordecone. 

There were also no studies regarding potential adverse morphological changes in chromosomes in 

somatic cells of whole animals after oral exposure to mirex or chlordecone. However, a dominant 

lethal assay was conducted in male rats (20 males/group; strain not specified) receiving oral doses of 

1.5, 3.0, or 6.0 mg/kg mirex by gavage daily for 10 consecutive days (Khera et al. 1976). At the end 

of treatment, individual males were mated with two untreated virgin females for 5 days; the mating 

sequence was continued until 14 sequential matings were completed. Females were sacrificed 

13-15 days following separation from the males, and the uterine contents were examined for 

deciduomas, corpora lutea, and viable embryos. Although there was a significant decrease in the 

incidence of pregnancies in the 6.0-mg/kg group following the first mating, parameters indicative of 

dominant lethality were unaffected by treatment. Mirex was also detected in the testes; therefore, the 

failure to induce a dominant lethal effect was not associated with an inability of the test material to 

reach the target organ. 

Chlordecone was evaluated in a dominant lethal mutation assay in which groups of 10 male SpragueDawley rats were administered 3.6 or 11.4 mg chlordecone/kg/day for 5 consecutive days by oral 
MIREX AND CHLORDECONE 94 

2. HEALTH EFFECTS 

gavage (Simon et al. 1986). Two days after administration of the final dose, individual males were 

mated with two naive, nulliparous females for 1 week; the mating sequence was continued for 

14 weeks. Females were sacrificed on gestation day 14, and uteri and ovaries were examined for 

deciduomata, corpora lutea, implantation sites, and live and dead implants. Reduced fertility indices 

(i.e., number inseminated/number mated) were seen in the high-dose group following the first two 

matings; however, no adverse effects on male fertility were seen at any week in either treatment group. 

Similarly, there was no consistent pattern of dose- or time-related dominant lethal action. In an 

additional phase of the study, chlordecone was shown to be distributed throughout the reproductive 

tract with the highest concentration initially observed in the vas deferens, and in decreasing order in 

seminal vesicular fluid, unwashed sperm, prostate, seminal vesicles, and washed sperm. This 

distribution persisted as levels declined over the 21-day observation period. Therefore, the absence of 

a dominant lethal effect was not due to a failure to expose spermatozoa. 

Administration of single oral doses of 90 or 120 mg/kg mirex by gavage to female Sprague-Dawley 

rats resulted in induction of hepatic ornithine decarboxylase activity; there was, however, no evidence 

of significant damage to deoxyribonucleic acid (DNA) as measured by alkaline elution (Mitra et al. 

1990). 

Marked disturbances in the distribution of ploidy (diploid and tetraploid nuclei) have been observed in 

the livers of male Sprague-Dawley rats fed a dietary concentration of 100 ppm mirex (equivalent to 

≈5 mg/kg/day) for 13 months (Abraham et al. 1983). Mirex selectively reduced the number of 

tetraploids with the most significant reduction noted in hepatocellular carcinomas; however, nuclei in 

the areas adjacent to these tumors were also primarily composed of diploids. These data should be 

interpreted with caution since isolation of nuclei from tumors is difficult and because “of the fantastic 

variety of forms that tumor nuclei assume” (Smuckler et al. 1976). Similarly, the relevance to humans 

is not clear since human liver is mainly composed of diploid cells (99%) and contains few tetraploids 

(Adler et al. 1981). 

In agreement with hepatic functional activity studies conducted with mirex, chlordecone administered 

orally to female Sprague-Dawley rats at l/5 and 3/5 of the LD50 (19 and 57 mg/kg, respectively) 

caused a significant increase in omithine decarboxylase activity, but there was no evidence of DNA 

damage at either level (Kitchin and Brown 1989). 
 

MIREX AND CHLORDECONE 95 

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The only data from an in vivo assay suggesting possible genotoxicity for chlordecone were reported by 

Ikegwuonu and Mehendale (1991). In this study, chlordecone was administered orally in corn oil at a 

dose of 10 mg/kg to groups of male Sprague-Dawley rats. Following treatment, animals were 

subdivided into groups that received either hydroxyurea (a DNA repair stimulator) or dimethyl 

sulfoxide (solvent for hydroxyurea). Animals were sacrificed at an unspecified time, and hepatocytes 

recovered from the various groups were subjected to a battery of biochemical assays to measure effects 

on DNA. Chlordecone alone induced a low level of unscheduled DNA synthesis in recovered 

hepatocytes; however, the response (≈1.2-fold over control) was too marginal to conclude a positive 

effect. The comparative evaluation of chlordecone effects on adenosine diphosphate-ribosyltransferase 

(ADPRT) activity and DNA strand breaks provided inconsistent results. Although the data suggest 

that chlordecone treatment increased DNA strand breaks, ADPRT activity was suppressed rather than 

stimulated, as would be expected when DNA strand breaks occur. 

Other genotoxicity studies are discussed in Section 2.4. 

2.2.2.8 Cancer 

No studies were located regarding cancer in humans following oral exposure to mirex. Extremely 

limited information was located regarding cancer in humans following oral exposure to chlordecone. 

Liver biopsy samples taken from 12 workers with hepatomegaly resulting from intermediate or 

chronic-duration exposures to high levels of chlordecone showed no evidence of cancer (Guzelian et 

al. 1980). However, conclusions from this study are limited by the very small number of workers 

sampled, the relatively brief duration of exposures, and the absence of a sufficient latent period for 

tumor development. The average exposure of the subjects was 5-6 months and were examined 

immediately after exposure. 

Mirex was found to be carcinogenic by the oral route in mice and rats in several studies. The 

predominant carcinogenic lesions observed in these studies were hepatomas and neoplastic nodules of 

the liver, and mononuclear cell leukemia and transitional cell papillomas of the kidney. A positive 

trend in pheochromocytomas was also observed in one of the studies. Both male and female mice 

(18/sex/dose) of the (C57BL/6 x C3H/ANF)F1 or (C57BL/6 x AKR)F1 strains showed a significant 

increase in the incidence of hepatomas in a screening study in which mirex was administered first by 
 

 

MIREX AND CHLORDECONE 96 

2. HEALTH EFFECTS 

gavage from 7 until 28 days of age and then in the diet until 18 months of age (time-weighted-average 

dose = 3.6 mg/kg/day) (Innes et al. 1969). 

In rats, an increase in the incidence of neoplastic nodules was also observed in male CD rats 

administered mirex (4.9 mg/kg/day) in the diet for 18 months. However, the number of rats (20-26 

males and females) tested was rather low and the duration of dosing should have been longer to have 

maximum sensitivity of testing (Ulland et al. 1977a). In 2-year feeding studies, F344/N rats (52/sex) 

were administered mirex in the diet for 104 weeks in two separate bioassays (NTP 1990). In one of 

the bioassays both sexes of F344/N rats were used, while only females were used in the second. It 

was concluded that under the conditions of the 2-year feeding studies of mirex, there is clear evidence 

of carcinogenic activity for male and female F344/N rats, as indicated by marked increased incidences 

of neoplastic nodules of the liver (at ≥0.7 mg/kg/day in males and ≥3.8 mg/kg/day in females) and by 

dose-related increase in the incidences of mononuclear cell leukemias in females (1.8 mg/kg/day in 

males, ≥1.8 mg/kg/day in females in the first study, and 7.7 mg/kg/day in females in the second study; 

p <0.05), as well as by a positive trend in the incidence of transitional cell papillomas of the renal 

pelvis in males (at 3.8 mg/kg/day; p = 0.018 by Life Table Tests). The audit summary of this report 

states that because of an apparent disproportionate number of liver tissue samples taken from the high 

dose groups, additional and comparative liver sections were made for control groups of both sexes and 

the high dose male group after the initial Pathology Working Group (PWG) review of this study. A 

second PWG, convened to review the liver sections, concluded that any discrepancies noted during the 

review of the pathology materials were minor in nature and not clustered in any one group of study 

animals. Consequently, the NTP considered the data produced from this study supportive of the 

conclusion of Clear Evidence of carcinogenic activity (CE) for mirex in F344/N rats under the 

conditions of the bioassay (NTP 1990). 

Chlordecone was also shown to be carcinogenic in rats and mice. The results of NCI (1976) bioassays 

in mice and rats clearly suggest that chlordecone induces hepatocellular carcinomas in both sexes of 

rats and mice. Administration of chlordecone to Osborne-Mendel rats via the diet for 80 weeks 

resulted in a significant increase in the incidence of hepatocellular carcinomas over pooled controls in 

both males and females at a time-weighted average of 1.2 mg/kg/day in males and 1.3 mg/kg/day in 

females (NCI 1976). In the NCI (1976) bioassay in rats, the incidence of hepatocellular carcinomas 

was significantly increased (p<0.05) in both with a dose-related trend. The incidence of hepatocellular 

carcinomas in high-dose males and females were 7% and 22% for males and females, respectively. 
 

MIREX AND CHLORDECONE 97 

2. HEALTH EFFECTS 

Nevertheless, this study had several limitations. Initial doses were not well tolerated because of 

exceedence of the Maximum Tolerated Dose (MTD) as indicated by excessive deaths. Doses were 

reduced 17-33% from initial doses once or twice during the experiment. During the final 75 days of 

treatment, high dose males received chlordecone on alternative weeks only. Doses above the MTD 

were used for 42-386 days. An unusually high mortality rate occurred in control animals also, and 

only pooled controls were used in this bioassay. 

Administration of chlordecone to B6C3F1 mice for 80 weeks also resulted in significantly increased 

incidences of hepatocellular carcinomas in both males and females at doses as low as 2.6 mg/kg/day 

(NCI 1976). In the NCI (1976) bioassay in mice, the incidence of hepatocellular carcinomas was 

significantly increased (p<0.05) in both with a dose-related trend. The incidence of hepatocellular 

carcinomas was 81% and 88% in low- and high-dose males, respectively, and 52% and 47% in low-and 

high-dose females, respectively. In addition, a decrease of latency time of tumor appearance was 

observed in treated mice, as compared to controls. Nevertheless, this study had several limitations. An 

abnormally high incidence (32%) of hepatocellular carcinomas was found in the matched control group 

of male mice. In addition, initial doses were not well tolerated because of exceedence of the 

Maximum Tolerated Dose (MTD) as indicated by excessive deaths. Doses were reduced 25-50% 

from initial doses once or twice during the experiment. Doses above the MTD were used for 

90-134 days. An unusually high mortality rate occurred in controls animals as well. 

In its evaluations, the DHHS has determined that both mirex and chlordecone may reasonably be 

anticipated to be carcinogenic on the basis of sufficient evidence of carcinogenicity in animals (NTP 

1994). However, neither mirex nor chlordecone has been classified by the EPA with regard to cancer 

inducing potential (EPA 1994). 

The cancer effect levels (CELs) for mirex and chlordecone in chronic-duration studies in rats and mice 

are recorded for mirex in Table 2-l and for chlordecone in Table 2-2 and plotted for mirex in Figure 

2-l and for chlordecone in Figure 2-2. 

2.2.3 Dermal Exposure 

No data on health effects resulting from dermal exposure to mirex in humans were located. Data on 

health effects resulting from dermal exposure to chlordecone are limited to information on a single 
MIREX AND CHLORDECONE 98 

2. HEALTH EFFECTS 

group of men exposed to chlordecone at a facility in Hopewell, Virginia, where chlordecone was 

manufactured over a 21-22-month period. Hygiene conditions at the plant were extremely poor and 

substantial dermal exposure could have occurred. Inhalation and oral exposures were also thought to 

have occurred. Studies of this group of men are limited by the uncertainties regarding exposure levels 

and route and by exposure to the precursor used to manufacture chlordecone, 

hexachlorocyclopentadiene. 

2.2.3.1 Death 

No studies were located regarding death in humans following dermal exposure to mirex. No deaths 

were reported in humans after exposure to chlordecone (Cannon et al. 1978; Taylor et al. 1978). 

The dermal LD50 value for both mirex and chlordecone in rats was reported to be in excess of 

2,000 mg/kg (Gaines 1969). In male rabbits exposed dermally to chlordecone in corn oil, an LD50 

value of 410 mg/kg was reported (Larson et al. 1979b). All reliable LD50 values for death in rats and 

rabbits following acute-duration exposure for mirex and chlordecone are recorded in Tables 2-3 

and 2-4, respectively. 

2.2.3.2 Systemic Effects 

Several studies were presented in Section 2.2.1.2 regarding the systemic effects experienced by 

workers occupationally exposed to chlordecone (Cannon et al. 1978; Guzelian et al. 1980; Martinez et 

al. 1978; Taylor 1982, 1985; Taylor et al. 1978). Dermal exposure was probably a major route of 

exposure in the occupational situation described in these studies; however, the results of these studies 

are not repeated in this section since Section 2.2.1.2 contains a complete description of the systemic 

effects associated with occupational exposure (route of exposure unspecified; either inhalation, oral, 

and/or dermal) to chlordecone. No additional studies were located regarding respiratory, 

cardiovascular, gastrointestinal, musculoskeletal, hepatic, endocrine, ocular, or bodyweight effects in 

humans or animals after dermal exposure to mirex or chlordecone. The systemic effects believed to 

result directly from dermal exposure are discussed below. The LOAEL value for systemic effects in 

mice after intermediate-duration dermal exposure is recorded for mirex in Table 2-3. 


MIREX AND CHLORDECONE 101 

2. HEALTH EFFECTS 

Hematological Effects. No studies were located regarding hematological effects in humans after 

dermal exposure to mirex or chlordecone. 

The only information located regarding hematological effects of mirex in animals was found in a study 

in which an unspecified amount of mirex was applied to the skin of rabbits for 9 weeks, 5 days/week, 

for 6-7 hours/day (Larson et al. 1979a). Hematological analyses from these rabbits revealed no 

compound-related effects. 

No studies were located regarding hematological effects in animals after dermal exposure to 

chlordecone. 

Renal Effects. No studies were located regarding renal effects in humans after dermal exposure to 

mirex or chlordecone. 

The only information located regarding the renal effects of mirex in experimental animals was found 

in a study in which an unspecified amount of mirex was placed in contact with the skin of rabbits for 

6-7 hours/day, 5 days/week, for 9 weeks (Larson et al. 1979a). Routine urinalyses revealed no 

compound-related effects on the kidneys. 

No studies were located regarding renal effects in animals after dermal exposure to chlordecone. 

Dermal Effects. No studies were located regarding dermal effects in humans after dermal exposure 

to mirex. Eighty-nine of the 133 workers interviewed as a result of intermediate- or chronic-duration 

exposures to high levels of chlordecone during its manufacture experienced skin rashes of an 

erythematous, macropapular nature at some time during their exposure (Cannon et al. 1978). Among 

23 workers with blood chlordecone levels in excess of 2 μg/L, 6 men reported exposure-related rashes 

(Taylor et al. 1978). It is likely that these rashes were the direct result of dermal exposure. However, 

insufficient information was given to eliminate the possibility of a systemic effect resulting from 

derrnal exposure. 

Dermal exposure of mice to 3.6 mg/kg of mirex, three times/week for 4 weeks, resulted in mild 

epidermal proliferation (Moser et al. 1992). Application of an unspecified amount of mirex to the skin 

of rabbits for 6-7 hours/day, 5 days/week for 9 weeks, resulted in slight erythema and scaling after 
MIREX AND CHLORDECONE 102 

2. HEALTH EFFECTS 

day 5 (Larson et al. 1979a). This effect was reported to be reversible after 2 days without treatment. 

No signs of dermal irritation were observed in rabbits exposed to varying amounts of a 20% solution 

of chlordecone in corn oil (Larson et al. 1979b). 

2.2.3.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans or animals after dermal exposure 

to mirex or chlordecone. 

2.2.3.4 Neurological Effects 

The neurological effects observed after occupational exposure to chlordecone were described in 

Section 2.2.1.4 (Cannon et al. 1978; Martinez et al. 1978; Sanbom et al. 1979; Taylor 1982, 1985; 

Taylor et al. 1978). Dermal exposure to chlordecone probably constituted a major route of such 

occupational exposures. Section 2.2.1.4 contains a complete description of the neurological effects 

associated with occupational exposure to chlordecone. No additional studies were located regarding 

neurological effects in humans or animals after dermal exposure to mirex or chlordecone. 

2.2.3.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after dermal exposure to mirex. The 

available data in humans indicate that chlordecone causes male reproductive effects. Occupational 

exposure to chlordecone for up to 1.5 years caused oligospermia and decreased sperm motility in male 

workers. However, there were no reported infertility in these male subjects despite loss of sperm 

motility in some workers (refer to Section 2.2.1.5 for further details). 

No studies were located regarding reproductive effects in animals after dermal exposure to mirex. The 

only animal study that referred to reproductive effects following dermal exposure to chlordecone was 

conducted in rabbits by Allied Chemical. This study was not available for review. A published 

review of the study (Epstein 1978) indicated that chlordecone applied to shaved skin at dose levels of 

5 or 10 mg/kg for 8 hours/day, 5 days/week, for 3 weeks induced testicular atrophy in two of six 

rabbits at 5 mg/kg and in one of six rabbits at 10 mg/kg. No other toxic effects were noted. This 

study is limited by the lack of dose response and lack of a NOAEL for the effect observed. 
MIREX AND CHLORDECONE 103 

2. HEALTH EFFECTS 

2.2.3.6 Developmental Effects 

No studies were located regarding developmental effects in humans after dermal exposure to mirex or 

chlordecone. Although impaired spermatogenesis among male workers exposed to chlordecone was 

not reported to have affected their fertility (Guzelian 1982a; Taylor 1982, 1985; Taylor et al. 1978), it 

is unclear whether sperm abnormalities resulted in developmental effects in offspring. A follow-up of 

workers with initially lowered sperm levels did not indicate an increase in birth defects among 

offspring (Taylor 1982, 1985). 

No studies were located regarding developmental effects in animals after dermal exposure to mirex or 

chlordecone. 

2.2.3.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans or animals after dermal exposure to 

mirex or chlordecone. 

Genotoxicity studies are discussed in Section 2.4. 

2.2.3.8 Cancer 

No studies were located regarding cancer in humans after dermal exposure to mirex or chlordecone. 

In animals, mirex has been shown to be a nonmutagenic hepatocarcinogen (see Sect. 2.2.2.7, 2.2.2.8, 

2.4). In animal studies, mirex, was tested at a dermal dose of 3.6 mg/kg 4 weeks in female CD-l 

mice for tumor promoter activity and evidence of epidermal hyperplasia after initiation with 200 

nmol/day 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Positive control mice were treated 

with 2 nmol/day of the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), 

following initiation with DMBA. A third group of mice were treated with both 3.6 mg/kg mirex and 

2 nmol/day TPA for 4 week following initiation with DMBA. Multiple applications of mirex for 

4 weeks to the DMBA-initiated mice resulted only in minimal increase in the number of nucleated 

epidermal cell layers. In contrast, a definitive hyperplastic response of 6-7 cell layers was observed 

after repeated application with TPA to the DMBA-initiated mice. Mice that were promoted with 
 

MIREX AND CHLORDECONE 104 

2. HEALTH EFFECTS 

mirex or TPA without DMBA initiation did not develop tumors. At 20 weeks, DMBA-initiated mice 

promoted with 3.6 mg/kg mirex developed an average of 14.2 tumors. Mice promoted with 

2 nmol/day TPA bore 4.7 tumors per mouse. Mice co-promoted with 3.6 mg/kg mirex and 2 nmol 

TPA gave a greater than additive response (35.4 tumors per mouse). The tumor incidence was also 

greater than additive in mice co-promoted with 3.6 mg/kg mirex and 2 nmol/day TPA. The tumors 

consisted mainly of papillomas with some squamous cell carcinomas. The study also found a 90% 

incidence (activation) of the c-Ha-ras tumor gene in these co-promoted tumors. Under conditions 

where both 3.6 mg/kg/day mirex and 2 nmol/day give a similar tumor yield, only the TPA response 

was associated with biochemical markers of enhanced cell proliferation, induction of epidermal 

ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. On the basis of the 

data, the authors concluded that there is evidence for a dual effect of mirex during co-promotion: first, 

as an independent tumor promoter with a mechanism different than that of phorbol esters and, second, 

as a compound that also potentiates skin tumor promotion by TPA (Meyer et al. 1993, Moser et al. 

1992, 1993). A second study examined the effects of DMBA initiated mirex-promoted tumors in 

female mice on ovarian hormones. This study found that the loss of ovary (OVX) protected the 

female mice (40%) from mirex tumor promotion. Tumor promotion was unaffected in DMBA-initiated 

OVX mice promoted with TPA. Based on the data, the authors also concluded that there is a 

structural specificity in the tumor-promoting ability of mirex in mouse skin and that mirex is a much 

more effective skin tumor promoter in female CD-l mice than in male CD-l mice or OVX mice 

(Meyer et al. 1994). 

2.3 TOXICOKINETICS 

Mirex is absorbed from the digestive tract of animals. Following exposure to mirex, an initial rapid 

excretion of the majority of the ingested mirex occurs via the feces within the first 48 hours postdosing. 

This fecal .mirex represents unabsorbed compound. Once absorbed, mirex is widely 

distributed throughout the body but is sequestered in the fat. It has a long retention time in the body. 

Mirex is not metabolized in humans, rodents, cows, or minipigs. The parent compound is the only 

radiolabeled compound that has been found in the plasma, fat, and feces. In animals, mirex is 

excreted unchanged mainly in the feces; urinary excretion is negligible. Mirex is also excreted in 

human milk. Only a very limited number of studies were located regarding the toxicokinetics of mirex 

via the inhalation and dermal routes. Limited data indicate that mirex is absorbed by rats following 

exposure to the compound in cigarette smoke. 
 

MIREX AND CHLORDECONE 105 

2. HEALTH EFFECTS 

Occupational studies indicate that chlordecone is absorbed via the inhalation and oral routes. 

Chlordecone is readily absorbed from the gastrointestinal tract of humans and animals. Chlordecone is 

widely distributed throughout the body and concentrates in the liver of humans and animals. It has a 

long retention time in the body. Chlordecone is metabolized to chlordecone alcohol in humans, 

gerbils, and pigs. Rats, guinea pigs, and hamsters cannot convert chlordecone to chlordecone alcohol. 

Chlordecone, chlordecone alcohol, and their glucuronide conjugates are slowly excreted in the bile and 

eliminated in the feces. However, a substantial enterohepatic recirculation of chlordecone exists that 

curtails its excretion in the feces. Chlordecone is also excreted in saliva and mother’s milk. Only a 

very limited number of studies were located regarding the toxicokinetics of chlordecone via the 

inhalation and dermal routes. Occupational studies indicate that chlordecone is absorbed via the 

inhalation and oral routes. Limited animal data indicate that dermal absorption of chlordecone is low. 

The specific mechanisms by which mirex and chlordecone are transferred from the gut, lungs, or skin 

to the blood are not known. However, mirex is a highly stable, lipophilic compound that is resistant 

to metabolism. It has a high 1ipid:water partition coefficient, so it partitions readily into fat and 

demonstrates a very high potential for accumulation in tissues. The preferential distribution of 

chlordecone to the liver rather than to the fat tissue is due to its association with plasma proteins. 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

No data were located regarding absorption of mirex in humans after inhalation exposure. 

Very limited data show that inhaled mirex can be rapidly absorbed into the blood of rats (Atallah and 

Dorough 1975; Dorough and Atallah 1975). The fate of [14 C] mirex in cigarette smoke in rats was 

assessed using a smoking device (Atallah and Dorough 1975; Dorough and Atallah 1975). Eight 5-mL 

puffs were administered to the trachea of rats at 15-second intervals. Two to four minutes after 

inhalation, 47% of the radiolabel was exhaled, 36% was found in the lung, 11% was in the blood, and 

1% was in the heart. No quantitative conclusions regarding absorption in humans following inhalation 

can be drawn from this assay since the relationship of the inhalation parameters of the rat to normal 

human breathing was not determined. 
 

 

 

 

MIREX AND CHLORDECONE 106 

2. HEALTH EFFECTS 

Chlordecone is absorbed following occupational exposure (Cannon et al. 1978; Cohn et al. 1978; 

Taylor 1982, 1985). Mean blood levels of workers exposed to chlordecone at a manufacturing plant in 

Hopewell, Virginia, were 2.53 ppm for workers manifesting illness (nervousness or unfounded anxiety; 

pleuritic chest pain; weight loss of up to 60 pounds in 4 months; visual difficulties; skin rashes of an 

erythematous, macropapular nature) and 0.6 ppm for workers with no illness (Cannon et al. 1978). 

Two months following cessation of exposure, blood levels in workers were in excess of 2 ppm (Taylor 

1982, 1985). Following exposure in humans, mean half-lives of 96 days (range of 63-148 days) (Adir 

et al. 1978) and 165 days (Cohn et al. 1978) in blood have been reported for chlordecone. This 

relatively long half-life may be due to the high degree of lipid solubility and limited metabolism of 

chlordecone. 

No studies were located regarding absorption in animals after inhalation exposure to chlordecone. 

2.3.1.2 Oral Exposure 

No studies were located regarding absorption in humans after oral exposure to mirex. 

Several studies in rats indicate that mirex is absorbed from the digestive tract (Byrd et al. 1982; 

Gibson et al. 1972; Mehendale et al. 1972). Experiments with rats given single oral doses of mirex 

ranging from 0.2 to 10 mg/kg showed that an initial rapid excretion of mirex occurs in the feces 

within the first 48 hours post-dosing (Byrd et al. 1982; Gibson et al. 1972; Mehendale et al. 1972). 

The excretion of mirex in the feces within this time period,is attributed to unabsorbed mirex. A 

majority (85-94%) of the total quantity excreted after 7 days is eliminated in this first rapid excretion 

phase (Gibson et al. 1972; Mehendale et al. 1972). Other data provided an absorption estimate of 

69%, which occurred with female rats given a single oral dose of 10 mg/kg (Byrd et al. 1982). 

Similarly, most of the fecal mirex was recovered within the first 48 hours. This was attributed to the 

elimination of unabsorbed mirex (Byrd et al. 1982). Intestinal absorption of mirex was slightly 

decreased by the presence of an existing body burden (Gibson et al. 1972). For example, rats fed 

12.5 mg/kg of unlabeled mirex before administration of a single dose (0.2 mg/kg) of mirex excreted 

25% of the administered dose in the feces, as compared with 18% excretion for the animals given only 

a single dose (Gibson et al. 1972). 
MIREX AND CHLORDECONE 107 

2. HEALTH EFFECTS 

Mirex is rapidly absorbed by rats and monkeys. Peak plasma concentrations of 14C-mirex occurred 

within 4-7 hours after female rats were given a single oral dose of 10 mg/kg (Byrd et al. 1982) and 

within 2 hours after male rats were administered a single oral dose of 100 mg/kg (Brown and 

Yarbrough 1988). 14 C-Mirex levels in plasma peaked 5 hours after oral administration of 1 mg/kg to a 

female rhesus monkey (Wiener et al. 1976). Thereafter, the decline in plasma 14C concentration 

continued at a much slower rate and paralleled that in the intravenously dosed monkeys (Wiener et al. 

1976). 

Mirex rapidly entered the maternal bloodstream of pregnant rats dosed orally with 5 mg/kg of mirex 

on gestation days 15, 18, or 20 (Kavlock et al. 1980). Four hours after oral dosing on gestation day 

15, the plasma concentration of mirex was 13 ppm. Mirex plasma concentrations were significantly 

affected by both the time of administration and the hour of observation (p<0.01). Higher plasma 

concentrations were found at older gestation ages (13 ppm on gestation day 15, compared to 23 ppm 

on gestation day 20, measured 4 hours after administration). Plasma concentrations declined with time 

after dosing (Kavlock et al. 1980). 

Mirex concentrations in plasma of pregnant goats fed daily doses of 1 mg/kg for 61 weeks stabilized 

after 15 weeks (Smrek et al. 1977). An increase in the dose from 1 to 10 mg/kg at the end of the 

study resulted in an increase in the plasma level of mirex. Females dosed for 18 weeks starting at the 

first day postpartum had plasma levels that were similar to females that were started on mirex in early 

pregnancy (Smrek et al. 1977). 

As noted in Section 2.3.1.1, chlordecone is absorbed after occupational exposure (Cannon et al. 1978; 

Cohn et al. 1978; Taylor 1982, 1985). Although the route of exposure was not specified, hygiene at 

the workplace was extremely poor and unintentional ingestion of chlordecone was possible. For a 

description of the absorption of chlordecone following occupational exposure see Section 2.3.1.1. 

Chlordecone is readily absorbed (90%) from the gastrointestinal tract of rodents and has a long half-life 

(Egle et al. 1978). In rats exposed to a single oral dose of 40 mg/kg chlordecone, the blood halflives 

at 4, 8, and 14 weeks were 8.5, 24, and 45 days, respectively (Egle et al. 1978). Chlordecone is 

also rapidly absorbed by pregnant rats (Kavlock et al. 1980). Four hours after dosing (5 mg/kg) on 

gestation day 15, the plasma concentration of chlordecone was 6 ppm. 
MIREX AND CHLORDECONE 108 

2. HEALTH EFFECTS 

2.3.1.3 Dermal Exposure 

No data were located regarding absorption of mirex in humans or animals after dermal exposure. 

As noted in Section 2.3.1.1, studies have shown that chlordecone is absorbed after occupational 

exposure (Cannon et al. 1978; Cohn et al. 1978; Taylor 1982, 1985). Although the route of exposure 

was not specified in the studies, dermal exposures probably constituted a major portion of the exposure 

in these occupational situations. For a description of the absorption of chlordecone following 

occupational exposure see Section 2.3.1.1. 

Chlordecone is absorbed to a limited extent following dermal exposure in rats (Hall et al. 1988; Shah 

et al. 1987). The percent of dose absorbed was determined by dividing the radioactivity in the body 

(carcass) and in the excreta by the total radioactivity recovered (in carcass, excreta, treated skin, and 

washes of the application materials). The results showed that fractional absorption decreased as the 

dose of chlordecone increased. At 72 hours after exposure to 0.29, 0.54, or 2.68 μmol 

14C-chlordecone/cm2

, skin penetration of chlordecone in young rats was 10.17%, 7.23%, and 1.93%, 

respectively, of the applied dose. Skin penetration of chlordecone in adult rats at 72 hours was 9.2%, 

5.96%, and 1.03% for the low-, middle-, and high-dose groups, respectively. The area of application 

when expressed as the percentage of the total surface area (≈2.3%) was the same in both young and 

adult rats. The actual amount of chlordecone absorbed per cm2

 (0.03 pmol/cm2) was similar for all 

dose groups suggesting that saturation occurred at the low dose. No significant age-dependent 

differences in dermal absorption were seen. 

2.3.2 Distribution 

2.3.2.1 Inhalation Exposure 

Mirex has been found in human adipose tissue (Burse et al. 1989; Kutz et al. 1974). Although the 

route of exposure was not specified, exposure was probably via the inhalation, oral, and dermal routes. 

Levels of 0.16-5.94 ppm and 0.3-l .13 ppm in males and females, respectively, were found in tissue 

samples taken either from postmortem examinations or during surgery (Kutz et al. 1974). The adipose 

tissue samples came from individuals who lived in areas in which mirex was used extensively in a 
MIREX AND CHLORDECONE 109 

2. HEALTH EFFECTS 

program to control fire ants. Adipose tissue levels of mirex ranging from 0.03 to 3.72 ppm have been 

found in residents living near a dump site in Tennessee (Burse et al. 1989). 

Only very limited animal data were located regarding the distribution of mirex following inhalation 

exposure (Atallah and Dorough 1975; Dorough and Atallah 1975). Mirex was found in the lungs 

(36%), blood (11%), and hearts (1%) of rats exposed to mirex in cigarette smoke (Atallah and 

Dorough 1975; Dorough and Atallah 1975). The exposure concentration was not reported. 

In humans, chlordecone is absorbed and distributed to various tissues and has a long retention time in 

the body (Cannon et al. 1978; Cohn et al. 1978; Taylor 1982, 1985). Chlordecone was eliminated 

slowly from the blood (half-life of 165 days) and fat (half-life of 125 days) of industrial workers 

(Cohn et al. 1978). Tissue-to-blood ratios for the liver, fat, muscle, and gallbladder bile were 15, 6.7, 

2.9, and 2.5, respectively (Guzelian et al. 1981). The high concentration in blood as compared to its 

concentration in fat (1 versus 6.7) may be explained by the fact that chlordecone is bound specifically 

by the proteins in plasma, particularly high-density lipoproteins (HDLs), unlike most organochlorine 

pesticides which distribute among tissues in direct proportion to the concentration of tissue fat 

(Guzelian et al. 1981). 

No studies were located regarding distribution in animals following inhalation exposure to 

chlordecone. 

2.3.2.2 Oral Exposure 

Mirex has been found in human adipose tissue (Burse et al. 1989; Kutz et al. 1974). Although the 

route of exposure is not specified, these individuals were probably exposed via the inhalation, oral, and 

dermal routes. Levels of 0.16-5.94 ppm and 0.3-l .13 ppm in males and females, respectively, were 

found in tissue samples taken either from postmortem examinations or during surgery (Kutz et al. 

1974). The adipose tissue samples came from individuals who lived in areas where mirex was used 

extensively in a program to control fire ants. Adipose tissue levels of mirex ranging from 0.03 to 

3.72 ppm have been found in residents living near a dump site in Tennessee (Burse et al. 1989). 

Following oral dosing in animals, mirex is distributed to various tissues and sequestered in the fat. 

Females generally accumulated greater amounts than males. Mirex demonstrated an affinity for lipids 
 

MIREX AND CHLORDECONE 110 

2. HEALTH EFFECTS 

in rats given a single oral dose of mirex (0.2 mg/kg) (Chambers et al. 1982; Gibson et al. 1972). 

Male and female rats given a single oral dose of 0.2 mg/kg mirex also accumulated the highest 

concentrations in the fat (Chambers et al. 1982; Gibson et al. 1972). The levels in fat of females were 

approximately two times higher than levels measured in the fat of males (Chambers et al. 1982). For 

females, mirex levels in the fat ranged from 338 to 944 ng/g at 7 days and increased to 

483-1,043 ng/g at 14 days (Chambers et al. 1982). For males, mirex levels in fat ranged from 161 to 

479 ng/g at 7 days and from 419 to 530 ng/g at 14 days (Chambers et al. 1982). Mirex also 

accumulated in the nervous tissue, with females accumulating higher amounts than males (Chambers et 

al. 1982). Accumulation of mirex in the nervous tissue in females peaked at 7 days (40-59 ng/g) and 

then decreased from 7 to 14 days (Chambers et al. 1982). Mirex levels in the nervous tissue of males 

ranged from 13.2 to 28 ng/g at 7 days post-dosing and decreased from 7 to 14 days (Chambers et al. 

1982). Mirex accumulated in various other tissues of both males and females, including 

gastrointestinal tract, liver, lung, heart, kidney, adrenals, brain, skeletal muscle, spleen, and thymus 

(Chambers et al. 1982; Gibson et al. 1972). 

Seven days after a single administration of mirex (6 mg/kg) to rats, 34% of the total dose was retained 

in the tissues and organs; 27.8% was stored in the fat, 3.2% in the muscle, and 1.75% in the liver 

(Mehendale et al. 1972). The remaining tissues each retained less than 1% of the total dose 

(Mehendale et al. 1972). No metabolite of mirex was detected in the tissues (Mehendale et al. 1972). 

The repetitive administration of 10 mg/kg mirex to rats resulted in an accumulation of mirex in several 

tissues (plasma, liver, kidney, fat), with more accumulating in the fat tissue (Plaa et al. 1987). 

Following oral administration of 1 mg/kg 14 C-mirex to a female rhesus monkey, the 14 C-mirex was 

distributed to the tissues (Wiener et al. 1976). The highest tissue concentrations were found in the fat, 

followed by the large intestine, adrenal glands, liver, ovaries, and peripheral nerves. The administered 

dose was distributed as follows: 55.3% was recovered in the fat and ≤2% was recovered in the 

remaining tissues (Wiener et al. 1976). Mirex was the only labeled compound identified in the fat 

(Wiener et al. 1976). Mirex fed to minipigs for 7 consecutive days (3-4.5 mg/kg/day) was distributed 

to backfat (41.5 ppm), liver (1.24 ppm), kidney (0.44 ppm), plasma (0.04 ppm), and red blood cells 

(0.01 ppm) 9 days after dosing (Morgan et al. 1979). 

Mirex was detected in the brains of male rats within 0.5-2 hours after receiving a single oral dose of 

100 mg/kg mirex (Brown and Yarbrough 1988). By 96 hours, the following concentrations (μm01 

14 C-mirex/g) were measured in the brain regions: cerebral cortex (0.47), cerebellum (0.50), brain stem 
 

MIREX AND CHLORDECONE 111 

2. HEALTH EFFECTS 

(0.73), and spinal cord (0.75). Mirex was also distributed to the liver, kidneys, testes, and omental fat. 

Peak tissue concentrations of mirex in the kidneys, testes, liver, and omental fat occurred 12, 48, 48, 

and 96 hours post-dosing, respectively. Following a single oral dose of 50 mg/kg mirex to mice, 

mirex was distributed to the brain (Fujimori et al. 1982a). Mirex levels in the striatum and 

medulla/pans were significantly higher than in the cortex, midbrain, or cerebellum (p<0.05) 48 hours 

post-dosing (Fujimori et al. 1982a). However, at 6, 12, and 96 hours, discrete brain area levels of 

mirex did not differ significantly. Mirex levels in whole brain and plasma were 3-40 times lower than 

levels found in chlordecone-treated mice (Fujimori et al. 1982a). Mirex showed less-specific 

distribution in discrete areas of the brain than did chlordecone (Fujimori et al. 1982a). Samples of 

brain tissue from rats fed 0, 0.089, or 0.89 mg/kg/day for 34-49 days showed that mirex accumulates 

in rat brain tissue in a dose-dependent manner (Thome et al. 1978). Mirex levels in brain tissue were 

7-8 times higher in the high-dose group than in the low-dose group (Thorne et al. 1978). 

Mirex accumulates in maternal tissues, readily crosses the placenta of animals, and accumulates in 

fetal tissues (Kavlock et al. 1980; Khera et al. 1976). Maximum concentrations of mirex found in the 

placenta of rats ranged from 3.5 to 4 ppm at 4 hours post-dosing (Kavlock et al. 1980). Mirex levels 

in the placenta 48 hours after dosing were less than 50% of the 4-hour level (Kavlock et al. 1980). 

The uptake of mirex by fetal organs was in the order of liver > brain = heart > kidney in a ratio of 

3:2:2:1 (Kavlock et al. 1980). Mirex concentrations in the fetuses remained low at 4 hours after 

dosing, increased slightly at 24 hours, and decreased thereafter (Kavlock et al. 1980). The decline 

noted in the second 24-hour period was due to both organ growth and mirex elimination (Kavlock et 

al. 1980). Mirex accumulated in maternal and fetal tissues at all dose levels (1.5, 3, 6, 12.5 mg/kg 

given on gestation days 6-15) (Khera et al. 1976). Fetal brain levels were more than three times 

higher (31.5 ppm) than mean maternal brain levels (8.87 ppm) at 12.5 mg/kg. All other mean fetal 

tissue values were lower than mean maternal values (Khera et al. 1976). The highest maternal levels 

of mirex were found in the fat, indicating the potential for long-term sequestering of the compound 

(Khera et al. 1976). 

In a study in which dams were dosed with 1 or 10 mg/kg of mirex on days 2-5 postpartum, mirex was 

found in the stomach milk of pups (Kavlock et al. 1980). Mirex appeared in the milk in direct 

proportion to the dose. Mirex was also distributed to the liver, brain, and eyes of the pups in the 

approximate ratio of 40:4:1 (Kavlock et al. 1980). Mirex tissue levels paralleled milk levels (Kavlock 

et al. 1980). 
 

 

MIREX AND CHLORDECONE 112 

2. HEALTH EFFECTS 

Mirex concentrations in adipose tissues of goats fed daily doses of 1 mg/kg did not reach a steady 

state but continued to increase throughout a 61-week exposure period and did not seem to be affected 

by pregnancy or lactation (Smrek et al. 1977). When the dose was increased from 1 to 10 mg/kg, the 

adipose tissue levels did not increase dramatically (Smrek et al. 1977). Twenty-eight days post-dosing, 

the following residue levels were found in the tissues of lactating cows given daily doses of 

0.005 mg/kg/day for 28 days: 0.21 ppm in fat, 0.03 ppm in liver, and 0.02 ppm in kidney (Dorough 

and Ivie 1974). The muscle and brain contained no detectable residues. Mirex was the only 

compound identified in the fat (Dorough and Ivie 1974). Analyses of the composition of the residues 

in liver and kidney were not performed. 

There was a dose-related increase in the levels of mirex found in the fat of rats fed 0.02, 0.2, or 

1.5 mg/kg/day for 16 months (Ivie et al. 1974b). The mirex levels in the fat were 120-fold higher 

than the corresponding dietary intakes. Mirex levels increased in the tissues throughout the exposure 

period, with the fat accumulating the highest amounts of mirex. No plateau of residue accumulation 

occurred in any tissue during the feeding period. Removal of animals from treatment after 6 months 

resulted in a decline of residue levels in all tissues (Ivie et al. 1974b). 

As indicated in Section 2.3.2.1, occupational exposure studies have shown that chlordecone is 

absorbed and distributed to various tissues and has a long retention time in the body (Cannon et al. 

1978; Cohn et al. 1978; Taylor 1982, 1985). Because of the poor hygiene practices at the workplace 

studied, ingestion of the chlordecone was also likely by the workers in these studies. For a more 

complete discussion of the distribution of chlordecone after occupational exposure see Section 2.3.2.1. 

In rats, chlordecone was absorbed and distributed to various tissues, with the highest concentrations 

being found in the liver (Egle et al. 1978; Hewitt et al. 1986b; Plaa et al. 1987). Chlordecone was 

detected in the liver (125.8 mg/kg), adipose tissue (27.3 mg/kg), kidney (25.2 mg/kg), and plasma 

(4.9 mg/L) of rats 8 days following a single oral dose of 50 mg/kg (Hewitt et al. 1986b). Chlordecone 

was detected in the liver, kidney, and fat of rats following single or repetitive dosing (0.5, 1, 2, 2.5, 5, 

10, or 25 mg/kg) (Plaa et al. 1987). For all dose groups, the liver contained the highest concentration, 

followed by the kidney, then fat. The ratios of tissue levels in animals that received multiple doses to 

levels in animals that received single doses were as follows: 4.27 (plasma), 3.27 (liver), 3.74 (kidney), 

and 3.42 (fat). These ratios show an even accumulation of chlordecone in the tissues. Rats given four 
 

MIREX AND CHLORDECONE 113 

2. HEALTH EFFECTS 

daily doses of 10 mg/kg chlordecone had tissue-to-blood distribution ratios for fat, liver, muscle, and 

skin of 15, 55, 5, and 6, respectively (Bungay et al. 1981). 

Studies show that pretreatment with an inducer (phenobarbital) or inhibitor (SKF-525A) of P-450 

causes an alteration in the distribution of chlordecone in rats (Aldous et al. 1983). Following a single 

oral dose of chlordecone alone, the liver had the highest levels of chlordecone, followed by the adrenal 

gland, lung, kidney, and spinal cord (Aldous et al. 1983). Pretreatment with phenobarbital 

(particularly with multiple phenobarbital doses) caused an increase in the accumulation of chlordecone 

in the liver compared to animals given no pretreatment. This hepatic increase resulted in a significant 

decrease of chlordecone levels in other tissue (e.g., brain, kidney, muscle) as well as significantly 

reduced excretion. Pretreatment with SKF-525A caused a nonsignificant reduction in chlordecone 

levels in the liver and significant increases in the digestive system tissues. The results of the 

chlordecone distribution following SKF-525A pre-dosing must be interpreted with caution, since the 

effects may have resulted partly from SKF-525A-mediated decreases in absorption of the chlordecone 

(Aldous et al. 1983). 

Following a single oral dose of 50 mg/kg chlordecone to male mice, chlordecone was distributed to 

the brain (Fujimori et al. 1982a; Wang et al. 1981). The results showed that the striatum and 

medulla/pans had significantly higher levels of chlordecone than the cortex, midbrain, or cerebellum 

(Fujimori et al. 1982a). Mirex-treated mice did not exhibit marked differences in distribution among 

these brain areas (Fujimori et al. 1982b). Chlordecone levels were 3-40 times higher than mirex 

levels in plasma and brain (Fujimori et al. 1982b). Following repeated oral doses. of chlordecone 

(10 mg/kg/day) for 12 days, the compound was rapidly absorbed and distributed to the brain (Wang et 

al. 1981). Plasma levels of chlordecone increased during the 12-day treatment period. Brain levels of 

chlordecone increased linearly for the first 8 days and reached a plateau of 90 μg/g on the 10th day 

(Wang et al. 1981). 

Chlordecone is well distributed throughout the male reproductive tract of rats and appears in the 

ejaculate. In rats given a single oral dose of 40 mg/kg chlordecone, the descending order of 

concentration was vas deferens (81.6) > seminal vesicular fluid (19.7) > unwashed sperm (14.6) > 

prostate (11.3) > seminal vesicle (6.2) > washed sperm (1.97). This relationship persisted as levels 

declined over the 21-day observation period (Simon et al. 1986). 
MIREX AND CHLORDECONE 114 

2. HEALTH EFFECTS 

Chlordecone accumulates in maternal tissues, readily crosses the placenta of rats, and accumulates in 

fetal tissues (Chernoff et al. 1979a; Kavlock et al. 1980). Four hours following a single oral dose of 

5 mg/kg, maximal concentrations of chlordecone in the placenta ranged from 3.5 to 4 ppm (Kavlock et 

al. 1980). Concentrations of chlordecone in the placenta remained steady for up to 48 hours postdosing. 

Chlordecone levels in the fetus were generally highest in the liver, followed by the brain, 

heart, and kidney. Concentrations increased during the first 24 hours after dosing and declined in the 

second 24-hour period, regardless of gestation age at the time of dosing (Kavlock et al. 1980). 

Chlordecone levels found in maternal and fetal tissues were slightly higher than the levels of mirex 

following administration of equal doses (Kavlock et al. 1980). The livers of weanling rats fed diets of 

0.05 mg/kg chlordecone or mirex for 28 days accumulated higher levels of chlordecone (6.1 ppm) than 

mirex (0.89 ppm) (Chu et al. 1980a). Possible explanations for this are that mirex is more poorly 

absorbed from the feed than is chlordecone or that the absorbed dose of mirex accumulates in the liver 

to a lesser extent than chlordecone (Chu et al. 1980a). 

In a study in which lactating dams were dosed with 1 or 10 mg/kg of chlordecone on days 2-5 

postpartum, chlordecone was found in the stomach milk of pups (Kavlock et al. 1980). Chlordecone 

appeared in the milk in direct proportion to the dose. Chlordecone was distributed to the liver, brain, 

and eyes of the pups in the approximate ratio of 16:4:1 (Kavlock et al. 1980). 

2.3.2.3 Dermal Exposure 

Mirex has been found in human adipose tissue (Burse et al. 1989; Kutz et al. 1974). Although the 

route of exposure is not specified, exposure was probably via the inhalation, oral, and dermal routes. 

Levels of 0.16-5.94 ppm and 0.3-1.13 ppm in males and females, respectively, were found in tissue 

samples taken during postmortem examinations or during surgery (Kutz et al. 1974). The adipose 

tissue samples came from individuals who lived in areas in which mirex was used extensively. Levels 

of mirex in adipose tissue ranging from 0.03 to 3.72 ppm have been found in residents living near a 

dump site in Tennessee (Burse et al. 1989). No other studies were located regarding distribution in 

humans or animals following dermal exposure to mirex. 

As indicated in Section 2.3.2.1, studies in workers occupationally exposed to chlordecone have shown 

that it is absorbed, distributed to various tissues, and has a long retention time in the body (Cannon et 

al. 1978; Cohn et al. 1978; Taylor 1982, 1985). Since dermal exposures probably constituted a major 
MIREX AND CHLORDECONE 115 

2. HEALTH EFFECTS 

portion of the exposure in these occupational studies, information presented in Section 2.3.2.1 is also 

applicable here. No studies were located regarding distribution in animals after dermal exposure to 

chlordecone. 

2.3.2.4 Other Routes of Exposure 

Mirex is rapidly absorbed and distributes to the plasma and liver after intraperitoneal injection. Peak 

concentrations were seen at 3 hours in the plasma and 6 hours in the liver following single or multiple 

doses of mirex (4 mg/kg) injected intraperitoneally into mice (Charles et al. 1985). Significant 

amounts were rapidly taken up by the liver (21-29%) within the first 3-6 hours. Plasma-to-liver ratios 

were low (<l) indicating an increased influx of the chemical into the tissue. Mirex decay curves for 

plasma and liver for 72 hours showed a biphasic pattern that consisted of a rapid phase (up to 

24 hours) and a slow phase (24-72 hours) (Charles et al. 1985). For plasma, the half-lives were 9.2 

and 62.8 hours for the rapid and slow phases, respectively. For liver, the half-lives for the slow and 

rapid phases were 12.1 and 62.4 hours, respectively (Charles et al. 1985). 

Mirex was rapidly cleared from the blood of rats following an intravenous injection of 10 mg/kg (Byrd 

et al. 1982). Mirex blood levels at 8 hours were less than 4% of the levels seen 2 minutes after 

injection. Pharmacokinetic modeling predicted that intravenously administered mirex was quickly 

cleared from the blood into a rapidly equilibrating compartment. Over the next several weeks, mirex 

was redistributed to a slowly equilibrating compartment, which acted as a depot for mirex storage 

(Byrd et al. 1982). The biological half-life of mirex was estimated to be 435 days (Byrd et al. 1982). 

Following a single intravenous dose of 1 mg/kg to female rhesus monkeys, 86-87% of the 

administered dose was recovered in the fat, 3.7-10% in the skin, 0.6-1.7% in the skeletal muscle, and 

<0.5% in the remaining tissues (Wiener et al. 1976). Mirex was the only compound identified in the 

fat. 

2.3.3 Metabolism 

Radiolabeling experiments showed that mirex is not metabolized in humans, rodents, cows, or 

minipigs; the parent compound was the only radiolabeled compound present in the plasma, fat, and 

feces (Dorough and Ivie 1974; Gibson et al. 1972; Kutz et al. 1974; Mehendale et al. 1972; Morgan et 
 

MIREX AND CHLORDECONE 116 

2. HEALTH EFFECTS 

al. 1979). However, a monohydro derivative of mirex was identified in the feces, but not the fat or 

plasma, of rhesus monkeys given an oral or intravenous dose of mirex (Pittman et al. 1976; Stein et al. 

1976; Wiener et al. 1976). It is believed that the suspected metabolite may have arisen as a result of 

bacterial action in the lower gut or in the feces (Stein et al. 1976). 

The potential for in vivo conversion of mirex to chlordecone was also examined (Morgan et al. 1979). 

Chlordecone was not detected in the tissues; therefore, no evidence was found of in vivo conversion 

(Morgan et al. 1979). 

The fate of chlordecone in humans involves uptake by the liver, enzymatic reduction to chlordecone 

alcohol, conjugation with glucuronic acid, partial conversion to unidentified polar forms, and excretion 

of these metabolites mainly as glucuronide conjugates into bile (Fariss et al. 1980; Guzelian et al. 

1981) (see Figure 2-3). Of the total chlordecone measured in bile of occupationally exposed workers, 

the predominant portion (72%) was unconjugated, with only a small portion conjugated with 

glucuronic acid or sulfate (9%) (Fariss et al. 1980). The remaining fraction (19%) of total chlordecone 

measured in the bile was stable polar metabolites which were resistant to β-glucuronidase. Following 

treatment of bile with β-glucuronidase plus sulfatase, the ratio of total chlordecone to total chlordecone 

alcohol was 1:3 in human bile (Fariss et al. 1980). Bioreduction of chlordecone to chlordecone 

alcohol is species-specific since rats treated orally or intraperitoneally with chlordecone produced no 

chlordecone alcohol in the feces, bile, or liver (Fariss et al. 1980; Guzelian et al. 1981; Houston et al. 

1981). Following treatment of bile with β-glucuronidase plus sulfatase, the ratio of total chlordecone 

to total chlordecone alcohol in rat bile was in excess of 150:l for orally exposed rats (Fariss et al. 

1980; Guzelian et al. 1981). Guinea pigs and hamsters given an intraperitoneal dose of 20 mg/kg 

chlordecone also did not convert chlordecone to chlordecone alcohol, as indicated by the fact that no 

chlordecone alcohol was detected in the feces, bile, or liver (Houston et al. 1981). Therefore, rats, 

guinea pigs, and hamsters are not good animal models for predicting chlordecone metabolism in 

humans because they do not convert chlordecone to chlordecone alcohol (Fariss et al. 1980; Guzelian 

et al. 1981; Houston et al. 1981). Gerbils were found to be the most suitable animal model of 

chlordecone metabolism in humans because only gerbils converted chlordecone to its alcohol (Houston 

et al. 1981). Reduction of chlordecone is catalyzed in gerbil liver by a species-specific reductase, 

chlordecone reductase. This chlordecone reductase was characterized in gerbil liver cytosol in vitro 

and determined to be of the “aldo-keto reductase” family (Molowa et al. 1986b). It is specific to 

gerbils and humans (Molowa et al. 1986b). Like humans, chlordecone-treated gerbils excreted 

 

MIREX AND CHLORDECONE 118 

2. HEALTH EFFECTS 

chlordecone alcohol exclusively in the stool and not in the urine (Houston et al. 1981). Following 

intraperitoneal dosing of 20 mg/kg 14C-chlordecone, the ratio of chlordecone to chlordecone alcohol in 

the bile of gerbils was approximately 2.5: 1. No quantitative estimate of the extent to which 

chlordecone was metabolized was reported. Following treatment of bile with β-glucuronidase plus 

acid hydrolysis, the ratio of chlordecone to chlordecone alcohol in the bile was 1:2, indicating that 

chlordecone is present in the bile largely in the form of its glucuronide conjugate (Houston et al. 

1981). Incubation of chlordecone with the cytosolic fraction of gerbil liver homogenate in the 

presence of NADPH produced chlordecone alcohol (Houston et al. 1981). Reduction and conjugation 

of chlordecone also occur in pigs (Soine et al. 1983). Chlordecone is biotransformed in pigs to 

conjugated chlordecone, chlordecone alcohol, and conjugated chlordecone alcohol, which are excreted 

in the bile and eliminated in the feces (Soine et al. 1983). The high levels of chlordecone alcohol and 

conjugated chlordecone alcohol in the bile and the absence of these metabolites in the plasma and liver 

suggest that chlordecone alcohol is formed and conjugated in the liver and excreted into the bile 

(Soine et al. 1983). 

2.3.4 Excretion 

2.3.4.1 Inhalation Exposure 

No studies were located regarding excretion in humans or animals after inhalation exposure to mirex 

or chlordecone. 

2.3.4.2 Oral Exposure 

Limited data indicate that mirex is excreted in human milk; it was identified in 3 of 14 human milk 

samples obtained from Canadians (Mes et al. 1978). The dose was not reported. However, the 

exposure was assumed to be chronic in nature, and the route of exposure was proposed to be through 

the diet or skin contact (Mes et al. 1978). No other studies were located. 

In animals, mirex is excreted unchanged mainly in the feces; urinary excretion is negligible (Byrd et 

al. 1982; Chambers et al. 1982; Gibson et al. 1972; Ivie et al. 1974b). Female rats receiving a single 

oral dose of 14 C-mirex (0.2 mg/kg) excreted 18% of the total administered dose in the feces (Gibson et 

al. 1972). Very little was excreted in the urine (0.3% of the total dose) during the 7-day period. Of 
 

MIREX AND CHLORDECONE 119 

2. HEALTH EFFECTS 

the total quantity eliminated, 85% was excreted in the feces within the first 48 hours. This percentage 

represents unabsorbed material. The virtual lack of urinary excretion and the fact that fecal excretion 

was only about 3% of the administered dose after the initial 48 hours suggest that mirex is not 

metabolized in rats and that the absorbed portion is only slowly excreted (Gibson et al. 1972). 

Cumulative fecal excretion was 18-45% 21 days after female rats were given a single oral dose of 

10 mg/kg mirex (Byrd et al. 1982). Most of the fecal mirex was excreted within 48 hours and 

represented unabsorbed mirex (Byrd et al. 1982). A biological half-life of mirex was estimated to be 

460 days by a model developed to simulate mirex pharmacokinetics after oral administration (Byrd et 

al. 1982). Male rats receiving a single oral dose of 6 mg/kg excreted 58.5% of the administered dose 

in the feces 7 days after administration (Mehendale et al. 1972). Fifty-five percent of the administered 

dose was excreted in the feces within the first 48 hours post-dosing and probably represented 

unabsorbed dose from the gut (Mehendale et al. 1972). Only 0.69% of the administered dose was 

excreted in the urine (Mehendale et al. 1972). Mirex was the only compound identified in the urine or 

feces (Mehendale et al. 1972). A half-life of 38 hours was estimated based on the first rapid 

elimination (Mehendale et al. 1972). A second half-life was projected to be >l00 days, indicating a 

very slow rate of elimination from the body (Mehendale et al. 1972). 

Following oral administration of 1 mg/kg 14 C-mirex to a female rhesus monkey, 25% of the 14 C was 

recovered in the feces within 48 hours, with a cumulative excretion of 26.5% over 23 days. Less than 

1% was recovered in the urine over 23 days (Wiener et al. 1976). A monohydro derivative of mirex 

was identified in the feces of rhesus monkeys given daily doses of 1 mg/kg mirex (Stein and Pittman 

1977). The exact duration of dosing was not specified (Stein and Pittman 1977). 

Another route of elimination is via milk. The secretion of mirex in milk was a major route of 

elimination for nursing dams given either 1 or 10 mg/kg of mirex on days 2-5 postpartum (Kavlock et 

al. 1980). The dams excreted 11,000 μg of mirex via the milk during the entire lactation period. This 

represents 95% of the total amount of mirex administered. Mirex entered the milk supply more 

quickly than chlordecone. Greater amounts of mirex were excreted via the milk as compared with 

chlordecone because of the octanol-water partition coefficient (Kavlock et al. 1980). Mirex was also 

excreted in the milk of lactating goats given daily doses of 1 mg/kg for 18 or 61 weeks followed by 

daily doses of 10 mg/kg for 4 weeks (Smrek et al. 1977). The concentration of mirex in colostrum fat 

ranged from 16 to 20 ppm. Colostrum, which is fluid secreted for the first few days after parturition, 

is characterized by high protein and antibody content. Over 8 weeks, the levels of mirex in milk fat 
 

MIREX AND CHLORDECONE 120 

2. HEALTH EFFECTS 

decreased to less than half the amount excreted in colostrum immediately after birth of the kids. The 

goats eliminated more mirex in colostmm than in regular milk. A lactating Jersey cow given a daily 

dose equivalent to 0.005 mg/kg/day in the diet for 28 days, excreted 50% of the administered dose in 

the feces during the 28-day exposure period (Dorough and Ivie 1974). Only approximately 3% of the 

administered dose of mirex was excreted in the feces in the 28 days after treatment ended. These 

results show that the radioactivity in the feces represents unabsorbed mirex, and that the turnover rate 

of mirex stored in the tissues is very low. In this study, mirex was also found in cow’s milk. About 

10% of the administered dose was excreted in the milk 10 days after treatment began. Cumulative 

excretion in the milk was 13% after 28 days of exposure. Only 2% of the administered dose was 

excreted in the milk during the entire 28-day post-treatment period. The levels of mirex in milk 

equilibrated after 1 week of treatment, with the concentration in whole milk being 0.058 ppm. 

One week after treatment ended, the residues in the milk dropped to 0.006 ppm and then declined to 

0.002 ppm after 28 days (Dorough and Ivie 1974). Mirex was the only compound identified in the 

feces and cow’s milk. 

Chlordecone and chlordecone alcohol (chlordecol) are excreted in the bile and eliminated via the feces 

of humans occupationally exposed to chlordecone (Blanke et al. 1978; Boylan et al. 1979; Cohn et al. 

1978; Guzelian et al. 1981). However, a substantial enterohepatic recirculation of chlordecone exists 

that curtails its excretion (Boylan et al. 1979; Cohn et al. 1978; Guzelian et al. 1981). Only 5-10% of 

the biliary chlordecone entering the lumen of the duodenum appeared in the feces (Cohn et al. 1978; 

Guzelian et al. 1981). Similarly, the rate of chlordecone excretion in the bile was on the average 19 

times greater than the rate of elimination of chlordecone in the stool (Cohn et al. 1978). Chlordecone 

was not detected in the sweat and was detected in only minor quantities in urine, saliva, and gastric 

juice (Cohn et al. 1978). Similarly, stool contained 11-34% of the quantities excreted in bile for 

workers exposed for 6 months (Boylan et al. 1979). When biliary contents were diverted, fecal 

excretion of chlordecone alcohol fell to low or undetectable levels; however, chlordecone excretion in 

feces persisted, suggesting a nonbiliary mechanism for the excretion of chlordecone into the intestine 

and feces (Boylan et al. 1979). Analogous experiments with rats gave similar results (Boylan et al. 

1979). With no bile in the gut, the average amount of chlordecone in the human stool in two 72-hour 

collections was eight times as great as with the biliary circuit intact (Boylan et al. 1979). This 

suggests that bile may suppress nonbiliary excretion of chlordecone (Boylan et al. 1979). When bile 

was completely diverted from the intestines of rats, however, fecal excretion of radiolabel -was 

unchanged (Boylan et al. 1979). 
MIREX AND CHLORDECONE 121 

2. HEALTH EFFECTS 

Chlordecone, chlordecone alcohol, and their glucuronide conjugates were identified in human bile of 

occupationally exposed workers (Guzelian et al. 1981). Of the total chlordecone measured in bile, 

most (72%) is unconjugated, a small amount (9%) is conjugated with glucuronic acid, and the final 

portion (19%) is present as an uncharacterized “acid releasable” form (Guzelian et al. 1981). 

However, only a minor amount of chlordecone alcohol (<10%) was present in bile as the free 

metabolite. The remainder was conjugated with glucuronide (Guzelian et al. 1981). 

In rats, chlordecone is slowly eliminated in the feces (Egle et al. 1978). Rats given a single oral dose 

of 40 mg/kg 14C-chlordecone excreted 65.5% of the administered dose in the feces and 1.6% of the 

dose in the urine by 84 days (Egle et al. 1978). Less than 1% of the administered dose was expired as 

radiolabeled carbon dioxide (14 C-CO2

) (Egle et al. 1978). Rats fed 14C-chlordecone (0.2 mg/kg/day for 

3 days) excreted 52.16% of the radioactivity in the feces .and 0.52% in the urine 25 days post-dosing 

(Richter et al. 1979). 

Chlordecone was excreted in the saliva of rats following administration of 50 mg/kg (Borzelleca and 

Skalsky 1980; Skalsky et al 1980). Peak levels of chlordecone in saliva were reached 6-24 hours 

post-dosing (Borzelleca and Skalsky 1980; Skalsky et al. 1980). The saliva-to-plasma ratios were <l 

throughout the study period indicating that chlordecone is not actively concentrated by the salivary 

glands (Borzelleca and Skalsky 1980). Thus, chlordecone enters the salivary tissue (submaxillary, 

parotid, and sublingual tissues) and saliva by passive diffusion (Borzelleca and Skalsky 1980; Skalsky 

et al. 1980). 

Chlordecone is also excreted in the milk of nursing rats (Kavlock et al. 1980). Dams excreted 

6,000 μg of chlordecone via the milk during the entire lactation period. This represents 52% of the 

total amount of chlordecone administered. When compared with mirex-treated rats, chlordecone 

entered the milk supply more slowly than mirex. More mirex was excreted via the milk than 

chlordecone because of a higher octanol-water partition coefficient. 

2.3.4.3 Dermal Exposure 

Mirex is excreted in human milk. Mirex was identified in 3 of 14 milk samples obtained from 

Canadian women (Mes et al. 1978). The dose was not reported, but exposure was assumed to be of 

chronic duration via the diet or via dermal contact (Mes et al. 1978). 
 

 

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No studies were located regarding excretion of mirex in animals following dermal exposure. 

Chlordecone and chlordecone alcohol (chlordecol) are excreted in the bile and eliminated in the feces 

of humans occupationally exposed to chlordecone (Blanke et al. 1978; Boylan et al. 1979; Cohn et al. 

1978; Guzelian et al. 1981). See Section 2.3.4.2 for more details. 

No studies were located regarding excretion of chlordecone in animals following dermal exposure. 

2.3.4.4 Other Routes of Exposure 

Mirex has a long retention time in the body and is excreted slowly. Cumulative fecal excretion was 

7% of the administered dose 21 days following intravenous dosing of 10 mg/kg in rats (Byrd et al. 

1982). Cumulative urinary excretion was <1% of the administered dose (Byrd et al. 1982). The 

biological half-life of mirex was estimated to be 435 days (Byrd et al. 1982). Cumulative fecal 

excretion was 4.69% and 6.91% of the dose after 106 and 388 days, respectively, following a single 

intravenous dose of 1 mg/kg to female monkeys (Wiener et al. 1976). Cumulative urinary excretion 

accounted for 0.18-0.37% of the administered dose by the end of 1 week. Mirex was the only labeled 

compound identified in the feces. An unidentified substance found in the feces was thought to be a 

decomposition product of mirex, not a metabolite (Wiener et al. 1976). Mirex and an unidentified 

metabolite, a nonpolar derivative, were found in the feces of rhesus monkeys given an intravenous 

dose of 1 mg/kg of mirex (Stein et al. 1976). It is believed that the suspected metabolite may have 

arisen as a result of bacterial action in the lower gut or in the feces (Stein et al. 1976). 

Chlordecone was detected in the bile and feces of rats, guinea pigs, hamsters, gerbils, and pigs given 

intraperitoneal doses of 20 mg/kg chlordecone (Houston et al. 1981; Soine et al. 1983). Rats given 

intraperitoneal injections of chlordecone had a fecal excretion half-life of 40 days (Pore 1984). 

Chlordecone alcohol was detected in the bile and feces of gerbils and pigs only (Houston et al. 1981; 

Soine et al. 1983). 

Chlordecone appeared in the bile within l-3 hours after intravenous dosing of rats (0.1, 1, or 

10 mg/kg) (Bungay et al. 1981). The average concentration of chlordecone in the bile varied linearly 

with dose: 0.051, 0.50, and 5 μg/g in the low-, middle-, and high-dose groups, respectively (Bungay et 
 

MIREX AND CHLORDECONE 123 

2. HEALTH EFFECTS 

al. 1981). Rats given a single intravenous dose of 1 mg/kg had a chlordecone excretion rate in the 

bile of 0.22% of the dose per hour (Bungay et al. 1981). 

2.3.5 Mechanisms of Action 

The specific mechanism by which mirex is transferred from the gut, lungs, or skin to the blood is not 

known. However, mirex is a highly stable, lipophilic compound that is resistant to metabolism. It has 

a high 1ipid:water partition coefficient (HSDB 1994a, 1994b), so it partitions readily to fat and 

demonstrates a very high potential for accumulation in tissues (Chambers et al. 1982; Ivie et al. 

1974b). 

The specific mechanism by which chlordecone is transferred from the gut, lungs, or skin to the blood 

is not known. However, the preferential distribution of chlordecone to the liver rather than the fat 

tissues suggests that it may be transported in the plasma differently from other organochlorine 

compounds (Soine et al. 1982). In vitro and in vivo studies of human, rat, and pig plasma showed that 

chlordecone is preferentially bound by albumin and high-density lipoproteins (HDL), which may 

explain its tissue distribution. Other organochlorine pesticides such as aldrin and dieldrin bind to verylowdensity lipoproteins (VLDL) and low-density lipoproteins (LDL) and distribute preferentially to fat 

(Soine et al. 1982). 

Several studies have attempted to define the mechanism by which mirex and chlordecone inhibit 

hepatobiliary excretion. At very high levels, both mirex (Chetty et al. 1983a; Desaiah 1980) and 

chlordecone (Bansal and Desaiah 1985; Chetty et al. 1983a; Curtis and Mehendale 1979; Desaiah et al. 

1980a, 1991; Jinna et al. 1989; Jordan et al. 1981; Kodavanti et al. 1990a; Mehendale 1979) depress 

ATPase activity or cellular energy utilization at moderate to relatively high doses (2.5 to 

100 mg/kg/day and 50 to 100 mg/kg/day, respectively) thereby inhibiting the biliary excretion of 

substances. The inhibition does not appear to be due to inhibition of the metabolism of the substance 

to be excreted in the bile or to decreased bile flow (Mehendale 1977c). Possible explanations for the 

decreased excretion of metabolites in the bile include decreased uptake of substances by the hepatocyte 

(Teo and Vore 1990), a decreased transfer of chemicals from the hepatocyte to the bile (Berman et al. 

1986), and leaking of metabolites from the bile duct via a paracellular pathway (Curtis and Hoyt 

1984). The decrease in transfer may be due to decreased permeability of the canalicular membrane 

(Hewitt et al. 1986a) resulting from inhibition of the mg2+ATPase activity of the bile canaliculi (Bansal 
 

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2. HEALTH EFFECTS 

and Desaiah 1985; Curtis 1988; Curtis and Mehendale 1981) or perturbations of plasma membrane 

(Rochelle et al. 1990). 

Although the precise mechanism for the hypothermia induced by chlordecone is unknown, data suggest 

a role of central nervous system (CNS) dopaminergic or a-noradrenergic activity in expression of 

hypothermia. The decrease in body temperature produced by chlordecone was mimicked by 

intracistemal norepinephrine (Cook et al. 1988a, 1988b) and was blocked by administration of 

a-noradrenergic antagonists and by 6-hydroxydopamine, a treatment that depletes noradrenergic 

neurons in the brain (Cook et al. 1988b). Pretreatment with the dopamine-antagonist, haloperidol, was 

also capable of blocking the hypothermia (Hsu et al. 1986). It has been suggested that the decrease in 

body temperature is the result of centrally mediated vasodilation (Cook et al. 1988a, 1988b), but direct 

evidence for this has not yet been obtained. 

Mitochondrial oligomycin-sensitive mg2+ATPase is thought to play a major role in oxidative 

phosphorylation (Boyer et al. 1977). It has been suggested that impairment of mitochondrial energy 

metabolism by chlordecone may contribute to the decreases in body weight observed following 

exposure to this chemical (Desaiah 1981). 

Several studies have been undertaken in an attempt to define the mechanism of the neurotoxic effects 

of chlordecone. No single mechanism has been identified that readily explains the neurotoxic effects 

of chlordecone. However, studies have revealed substantial information regarding the effects of 

chlordecone on the nervous system. Chlordecone does not appear to act through a mechanism similar 

to other chlorinated hydrocarbon insecticides such as dieldrin or lindane. Chlordecone has a different 

profile of neurotoxicity in that it primarily causes hyperexcitability and tremors, but no convulsions 

and appears to lack activity at the γ-aminobutyric acid (GABA) receptor in mammals (Bloomquist et 

al. 1986; Chang-Tsui and Ho 1979; Lawrence and Casida 1984; Seth et al. 1981). Chlordecone has 

been shown to be a potent antagonist of the picrotoxinin binding site on the GABA receptor in 

cockroaches (Matsumura 1985). However, this finding is difficult to interpret based on the poor 

binding at a comparable site in mammalian tissues. 

The hyperexcitability and tremor induced by chlordecone are similar to that produced by 

dichlorodiphenyldichloroethane (DDT). However, it has been suggested that the mechanism of these 

tremors is different; diphenylhydantoin exacerbates chlordecone-induced tremor but suppresses tremor 
 

MIREX AND CHLORDECONE 125 

2. HEALTH EFFECTS 

induced by DDT (Hong et al. 1986; Tilson et al. 1985, 1986b). The tremors induced by chlordecone 

appear to be initiated in the central nervous system above the level of the spinal cord, since transection 

of the spinal cord resulted in elimination of the tremors below the level of transection (Hwang and 

Van Woert 1979). 

Several pharmacological studies indicate that α-noradrenergic and serotonergic transmitter systems in 

the central nervous system are the primary neurotransmitter systems involved in the expression of the 

tremor and enhanced startle response produced by chlordecone (Gerhart et al. 1982, 1983, 1985; Herr 

et al. 1987; Hong et al. 1984; Hwang and Van Woert 1979). These conclusions are supported by a 

number of studies examining brain neurochemistry following administration of tremongenic doses of 

chlordecone (Brown et al. 1991; Chen et al. 1985; Hong et al. 1984; Tilson et al. 1986b; Uphouse and 

Eckols 1986). However, dopamine (Desaiah 1985; Fujimori et al. 1982b) and acetylcholine (Aronstam 

and Hong 1986; Gerhart et al. 1983, 1985) have also been implicated. 

At the cellular level, chlordecone causes spontaneous neurotransmitter release (End et al. 1981) and 

increases in free intracellular calcium in synaptosomes (Bondy and Halsall 1988; Bondy and McKee 

1990; Bondy et al. 1989; Komulainen and Bondy 1987). This appears to be due at least in part to 

increased permeability of the plasma membrane (Bondy and Halsall 1988; Bondy and McKee 1990; 

Bondy et al. 1989; Komulainen and Bondy 1987), activation of voltage-dependent calcium channels 

(Komulainen and Bondy 1987), and inhibition of brain mitochondrial calcium uptake (End et al. 1979, 

1981). 

Chlordecone also decreased the activity of calmodulin-stimulated enzymes (Kodavanti et al. 1988, 

1989c; Vig et al. 1990b, 1991) and of enzymes integral to maintenance of neuronal energy and ionic 

gradients; Na+

K+ATPase (Bansal and Desaiah 1982; Chetty et al. 1983b; Desaiah 1981; Desaiah et al. 

1980a, 1980b; Folmar 1978; Jinna et al. 1989; Singh et al. 1984), oligomycin-sensitive mg2+ATPase 

(Chetty et al. 1983b; Desaiah et al. 1980a, 1980b; Jinna et al. 1989; Mishra et al. 1980), and 

Ca2+ATPase (Desaiah et al. 1991; Jinna et al. 1989; Mishra et al. 1980) activities in brain tissues have 

been shown to be decreased by exposure to chlordecone both in vivo and in vitro. It is unclear 

whether inhibition of these enzymes is directly responsible for the effects of chlordecone on 

intracellular calcium or whether these changes are coincident with the changes in intracellular calcium. 
 

MIREX AND CHLORDECONE 126 

2. HEALTH EFFECTS 

The mechanism underlying many of the adverse effects of chlordecone on reproductive function is 

believed to be due to the estrogenic properties of chlordecone. Following both in vitro (Bulger et al. 

1979; Hammond et al. 1979) and parenteral administration (Williams et al. 1989a), chlordecone was 

shown to bind to estrogen receptors and to cause translocation of the receptor from the cytoplasm to 

the nuclear fraction. When the activity of chlordecone was compared in uterine and brain tissues, the 

effect was greater in the uterine tissue (Williams et al. 1989a). The differential sensitivity of these 

tissues may explain the failure of chlordecone to completely mimic estrogen in functions mediated by 

central nervous system estrogen receptors. 

Substantially less is known about the mechanism by which mirex causes reproductive toxicity. Mirex 

does not, however, appear to produce its reproductive toxicity by mimicking estrogen (Gellert 1978; 

Hammond et al. 1979). 

In animal studies, mirex (a nonmutagenic hepatocarcinogen) promoted mouse skin squamous 

carcinomas and papillomas after initiation with 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. 

Mirex, also, potentiated the promotional potency of the phorbol ester tumor promoter, 

12-O-tetradecanoylphorbol- 13-acetate (TPA). There was a 90% incidence (activation) of the c-Ha-ras 

tumor gene in these co-promoted tumors. When both mirex and TPA gave a similar tumor yield, only 

the TPA response was associated with biochemical markers of enhanced cell proliferation, induction of 

epidermal ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. Thus, there 

is evidence for a dual effect of mirex during co-promotion: first, as an independent tumor promoter 

with a mechanism different than that of phorbol esters; and second, as a compound that also 

potentiates skin tumor promotion by TPA (Meyer et al. 1993, 1994; Moser et al. 1992, 1993). 

2.4 RELEVANCE TO PUBLIC HEALTH 

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

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

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

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

mirex or chlordecone can be found adsorbed to soil particles suspended in uncontaminated water, 

ingestion of these chemicals in drinking water is unlikely because of their limited solubility in water. 

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

 

MIREX AND CHLORDECONE 127 

2. HEALTH EFFECTS 

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

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

of residues on contaminated food. Both of these chemicals are excreted very slowly and 

bioaccumulate in the body after exposure. 

Although mirex and chlordecone are structurally very similar (differing only in the replacement of 

two bridgehead chlorine atoms on the mirex molecule with a carbonyl oxygen on the chlordecone 

molecule), significant differences exist in the toxicity profiles of these two chemicals. Therefore, 

mirex and chlordecone will be discussed separately below. 

No information was located regarding toxicity of mirex in humans, but animal studies indicate that 

mirex exposure may result in a variety of adverse health effects in exposed populations. The primary 

organs affected by mirex in experimental animals are the liver, kidneys, eyes, and thyroid. In the 

liver, mirex causes adaptive changes similar to those seen with other chlorinated hydrocarbon 

insecticides as well as decreased hepatobiliary function and decreased glycogen storage. In the 

kidneys, an increase in glomerulosclerosis and proteinuria have been observed. Ocular lesions include 

the development of cataracts in the eyes of the young if exposure occurs during a critical period 

immediately after birth. In the thyroid, an increase in cystic follicles or a collapse of follicles has been 

observed. Decreased fertility and marked developmental toxicity have been observed following 

exposure to mirex. Mirex exposure results in testicular atrophy and reproductive failure. Adverse 

developmental effects seen in fetuses following maternal exposure to mirex include cataracts, 

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

mirex is a liver carcinogen in animals. 

Studies in humans exposed occupationally to chlordecone demonstrate toxic effects on the nervous 

system, liver, and reproductive system. Tremors, unfounded anxiety or irritability, blurring of vision, 

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

of chlordecone during its manufacture. In addition, several workers had hepatomegaly, evidence of 

increased microsomal enzyme activity, mild inflammatory changes, and fatty degeneration. 

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

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

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

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

MIREX AND CHLORDECONE 128 

2. HEALTH EFFECTS 

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

hepatotoxicity of haloalkanes such as carbon tetrachloride after exposure to chlordecone. 

Minimal Risk Levels for Mirex and Chlordecone 

Inhalation MRLs 

No inhalation MRLs were derived for either mirex or chlordecone because of the absence of reliable 

data following inhalation exposure. 

Oral MRLs 

No acute-duration oral MRL was derived for mirex because serious effects (arrhythmias in neonatal 

pups from maternal exposure during gestation) were observed at the lowest dose tested 

(0.1 mg/kg/day) (Grabowski 1983a). 

z An MRL of 0.01 mg/kg/day has been developed for acute-duration oral exposure (14 days or

 less) to chlordecone. 

This MRL for chlordecone is based on a NOAEL of 1.25 mg/kg for neurological effects (increased 

startle response) in offspring Fischer 344 rats in a 10-day study conducted by EPA (1986c). This 

study was part of a toxicity screen performed at EPA in which male Fischer 344 rats received gavage 

doses of chlordecone for 10 consecutive days. At 2.5 mg/kg/day and above, the amplitude of the 

acoustic startle response was significantly increased. At the other two doses, the amplitude was 

increased with all decibel stimuli. Motor activity in a figure-8 maze was decreased at the highest dose 

tested. Startle response, as a measure of adverse neurological effects, and other parameters such as 

tremors and abnormal gait have been reported in studies with animals following acute exposure to 

chlordecone (Egle et al. 1979; Jordan et al. 1981; Klingensmith and Mehendale 1982a; Mactutus et al. 

1984a; Maier and Costa 1990; Swanson and Wooley 1982; Tilson et al. 1985). 

Intermediate-duration oral studies in humans for mirex are lacking. A review of the animal oral 

intermediate toxicity data for mirex indicates that the available studies are not adequate to derive 

intermediate oral MRL for mirex. The most suitable study provides a LOAEL of 0.25 mg/kg/day for 
 

 

 

MIREX AND CHLORDECONE 129 

2. HEALTH EFFECTS 

endocrine effects-dilation of rough endoplasmic reticulum cistemae of the thyroid of weanling 

Sprague-Dawley rats (Singh et al. 1985). Adjusting the LOAEL of 0.25 mg/kg/day determined from 

this study with a total uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for animal to human 

extrapolation, and 10 for interspecies variability) yields an intermediate oral MRL of 

0.0003 mg/kg/day, which is lower than the chronic-duration oral MRL of 0.0008 mg/kg/day derived 

from an NTP (1990) study in rats (see chronic-duration MRL). Therefore, no oral intermediate-duration 

MRL was developed for mirex. 

z An MRL of 0.0005 mg/kg/day has been derived for intermediate-duration oral exposure

 (15-364 days) to chlordecone. 

The MRL is based on a NOAEL of 0.05 mg/kg/day for renal effects in rats at a LOAEL of 

0.25 mg/kg/day. In the study by Larson et al. (1979b) in which the NOAEL was derived, groups of 

Wistar strain rats of both sexes were administered 0, 0.05, 0.25, 0.5, 1.25, 2.5, or 4.0 mg/kg/day for a 

period of one year. After one year (in a 2-year feeding study), 5 rats/sex/dose group were sacrificed. 

Additionally, 3 to 5 rats of each sex receiving 0.25 or 0.5 mg/kg/day and 3 males receiving 

1.25 mg/kg/day were returned to the control diet for 4 weeks and then sacrificed. Proteinuria was 

noted in all treatment groups at all intervals after 3 months except in males at 21 and 24 months when 

control levels were elevated, and in females at 24 months when the levels in only the 0.5 and 

1.25 mg/kg/day groups were elevated. The severity of observed glomemlosclerosis was increased in 

both males and females at >0.25 mg/kg/day. Increase in kidney weight relative to body weight was 

reported, but was not considered seriously adverse (Larson et al. 1979b). 

z An MRL of 0.0008 mg/kg/day has been derived for chronic-duration oral exposure (365 days

 or more) to mirex. 

This MRL for mirex was derived using a NOAEL of 0.075 mg/kg/day for dose-dependent hepatic 

changes from a study by NTP (1990). The dose-dependent changes included increased fatty 

metamorphosis (cytoplasmic vacuoles consistent with intracellular fat accumulation) and necrosis of 

hepatocytes (focal and/or centrilobular) in F344/N rats of both sexes at a dose of 0.7 mg/kg/day 

following a 2-year oral exposure to mirex doses of 0-7.7 mg/kg/day (males: 0, 0.007, 0.075, 0.7, 1.8, 

3.8; females: 0, 3.9, 7.7). Dilation of the sinusoids (by blood or proteinaceous material) was also 

observed in males at >0.7 mg/kg/day and in females at 3.9 mg/kg/day. Increased nephropathy was 
 

 

MIREX AND CHLORDECONE 130 

2. HEALTH EFFECTS 

also observed in male rats at >0.7 mg/kg/day and in female rats at >2 mg/kg/day. Epithelial 

hyperplasia of the renal pelvis and parathyroid hyperplasia were increased in males at 0.7 mg/kg/day 

and above; these lesions were probably secondary to the nephropathy. Cystic follicles of the thyroid 

were increased in male rats at >0.7 mg/kg/day. Body weight was decreased in males and females by 

more than 10% in males (ll-18%) at 3.8 mg/kg/day and in females (15-17%) at 3.9 mg/kg/day (NTP 

1990). In another chronic animal study, hepatobiliary changes-which included dose-dependent focal 

biliary hyperplasia and hepatic pericentral cytoplasmic vacuolization and lobular pattern with mild 

anisokaryosis at a mirex dose of 0.07 mg/kg/day and marked hepatic panlobular cytoplasmic 

vacuolization with loss of basophilia, fatty infiltration, and marked anisokaryosis at higher 

doses-were reported in Sprague-Dawley rats following chronic oral exposure to mirex. At 

0.07 mg/kg of mirex, significant increases in the hepatic microsomal aniline hydroxylase (AH) and 

aminopyrine-N-demethylase (APDM) were observed; however, at 0.32 mg/kg of mirex only APDM 

increased significantly. Mirex tended to increase slightly, but insignificantly, the liver weight of over 

the control rats at doses >0.07. The thyroids of the rats also exhibited dose-dependent degenerative 

and proliferative changes in the follicular epithelium but without alteration in the colloidal density at 

doses >0.07 mg/kg/day (Chu et al. 1981c). Several other chronic feeding studies of rodents with 

mirex reported a variety of adverse hepatic effects which included hepatic lesions (fatty 

metamorphosis, cystic degeneration, necrosis, and biliary hyperplasia with periportal fibrosis) in CD 

rats (Ulland et al. 1977a); enlarged and mottled surfaces of the liver and some discoloration on gross 

necropsy, centrilobular hypertrophy of hepatocytes, increased glucose 6-phosphatase in the 

centrilobular region and decreased acid phosphatase in the centrilobular region of the liver, increased 

activity in Kupffer cells, and extensive proliferation of smooth endoplasmic reticulum with nuclear 

changes and lipid accumulation (Fulfs et al. 1977) in CD-l mice; and significantly increased total liver 

DNA and microsomal enzyme activity in CD-l mice (Byard et al. 1975). Several intermediateduration 

studies in rats also indicate that the thyroid is a target organ for mirex toxicity (Chu et al. 

1981a, 1981b; Singh et al. 1982, 1985). These studies showed reduced colloid, thickening of the 

follicular epithelium, angular collapse of the follicles, and dilation of the rough endoplasmic reticulum 

of thyroid cells at 0.25 mg/kg/day for 28 days. Reproductive toxicity (a sensitive end point in acuteand 

intermediate-duration studies) was tested at doses higher than the LOAEL from this study, and 

inhibition of reproduction was observed (Wolfe et al. 1979). 

z An MRL of 0.0005 mg/kg/day has been derived for chronic-duration oral exposure (365 days

 or more) to chlordecone. 
 

 

 

 

MIREX AND CHLORDECONE 131 

2. HEALTH EFFECTS 

The MRL is based on a NOAEL of 0.05 mg/kg/day for renal effects in rats at a LOAEL of 

0.25 mg/kg/day. In the study by Larson et al. (1979b) in which the NOAEL was derived, groups of 

Wistar strain rats of both sexes were administered 0, 0.05, 0.25, 0.5, 1.25, 2.5, or 4.0 mg/kg/day for a 

period of 2 years. After one year (in a 2-year feeding study), 5 rats/sex/dose group were sacrificed. 

Additionally, 3 to 5 rats of each sex receiving 0.25 or 0.5 mg/kg/day and 3 males receiving 

1.25 mg/kg/day were returned to the control diet for 4 weeks and then sacrificed. Proteinuria was 

noted in all treatment groups at all intervals after 3 months except in males at 21 and 24 months when 

control levels were elevated, and in females at 24 months when the levels in only the 0.5 and 

1.25 mg/kg/day groups were elevated. The severity of observed glomerulosclerosis was increased in 

both males and females at >0.25 mg/kg/day. Increase in kidney weight relative to body weight was 

reported, but was not considered seriously adverse (Larson et al. 1979b). 

Death. No reports of mirex- or chlordecone-related deaths in humans were located in the literature. 

Animal studies regarding death have been limited to oral, dermal, and parenteral studies. Studies 

examining exposure in animals by the oral route indicate that large single oral doses of mirex are 

necessary to cause death, with dogs less sensitive to the lethal effects of mirex than rats (Gaines 1969; 

Gaines and Kimbrough 1970; Larson et al. 1979a). However, with repeated exposures, death is 

observed at much lower doses (Fujimori et al. 1983; Gaines and Kimbrough 1970; Khera et al. 1976; 

Larson et al. 1979a; Mehendale et al. 1973; Ware and Good 1967). Substantial differences were also 

observed in the magnitude of single versus multiple doses of chlordecone that resulted in death 

(Desaiah et al. 1980a; Kavlock et al. 1985; Larson et al. 1979b; Simmons et al. 1987). In longer-term 

studies, juvenile animals appeared more sensitive to the lethal effects of chlordecone than adults 

(Huber 1965). No cause of death was identified in these studies. Based on the relatively high doses 

of mirex and chlordecone necessary to cause death in animal studies and the absence of reports of 

death due to these chemicals after high occupational exposures, it is unlikely that death would occur in 

persons exposed to mirex or chlordecone at hazardous waste sites. 

Systemic Effects 

Respiratory Effects. No studies were located regarding the respiratory toxicity of mirex in humans or 

animals. Thus, insufficient information is available to determine whether persons exposed to mirex at 

hazardous waste sites might experience adverse respiratory effects. 
 

 

MIREX AND CHLORDECONE 132 

2. HEALTH EFFECTS 

Studies of workers exposed to high levels of chlordecone indicated that pleuritic chest pain was a 

relatively common complaint (Cannon et al. 1978; Taylor 1982, 1985). Examination of workers with 

this complaint revealed no cause for the pains. Since oral exposure studies in animals did not identify 

any respiratory end points that may have been affected following ingestion of chlordecone (Larson et 

al. 1979b) and no inhalation exposure studies were located, a possible physiological basis for the 

workers’ complaints has not been identified. Insufficient information is available to determine whether 

persons exposed to low levels of chlordecone at hazardous waste sites would experience adverse 

respiratory effects, but the possibility cannot be discounted. 

Cardiovascular Effects. No studies were located regarding the cardiovascular effects of mirex in 

humans. A study in animals suggested that ingestion of mirex has a transient effect on cardiac output 

and alters flow to essential internal organs (Buelke-Sam et al. 1983), but the toxicological significance 

of this finding is unclear. No increase in lesions of the heart or vasculature was observed upon 

histological examination (Larson et al. 1979a), and biochemical changes in the heart following 

ingestion were slight (Desaiah 1980). Thus, persons at hazardous waste sites would not be likely to 

experience adverse effects from low-level exposures to mirex. 

The available information indicates that chlordecone is not markedly cardiotoxic in humans (Cannon et 

al. 1978; Taylor 1982, 1985; Taylor et al. 1978). Rat studies with chlordecone have shown that 

chronic low-dose ingestion does not cause histologically evident cardiac lesions (Larson et al. 1979b), 

but acute-duration exposure to higher doses results in inhibition of a number of biochemical 

parameters in the heart involved in contractility and energy production (Desaiah 1980; Kodavanti et al. 

1990a). Also, intermediate-duration exposure to moderate doses results in vasodilation (Larson et al. 

1979b). The vasodilatory effect may be due to central nervous system effects on the noradrenergic 

mechanism controlling body temperature (Cook et al. 1988a, 1988b). Thus, the possibility that 

persons exposed to chlordecone may experience adverse cardiovascular effects cannot be discounted. 

Gastrointestinal Effects. No information on the gastrointestinal effects of mirex in humans was 

located. Animal studies indicate that mirex is not highly toxic to the gastrointestinal tract, but diarrhea 

has been observed in animals following acute high-level oral exposure and longer-term lower-level oral 

exposure (Dietz and McMillan 1979; Fujimori et al. 1983; Gaines and Kimbrough 1970; Kendall 

1974a; Khera et al. 1976; Mehendale 1981b). Gross pathologic examination of gastrointestinal tissues 

from one of these studies (Fujimori et al. 1983) showed intestinal lesions, suggesting that the diarrhea 
 

MIREX AND CHLORDECONE 133 

2. HEALTH EFFECTS 

may have been a direct effect of the mirex on the gastrointestinal tract. However, a neurologic 

component of the diarrhea cannot be eliminated. It is possible that humans exposed to high levels of 

mirex at hazardous waste sites may experience some diarrhea. 

No information was located regarding the gastrointestinal toxicity of chlordecone in humans. Only 

very limited evidence of gastrointestinal effects has been observed in oral studies in experimental 

animals (Fujimori et al. 1983; Larson et al. 1979b). Thus, it is unlikely that chlordecone exposure 

would result in adverse effects on the gastrointestinal tracts of persons exposed to low levels at 

hazardous waste sites. 

Hematological Effects. No studies were located regarding hematological effects of mirex or 

chlordecone in humans. Limited information was located regarding the hematological effects of mirex 

and chlordecone in experimental animals, but the results reported in the studies were predominantly 

negative for adverse effects for both mirex (Chu et al. 1980a; Ervin and Yarbrough 1983; Larson et al. 

1979a; Yarbrough et al. 1981) and chlordecone (Chu et al. 1980a; Larson et al. 1979b). Thus, it is 

unlikely that persons exposed to low levels of mirex or chlordecone at hazardous waste sites would 

experience adverse hematological effects. 

Musculoskeletal Effects. No information was located regarding musculoskeletal effects in humans or 

animals exposed to mirex. Thus, insufficient information is available to determine whether persons 

exposed to mirex at hazardous waste sites may experience adverse musculoskeletal effects. 

Workers exposed to high levels of chlordecone experienced tremors, muscle weakness, gait ataxia, and 

incoordination (Cannon et al. 1978; Taylor 1982, 1985). Although these effects may be attributable to 

adverse effects of chlordecone on the nervous system, muscle biopsies obtained from six of the 

workers showed evidence of a myopathic condition (Martinez et al. 1978). Animal studies have not 

extensively examined the effects of chlordecone on muscle; however, weakness that increased in 

severity with time was observed in rats following a single large oral dose of chlordecone (Egle et al. 

1979). Histopathological analyses of muscle taken from rats after parenteral administration of 

chlordecone showed mitochondrial damage and glycogen and lipid depletion (Phillips and Eroschenko 

1982). The authors speculated that the effects on muscle were the result of altered mitochondrial 

oxidative metabolism and membrane calcium permeability. In support of this hypothesis, biochemical 

analyses of sarcoplasmic reticulum from muscle of exposed rats showed inhibition of mg2+ATPase 
MIREX AND CHLORDECONE 134 

2. HEALTH EFFECTS 

(Mishra et al. 1980). Additional in vitro studies showed inhibition of sarcoplasmic Ca2+ATPase 

and mg2+ATPase (Mishra et al. 1980) and inhibition of muscle lactate dehydrogenase (Anderson and 

Noble 1977; Anderson et al. 1978), although the inhibition of the lactate dehydrogenase may have 

been an artifact (Meany and Packer 1979). These data suggest that chlordecone may have a direct 

toxic effect on muscle. Therefore, the possibility that persons exposed to sufficiently high 

concentrations of chlordecone at hazardous waste sites may experience adverse muscular effects cannot 

be discounted. 

Hepatic Effects. Although human data on the hepatic effects of mirex are minimal, animal studies 

have shown that the liver undergoes both adaptive and toxic changes following oral exposure. The 

primary toxic effects of mirex are inhibition of hepatobiliary excretion (Berrnan et al. 1986; Davison et 

al. 1976; Mehendale 1976, 1977c; Teo and Vore 1991) and depletion of hepatic glycogen stores (Elgin 

et al. 1990; Ervin and Yarbrough 1983; Fujimori et al. 1983; Jovanovich et al. 1987; Kendall 1979). 

The precise mechanism for the inhibition of hepatobiliary excretion is unclear but may involve a 

combination of decreased uptake of substances from the blood by hepatocytes (Teo and Vore 1990), 

decreased transfer of chemicals from the hepatocyte to the bile (Berman et al. 1986), and leaking from 

the bile duct via a paracellular pathway (Curtis and Hoyt 1984) (see also Section 2.3.5, Mechanism of 

Action). A 28-day study in Sprague-Dawley rats reported a decrease in hepatic microsomal aniline 

hydroxylase. Histopathological findings in this study included fatty vacuolation, panlobular ballooning 

of hepatocytes, moderate lobular pattern with perinuclear clear zone and perivenous cytoplasmic 

ballooning with anisokaryosis in liver (Chu et al. 1980b, 1981b). A 21-month study in SpragueDawley rats reported a decrease in hepatic rnicrosomal aniline hydroxylase. Histopathological findings 

in this study included panlobular cytoplasmic vacuolation with loss of basophilia, fatty infiltration, and 

anisokaryosis in liver (Chu et al. 1981c). F344/N male and female rats fed mirex doses (males = 

0.007, 0.07, 0.7, 1.8, 3.8 mg/kg/day; females = 0.007, 0.08, 0.7, 2.0, 3.9 mg/kg/day) for 2 years 

developed histopathological changes, which included hepatocytomegaly with eosinophilic cytoplasm 

observed in males and females at >0.7 mg/kg/day. Fatty metamorphosis (cytoplasmic vacuoles 

consistent with intracellular fat accumulation) and necrosis of hepatocytes (focal and centrilobular) 

were increased in males and females at >0.7 mg/kg/day. Dilation of the sinusoids (by blood or 

proteinaceous material) was observed in males at >0.7 mg/kg/day and in females only at the highest 

dose tested (NTP 1990). A chronic-duration MRL of 0.0008 mg/kg/day for mirex is based on hepatic 

effects in rats observed in this study. Based on the animal data, persons exposed to sufficiently high 

concentrations of mirex at hazardous waste sites may suffer liver damage. 
 

 

MIREX AND CHLORDECONE 135 

2. HEALTH EFFECTS 

Examination of workers exposed to high levels of chlordecone has shown adaptive changes (increased 

liver size, proliferation of the smooth endoplasmic reticulum, and increased microsomal enzyme 

activity) but only limited evidence of hepatotoxicity (increased serum alkaline phosphatase, lipofuscin 

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

mitochondrial inclusions) (Guzelian et al. 1980). Sulfobromophthalein clearance was unaffected. The 

results of animal studies support these findings and indicate that exposure to moderate or high 

concentrations of chlordecone may also result in decreased hepatobiliary function (Curtis and Hoyt 

1984; Curtis and Mehendale 1979; Curtis et al. 1979b, 1981; Mehendale 1977b, 1981b; Teo and Vore 

1991); decreased hepatic glycogen (Fujimori et al. 1983); and increased serum nonprotein nitrogen 

compounds and enzymes, decreased serum tnglycerides and LDL cholesterol chlordecone (Chetty et al. 

1993a, 1993b). Given the extremely poor hygiene at the plant where the workers were employed and 

the high levels of exposure that occurred, it is unlikely that persons living in the vicinity of hazardous 

waste sites would experience more severe effects than the workers who were examined. However, the 

possibility of mild hepatobiliary dysfunction among exposed persons at hazardous waste sites cannot 

be dismissed. 

Renal Effects. No studies were located regarding renal effects of mirex or chlordecone in humans. 

However, studies in animals indicated an increase in the severity of renal lesions observed in rats 

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

1979b). Intermediate- and chronic-duration MRLs of 0.0005 mg/kg/day were derived for oral 

exposure to chlordecone based on the NOAEL of 0.05 mg/kg/day for histopathological evidence of 

renal damage from this study. Thus, it is possible that persons exposed to sufficiently high 

concentrations of mirex or chlordecone for long periods may experience adverse renal effects. 

Endocrine Effects No studies were located regarding thyroid or adrenal effects in humans after oral 

exposure to mirex or chlordecone. Result of studies in rats indicate that mirex is toxic to the thyroid. 

Reversible reduction in colloid density, a thickening of follicular epithelium, and angular collapse of 

the follicles, but no effect on serum levels of T3 or T4 were reported in rats following oral exposure to 

mirex (Chu et al. 1980a, 1981a, 1981b). In other studies, ultrastructural analyses of thyroids from rats 

treated for 28 days showed dilation of the rough endoplasmic reticulum and increased columnar cells 

with irregularly shaped lysosomal bodies, dilation of cistemae, and increased vacuolization (Singh et 

al. 1982, 1985). Similar effects were observed following dietary exposure for 148 days (Chu et al. 

1981a). Dietary exposure for 2 years also resulted in an increase in cystic follicles in male rats (NTP 
MIREX AND CHLORDECONE 136 

2. HEALTH EFFECTS 

1990). Mirex had no effect on the adrenal medulla (Baggett et al. 1980). No studies were located 

regarding thyroid effects in animals following oral exposure to chlordecone. Studies in animals also 

indicate that the adrenal gland hypertrophies and releases increased levels of corticosterone in response 

to mirex exposure (Ervin and Yarbrough 1985; Jovanovich et al. 1987; Williams and Yarbrough 

1983). Other studies in animals have demonstrated increased adrenal weight; increased cholesterol, 

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

serum adrenocorticotropic hormone (Ervin and Yarbrough 1985; Jovanovich et al. 1987); and 

decreased body fats (Jovanovich et al. 1987). Less information is available regarding the effects of 

chlordecone on the adrenal glands of animals. Increased relative adrenal weight was observed 

following a single oral dose of chlordecone in rats (Swanson and Wooley 1982). Enlargement of the 

adrenal gland, with hyperplasia and hypertrophy of the cortical cells, was observed in a 30-day dietary 

study in rats (Cannon and Kimbrough 1979); decreased adrenal lipid was observed in a 90-day dietary 

study in rats (Larson et al. 1979b). Consistent with a corticosterone-induced increase in lipid 

utilization, decreased body fat was observed following a dietary exposure in rats for 16 days 

(Mehendale et al. 1977b, 1978b), and 15 or 20 days (Klingensmith and Mehendale 1982a), or 

exposure of mice for 33 days (Fujimori et al. 1983). In contrast to the absence of effects of mirex on 

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

content of epinephrine in rats (Baggett et al. 1980). The evidence indicates that human exposure to 

mirex or chlordecone can result in endocrine toxicity. 

Dermal Effects. No studies were located regarding dermal effects in humans after exposure to mirex. 

A study using rabbits showed slight erythema and scaling resulting from dermal exposure to an 

unspecified amount of chlordecone (Larson et al. 1979a). Therefore, the possibility exists that persons 

exposed dermally to mirex in the vicinity of hazardous waste sites may also experience some skin 

irritation. 

Workers exposed to high levels of chlordecone reported a high incidence of skin rashes (Cannon et al. 

1978; Taylor 1982, 1985; Taylor et al. 1978). Acute-duration dermal exposure of rabbits to 

chlordecone resulted in no signs of irritation (Larson et al. 1979b), but the experience of workers 

suggests that skin irritation or rashes from exposure at hazardous waste sites are possible. 

Ocular Effects. No studies were located regarding ocular effects in humans after exposure to mirex. 

However, studies using neonatal animals have demonstrated that cataracts and other lesions of the lens 
 

MIREX AND CHLORDECONE 137 

2. HEALTH EFFECTS 

may be induced if exposure to mirex occurs during a critical period (between postpartum days 1 and 

8) (Chernoff et al. 1979b; Gaines and Kimbrough 1970; Rogers and Grabowski 1984; Scotti et al. 

1981). While it is unclear whether lens development in human infants parallels that in rats and mice, 

the possibility exists that cataracts may develop in infants as a result of mirex exposure. 

Body Weight Effects. Animal studies show decreases in serum glucose (Chu et al. 1981b; Ervin and 

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

Williams and Yarbrough 1983; Yarbrough et al. 1981) and decreases in body weight or body weight 

gain (Buelke-Sam et al. 1983; Byrd et al. 1981; Chadwick et al. 1977; Chernoff et al. 1979a, 1979b; 

Chu et al. 1981a; Curtis and Hoyt 1984; Davison et al. 1976; Elgin et al. 1990; Fujimori et al. 1983; 

Jovanovich et al. 1987; Khera et al. 1976; Larson et al. 1979a; Mehendale et al. 1973; NTP 1990; 

Ritchie and Ho 1982; Rogers and Grabowski 1984; Villeneuve et al. 1977). 

Workers exposed to high levels of chlordecone at a facility where it was manufactured experienced an 

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

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

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

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

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

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

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

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

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

1983) were seen. On the basis of these observations in humans and laboratory animals, it is possible 

that body weight loss may occur following intermediate and chronic exposures to relative high levels 

of chlordecone. 

Other Systemic Effects. No studies were located regarding other systemic effects in humans exposed 

to mirex or chlordecone. However, animal studies in which mirex and chlordecone exposure resulted 

in loss of body fat (Fujimori et al. 1983; Klingensmith and Mehendale 1982a; Mehendale et al. 1977b, 

1978b) and decreased serum glucose levels (Fujimori et al. 1983), combined with the observation that 

both chemicals cause depletion of hepatic glycogen levels, suggest an increased utilization of fat and 

glucose. In vitro studies with chlordecone suggest that it stimulates cellular respiration (Carmines et 
MIREX AND CHLORDECONE 138 

2. HEALTH EFFECTS 

al. 1979) and uncouples oxidative phosphorylation (Manring and Moreland 1981), as well as 

supporting the hypothesis that the increased utilization of substrates for energy production may result 

from the failure of oxidative phosphorylation to produce energy. A similar phenomenon may occur 

with mirex. In addition to the possible metabolic dysfunction, chlordecone has also been demonstrated 

to cause hypothermia following oral (Swanson and Wooley 1982) and parenteral administration (Cook 

et al. 1988a, 1988b; Hong et al. 1984; Hsu et al. 1986). Although the hypothermia has been proposed 

to be a result of decreased metabolic heat production (Hsu et al. 1986), recent studies manipulating 

brain neurotransmitter levels have shown that the decrease in body temperature may be due to 

noradrenergic stimulation of peripheral vasodilation (Cook et al. 1988a, 1988b). This explanation 

would help explain the paradoxical increase in tail temperature seen concomitant with the decrease in 

core temperature (Cook et al. 1988a, 1988b). These data suggest that persons exposed to sufficiently 

high concentrations of chlordecone at hazardous waste sites may experience some decrease in body 

temperature. 

Immunological Effects. No data on immunotoxicity of mirex in were located. The only 

information about the immunological effects of mirex exposure in animals was provided by one acute 

oral study in rats in which decrease spleen weight was reported (Buelke-Sam et al. 1983). Thus, it is 

uncertain whether persons exposed to mirex at hazardous waste sites might experience adverse effects 

on the immune system. 

It is not known if the immune system is the target of chlordecone toxicity in humans. In rats that 

received high oral doses of chlordecone, adverse immunological effects included reductions in spleen 

and thymus weights, numbers of neutrophils, and natural killer cell activity (EPA 1986c; Smialowicz 

et al. 1985). However, these effects were most likely due to general toxicity rather than a direct toxic 

effect on the immune system. One study with rats fed calcium-deficient diets found an increase in 

plaque-forming cells at the lowest dose tested (0.5 mg/kg/day). The effect on plaque-forming cells was 

found to be more severe in calcium-sufficient animals than in calcium-deficient animals (Chetty et al. 

1993c). 

Because of the lack of human data and the limited animal data on the immunologic effects of 

chlordecone, it is not known whether low concentrations of chlordecone would induce immunotoxic 

effects in populations living in the vicinity of hazardous waste sites. 
 

 

MIREX AND CHLORDECONE 139 

2. HEALTH EFFECTS 

Neurological Effects. No studies were located regarding neurological effects in humans following 

exposure to mirex, but animal studies have demonstrated lethargy, weakness, diarrhea, 

hyperexcitability, tremors, and convulsions as a result of mirex exposure (Chu et al. 1981a; Curtis and 

Hoyt 1984; Fujimori et al. 1983; Gaines and Kimbrough 1970; Kendall 1974a; Larson et al. 1979a; 

Mehendale 1981b). Although the lethargy and diarrhea may be attributable to other systemic effects, 

the hyperexcitability, tremors, and convulsions are probably of neural ongin. However, no information 

was located that might explain the mechanism for these effects. 

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

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

workers with histories of tremors, unfounded nervousness or anxiety, and visual difficulties (Cannon et 

al. 1978). The tremors were characterized as resembling intention tremors and occurred mainly in the 

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

gait disturbances were apparent. Nerve biopsies of the more severely affected workers showed 

decreases in small myelinated and unmyelinated neurons (Martinez et al. 1978). Although mood and 

memory disturbances were reported by many workers, testing revealed active encephalopathy in only 

one subject (Taylor 1982, 1985). Reports of blurring of vision were found to be associated with an 

opsoclonus-like phenomenon, in which rapid random eye movements followed horizontal saccades 

(Taylor 1982, 1985). This was attributed to a loss of inhibitory control of saccadic activity. 

Headaches were also reported by a number of workers (Taylor 1982, 1985). Cerebrospinal fluid 

pressure was elevated in three of these individuals, and relief of cerebrospinal fluid pressure resulted in 

amelioration of the headaches (Sanbom et al. 1979). 

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

(Albertson et al. 1985; Aldous et al. 1984; Baggett et al. 1980; Chang-Tsui and Ho 1979; Desaiah et 

al. 1980a; Egle et al. 1979; End et al. 1981; Fujimori et al. 1982b; Hoskins and Ho 1982; Huang et al. 

1980; Hwang and Van Woert 1979; Jordan et al. 1981; Klingensmith and Mehendale 1982b; Maier 

and Costa 1990; Mishra et al. 1980; Smialowicz et al. 1985; Swanson and Wooley 1982; Uzodinma et 

al. 1984a). Numerous studies have been conducted in animals to determine the underlying cause for 

the tremoring. From these studies, it has been concluded that the tremors are induced in the central 

nervous system at a level above the spinal cord (Hwang and Van Woert 1979) and that the central 

nervous system effects are unlike those of other chlorinated hydrocarbons (Bloomquist et al. 1986; 

Chang-Tsui and Ho 1979; Lawrence and Casida 1984; Seth et al. 1981). In addition, the tremors are 
 

 

 

MIREX AND CHLORDECONE 140 

2. HEALTH EFFECTS 

unlike those produced by DDT (Hong et al. 1986; Tilson et al. 1985, 1986b). Also, animal studies 

indicate that more than one neurotransmitter system may be involved in expression of the tremors 

(Aronstam and Hong 1986; Brown et al. 1991; Chen et al. 1985; Desaiah 1985; Fujimori et al. 1982b; 

Gerhart et al. 1982, 1983, 1985; Herr et al. 1987; Hong et al. 1984; Hwang and Van Woert 1979; 

Tilson et al. 1986b; Uphouse and Eckols 1986). Experiments at the cellular level have indicated 

effects on calcium regulation of neuronal function (Bondy and Halsall 1988; Bondy and McKee 1990; 

Bondy et al. 1989; End et al. 1979, 1981; Kodavanti et al. 1988, 1989c; Komulainen and Bondy 1987; 

Vig et al. 1990b, 1991) and several enzymes involved in maintenance of ionic gradients (Bansal and 

Desaiah 1982; Chetty et al. 1983b; Desaiah 1981; Desaiah et al. 1980a, 1980b, 1991; Folmar 1978; 

Jinna et al. 1989; Mishra et al. 1980; Singh et al. 1984). For a further description of these studies see 

Section 2.3.5, Mechanisms of Action. 

Studies in animals have also examined the peripheral nerve damage associated with chlordecone 

exposure and have shown that the damage is to unmyelinated axons and consists of vesiculation of the 

Schwann cell cytoplasm and swelling of unmyelinated axons with dissolution of microtubules and 

inclusion of paracrystalline material in mitochondria (Phillips and Eroschenko 1982). The effects of 

chlordecone on the cerebrospinal fluid have also been further studied in animals, and results show 

degenerative changes in the choroid plexus, the tissue responsible for production of cerebrospinal fluid 

and regulation of its flow (Schumacher and Eroschenko 1985). These results suggest that persons 

exposed to mirex or chlordecone at hazardous waste sites might also experience adverse neurological 

effects if they are exposed to sufficiently high concentrations. An acute MRL of 0.01 mg/kg/day has 

been developed for chlordecone based on a NOAEL of 1.25 mg/kg for neurological effects (increased 

startle response) in Fischer 344 rats in a 10-day study conducted by EPA (1986c). 

Reproductive Effects. No human studies are available to assess the reproductive effects of mirex. 

The available studies involving human exposure to chlordecone suggest that adverse reproductive 

effects can occur in males as a result of occupational exposure to chlordecone (Guzelian 1982a; Taylor 

1982, 1985; Taylor et al. 1978). However, these studies did not quantify the exposure levels of 

chlordecone. Mammalian studies indicate that testicular atrophy can occur at low doses of 

chlordecone in the diet for 3 months, a dose well below the level that causes overt maternal toxicity 

(Larson et al. 1979b). Dietary exposure at twice the higher levels for 3 months resulted in complete 

reproductive failure of female mice (Huber 1965). Chlordecone is well known for its estrogenic 

effects on mammalian reproductive organs when administered by oral or parenteral routes. A single 
 

 

MIREX AND CHLORDECONE 141 

2. HEALTH EFFECTS 

intraperitoneal injection of chlordecone to ovariectomized rats with an implanted progesteronereleasing 

source was found to decrease progesterone levels (Johnson et al. 1990), and a single injection 

of chlordecone also induced persistent vaginal estrus when administered intraperitoneally or 

subcutaneously in female rats (Sierra and Uphouse 1986; Uphouse et al. 1984). Young females 

exposed to the same levels of chlordecone developed persistent vaginal estrus and anovulation, as did 

the mature females when treated with chlordecone (Hammond et al. 1978). A single intraperitoneal 

injection of chlordecone to hypophysectomized female rats followed by daily administration of 

progesterone doses induced a normal number of implantation sites by acting as an estrogen substitute 

(Johnson et al. 1992). When exposure to chlordecone was delayed until the day following ovulation, 

decreased fertility and inhibition of implantation occurred (Pinkston and Uphouse 1988). The effects 

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

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

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

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

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

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

Mousa 1979). In neonatal male mice, daily dietary administration of chlordecone was less effective 

than estradiol in suppressing spermatogenesis (Huber 1965). 

The mechanism by which chlordecone acts possibly involves direct binding to estrogen receptors. 

Chlordecone may act at the neuroendocrine level to influence gonadotrophin release (Bulger and 

Kupfer 1985). Chlordecone affects the male reproductive capacity following prenatal exposure and 

produces postnatal functional changes in the reproductive capacity of female offspring at even lower 

levels of exposure during the prenatal and/or neonatal period (Gellert and Wilson 1979). After longer 

exposure (in utero and lactational), the offspring showed reduced fertility (Good et al. 1965). Thus, 

the potential hazard of chlordecone to the progeny that survive prenatal and/or neonatal treatment is an 

adverse effect on the subsequent reproductive capacity of females, and therefore, cannot be ruled out. 

The effect observed is similar to that seen following neonatal steroid-induced sterility and, thus, may 

reflect an estrogenic action of chlordecone on the developing brain. Unlike chlordecone, mirex is not 

uterotropic in rats (Hammond et al. 1979). However, mirex has estrogenic potential because it 

undergoes degradation to chlordecone in nature (Carlson et al. 1976), and therefore, its potential to 

produce reproductive toxicity cannot be ignored. Chlordecone has demonstrated an estrogen-like 

action in animals (Huber 1965; Uphouse et al. 1984). Abnormal spermatogenesis has been observed 
 

 

MIREX AND CHLORDECONE 142 

2. HEALTH EFFECTS 

among workers exposed at a chemical plant (Guzelian 1982a, 1982b). Possible detrimental effects on 

the reproductive processes of workers or populations inadvertently exposed to chlordecone at 

hazardous waste sites cannot be excluded. 

Developmental Effects. No human studies.are available to assess the developmental effects of 

mirex. The available studies of chlordecone in humans have not addressed whether adverse 

developmental effects can occur as a result of paternal exposure to chlordecone. Transplacental and 

lactational transfer of chlordecone has been demonstrated in animals (Huber 1965). Animal studies 

demonstrated that prenatal exposure to mirex can induce a high incidence of dysrhythmias that can 

persist into the postnatal period (Grabowski 1983a). These problems are sufficiently severe to cause 

some fetal deaths (Grabowski and Payne 1983a). Following gestational exposure of rats and mice to 

chlordecone, significant embryo/fetotoxicity and teratogenicity were seen at doses (≥10 mg/kg/day) 

that were severely toxic to dams (Byrd et al. 1981). Reduction in fetal body weight, delayed 

ossification, and increased incidence of malformations (cataract and edema) at doses below 

10 mg/kg/day were also observed in rat fetuses (Gaines and Kimbrough 1970); other malformations 

seen were undescended testes and enlarged cerebral ventricles which often indicate developmental 

delays (Chernoff et al. 1979a; Grabowski 1983a). Thus, chlordecone also appears to be a teratogen. 

However, lower doses of chlordecone also caused tremors and reduced body weight gain in dams and 

increased fetal and neonatal mortality (Rogers and Grabowski 1983). The mechanism by which these 

effects occur is not known. No human data exist to establish whether exposure to mothers at 

hazardous waste sites may cause adverse developmental effects in the progeny, but the possibility that 

parental exposure to sufficiently high amounts of mirex or chlordecone may cause adverse effects on 

offspring cannot be excluded. 

Genotoxic Effects. No genotoxicity studies involving the inhalation, oral, or dermal exposure of 

humans to mirex or chlordecone were found. Mirex was not mutagenic in the single assay that used a 

human cell line (Tong et al. 1981). In this test system, the ability of mirex (purity not specified) to 

induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in 

cultured human foreskin fibroblasts (Detroit-550) was investigated in the absence of an exogenous 

metabolic activation system and in the presence of metabolic activation provided by primary Fischer 

rat hepatocytes. At log doses below the cytotoxic level (10-4 and 10-5 molar), no significant increase in 

the mutation frequency was observed in the human cells exposed either in the presence or absence of 

hepatocytes. 
 

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2. HEALTH EFFECTS 

There has been very little testing of mirex and chlordecone in whole-animal genotoxicity assays. In 

the available in vivo animal studies, mirex and chlordecone were not clastogenic for male rat germinal 

cells in well-conducted dominant lethal assays (Khera et al. 1976; Simon et al. 1986). Although both 

mirex and chlordecone clearly increased ornithine decarboxylase activity (indicative of cellular 

proliferation) in rat livers following oral exposure, neither agent induced DNA damage in the target 

organ (Kitchin and Brown 1989; Mitra et al. 1990). 

Mirex does appear to be capable of selectively reducing the proportion of tetraploid hepatocytes in 

adult rat livers (Abraham et al. 1983). There is also evidence from an in vitro assay that mirex (purity 

not specified) preferentially binds to freshly prepared polyploid mouse hepatocytes (Rosenbaum and 

Charles 1986). While binding of increasing concentrations of 14 C-mirex (0.2-1 micromolar) to both 

diploid and polyploid cells gradually attained saturation at doses between 0.4 and 0.8 micromolar, 

polyploid cells were saturated by relatively low concentrations (two to three times lower than for 

diploid cells). Regardless of hepatocyte class, the response was partially Na2+ dependent and 

completely Ca2+ dependent. The inhibition or enhancement of normal hepatic cell ploidy in animals 

may prove to be important in understanding the mechanism of mirex-induced tnmongenesis; however, 

the pathogenic implications of ploidy alteration in carcinogenesis are not well characterized. 

Additionally, the overall results of these studies tend to suggest that polyploid cells in rodent livers 

may be predisposed to ploidy alterations because of the high percentage of tetraploids. In contrast, 

hepatocyte populations in humans, other species, or young animals are predominantly diploid. 

Approximately 99% of human liver cells are diploid. Support for the assumption that tetraploid 

hepatocytes may be preferentially at risk from mirex exposure was provided by the results of the study 

by Carlson and Abraham (1985) who investigated the effects of mirex (99%) on the distribution of 

ploidy cells in neonatal rats (5 days of age at initiation of treatment) exposed to 4.5 mg/kg mirex 

(route of exposure not specified but presumed to be intraperitoneal injection). The results indicated 

that mirex had no effect on the relative frequency of hepatic diploids or tetraploids, there were no 

significant differences in 3

H-thymidine incorporation into the DNA of either class of hepatocytes, and 

there were no clear effects on the mitotic index. The findings of this study are noteworthy because 

young rodents have a preponderance of diploid hepatocytes. It has been established that neonatal 

rodent livers contain = 80-85% diploid cells, while polyploid hepatocytes make their appearance and 

increase in an orderly and time-related manner at = 21 days of age (Carriere 1969). Refer to Table 2-5 

for a further summary of the in vivo results and Table 2-6 for the in vitro results. 




MIREX AND CHLORDECONE 148 

2. HEALTH EFFECTS 

Neither mirex nor chlordecone have been extensively tested in in vitro genotoxicity assays. In 

microbial systems, mirex (10-10,000 μg/plate) was not mutagenic in Salmonella typhimurium TA1535, 

TA1537, TA98, or Tal00 in the absence or presence of S9 fractions prepared from induced rat or 

hamster livers (Mortelmans et al. 1986). In another study, Schoeny et al. (1979) found that mirex 

(0.1-100 μg/plate) was devoid of mutagenic activity in the same S. typhimurium strain, with or without 

conventional microsomal activation; or when the S9 liver fraction was prepared from rats induced with 

mirex. Using a battery of eight histidine auxotrophs of S. typhimurium and two tryptophan auxotrophs 

of Escherichia coli (WP2 and WP2 uvrA-

), no evidence of mutagenesis was uncovered when mirex 

was tested in a concentration agar gradient assay (Probst et al. 1981). Mirex was also negative for the 

induction of prophage in E. coli at eight nonactivated and S9-activated doses which included soluble 

levels (0.04 and 0.07 millimolar) and insoluble levels (0.14-4.55 millimolar) (Houk and DeMarini 

1987). 

In agreement with the findings from microbial gene mutation studies with mirex, there is no evidence 

that chlordecone is a mutagen for S. typhimurium or E. coli (Mortelmans et al. 1986; Probst et al. 

1981; Schoeny et al. 1979). Similarly, chlordecone alcohol, the major metabolite of chlordecone in 

humans, is not mutagenic in S. typhimurium (Mortelmans et al. 1986). 

With the exception of the human cell line gene mutation assay, mirex has not been investigated for 

possible mutagenic or clastogenic effects in mammalian cell lines. However, chlordecone (10-5 and 

10-6 molar) did not increase the frequency of mutations at the HGPRT locus in adult rat liver epithelial 

cells cocultivated with freshly dissociated adult male Fischer-344 hepatocytes which served as the 

feeder system for metabolism (Williams 1980). Chlordecone and chlordecone alcohol were also 

investigated for potential clastogenic activity in Chinese hamster ovary (CHO) cells. Chlordecone did 

not increase the frequency of CHO cells with abnormal chromosome morphology over a nonactivated 

concentration range of 10-20 mg/L or over an Aroclor 1254-induced rat liver S9-activated 

concentration range of 5-15 mg/L (Galloway et al. 1987). Chlordecone alcohol caused a slight 

increase in chromosome aberrations in CHO cells at 4, 8, and 16 mg/L +S9; however, the suggestive 

evidence of clastogenesis was not reproducible. Similarly, the evidence of a clastogenic effect 

reported by Bale (1983) for Chinese hamster M3-1 cells exposed to 2, 4, or 6 mg/L chlordecone was 

inconclusive. The significant (p<0.05) increase in the aberration yield at 6 mg/L could not be fully 

assessed because chromatid and chromosome gaps (the predominant type of aberration) were included 
MIREX AND CHLORDECONE 149 

2. HEALTH EFFECTS 

in the statistical analysis and there was a high background frequency of cells treated with solvent 

(dimethyl sulfoxide) that had abnormal values. 

Chlordecone (1.67-10.00 mg/L) increased the frequency of sister chromatid exchange in CHO cells but 

only in the absence of S9 activation and only in the presence of cell-cycle delay; the results were 

confirmed in a repeat trial (Galloway et al. 1987). By contrast, chlordecone alcohol was negative for 

sister chromatid exchange induction both with and without S9 activation (Galloway et al. 1987). 

Subcytotoxic doses of mirex did not induce unscheduled DNA synthesis in primary hepatocytes 

recovered from rats, mice, or hamsters (Maslansky and Williams 1981; Williams 1980). Similar 

results were obtained by Probst et al. (1981) using primary rat hepatocytes exposed to 1,000 μmol/L 

mirex. Chlordecone was also uniformly negative in unscheduled DNA synthesis assays of primary rat 

hepatocytes (Probst et al. 1981; Williams 1980). 

Metabolic cooperation between 6-thioguanine-resistant (6-TGr

) mutants (HGPRT-) and 6-thioguanineinsensitive (6-TGs

) wild-type (HGPRT+) Chinese hamster lung fibroblasts (V79) was, however, inhibited 

by both mirex and chlordecone (Tsushimoto et al. 1982). In this assay system, the ability of HGPRT+

 cells 

to transport a lethal substrate (formed from the metabolism of 6-thioguanine) to HGPRT cells (6-TGr

) is 

evaluated. Transport of the mononucleotide of thioguanine from the HGPRT+

 to the 

HGPRT-

 cells occurs presumably through gap junctions and results in the killing of heretofore 6-TGr 

cells. Therefore, increased survivol of the HGPRT- cells in the presence of a test material indicates an 

interference with metabolic cooperation. Mirex doses ranging from 3 to 12 mg/L induced a doserelated 

increase in the recovery of 6-TGr

 colonies. The maximum percentage recovery of 6-TGr cells 

(≈70%) was noted at 12 mg/L. Chlordecone also inhibited metabolic cooperation at concentrations 

well below the cytotoxic level. However, in contrast to the mirex data, chlordecone produced a much 

steeper dose-response between 1 and 4 mg/L with the maximum percentage of 6-TGr

 cell recovery 

(70%) occurring at 4 mg/L. While it is tempting to speculate that chlordecone is a more potent 

inhibitor of metabolic cooperation, the differences observed may be explained by differences in 

solubility. Chlordecone also reversibly disrupted gap junctional communication in human embryonic 

palatal mesenchyme cells when tested by assessing Lucifer yellow dye transfer (Caldwell and LochCaruso 1992). These results provide persuasive evidence that both mirex and chlordecone interfere 

with cell-to-cell communication. 

Refer to Table 2-6 for a further summary of the in vitro results. 
 

 

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Mirex and chlordecone have not been extensively tested in in vivo and in vitro genetic toxicology test 

systems. Nevertheless, the picture that emerges for both compounds, which differ only in the 

placement of an oxygen atom on carbon 2, provides compelling evidence that neither mirex nor 

chlordecone are genotoxic. There are also convincing data from a metabolic cooperation assay 

(Tsushimoto et al. 1982) and a dye transfer assay (Caldwell and Loch-Caruso 1992) indicating that 

mirex and chlordecone interfere with intracellular communication. Inhibition of cell-to-cell 

communication is a property exhibited by numerous promoters (Williams 1980). Similarly, the data 

indicating that both agents probably induce liver tumors in rodents through epigenetic/promoter 

mechanisms are supported by the striking similarities that these test materials share with many 

established promoters: (1) tumors induced by mirex or chlordecone are found predominantly in rat or 

mouse livers; (2) neither agent is genotoxic; (3) both agents induce omithine decarboxylase activity; 

(4) there is no evidence of covalent binding to DNA; and (5) both agents lack reactive functional 

groups. Mirex has not been evaluated for promoter activity in vivo; however, chlordecone was shown 

to be a tumor promotor in a two-stage assay in which the initiator, diethylnitrosamine (20 mg/kg), was 

given orally to partially hepatectomized Sprague-Dawley rats followed by two subcutaneous doses of 

3 or 9 mg/kg chlordecone per week for 27 weeks (0.86 or 2.6 mg/kg/day). The higher dose resulted 

in hyperplastic liver nodules in seven of eight initiated males and hepatocellular carcinomas in five of 

six initiated females. No tumor initiation activity was seen with a single oral dose of 30 mg/kg 

chlordecone 24 hours after hepatectomy followed by phenobarbital promotion (Sirica et al. 1989). 

The steady-state liver concentrations of chlordecone were similar in male and female rats and mice at 

each of the doses. These levels may, therefore, be important for interspecies comparisons since 

chlordecone is not metabolized in rats but is metabolized in humans. 

The weight of evidence from in vivo and in vitro genetic toxicology tests, in vivo liver function 

studies, and the two-stage tumor promotion assay is adequate to conclude that chlordecone is a 

promotor rather than an initiator of carcinogenesis. While the evaluation of mirex in an in vivo tumor 

promoter assay is desirable, it is, nevertheless, concluded that there is sufficient evidence to consider 

mirex a probable promoter. 
 

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Cancer. No studies have been conducted in human populations to determine whether mirex or 

chlordecone causes cancer. However, studies in mice and rats have demonstrated the ability of mirex 

to cause liver tumors (Innes et al. 1969; NTP 1990; Ulland et al. 1977a), pheochromocytomas (NTP 

1990), and rare renal tumors (NTP 1990). A study in mice and rats also showed the ability of 

chlordecone to increase liver tumors (NCI 1976). As indicated above, available data on the 

genotoxicity of mirex and chlordecone indicate that these chemicals do not cause cancer by a 

mutagenic mechanism but rather by tumor promotion. Both mirex and chlordecone are considered by 

the DHHS to be substances that may reasonably be anticipated to be carcinogens and by IARC to be 

possible human carcinogens. EPA has not classified mirex or chlordecone as to their carcinogenicity. 

As indicated above in the section on “Genotoxic Effects”, it is likely that mirex and chlordecone are 

tumor promoters and not tumor initiators. Initiators irreversibly alter DNA by a mutation, 

chromosomal aberration, or other alteration. Promoters act by facilitating the proliferation of 

previously initiated preneoplastic cells. One of the mechanisms for promotion is believed to involve 

suppression of inhibitory proliferative control through inhibition of gap-junctional-mediated 

intercellular communication as well as enzyme induction (Trosko et al. 1983). The results of studies 

to evaluate the promotional activity potential of mirex in mice indicate that mirex is a mouse skin 

cancer promoter but exerts this toxicity through a hitherto unknown mechanism that is different from 

that of phorbol esters, such as TPA (Meyer et al. 1993, 1994; Moser et al. 1992, 1993). Unlike 

initiation, promotion is a reversible process to a point. This implies, at least in theory, that there may 

be justification for setting NOAELs for promoters. 

2.5 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). 

A biomarker of exposure is a xenobiotic substance or its metabolite(s), or the product of an interaction 

between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a 

compartment of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally 

the substance itself 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 
 

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2. HEALTH EFFECTS 

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 mirex and chlordecone are discussed in Section 2.5.1. 

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 mirex and chlordecone are discussed in Section 2.5.2. 

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 2.7, Populations That Are Unusually Susceptible. 

2.5.1 Biomarkers Used to Identify or Quantify Exposure to Mirex or 

Chlordecone 

The primary biomarkers of exposure to mirex include mirex concentrations in blood (Byrd et al. 1982; 

Kavlock et al. 1980; Smrek et al. 1977; Wiener et al. 1976), fat (Burse et al. 1989; Kutz et al. 1974), 

feces (Byrd et al. 1982; Chambers et al. 1982; Gibson et al. 1972; Ivie et al. 1974b), or milk (Dorough 

and Ivie 1974; Kavlock et al. 1980; Mes et al. 1978; Smrek et al. 1977). Since mirex is not 

metabolized, it is the only biomarker to be measured in these biological media. Since mirex is 

retained in the body for long periods of time and only slowly excreted, its measurement is useful as a 

biomarker of acute, intermediate, or chronic exposures to both low and high levels. 
 

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2. HEALTH EFFECTS 

The biomarkers of exposure to chlordecone include blood or saliva concentrations of chlordecone, and 

fecal or bile concentrations of chlordecone, chlordecone alcohol, and/or their glucuronide conjugates. 

Blood samples are the most useful tool for epidemiological studies of exposure to chlordecone 

(Guzelian et al. 1981). The unusually high concentration of chlordecone in blood compared with its 

concentration in fat (1:7 in humans), which is due to chlordecone’s association with plasma proteins, 

and its long half-life make chlordecone in blood (a readily sampled tissue) a good biomarker of 

exposure (Guzelian et al. 1981). The blood concentration of chlordecone serves as an accurate 

reflection of total body content of chlordecone (Guzelian et al. 1981). Blood is the best biological 

material to monitor and to use for determining acute, intermediate, and chronic exposures to both low 

and high levels of chlordecone. 

Blood is a better indicator of exposure to chlordecone than is saliva (Borzelleca and Skalsky 1980; 

Skalsky et al. 1980). Chlordecone has been detected in saliva of humans only in trace amounts and in 

rats at concentrations three to four times lower than in blood (Guzelian et al. 1981; Skalsky et al. 

1980). Peak chlordecone concentrations occurred within the first 24 hours of exposure; therefore, the 

period of utility of saliva as a biomarker is limited. The movement of chlordecone from the blood 

into the saliva is one of passive diffusion and is not concentration dependent (Borzelleca and Skalsky 

1980; Skalsky et al. 1980). Thus, blood is a better biological material than saliva for monitoring 

exposure. 

Other biomarkers of exposure include tissue concentrations of chlordecone (Bungay et al. 1981; 

Cannon et al. 1978; Cohn et al. 1978; Egle et al. 1978; Hewitt et al. 1986b; Plaa et al. 1987; Taylor 

1982, 1985) and fecal or bile concentrations of chlordecone, chlordecone alcohol, and their 

glucuronide conjugates (Blanke et al. 1978; Boylan et al. 1979; Cohn et al. 1978; Guzelian et al. 

1981). These can be measured and are reliable indicators of exposure to chlordecone. 

2.5.2 Biomarkers Used to Characterize Effects Caused by Mirex or Chlordecone 

Microsomal enzyme induction has been shown to be increased by both mirex and chlordecone in 

humans and/or experimental animals. Serum levels of chlordecone associated with enzyme induction 

in exposed workers were estimated to range from 100 to 500 μg/L (Guzelian 1985). Urinary 

D-glucaric acid levels have been shown to be a sensitive indicator of microsomal enzyme induction in 

workers exposed to chlordecone (Guzelian 1985). However, other substances such as barbiturates, 
 

 

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2. HEALTH EFFECTS 

phenytoin, chlorbutanol, aminopyrine, phenylbutazone, and contraceptive steroids as well as other 

organochlorinated pesticides also cause microsomal enzyme induction and cause changes in urinary 

D-glucaric acid (Morgan and Roan 1974). 

Studies in experimental animals suggest that biliary excretion of chemicals from the liver may be 

impaired by mirex or chlordecone (Berman et al. 1986; Curtis and Hoyt 1984; Curtis and Mehendale 

1979; Curtis et al. 1979b, 1981; Davison et al. 1976; Mehendale 1976, 1977b, 1977c, 1981b; Teo and 

Vore 1991). Measurement of serum bile acid levels may provide information regarding biliary 

excretory function. 

Studies in experimental animals have also shown increased urinary protein accompanied or 

unaccompanied by histopathological changes of the kidneys following exposure to mirex (NTP 1990) 

or chlordecone (Larson et al. 1979b). Although these changes are not specific for mirex or 

chlordecone, measurement of these parameters may provide information about renal damage in 

exposed populations. 

Chlordecone causes a number of neurotoxic responses in humans and animals exposed to sufficiently 

high levels. Tremor that is accentuated by intentional acts, sustained postural movement, anxiety, or 

fatigue has been observed in workers exposed to high levels of chlordecone. Tremorograms have been 

used to objectively assess the tremor associated with chlordecone exposure in humans (Taylor et al. 

1978). An infrared reflection technique and oculography have been used to assess the oculomotor 

disturbances caused by chlordecone (Taylor et al. 1978). Standard tests for memory and intelligence 

can be used to determine the presence of encephalopathy, but in the absence of baseline preexposure 

levels for individuals, subtle changes may be difficult to detect. 

Decreased sperm count has been observed following exposure to mirex or chlordecone in humans 

and/or experimental animals. Clinically, the most straightforward biomarker would be examination of 

sperm in the ejaculate. However, testicular biopsies may also be helpful. Both procedures have been 

used to assess the male reproductive toxicity of chlordecone in exposed persons (Taylor et al. 1978). 
 

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2. HEALTH EFFECTS 

2.6 INTERACTIONS WITH OTHER SUBSTANCES 

Both mirex and chlordecone are microsomal enzyme inducers, and as such enhance the metabolism of 

compounds oxidized or reduced by the mixed function oxygenase system. For example, the 

metabolism of lindane was enhanced in rats previously exposed to chlordecone (Chadwick et al. 1979). 

For chemicals that undergo a loss of activity with metabolism, a decrease in effectiveness would be 

likely in mirex- or chlordecone-exposed persons. For example, pretreatment of rats with chlordecone 

reduced the cholinesterase inhibition produced by a subsequent dose of methyl parathion (Tvede et al. 

1989). In this study, methyl parathion was apparently metabolized to its active metabolite, methyl 

paraoxon, and the methyl paraoxon was further metabolized to an inactive metabolite. For chemicals 

that undergo a transformation to an active or toxic metabolite, enhanced activity/toxicity would be 

likely in mirex- or chlordecone-exposed persons. An example of this type of interaction was shown in 

the enhancement of acetaminophen toxicity by 30 mg/kg of mirex or chlordecone (Fouse and 

Hodgson 1987). Acetaminophen causes hepatic necrosis as the result of the binding of the reactive 

intermediate, postulated to be N-acetylquinoneimine, formed by the microsomal cytochrome P-450­

dependent monooxygenase system. Mirex and chlordecone increased the activity of this system, and 

as a result, the toxicity of the acetaminophen was increased. 

By far the most extensively studied interaction of mirex or chlordecone is the ability of chlordecone to 

markedly potentiate the hepatotoxicity of halomethanes such as carbon tetrachloride (Agarwal and 

Mehendale 1983c; Bell and Mehendale 1985; Chaudhury and Mehendale 1991; Curtis et al. 1979b, 

1981; Davis and Mehendale 1980; Klingensmith and Mehendale 1981, 1982b, 1983a, 1983b; 

Klingensmith et al. 1983a, 1983b; Kodavanti et al. 1989a, 1990a, 1991; Lockard et al. 1983a, 1983b; 

Mehendale and Klingensmith 1988; Soni and Mehendale 1993), bromotrichloromethane (Agarwal and 

Mehendale 1982; Faroon and Mehendale 1990; Faroon et al. 1991; Klingensmith and Mehendale 

1981), and chloroform (Cianflone et al. 1980; Hewitt et al. 1979, 1983, 1986a, 1986b, 1990; Iijima et 

al. 1983; Mehendale et al. 1989; Purushotham et al. 1988). For example, pretreatment of rats with 

5 mg/kg chlordecone resulted in a 67-fold increase in carbon tetrachloride-induced lethality due to 

liver failure (Klingensmith and Mehendale 1982b). The increase in hepatotoxicity is characterized by 

increased serum enzymes, extensive necrosis, increased destruction of cytochrome P4.50 isozymes, and 

decreased biliary function. The potentiation of hepatotoxicity does not appear to be due solely to 

increased metabolism of the haloalkanes to toxic intermediates (CCl3, free radical and phosgene) and as 

such is distinct from the potentiation of halomethane toxicity by phenobarbital (Agarwal and 
 

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2. HEALTH EFFECTS 

Mehendale 1984a, 1984d; Bell and Mehendale 1987; Klingensmith and Mehendale 1983a, 1983b; 

Mehendale and Klingensmith 1988; Mehendale et al. 1990) or mirex (Bell and Mehendale 1985; 

Cianflone et al. 1980; Hewitt et al. 1979, 1986a; Mehendale and Klingensmith 1988; Mehendale et al. 

1989; Purushotham et al. 1988). 

The primary mechanism for potentiation of hepatotoxicity may be the suppression of the early tissue 

regenerative response normally seen in livers of rats and mice exposed to low doses of halomethanes 

(Mehendale 1992, 1994). The dramatic increase in mitotic activity that normally occurs soon after 

halomethane exposure does not occur in chlordecone-pretreated animals (Faroon and Mehendale 1990; 

Lockard et al. 1983b). Gerbils, which do not exhibit early hepatocellular regeneration following 

halomethane exposure (and thus are more susceptible to the toxic and lethal effects of halomethanes), 

do not exhibit potentiation following chlordecone pretreatment (Cai and Mehendale 1990, 1991b). 

Experiments performed with partially hepatectomized animals provide further evidence for the role of 

suppressed regeneration following carbon tetrachloride exposure (Cai and Mehendale 1991a). Partial 

hepatectomy, which stimulates tissue regeneration, afforded partial protection from the potentiating 

effects of chlordecone in rats (Bell et al. 1988; Rao et al. 1989; Young and Mehendale 1989). 

Similarly, a recent study (Cai and Mehendale 1993) has shown that young rats with greater 

hepatocellular regenerative activity than adult rats also experience less hepatocellular damage following 

exposure to both chlordecone and carbon tetrachloride. Cellular changes that may facilitate the 

chlordecone-induced suppression of regeneration include marked depletion of hepatocellular glycogen 

(Bell and Mehendale 1987; Faroon et al. 1991; Lockard et al. 1983a, 1983b), depletion of ATP 

(Faroon et al. 1991; Kodavanti et al. 1990a), and disruptions in the regulation of intracellular calcium 

(Agarwal and Mehendale 1984a, 1984c, 1984d, 1986; Hegarty et al. 1986; Kodavanti et al. 1991). It 

has been demonstrated that suppression of cell division due to glycogen depletion results in decreased 

ATP availability and, consequently, suppressed cellular regeneration (Soni and Mehendale 1993, 

1994). 

A number of pharmacological agents have been shown to decrease the tremors produced in rats by 

chlordecone (Gerhart et al. 1983, 1985; Herr et al. 1987). Agents shown to be effective in at least one 

study include yohimbe or phenoxybenzamine (α-noradrenergic antagonists), mecamylamine (a 

nicotinic antagonist), chlordiazepoxide (α benzodiazepine), muscimol (a GABA agonist), and 

mephenesin (a centrally acting muscle relaxant). These pharmacological agents were administered 

subcutaneously in animals at the following doses: yohimbe (an a-noradrenergic antagonist) = 0.5 or 
MIREX AND CHLORDECONE 157 

2. HEALTH EFFECTS 

1 mg/kg; phenoxybenzamine (an α-noradrenergic antagonists) = 5 mg/kg; mecamylamine (a nicotinic 

antagonist) = 1 mg/kg; chlordiazepoxide (a benzodiazepine) = 10 mg/kg; muscimol (a GABA agonist) 

= 1 mg/kg; and mephenesin (a centrally acting muscle relaxant) = 100 mg/kg. Persons being treated 

therapeutically with any of these drugs are likely to experience diminished tremors following exposure 

to chlordecone. In contrast, treatment with quipazine (a serotonergic agonist) was shown to potentiate 

chlordecone-induced tremors (Gerhart et al. 1983). It is possible that persons being treated for 

depression with quipazine or with Prozac® (a serotonin uptake inhibitor) may experience enhanced 

tremors. 

Pretreatment of rats with difluoromethylomithine (DFMO), an inhibitor of ornithine decarboxylase, 

prior to exposure to a tremongenic dose of chlordecone, also resulted in inhibition of the tremor 

(Tilson et al. 1986b). DFMO was more effective if given 5 hours prior to the chlordecone than if 

given 24 hours prior to exposure. The DFMO was ineffective if given 19 hours after chlordecone 

exposure. These results suggest an interaction of the polyamine synthetic pathway with tremors 

produced by chlordecone. The mechanism of the interaction is unclear but may involve effects of 

polyamines on intracellular calcium homeostasis. Persons being treated with DFMO for cancer or 

protozoa1 infections would be likely to have reduced tremor severity after exposure to chlordecone. 

In contrast to the reduction of tremors by DFMO, pretreatment of rats with diphenylhydantoin results 

in exacerbation of chlordecone-induced tremors (Hong et al. 1986; Tilson et al. 1985, 1986b). The 

mechanism for the exacerbation of the tremors is unknown. Therefore, if persons receiving 

diphenylhydantoin treatment for epilepsy were exposed to sufficiently high concentrations of 

chlordecone at a hazardous waste site, increased tremor severity would be likely to occur. 

Cholestyramine, a chelating agent, binds chlordecone present in the gastrointestinal tract and limits its 

enterohepatic recirculation (Boylan et al. 1978; Cohn et al. 1978). This interaction leads to increased 

excretion of the chlordecone and decreased toxicity. Thus, persons being treated with cholestyramine 

to lower plasma cholesterol may experience increased excretion of chlordecone and decreased toxicity. 

The use of cholestyramine as a therapeutic agent in cases of chlordecone poisoning is discussed more 

fully in Section 2.8.2, Reducing Body Burden. 
MIREX AND CHLORDECONE 158 

2. HEALTH EFFECTS 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to mirex and chlordecone than 

will most persons exposed to the same level of mirex or chlordecone in the environment. Reasons 

include genetic make-up, developmental stage, age, health and nutritional status (including dietary 

habits that may increase susceptibility, such as inconsistent diets or nutritional deficiencies), and 

substance exposure history (including smoking). These parameters result in decreased function of the 

detoxification and excretory processes (mainly hepatic, renal, and respiratory) or the pre-existing 

compromised function of target organs (including effects or clearance rates and any resulting endproduct 

metabolites). For these reasons we expect the elderly with declining organ function and the 

youngest of the population with immature and developing organs will generally be more vulnerable to 

toxic substances than healthy adults. Populations who are at greater risk due to their unusually high 

exposure are discussed in Section 5.6, Populations With Potentially High Exposure. 

Review of the literature regarding toxic effects of mirex and chlordecone did not reveal any human 

populations that are known to be unusually sensitive to mirex or chlordecone. However, based on 

knowledge of the toxicities of mirex and chlordecone, some populations can be identified that may 

demonstrate unusual sensitivity to these chemicals. Those with potentially high sensitivity to mirex 

include the very young. Those with potentially high sensitivity to chlordecone include juvenile and 

elderly person and persons being treated with some antidepressants or the anticonvulsant, 

diphenylhydantoin. 

In experimental animals, mirex administered within the week after birth causes a high incidence of 

cataracts and other lesions of the lens (Chernoff et al. 1979b; Gaines and Kimbrough 1970; Rogers 

and Grabowski 1984; Scotti et al. 1981). These effects were observed whether the neonatal animals 

received mirex through the milk of lactating dams or directly by gavage. Although it is unclear 

whether the lens of humans also undergoes a similar period of susceptibility, the possibility exists that 

newborn children may also develop cataracts if exposed to mirex shortly after birth. 

Studies in rats have demonstrated that certain treatments exacerbate the tremors associated with 

chlordecone exposure. These include pretreatment with the anticonvulsant, diphenylhydantoin (Hong 

et al. 1986; Tilson et al. 1985, 1986b), and treatment with the serotonergic agonist, quipazine (Gerhart 

et al. 1983). Therefore, persons being treated with diphenylhydantoin for epilepsy or quipazine for 
MIREX AND CHLORDECONE 159 

2. HEALTH EFFECTS 

depression may be likely to experience more severe tremors upon exposure to high levels of 

chlordecone. Extrapolating from the effects seen in animals with quipazine, it might be likely that 

persons taking the prescription drug Prozac@, a serotonin uptake inhibitor used to treat depression, will 

also experience more severe tremors. Furthermore, the elderly may be a susceptible population 

because serotonin metabolism is increased during aging (Walker and Fishman 1991). 

Studies in animals have also shown that juvenile animals experience a higher death rate than adults 

following exposure to chlordecone at equivalent mg/kg doses (Huber 1965). No explanation was 

given for these findings, but similar sensitivities may exist in children. Furthermore, although 

inhibition of Na+

-K+ATPase, mg2+ATPase, and Ca2+ATPase activities have not been definitively shown 

to be the mechanism underlying chlordecone toxicity, sufficient evidence exists to suggest that their 

inhibition may be involved in a number of adverse effect (see Section 2.3.5, Mechanism of Action). 

Neonatal rats have shown a greater inhibition of these enzymes than adult rats (Jinna et al. 1989). 

This provides additional support for the suggestion that infants and young children may represent a 

susceptible population to the toxic effects of chlordecone. 

In contrast, a recent study of developing postnatal rats has shown that the young may be less 

susceptible to at least one of the toxic effects of chlordecone. Young and adolescent rats show less 

potentiation of carbon tetrachloride toxicity than adult rats (Cai and Mehendale 1993). This may be 

due to a combination of incomplete development of the microsomal enzyme systems and a higher 

level of hepatic regenerating activity in the very young rats. In adolescent rats (35 and 45 days old) 

the microsomal enzyme activity is comparable to adult levels, but the level of damage is still less than 

in adult rats (60 days old). This may be due to that fact that hepatic regenerating activity remained 

higher in the adolescents than in the adults. 

2.8 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects 

of exposure to mirex or chlordecone. However, because some of the treatments discussed may be 

experimental and unproven, this section should not be used as a guide for treatment of exposure to 

mirex and chlordecone. When specific exposures have occurred, poison control centers and medical 

toxicologists should be consulted for medical advice. 
 

MIREX AND CHLORDECONE 160 

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2.8.1 Reducing Peak Absorption Following Exposure 

General recommendations reported for reducing absorption following acute, high-dose exposure to 

mirex and chlordecone include removing the individual from the source of the exposure and removing 

contaminated clothing (Haddad and Winchester 1990; Morgan et al. 1979). It has been suggested that 

the skin and hair be washed with soap and copious amounts of water. Most organochlorine pesticides 

are lipid soluble and are efficiently absorbed through the skin, so decontamination attempts should be 

accomplished quickly (Ellenhorn and Barceloux 1988). If the exposure has occurred by ingestion of 

chlordecone or mirex, several approaches have been proposed to limit the gastrointestinal absorption. 

One method is to induce emesis, provided the patient is conscious (HSDB 1994a, 1994b). However, 

the procedure is not without certain drawbacks. There is a risk of causing chemical pneumonitis in the 

patient by the aspiration of hydrocarbon solvent associated with the pesticide. Another suggested 

approach to reduce absorption is the administration of an activated charcoal slurry and a saline or 

sorbitol cathartic (HSDB 1994a, 1994b; Morgan et al. 1979). This technique has been found to 

increase the excretion of chlordecone twofold. If a patient has decreased levels of consciousness, 

gastric lavage has been suggested along with the use of a cuffed endotracheal tube to decrease the 

chance of aspiration (Morgan et al. 1979). The lipophilic properties of the halogenated hydrocarbons 

indicate that these chemicals will readily cross cell membranes such as the skin or the gastrointestinal 

epithelium. 

2.8.2 Reducing Body Burden 

Chlordecone, which is excreted mainly in the feces, appears to undergo enterohepatic recirculation, 

which limits its excretion (Boylan et al. 1978). Analysis of the amount of chlordecone excreted in the 

bile compared to the amount found in the stool has indicated that only 5-10% of the bile level of the 

pesticide is eliminated in the feces (Boylan et al. 1978). Approximately equal fractions of chlordecone 

and its metabolite, chlordecone alcohol, are excreted in the stool (Cohn et al. 1978). Like most 

halogenated hydrocarbon pesticides, very little of the chlordecone or its metabolites is excreted via the 

urine. Because of the apparent enterohepatic recirculation of chlordecone and chlordecone alcohol, 

most experimental approaches to chlordecone detoxification have focused on limiting reabsorption 

from the gastrointestinal tract using cholestyramine (Boylan et al. 1978; Cohn et al. 1978), liquid 

paraffin (Richter et al. 1979), and chlorella and chlorella-derived sporopollenin (Pore 1984). No 
 

 

MIREX AND CHLORDECONE 161 

2. HEALTH EFFECTS 

information was found that indicated that mirex undergoes enterohepatic recirculation, so it is not 

known whether use of these therapies would be effective in reducing absorption of mirex. 

The use of cholestyramine in reducing the body burden of chlordecone has been investigated in 

humans and rats. In the human study, 32 workers who had been heavily exposed to chlordecone over 

a period of from 3 to 16 months were treated for 5 months with cholestryramine (Cohn et al. 1978). 

Cholestyramine treatment resulted in a sevenfold increase in the fecal excretion of chlordecone. 

Similarly, a study using rats demonstrated a doubling of fecal excretion and a 30-50% decrease in 

tissue levels of chlordecone after 2 weeks treatment with cholestyramine following a single oral dose 

of chlordecone (Boylan et al. 1978). 

Cholestyramine use is not without limitations. It does not bind chlordecone alcohol, a metabolite of 

chlordecone that is also excreted in the bile (Guzelian 1981). It has a gritty texture in the mouth, and 

it causes several gastrointestinal disturbances, which may limit the willingness of patients to take it. It 

may also interfere with the absorption of fat-soluble vitamins and interact with other medications 

(Goldfrank 1990). 

Two other compounds have been examined for therapeutic action in animal (rat) models of 

chlordecone poisoning. Sporopollenin, a carotenoid polymer derived from the cell walls of the alga 

Chlorella prothecoides, was reported to bind to chlordecone (Pore 1984). In animal studies using 

rats, sporopollenin decreased the half life of chlordecone from 40 days to 19 days. The excretion rate in 

control animals fed a-cellulose, in the same bulk amount as sporopollenin, did not change. Prevention 

of enterohepatic recirculation of chlordecone was also evaluated with liquid paraffin. Rats exposed to 

14 C-chlordecone for 3 days and then to diets containing 8% liquid paraffin for 24 days excreted 

approximately 20% more of the labelled compound in the feces than did control animals (Richter et al. 

1979). Fourteen of 18 tissues examined had significantly less radioactivity than control tissues. 

Hemoperfusion has been tried experimentally without success (Guzelian 1981). In a study in which a 

16-unit plasmaphoresis was performed in one patient, chlordecone blood levels dropped during 

treatment but then returned to and even exceeded pretreatment levels. Although the fraction of 

chlordecone present in the blood relative to fat (1:7) was higher than that of halogenated pesticides 

(1:300 or greater) and indicated that hemoperfusion might be successful, the equilibrium was such that 

the compound moved readily from the fat to the blood, thus limiting the effect of a short duration 
 

MIREX AND CHLORDECONE 162 

2. HEALTH EFFECTS 

hemoperfusion. Dialysis is also not recommended because of the nature of the equilibrium of 

pesticide between the fat and the blood (HSDB 1994a, 1994b). One reason for the high blood levels 

of chlordecone is that it binds to plasma proteins (Guzelian 1981). 

2.8.3 Interfering with the Mechanism of Action for Toxic Effects 

No standard therapies have been reported for interfering with the mechanisms of mirex or chlordecone 

toxicities and, therefore, therapy has been directed towards supportive care. However, limited 

anecdotal information is available regarding treatments used to ameliorate the effects caused by 

chlordecone in the workers from the plant in Hopewell, Virginia. The administration of propranolol 

appeared to reduce tremor somewhat (Taylor 1982, 1985). The cause for effectiveness of this therapy 

is unclear; propranolol was ineffective in ameliorating tremor in rats (Gerhart et al. 1983). In 

experimental animals, phenoxybenzamine (an a-noradrenergic antagonist), pizotifen (a serotonin 

antagonist), mecamylamine (a nicotinic antagonist), trihexyphenidyl (a muscarinic antagonist), 

chlordiazepoxide (a benzodiazepine), muscimol (a GABA agonist), and mephenesin (a centrally acting 

muscle relaxant) resulted in attenuation of chlordecone-induced tremor (Gerhart et al. 1982, 1983, 

1985; Herr et al 1987; Hwang and Van Woert 1979). Mephenesin was the most effective agent. It is 

unclear whether these agents would be effective if administered to humans following chlordecone 

exposure. 

Prednisolone was observed to be effective in ameliorating the headache seen in 3 workers with 

elevated cerebral spinal fluid pressure and papilledema resulting from exposure to high levels of 

chlordecone (Sanbom et al. 1979). However, when prednisolone therapy was stopped, the headaches 

returned and did not dissipate until serum chlordecone levels were reduced. It is possible that the 

prednisolone blocked the headache by increasing vasoconstriction and decreasing intracranial cerebral 

spinal fluid volume. 

Pretreatment of rats with α-noradrenergic antagonists blocked the hypothermia induced by chlordecone 

(Cook et al. 1988b). It is possible that if similar effects are observed in humans, α-antagonists may be 

capable of blocking the hypothermia. 
 

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2. HEALTH EFFECTS 

2.9 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of mirex or chlordecone 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 mirex and chlordecone. 

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 fulfilled. In the future, the identified data needs 

will be evaluated and prioritized, and a substance-specific research agenda will be proposed. 

2.9.1 Existing Information on Health Effects of Mirex and Chlordecone 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

mirex and chlordecone are summarized in Figures 2-4 and 2-5, respectively. The purpose of the 

figures is to illustrate the existing information concerning the health effects of mirex and chlordecone. 

Each dot in the figure indicates that one or more studies provide information associated with that 

particular effect. The dot does not imply anything about the quality of the study or studies. Gaps in 

figures should not be interpreted as “data needs.” A data need, as defined in ATSDR’s Decision 

Guide for Identifying Substance-Specific Data Needs Related to Toxicological Projiles (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. 

There are no epidemiological or case reports of mirex-exposed individuals. The literature reviewed for 

the health effects of chlordecone in humans came from reports of one occupational cohort of workers 

exposed to chlordecone in a manufacturing plant. This exposure was classified as intermediate-tochronic; 

no precise duration or level of exposure to chlordecone could be quantified from these 

reports. A single route of exposure could not be established for this worker population; poor hygiene 


 

MIREX AND CHLORDECONE 166 

2. HEALTH EFFECTS 

in the plant made inhalation, oral, and dermal exposure routes likely to occur. The information on 

human exposure in this study is extremely limited because of the possible contamination with the 

precursor used to manufacture chlordecone, hexachloropentadiene. Therefore, information on human 

exposure to both mirex and chlordecone is limited. 

The database for the health effects of mirex and chlordecone following oral administration in 

experimental animals is more substantial. However, as can be seen in Figures 2-4 and 2-5, no 

information is available on the health effects of inhalation and dermal exposure to mirex or 

chlordecone in animals. 

People living near hazardous waste sites may be exposed to mirex or chlordecone primarily via dermal 

contact with or ingestion of contaminated soils since mirex and chlordecone are bound to soil particles. 

Another possible mechanism for oral exposure to mirex and chlordecone is the ingestion of pesticideladen 

dust carried by the wind from a waste site or treated field and deposited on garden crops. 

Ingestion of contaminated water is not likely to be a significant route of exposure since mirex and 

chlordecone have very limited water solubility and are generally not found in groundwater. Likewise, 

inhalation exposure to mirex and chlordecone via volatilization from contaminated media is not a 

likely major route of exposure since mirex and chlordecone are essentially nonvolatile. For the 

general population, the primary route of exposure to mirex and chlordecone is via ingestion of 

residues on contaminated foods. Therefore, information on the toxicity following ingestion and dermal 

exposure is most relevant for individuals living in the vicinity of hazardous waste sites. 

2.9.2 Identification of Data Needs 

Acute-Duration Exposure. No information is available regarding the effects of acute-duration 

exposure to mirex in humans following inhalation, oral, or dermal exposure. A large number of 

studies have been published for acute-duration oral exposure of rats and mice to mirex (Baggett et al. 

1980; Berman et al. 1986; Buelke-Sam et al. 1983; Chernoff et al. 1979a, 1979b; Chu et al. 1981a, 

1981b; Davison et al. 1976; Desaiah et al. 1980a; Elgin et al. 1990; Ervin and Yarbrough 1983, 1985; 

Fouse and Hodgson 1987; Fujimori et al. 1983; Gaines 1969; Gaines and Kimbrough 1970; Hewitt et 

al. 1979, 1986a; Jovanovich et al. 1987; Kendall 1974a, 1979; Khera et al. 1976; Larson et al. 1979a; 

Mehendale 1976, 1977c; Mehendale et al. 1973; Mitra et al. 1990; NTP 1990; Plaa et al. 1987; Rogers 

and Grabowski 1984; Scotti et al. 1981; Singh et al. 1982, 1985; Teo and Vore 1990, 1991; Williams 
MIREX AND CHLORDECONE 167 

2. HEALTH EFFECTS 

and Yarbrough 1983), many of them addressing interactions with other chemicals, such as the 

halogenated hydrocarbons, and adaptive liver effects (Abston and Yarbrough 1976; Baker et al. 1972; 

Byard et al. 1975; Chadwick et al. 1977; Chambers and Trevethan 1983; Chu et al. 1981a, 1981b; 

Cianflone et al. 1980; Curtis.and Hoyt 1984; Curtis et al. 1981; Davison et al. 1976; Elgin et al. 1990; 

Ervin and Yarbrough 1983; Fabacher and Hodgson 1976; Fujimori et al. 1983; Fulfs et al. 1977; 

Gaines and Kimbrough 1970; Hewitt et al. 1979; Iverson 1976; Jovanovich et al. 1987; Karl and 

Yarbrough 1984; Klingensmith and Mehendale 1983b; Kocarek et al. 1991; Larson et al. 1979a; 

Madhukar and Matsumura 1979; Mehendale 1981b; Mehendale et al. 1973, 1989; NTP 1990; Peppriell 

1981; Pittz et al. 1979; Plaa et al. 1987; Purbshotham et al. 1988; Ritchie and Ho 1982; Robacker et 

al. 1981; Robinson and Yarbrough 1978c; Stevens et al. 1979; Teo and Vore 1991; Thottassery and 

Yarbrough 1991; Ulland et al. 1977a; Villeneuve et al. 1977; Warren et al. 1978; Williams and 

Yarbrough 1983; Yarbrough et al. 1981, 1984, 1986a, 1986b). However, no information could be 

located for acute-duration inhalation or dermal exposure. 

Mirex may lead to death after oral exposure, depending upon dose (Fujimori et al. 1983; Gaines 1969; 

Gaines and Kimbrough 1970; Khera et al. 1976; Larson et al. 1979a; Mehendale et al. 1973); some 

evidence exists that pregnant rats may be more sensitive to the lethal effects of mirex (Mehendale et 

al. 1973). The main targets of mirex toxicity following acute exposure by the oral route are the liver, 

nervous system, developing fetus, and eyes. Impaired hepatobiliary excretion (Berman et al. 1986; 

Davison et al. 1976; Fouse and Hodgson 1987; Hewitt et al. 1986a; Kendall 1979; Mehendale 1976, 

1977c, 1981b; Mitra et al. 1990; Teo and Vore 1990, 1991) and hepatic glycogen depletion (Elgin et 

al. 1990; Ervin and Yarbrough 1983; Fujimori et al. 1983; Jovanovich et al. 1987; Kendall 1979) have 

been described as the major hepatic effects. Tremors, hyperactivity or lethargy, and weakness were 

observed following acute-duration oral exposure to large doses of mirex (Gaines and Kimbrough 1970; 

Kendall 1974a). Prenatal acute-duration exposure to mirex resulted in cardiac and visceral anomalies, 

cataracts, increased resorptions, and lethality of offspring (Buelke-Sam et al. 1983; Byrd et al. 1981; 

Chernoff and Kavlock 1982, 1973; Chernoff et al. 1979a, 1979b; Gaines and Kimbrough 1970; 

Grabowski 1983a; Grabowski and Payne 1983a; Gray and Kavlock 1984; Gray et al. 1983; Kavlock et 

al. 1982; Khera et al. 1976; Roger and Grabowski 1983, 1984). Cataract formation in newborns 

occurs after early postnatal exposure (Chernoff et al. 1979b; Gaines and Kimbrough 1970; Rogers and 

Grabowski 1984; Scotti et al. 1981). Diarrhea (resulting from gastric irritation) has also been found 

with acute-duration oral mirex administration, especially in dying animals; however, the dose at which 

this effect occurs is not clear (Gaines and Kimbrough 1970; Kendall 1974a; Khera et al. 1976). 
 

 

 

MIREX AND CHLORDECONE 168 

2. HEALTH EFFECTS 

Alterations in blood flow (Buelke-Sam et al. 1983), in addition to changes in membrane-bound 

enzymes responsible for electrolyte flux in cardiac cells, occurs after acute oral exposure (Desaiah 

1980). The physiological significance of these changes to the experimental animal is not known. 

Thyroid toxicity has also been documented in rats (Chu et al. 1981a, 1981b; NTP 1990; Singh et al. 

1982, 1985), in addition to adrenal hypertrophy and hyperfunction (Ervin and Yarbrough 1985; 

Jovanovich et al. 1987; Williams and Yarbrough 1983). There was no indication that mirex was 

genotoxic in a dominant lethal assay (Khera et al. 1976). It is not possible to determine the target 

organ for mirex toxicity after inhalation or dermal exposure due to the complete lack of data in these 

areas for this duration of exposure. 

No acute-duration inhalation MRL could be derived for mirex because no inhalation data could be 

located. No acute-duration oral MRL was derived for mirex because serious effects (heart block and 

arrhythmias in fetuses from dams exposed during gestation) were observed at the lowest dose tested 

(Grabowski 1983a). Studies examining the effects of mirex and chlordecone after acute-duration 

dermal exposure would be helpful since persons at hazardous waste sites may be exposed dermally to 

mirex. Additional dermal studies are certainly necessary because skin absorption of chlordecone 

appears to be an important route of exposure (Taylor et al. 1978). However, populations at hazardous 

waste sites are unlikely to be exposed via inhalation since these substances are virtually nonvolatile, so 

future studies using this route of exposure are not essential. 

No information is available regarding the effects of acute-duration exposure to chlordecone in humans 

following inhalation, oral, or dermal exposure. Some information is available regarding the effects of 

acute-duration exposure to chlordecone in animals by the oral route of administration (Cannon and 

Kimbrough 1979; Chernoff and Rogers 1976; Davis and Mehendale 1980; Desaiah 1980; Egle et al. 

1979; Fujimori et al 1983; Glende and Lee 1985; Huber 1965; Iijima et al. 1983; Kavlock et al. 1985; 

Khera et al. 1976; Klingensmith and Mehendale 1983b; Kodavanti et al. 1990a; Larson et al. 1979b; 

Mehendale 1977b; Mishra et al. 1980; Plaa et al. 1987; Seidenberg et al. 1986; Simmons et al. 1987; 

Swanson and Wooley 1982; Swartz et al. 1988; Teo and Vore 1991; Uzodinma et al. 198ia; 

Yarbrough et al. 1981), but no information was located for the inhalation or dermal exposure routes. 

Chlordecone may lead to death after oral administration, depending on dose (Larson et al. 1979b; 

Simmons et al. 1987); pregnant animals may be more sensitive to lethal effects of chlordecone 

(Chernoff and Rogers 1976; Kavlock et al. 1985; Seidenberg et al. 1986). 
MIREX AND CHLORDECONE 169 

2. HEALTH EFFECTS 

The main toxic effects of acute-duration oral chlordecone administration are reproductive, neurological, 

musculoskeletal, and hepatic. Studies in laboratory animals exposed orally to chlordecone have 

demonstrated reproductive effects such as decreased fertility or fecundity and litter size, reduced sperm 

count, and testicular atrophy in animals (Khera et al. 1976; Uzodinma et al. 1984a; Yarbrough et al. 

1981). Neurotoxicity is a well-studied toxic effect of chlordecone in rats and mice (Albertson et al. 

1985; Aldous et al. 1984; Baggett et al. 1980; Chang-Tsui and Ho 1979; Desaiah et al. 1980a; Egle et 

al. 1979; End et al. 1981; Fujimori et al. 1982b; Hoskins and Ho 1982; Huang et al. 1980; Hwang and 

Van Woert 1979; Jordan et al. 1981; Klingensmith and Mehendale 1982b; Maier and Costa 1990; 

Mishra et al. 1980; Smialowicz et al. 1985; Swanson and Wooley 1982; Uzodinma et al. 1984a). 

Toxicity to the musculoskeletal system of rats has been observed after single oral doses of chlordecone 

(Egle et al. 1979). Biochemical changes were also found in the muscle of rats after multiple 

chlordecone doses (Mishra et al. 1980). There are few studies which examine the musculoskeletal 

system after oral administration. Chlordecone has been found in rats and mice to result in impaired 

biliary excretion and/or other signs of liver toxicity in some studies (Fujimori et al. 1983; Mehendale 

1977b, 1981b; Teo and Vore 1991) but not in all (Davis and Mehendale 1980; Glende and Lee 1985; 

Iijima et al. 1983; Klingensmith and Mehendale 1983b; Plaa et al. 1987). 

Cardiovascular effects of chlordecone in rats after acute-duration exposure to chlordecone are limited 

to biochemical changes in cardiac tissue, such as membrane enzyme inhibitions and altered protein 

phosphorylation (Desaiah 1980; Kodavanti et al. 1990a). These effects may impact electrolyte balance 

across the cell; however, additional studies must be conducted to ascertain the functional effect of 

enzyme changes. Chlordecone has also been found to have an affect on thermoregulation in rats 

(Swanson and Wooley 1982). In contrast to mirex, chlordecone induced less serious developmental 

effects. Common developmental effects included decreased fetal weight and delayed skeletal 

ossification (Chernoff and Rogers 1976; Gellert and Wilson 1979; Gray and Kavlock 1984; Squibb 

and Tilson 1982a; Swartz et al. 1988). At higher doses, decreased viability occurred (Gray and 

Kavlock 1984; Seidenberg et al. 1986). Chlordecone did not result in dominant lethal effects in acute 

in vivo genotoxicity assays (Simon et al. 1986). 

No acute-duration inhalation MRL could be derived for chlordecone because no data could be located 

using this route of exposure. Since there are no animal data that examine gastrointestinal, 

hematological, respiratory, thyroid, or adrenal effects of acute-duration chlordecone administration, 

additional studies would be useful to establish chlordecone’s toxicity. Human studies for the acute 
 

 

MIREX AND CHLORDECONE 170 

2. HEALTH EFFECTS 

duration are completely lacking; therefore, it would be helpful if populations exposed to this substance 

were carefully monitored in order to better understand the toxic effects of humans exposed to 

chlordecone. 

Intermediate-Duration Exposure. No information is available regarding the toxicity of 

intermediate-duration exposure of humans to mirex by any route of administration. Information 

regarding exposure of animals to mirex for an intermediate duration is available for the oral route (Bell 

and Mehendale 1985; Chu et al. 1980a, 1981a, 1981b; Curtis and Hoyt 1984; Davison et al. 1976; 

Dietz and McMillan 1979; Fujimori et al. 1983; Gaines and Kimbrough 1970; Klingensmith and 

Mehendale 1982a, 1982b; Larson et al. 1979a; Mehendale 1981b; Mehendale et al. 1977a, 1978b; NTP 

1990; Singh et al. 1982, 1985; Ware and Good 1967). Animals exposed orally to mirex for an 

intermediate period of time demonstrated increased lethality according to dose (Gaines and Kimbrough 

1970; Larson et al. 1979a; Mehendale 1981b) and species (mice and dogs may be more sensitive) 

(Ware and Good 1967). Data from inhalation or dermal exposure to mirex could not be located; 

therefore, the concentration or dose that would be likely to cause death after these exposure routes 

cannot be established. The target organs of toxicity to orally administered mirex appear to be the 

liver, gastrointestinal system, and thyroid. Liver toxicity with intermediate-duration oral exposure to 

mirex is similar to that occurring after acute-duration exposure, with the exception that lower doses 

cause hepatotoxicity. The most prominent hepatic effects are impaired biliary excretion (Bell and 

Mehendale 1985; Curtis and Hoyt 1984; Larson et al. 1979a; Mehendale 1981b; Teo and Vore 1991) 

and liver histopathology (Davison et al. 1976). Mild diarrhea occurred in two studies in rats (Dietz 

and McMillan 1979; Mehendale 1981b); in one study with mice, severe diarrhea and hemorrhage of 

the intestines indicated a gastrointestinal ongin for the disturbance (Fujimori et al. 1983). 

Histopathological changes in the thyroid have been reported after intermediate-duration oral exposure 

of animals; however, no change in serum thyroid hormone levels was found (Chu et al. 1981a, 1981b; 

NTP 1990; Singh et al. 1982, 1985). 

Adrenal effects have been seen (Larson et al. 1979b) that are consistent with increased lipid utilization 

(Fujimori et al. 1983; Klingensmith and Mehendale 1982a; Mehendale et al. 1977a, 1978b). Body 

weight decreases have been found in intermediate-duration oral studies using mirex (Chu et al. 1981b; 

Larson et al. 1979a). No adverse cardiovascular effects were found in one study (Larson et al. 1979a); 

however, the data reported from this study were limited. No renal toxicity was found after 

intermediate-duration oral exposure to mirex (Chu et al. 1980a; Larson et al. 1979a), but these studies 
 

 

 

 

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2. HEALTH EFFECTS 

are flawed. No reports could be located describing the musculoskeletal effects of intermediateduration 

oral mirex administration. Well-conducted studies in animals to evaluate these end points for 

mirex following acute- and intermediate-duration inhalation, oral, and dermal exposures, and for 

chlordecone following inhalation and dermal exposures would be helpful. In addition, there is a lack 

of intermediate-duration human mirex exposure studies; therefore, populations exposed to this 

substance should be carefully monitored in order to better understand the toxic effects on humans 

exposed to it. 

The only information available for humans exposed to chlordecone pertains to a study of intermediatetochronic occupational exposures (exact durations not recorded) of one group of individuals employed 

at a facility in Hopewell, Virginia. Chlordecone was manufactured in this facility for 21-22 months; 

because of poor hygiene at the facility, exposure by all routes was likely. In addition, concomitant 

exposure to a precursor was possible. Several studies have been published to describe the toxicity in 

this human population (Cannon et al. 1978; Taylor 1982, 1985), and results of these studies will be 

considered here. These results pertain to the chronic-duration exposure also. No deaths were reported 

(Cannon et al. 1978; Taylor et al. 1978). Skeletal muscle biopsy was conducted on six workers who 

experienced adverse neurological clinical signs (such as tremors) as well as muscle weakness and 

incoordination (Martinez et al. 1978). Abnormal histological and biochemical indices were revealed in 

this tissue. Joint pain was also reported (Taylor 1982, 1985). Liver toxicity (Guzelian et al. 1980), 

skin rashes, and weight loss (described as severe in some individuals) occurred (Cannon et al. 1978; 

Taylor et al. 1978). Respiratory effects included pleuritic chest pains but no lung pathology (Taylor 

1982, 1985). Cardiovascular abnormalities were not observed on electrocardiographic study (Taylor 

1982, 1985). No data could be located regarding gastrointestinal, hematological, or renal effects in 

this population of individuals exposed to chlordecone for intermediate or chronic durations. 

There are no data for intermediate-duration inhalation or dermal exposure of animals to chlordecone, 

but there are several oral exposure studies (Agarwal and Mehendale 1983a, 1983c; Agarwal et al. 

1983; Bell and Mehendale 1985; Cannon and Kimbrough 1979; Chu et al. 1980a, 1981a, 1981b; 

Curtis and Hoyt 1984; Curtis and Mehendale 1979, 1980; Curtis et al. 1979b, 1981; Fabacher and 

Hodgson 1976; Fujimori et al. 1983; Huber 1965; Klingensmith and Mehendale 1982a, 1982b; Larson 

et al. 1979b; Mehendale 1981b; Mehendale et al. 1977a, 1978b; NTP 1990; Pryor et al. 1983; Singh et 

al. 1982, 1985; Squibb and Tilson 1982b). Oral exposure of animals to chlordecone can result in 

lethality; mortality is affected by dose (Fujimori et al. 1983; Mehendale 1981b; Pryor et al. 1983) and 
 

 

MIREX AND CHLORDECONE 172 

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age (Huber 1965). In animals, the major targets of intermediate-duration oral exposure to chlordecone 

are the liver and adrenal gland. Other major effects include neurological (exaggerated startle 

response), developmental (Ali et al. 1982; Rosecrans et al. 1982; Squibb and Tilson 1982a), and 

reproductive effects (testicular atrophy) (Larson et al. 1979b; Squibb and Tilson 1982b), which are 

discussed in the appropriate sections below. Impaired hepatobiliary excretion was found in 

intermediate-duration exposure studies (Curtis and Mehendale 1979; Curtis et al. 1979b; Mehendale 

1981b), in addition to inhibition of exogenous taurocholate (Curtis and Hoyt 1984) and 

histopathological findings (Cannon and Kimbrough 1979; Chu et al. 1980a; Curtis et al. 1979b, 1981; 

Huber 1965; Larson et al. 1979b). An intermediate-duration MRL of 0.0005 mg/kg/day was derived 

for oral exposure to chlordecone based on a NOAEL of 0.05 mg/kg/day for histopathological evidence 

of renal damage from the Larson et al. (1979b) study in rats. Thyroid ultrastructure was altered after 

intermediate-duration exposure (Chu et al. 1981a, 1981b; NTP 1990; Singh et al. 1982, 1985); this 

effect was reversible after discontinuation of the exposure. Although few studies are available, 

decreased adrenal lipid (Larson et al. 1979b) and increased lipid utilization, possibly mediated by 

corticosterone (Fujimori et al. 1983; Klingensmith and Mehendale 1982a; Mehendale et al. 1977a, 

1978b), occurred. Decreased body weight was also observed, perhaps by a similar mechanism 

(Cannon and Kimbrough 1979; Curtis and Mehendale 1979; Fabacher and Hodgson 1976; Larson et al. 

1979b; Klingensmith and Mehendale 1982a; Mehendale et al. 1977a, 1978b; Pryor et al. 1983). 

Limited data were located regarding the cardiovascular effects of chlordecone; vasodilation has been 

measured and may have been associated with thermoregulation (Larson et al. 1979b). No renal 

toxicity was found after intermediate-duration oral exposure to chlordecone (Agarwal et al. 1983; 

Larson et al. 1979b). The musculoskeletal effects observed in acute-duration exposures were not 

found in histopathological examination of skeletal muscle from intermediate-duration exposures 

(Larson et al. 1979b). It is unknown if the lower dose or some other factor contributed to the lack of 

an effect. 

Further human data should be gathered for intermediate-duration exposure to chlordecone by all routes. 

Human data were either absent (gastrointestinal, hematological, or renal effects) or limited to a 

population study with major restrictions (Cannon et al. 1978; Guzelian 1982a; Landngen et al. 1980; 

Martinez et al. 1978; Sanbom et al. 1979; Taylor 1982, 1985; Taylor et al. 1978). The toxicity of 

chlordecone after intermediate-duration exposure in animals is absent for inhalation and dermal routes. 

Additional information for this duration of exposure would be useful. Additional dermal studies are 

certainly necessary because skin absorption of chlordecone appears to be an important route of 
 

 

MIREX AND CHLORDECONE 173 

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exposure (Taylor et al. 1978). However, populations at hazardous waste sites are unlikely to be 

exposed via inhalation since these substances are virtually nonvolatile, so future studies using this 

route of exposure are not essential. 

Chronic-Duration Exposure and Cancer. No information is available regarding the toxicity of 

chronic-duration exposure of humans to mirex by the inhalation or dermal route of administration. 

Animal studies have not been located for chronic mirex administration by the inhalation or dermal 

routes; however, oral studies exist (Chu et al. 1981a; Gaines and Kimbrough 1970; NTP 1990; Ulland 

et al. 1977a; Wolfe et al. 1979). Chronic exposure to mirex by the oral route results in mortality in 

animals, especially at higher doses and for longer durations (NTP 1990; Wolfe et al. 1979). The 

major target organs for mirex after chronic-duration exposures appear to be the kidney, nervous 

system, reproductive system, liver, cardiovascular system, and thyroid. Although acute- and 

intermediate-duration exposures to mirex are without renal effects, chronic-duration exposure results in 

kidney toxicity. Sufficient data exist to speculate that the kidney is a primary site of mirex toxicity. 

Nephrotoxicity as characterized by histological changes (necrosis, nephritis) was documented (NTP 

1990). Chronic-duration exposures to mirex have been shown to increase excitability, hypoactivity, 

irritability, and tremors in treated rats (Chu et al. 1981a), as was found in shorter-term oral exposures. 

Reproductive effects of chronic-duration mirex exposure included cataract formation and decreased 

survivol in offspring (Gaines and Kimbrough 1970), and inhibition of reproduction (Wolfe et al. 1979). 

No data were located regarding the hepatobiliary effects of chronic-duration mirex administration, but 

histopathological examination of chronic exposure studies revealed hepatic necrosis (NTP 1990; Ulland 

et al. 1977a). Thyroid effects (histopathological) occurred in chronic-duration exposure to mirex (Chu 

et al. 1981c; NTP 1990). Several intermediate-duration studies in rats also indicate that the thyroid is 

a target organ for mirex toxicity (Chu et al. 1981a, 1981b; Singh et al. 1982, 1985). These studies 

showed reduced colloid, thickening of the follicular epithelium, angular collapse of the follicles, and 

dilation of the rough endoplasmic reticulum of thyroid cells at 0.25 mg/kg/day for 28 days. A 

chronic-duration oral MRL was derived using a NOAEL for hepatic, renal, and thyroid toxicity in a 

2-year feeding study in rats (NTP 1990). This is supported by data from other studies (Chu et al. 

1981c; Fulfs et al. 1977; Ulland et al. 1977a) that indicated that the liver and kidney were target 

organs following chronic-duration exposure to mirex. Reproductive toxicity was tested at doses higher 

than the NOAEL from this study, and only less serious effects (nonsignificant decrease in litter size) 

were observed (Wolfe et al. 1979). No chronic-duration inhalation MRL was derived for mirex 

because no data could be located for this duration and route. No reports could be located that 
 

MIREX AND CHLORDECONE 174 

2. HEALTH EFFECTS 

addressed the effects of chronic-duration exposure to mirex regarding gastrointestinal, hematological, 

musculoskeletal, dermal, or adrenal toxicity. Well-conducted studies in animals to evaluate these end 

points for mirex following acute- and intermediate-duration inhalation, oral, and dermal exposures 

would be helpful. As with the shorter duration exposures, monitoring humans who are chronically 

exposed to mirex by any route would be useful. 

The only information available for humans exposed to chlordecone pertains to the intermediate-tochronic 

occupational exposure study previously discussed in the intermediate-duration section (see the 

above section for a description of intermediate-to-chronic toxicity of chlordecone in humans). These 

studies are limited in usefulness because the exposures were to more than one substance in a facility 

where exposure by all routes was likely (Cannon et al. 1978; Taylor 1982, 1985). These and other 

available human studies described respiratory (Cannon et al. 1978; Landngen et al. 1980; Sanborn et 

al. 1979), hepatic (Guzelian 1982a; Guzelian et al. 1980; Landngen et al. 1980), renal (Larson et al. 

1979b), musculoskeletal (Landngen et al. 1980; Martinez et al. 1978; Taylor 1982, 1985), dermal 

(Cannon et al. 1978; Landngen et al. 1980), body weight (Cannon et al. 1978), neurological (Cannon 

et al. 1978; Landngen et al. 1980; Martinez et al. 1978; Sanborn et al. 1979; Taylor 1982, 1983, and 

reproductive (Cannon et al. 1978; Guzelian 1982a; Landngen et al. 1980; Taylor 1982, 1985) effects 

following chronic exposure to chlordecone. There are no inhalation or dermal data for chronicduration 

exposure to chlordecone in animals; however, there are a few oral studies (Larson et al. 

1979b; NCI 1976). Two chronic-duration animal studies exist that present survivol data (Larson et al. 

1979b; NCI 1976). Effects on mortality after inhalation or dermal exposure cannot be evaluated due 

to the lack of information. The target organs of chronic-duration oral exposure appear to be the 

kidney, nervous system, and male reproductive system. Like mirex, chlordecone caused significant 

renal toxicity only for chronic-duration oral exposures. Renal histopathological changes (eosinophilic 

inclusions, glomernlosclerosis) and increased urinary protein excretion occurred in rats (Larson et al. 

1979b). Other available human studies described hematological (Larson et al. 1979b; NCI 1976), 

hepatic (Larson et al. 1979b; NCI 1976), renal (Larson et al. 1979b), dermal (NCI 1976), body weight 

(Chu et al. 1981c; Larson et al. 1979b), neurological (Larson et al. 1979b; NCI 1976), reproductive 

(NCI 1976), endocrine (Chu et al. 1981c), and cancer (NCI 1976) effects following chronic exposure 

to chlordecone. A chronic-duration MRL of 0.0005 mg/kg/day was derived for oral exposure to 

chlordecone based on a NOAEL of 0.05 mg/kg/day for histopathological evidence of renal damage 

from the Larson et al. (1979b) study in rats. There may be a difference in species sensitivity because 

chronically exposed dogs did not have renal effects (Larson et al. 1979b). The neurotoxicity of 
 

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2. HEALTH EFFECTS 

chlordecone (e.g., exaggerated startle response) has been documented after chronic-duration exposure 

(Larson et al. 1979b). Testicular atrophy has been reported in dogs (Larson et al. 1979b). Limited 

data could be located regarding respiratory effects of chronic-duration oral exposure to chlordecone; 

routine histopathology in a few animal samples revealed no adverse lung effects in two species 

(Larson et al. 1979b). Similar examination of heart and gastrointestinal tissues in this study did not 

reveal adverse effects (Larson et al. 1979b). An independent review of the histopathological evidence 

from the cancer bioassay tissues reported polyarteritis in arteries and arterioles; however, no data were 

presented to support these conclusions (Reuber 1979b). Hematological effects were not found in one 

chronic-duration study in rats and dogs (Larson et al. 1979b). An independent review of this study 

reported anemia; however, no data were presented to support this conclusions (Reuber 1979b). Body 

weight was found to decrease, with concomitantly increased food consumption (Larson et al. 1979b). 

This indicated a decreased food efficiency. No adverse histopathological effects were reported on 

musculoskeletal, hepatic, or dermal tissues after oral exposure to mirex for 2 years (Larson et al. 

1979b). Data from laboratory animals indicate that chronic exposure to chlordecone adversely affects 

the thyroid gland (Chu et al. 1981c). No chronic-duration inhalation MRL was derived because of the 

absence of reliable data following inhalation exposure to chlordecone. Additional studies would be 

helpful to verify the effects seen in the existing studies. Additional dermal studies are certainly 

necessary because skin absorption of chlordecone appears to be an important route of exposure (Taylor 

et al. 1978). However, populations at hazardous waste sites are unlikely to be exposed via inhalation 

since these substances are virtually nonvolatile, so future studies using this route of exposure are not 

essential. 

No evidence for carcinogenicity in exposed humans was found in the available literature. Animal 

studies provide sufficient evidence that mirex and chlordecone are carcinogenic after oral exposure 

(Innes et al. 1969; NTF’ 1990; NCI 1976; Reuber 1978a, 1979b, 1979c; Ulland et al. 1977a). 

Carcinogenic potential has not been tested by the inhalation or dermal routes. Effects after inhalation 

exposure are unlikely because of low volatility. A carcinogenicity study in animals exposed by the 

dermal route would be desirable but comparison of steady-state levels of the chemicals in rat liver 

after repeated dermal or oral exposure may suffice to extrapolate to likely carcinogenicity concern by 

dermal exposure. Evidence suggests that chlordecone and mirex are epigenetic carcinogens (see the 

section on Genotoxicity below), and a two-stage initiation-promotion study in rats provides strong 

evidence for liver tumor promotion activity of chlordecone (Sirica et al. 1989). A similar evaluation 
 

 

 

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of mirex including measurement of levels of mirex in the liver at carcinogenic doses would allow 

comparisons and would be useful to elucidate mechanism of action and possible relevance to humans. 

Genotoxicity. Although neither mirex nor chlordecone have been extensively evaluated in in vivo 

or in vitro genetic toxicology test systems, the existing studies provide convincing evidence that 

neither compound is genotoxic. Both compounds were negative in microbial (Mortelmans et al. 1986; 

Probst et al. 1981; Schoeny et al. 1979) and mammalian cell (Tong et al. 1981; Williams 1980) gene 

mutation assays, and neither compound showed signs of clastogenesis in male rats in well-conducted 

dominant lethal assays (Khera et al. 1976; Simon et al. 1986). Further genetic toxicology testing 

would be unlikely to provide additional useful information. However, data from a metabolic 

cooperation assay (Tsushimoto et al. 1982) and a dye-transfer assay (Caldwell and Loch-Caruso 1992) 

indicate that mirex and chlordecone interfere with cell-to-cell communication, a characteristic of many 

tumor promoters. Chlordecone has been shown to be a tumor promoter in vivo (Sirica et al. 1989); 

however, a more comprehensive evaluation is necessary to determine the level at which no in vivo 

promotion occurs. A similar experiment should be conducted with mirex to confirm suspected tumor 

promoting activity and to ascertain the threshold level for promotion. Finally, the evidence suggesting 

that mirex selectively reduces the proportion of rat tetraploid hepatocytes (Abraham et al. 1983) and 

preferentially binds to mouse polyploid hepatocytes in vitro (Rosenbaum and Charles 1986) should be 

investigated further. Similar assays involving alterations in ploidy of rodent hepatocyte populations 

should be undertaken with chlordecone. Information regarding effects on normal hepatic cell ploidy in 

animals may provide important clues regarding the mechanism(s) for the epigenetic/promoter activity 

of mirex and/or chlordecone, and perhaps suggest a target subpopulation of cells. However, it is 

emphasized that the population of hepatocytes that appear to be at risk (tetraploids) occurs in human 

livers at an exceedingly low frequency (Adler et al. 1981), so the relevance to human health of effects 

on ploidy is not clear. 

Reproductive Toxicity. Studies in humans have attempted to correlate blood levels of 

chlordecone with the severity of loss of sperm motility (Guzelian 1982a; Taylor 1982, 1985; Taylor et 

al. 1978); however, these studies are limited by the lack of quantification of airborne concentrations of 

chlordecone, failure to examine the changes in sperm morphology, and a lack of control for 

confounding variables. No other human data regarding reproductive effects of chlordecone and mirex 

were located. Therefore, well-controlled epidemiological studies would be useful. Studies in 

laboratory animals exposed orally to chlordecone have demonstrated reproductive effects similar to 
 

MIREX AND CHLORDECONE 177 

2. HEALTH EFFECTS 

those produced by mirex in animals. Oral administration of these compounds decreased the fertility or 

fecundity and litter size, reduced the sperm count, and caused testicular atrophy in animals (Khera et 

al. 1976; Linder et al. 1983; Uzodinma et al. 1984a; Yarbrough et al. 1981). In a study performed in 

rabbits, dermal application of chlordecone produced testicular atrophy (Epstein 1978); however, the 

study was limited because of lack of dose response. No other studies in animals were found regarding 

reproductive effects of chlordecone or mirex via inhalation or dermal routes. Thus, studies examining 

effects on reproduction by these routes would be useful. Additional dermal studies are certainly 

necessary because skin absorption of chlordecone appears to be an important route of exposure (Taylor 

et al. 1978). However, populations at hazardous waste sites are unlikely to be exposed via inhalation 

since these substances are virtually nonvolatile, so future studies using this route of exposure are not 

essential. Studies conducted by the parenteral routes of exposure indicate that mirex is stable in the 

biological system. Animal studies performed via parenteral routes have demonstrated the estrogenic 

effects of chlordecone in female rats and mice (Eroschenko and Mousa 1979; Gellert 1978; Hammond 

et al. 1978; Johnson et al. 1992). The mechanism involving interaction with estrogen receptors has 

been postulated (Huber 1965). Additional studies would be useful in elucidating the mechanism of 

action of chlordecone. Mirex is not uterotropic in rats (Hammond et al. 1979); however, it has a 

potential to degrade to chlordecone in nature (Carlson et al. 1976). Therefore, studies examining the 

estrogenic effects of mirex would be useful. 

Developmental Toxicity. No human studies are available on developmental effects of 

chlordecone or mirex in humans for any exposure route. Similarly, no studies are available for 

animals via the inhalation or dermal routes. Placental transfer and lactational transfer of chlordecone 

have been demonstrated in mice after oral exposure, though in a very limited number of animals 

(Huber 1965). Developmental effects of chlordecone and mirex via oral exposure have been well 

documented in animals (Buelke-Sam et al. 1983; Chernoff and Kavlock 1973; Chernoff et al. 1979a, 

1979b; Grabowski 1983a; Gray and Kavlock 1984; Kavlock et al. 1982; Swartz et al. 1988). 

Therefore, additional studies via inhalation and dermal routes would be useful to examine the postnatal 

developmental effects of prenatal exposure to chlordecone and mirex. Additional dermal studies are 

certainly necessary because skin absorption of chlordecone appears to be an important route of 

exposure (Taylor et al. 1978). However, populations at hazardous waste sites are unlikely to be 

exposed via inhalation since these substances are virtually nonvolatile, so future studies using this 

route of exposure are not essential. 
 

MIREX AND CHLORDECONE 178 

2. HEALTH EFFECTS 

Immunotoxicity. No information is available regarding immunological effects of mirex or 

chlordecone in humans following inhalation, oral, or dermal exposures. The only information about 

the immunological effects of mirex exposure in animals was provided by one acute oral study in rats 

in which decreased spleen weight was reported (Buelke-Sam et al. 1983). Oral chlordecone treatment 

caused decreased spleen and thymus weights, leukocyte counts, natural killer cell activity, and 

mitogenic responsiveness (EPA 1986c; Smialowicz et al. 1985; Swanson and Wooley 1982); decreased 

natural killer cell activity (Smialowicz et al. 1985); and significant increase in plaque-forming cells 

(Chetty et al. 1993c). Consequently, there is a need for confirmatory information on whether these 

chemicals affect cell-mediated and/or humoral immunity in humans. Skin absorption of chlordecone 

appears to be an important route of exposure (Taylor et al. 1978). Therefore, dermal sensitization tests 

done on exposed workers would provide information on the likelihood of an allergic response in 

humans following chlordecone exposure. An indication for this testing is the development of skin 

rashes in workers who worked in chlordecone-manufacturing plants (Cannon et al. 1978; Taylor 1982; 

Taylor et al. 1978). As with many of the occupational exposure studies, the routes of exposure, dose, 

and duration were not precisely defined in these studies. 

No studies were located that examined the immunotoxicity of mirex in experimental animals. The 

information available from one acute study in rats indicates that the immune system is not a target of 

chlordecone toxicity. There is a need for information from animal model systems on cell-mediated 

and humoral immunity following inhalation, oral, and dermal exposures to mirex and chlordecone. 

The results from these studies would help elucidate whether there are thresholds of chlordecone 

immunotoxicity after acute, intermediate, and chronic exposures via these routes. 

Diethylstilbestrol, a nonsteroidal compound with estrogenic activity, has been shown to suppress 

immune responsiveness in a number of experiments (Dean et al. 1980). The immunosuppression is 

suggested to be mediated, at least in part, through interactions with estrogen receptors on thymic 

epithelial and lymphoid cells. Chlordecone has been shown to interact with estrogen receptors (Bulger 

et al. 1979; Hammond et al. 1979) and to mimic estrogen in a number of reproductive parameters; 

therefore, it is possible that chlordecone may also adversely affect immune function. Studies designed 

to test this hypothesis would be useful. 
 

MIREX AND CHLORDECONE 179 

2. HEALTH EFFECTS 

Neurotoxicity. Information on the neurotoxicity of mirex in humans following exposure by the 

inhalation, oral, or dermal routes was not located. Several reports regarding a single group of workers 

exposed to chlordecone during its manufacture noted a high incidence of nervous system toxicity 

(Cannon et al. 1978; Martinez et al. 1978; Sanbom et al. 1979; Taylor 1982, 1985; Taylor et al. 1978). 

Exposure of this population occurred by a combination of inhalation, oral, and dermal exposures, 

although the dermal route was suggested to be the predominant route. The toxicity was manifested as 

tremors, visual difficulties, muscle weakness, gait ataxia, incoordination, headache, and increased 

cerebrospinal fluid pressure. A few studies indicate that ingestion of mirex may also cause tremors, 

hyperexcitability, and/or convulsions (Chu et al. 1981a; Gaines and Kimbrough 1970; Kendall 1974a; 

Larson et al. 1979a). Studies directed at examining the mechanism of mirex-induced neurotoxicity 

would be helpful for determining whether mirex is acting by a mechanism similar to chlordecone. 

Several studies in animals have been undertaken in an attempt to elucidate the mechanism underlying 

the effects observed (Aronstam and Hong 1986; Bansal and Desaiah 1982; Bloomquist et al. 1986; 

Bondy and Halsall 1988; Bondy and McKee 1990; Bondy et al. 1989; Chetty et al. 1983b; Desaiah 

1981, 1985; Desaiah et al. 1980a, 1980b, 1991; End et al. 1979, 1981; Folmar 1978; Gerhart et al. 

1982, 1983; Herr et al. 1987; Hong et al. 1984, 1986; Hwang and Van Woert 1979; Jinna et al. 1989; 

Kodavanti et al. 1988, 1989c; Komulainen and Bondy 1987; Mishra et al. 1980; Singh et al. 1984; 

Tilson et al. 1985, 1986b; Vig et al. 1990b, 1991). However, the precise neurotoxic mechanism of 

chlordecone remains unclear. Additional toxicokinetic studies directed at assessing the mechanism of 

neurotoxicity of chlordecone would be helpful for the development of treatment strategies. 

Epidemiological and Human Dosimetry Studies. No epidemiological studies are available for 

mirex exposure. Individuals living in areas that have been treated for fire ants or near hazardous 

waste sites containing mirex or chlordecone are the most likely exposed subpopulation because of the 

relatively long half-lives of these substances-estimated half-life of 10 years-(Carlson et al. 1976; 

La1 and Saxena 1982). A single epidemiological cohort was located for occupational exposure to 

chlordecone (Cannon et al. 1978; Guzelian et al. 1980; Sanbom et al. 1979; Taylor 1982, 1985). The 

routes of exposure in this study were probably mixed because of the poor hygiene in the chlordecone 

manufacturing plant (Taylor 1982, 1985). The most likely identifiable subpopulation exposed to 

chlordecone would be individuals who live in the Hopewell, Virginia, vicinity who may consume 

wildlife in which the chemical is bioconcentrated. Well-designed epidemiological studies of these 

subpopulations specifically examining neurological, hepatic, reproductive, developmental, 
 

 

 

MIREX AND CHLORDECONE 180 

2. HEALTH EFFECTS 

thyroid, and musculoskeletal toxicity and carcinogenicity would be useful to verify effects seen in the 

limited human and animal studies. 

Biomarkers of Exposure and Effect 

Exposure. The biomarkers of exposure to mirex and chlordecone are well established and specific to 

each compound. The known biomarkers of exposure to mirex are mirex concentrations in blood, fat, 

feces, and milk (Burse et al. 1989; Byrd et al. 1982; Chambers et al. 1982; Dorough and Ivie 1974; 

Gibson et al. 1972; Ivie et al. 1974b; Kavlock et al. 1980; Kutz et al. 1974; Smrek et al. 1977; Wiener 

et al. 1976). All these biological materials are useful and can be monitored to determine the acute, 

intermediate, and chronic exposures to mirex. The known biomarkers of exposure for chlordecone 

include chlordecone concentrations in blood, saliva, and tissues, and concentrations of chlordecone or 

its metabolite in feces or bile (Borzelleca and Skalsky 1980; Bungay et al. 1981; Cannon et al. 1978; 

Cohn et al. 1978; Egle et al. 1978; Guzelian et al. 1981; Hewitt et al. 1986b; Skalsky et al. 1980; Plaa 

et al. 1987; Taylor 1982, 1985). Of the biomarkers of exposure listed for chlordecone, the blood is 

the most useful biological material to monitor in order to determine acute, intermediate, and chronic 

exposure to chlordecone. No relationship has been established between mirex or chlordecone exposure 

levels, levels of mirex or chlordecone in the biological fluids, and their associated health effects for all 

exposure durations. Data identifying the correlations between these parameters would be useful. 

Effect. Several potential biomarkers for the effects of mirex and chlordecone have been identified. 

These include levels of urinary D-glucaric acid to measure hepatic enzyme induction, elevated urinary 

protein and renal histopathology to assess renal damage, electromyography and tremorograms to assess 

tremor, oculography to measure visual disturbances, and sperm counts and tests of motility to assess 

toxic effects on sperm (Guzelian 1985; Larson et al. 1979b; Taylor et al. 1978). However, these 

biomarkers are not specific for either mirex or chlordecone. Measurement of serum bile acids may be 

helpful in assessing hepatobiliary function after exposure to chlordecone. Examination of this 

possibility and further investigation of other serum biomarkers of effect in populations exposed to 

mirex or chlordecone would be helpful. 
 

 

 

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Absorption, Distribution, Metabolism, and Excretion. No data were located regarding 

absorption of mirex in humans following inhalation, oral, or dermal exposure. Limited 

epidemiological data were located regarding the distribution and excretion of mirex following 

inhalation, oral, and dermal exposure (Burse et al. 1989; Kutz et al. 1974; Mes et al. 1978). Mirex is 

not metabolized by humans or animals (Dorough and Ivie 1974; Gibson et al. 1972; Kutz et al. 1974; 

Mehendale et al. 1972; Morgan et al. 1979). There are a number of animal studies describing 

absorption, distribution, metabolism, and excretion of mirex following oral exposure (Brown and 

Yarbrough 1988; Byrd et al. 1982; Chambers et al. 1982; Gibson et al. 1972; Ivie et al. 1974b; 

Kavlock et al. 1980; Mehendale et al. 1972; Morgan et al. 1979; Plaa et al. 1987; Smrek et al. 1977; 

Wiener et al. 1976). Information is available to assess the relative rates and extent of these 

toxicokinetic parameters by the oral route. Based on the available data, saturation phenomena do not 

appear to affect absorption, distribution, metabolism, or excretion of mirex. Most of the toxicokinetic 

data, however, involve acute exposures to mirex; only very limited data deal with intermediate or 

chronic exposures. Additional intermediate and chronic data are needed in order to adequately assess 

the rates and extent of the toxicokinetic parameters for these durations. Limited animal data were 

located regarding the absorption, distribution, and excretion of mirex following inhalation exposure 

(Atallah and Dorough 1975; Dorough and Atallah 1975). More acute, intermediate, and chronic data 

are needed to adequately assess the relative rates and extent of the toxicokinetic parameters by this 

route. No animal data were located for the toxicokinetic parameters by the dermal exposure route. 

Limited occupational data exist regarding absorption, distribution, metabolism, and excretion of 

chlordecone by humans following all three routes of exposure (Adir et al. 1978; Blanke et al. 1978; 

Boylan et al. 1978; Cannon et al. 1978; Cohn et al. 1978; Guzelian et al. 1981; Taylor 1982, 1985). 

There are a number of animal studies describing the absorption, distribution, metabolism, and excretion 

of chlordecone following oral exposure (Blanke et al. 1978; Borzelleca and Skalsky 1980; Boylan et 

al. 1979; Cohn et al. 1978; Egle et al. 1978; Fujimori et al. 1982a; Guzelian et al. 1981; Hewitt et al. 

1986b; Kavlock et al. 1980; Plaa et al. 1987; Richter et al. 1979; Skalsky et al. 1980; Wang et al. 

1981). Most of these data concern acute exposures. However, the available data are sufficient to 

assess the relative rates and extent of the pharmacokinetics following oral exposure. Dermal 

absorption does occur, but to a limited extent (Hall et al. 1988; Shah et al. 1987). No studies were 

located regarding distribution, metabolism, or excretion following dermal exposure. No animal data 

were located regarding absorption, distribution, metabolism, or excretion of chlordecone following 
MIREX AND CHLORDECONE 182 

2. HEALTH EFFECTS 

inhalation exposure. Additional data (acute, intermediate, and chronic) for both humans and animals 

are needed to adequately compare the toxicokinetic parameters across all routes of exposure. 

Comparative Toxicokinetics. The absorption, distribution, metabolism, and excretion of mirex 

have been studied in animals (Atallah and Dorough 1975; Brown and Yarbrough 1988; Byrd et al. 

1982; Chambers et al. 1982; Dorough and Atallah 1975; Gibson et al. 1972; Ivie et al. 1974b; Kavlock 

et al. 1980; Mehendale et al. 1972; Morgan et al. 1979; Plaa et al. 1987; Smrek et al. 1977; Wiener et 

al. 1976). However, information on the toxicokinetics of mirex in humans is very limited (Burse et al. 

1989; Kutz et al. 1974; Mes et al. 1978). The target organs identified in animals include the liver, 

kidney, eyes, thyroid, reproductive tract, and fetus. Since the human data are so limited, no target 

organs have been identified. Therefore, no comparisons can be made between humans and animals at 

this time. Based on the available data in both humans and animals, mirex accumulates and is retained 

in the tissues, particularly in the fat. It is not metabolized and is slowly excreted in the feces. 

Limited information is available regarding interspecies differences in kinetics. Most of the 

toxicokinetic studies have been conducted using rats. A few studies using monkeys, goats, and cows 

yielded similar results. Therefore, based on the available data, humans would be expected to handle 

mirex similarly (i.e., they would probably have similar target organs). 

The absorption, distribution, metabolism, and excretion of chlordecone have been studied in animals 

(Blanke et al. 1978; Borzelleca and Skalsky 1980; Boylan et al. 1979; Cohn et al. 1978; Egle et al. 

1978; Fariss et al. 1980; Fujimori et al. 1982a; Guzelian et al. 1981; Hall et al. 1988; Hewitt et al. 

1986b; Kavlock et al. 1980; Plaa et al. 1987; Richter et al. 1979; Shah et al. 1987; Skalsky et al. 1980; 

Wang et al. 1981). However, information on the toxicokinetics of chlordecone in humans is limited 

(Adir et al. 1978; Blanke et al. 1978; Boylan et al. 1978; Cannon et al. 1978; Cohn et al. 1978; 

Guzelian et al. 1981; Taylor 1982, 1985). Human and animal data indicate similar target organs (liver, 

central nervous system, reproductive system) for the toxic effects of chlordecone, suggesting some 

similarities of kinetics. Appropriate assessment of potential adverse human health consequences of 

chronic exposure to chlordecone in the environment should take into account interspecies differences 

in chlordecone metabolism (Guzelian et al. 1981). Toxicokinetic studies have been performed on 

multiple species. Based on the available data, rats, guinea pigs, and hamsters are not good animal 

models for studying chlordecone metabolism in humans because they do not convert chlordecone to 

chlordecone alcohol (Fariss et al. 1980; Guzelian et al. 1981; Houston et al. 1981). On the other hand, 

gerbils and pigs were found to be the most practical animal models of chlordecone metabolism in 
 

MIREX AND CHLORDECONE 183 

2. HEALTH EFFECTS 

humans because they converted chlordecone to chlordecone alcohol (Houston et al. 1981; Soine et al. 

1983). 

Methods for Reducing Toxic Effects. Methods used to reduce absorption immediately after 

exposure to mirex and chlordecone include removal from the source of exposure; cleansing of 

contaminated parts; and in cases of ingestion, speeding the removal of the unabsorbed material from 

the gastrointestinal tract (Haddad and Winchester 1990; HSDB 1994a, 1994b; Morgan et al. 1979). 

Chlordecone and chlordecone alcohol, which are excreted mainly in the feces, undergo enterohepatic 

recirculation, which limits their excretion (Boylan et al. 1978). Because of this, detoxification has 

focused on limiting reabsorption of chlordecone from the gastrointestinal tract using cholestyramine 

(Boylan et al. 1978; Cohn et al. 1978), liquid paraffin (Richter et al. 1979), chlorella, and chlorelladerived 

sporopollenin (Pore 1984). Since cholestyramine did not interact with chlordecone alcohol 

(Guzelian 1981), other anion exchange resins or test compounds that bind to chlordecone alcohol need 

to be further investigated. No information was available to indicate that mirex undergoes 

enterohepatic recirculation; therefore, it is not known whether use of these therapies would be effective 

in reducing absorption of mirex. Studies investigating whether mirex undergoes enterohepatic 

recirculation are needed to determine if the three therapies listed above would be effective in reducing 

absorption. Since mirex and chlordecone have long retention times in the body and are only slowly 

excreted, studies aimed at reducing body burden would be useful. Additional studies directed toward 

developing effective therapies for blocking the neurotoxicity of chlordecone would be helpful, but the 

development of such therapies may be dependent on a more complete understanding of the mechanism 

for neurotoxicity than are currently available. Use of antibodies to block the effects of mirex and 

chlordecone in vivo should be examined further, either to develop antibodies that are well tolerated, or 

to more closely study the interaction that blocks the effects and develop drugs based on that 

interaction. 

2.9.3 Ongoing Studies 

No ongoing studies regarding the health effects of mirex and/or chlordecone were found. 

MIREX AND CHLORDECONE 185 

3. CHEMICAL AND PHYSICAL INFORMATION 

3.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of mirex and chlordecone is located in Table 3-l. 

3.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of mirex and chlordecone is located in 

Table 3-2. 



 

MIREX AND CHLORDECONE 189 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
 

4.1 PRODUCTION 

Mirex is not known to occur in the environment as a natural product (IARC 1979c; Waters et al. 

1977b). Although it was originally synthesized in 1946, mirex was not commercially introduced in the 

United States until 1959, when it was produced by the Allied Chemical Company under the name 

GC-1283 for use in pesticide formulations and as an industrial fire retardant under the trade name 

Dechlorane® (EPA 1978b; IARC 1979c; Waters et al. 1977b). Mirex was produced as a result of the 

dimerization of hexachlorocyclopentadiene in the presence of an aluminum chloride catalyst (IARC 

1979c; Sittig 1980). 

The technical grade of mirex consisted of a white crystalline solid in two particle size ranges, 5-10 

and 40-70 microns (IARC 1979c). Technical grade preparations of mirex contained 95.18% mirex, 

with 2.58 mg/kg chlordecone as a contaminant (EPA 1978b; WHO 1984a). Several formulations of 

mirex have been prepared in the past for various pesticide uses. Some of the more commonly used 

formulations of mirex used as baits were made from corn cob grit impregnated with vegetable oil and 

various concentrations of mirex. Insect bait formulations for aerial or ground applications contained 

0.3-0.5% mirex, and fire ant formulations contained 0.075-0.3% mirex (IARC 1979c). 

Mirex is no longer produced commercially in the United States. Hooker Chemical Company (Niagara 

Falls, New York) manufactured and processed mirex from 1957 to 1976 (Lewis and Makarewicz 

1988). An estimated 3.3 million pounds (1.5x106

 kg) of mirex were produced by Hooker Chemical 

Company between 1959 and 1975, with peak production occurring between 1963 and 1968 (EPA 

1978b). About 25% of the mirex produced was used as a pesticide and the remaining 75% was used 

as an industrial fire retardant additive (EPA 1978b). Hooker Chemical Company reported purchasing 

1.5 million pounds of mirex (680,400 kg) from Nease Chemical Company during this period. The 

Nease Chemical Company of State College, Pennsylvania, manufactured mirex from 1966 to 1974 

(EPA 1978b). Allied Chemical Company also manufactured technical grade mirex and mirex bait in 

Aberdeen, Mississippi (EPA 1978b), but Allied Chemical formally transferred all registrations on 

mirex, along with the nght to manufacture and sell mirex bait, to the Mississippi Department of 

Agriculture on May 7, 1976 (IARC 1979c; Waters et al. 1977a, 1977b). 
 

MIREX AND CHLORDECONE 190 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Chlordecone is not known to occur in the environment as a natural product (IARC 1979a). 

Chlordecone has been produced by reacting hexachlorocyclopentadiene and sulfur trioxide under heat 

and pressure in the presence of antimony pentachloride as a catalyst. The reaction product is 

hydrolyzed with aqueous alkali, neutralized with acid; chlordecone is recovered via centrifugation or 

filtration and hot air drying (Epstein 1978). Chlordecone was produced in 1951, patented in 1952, and 

introduced commercially in the United States by Allied Chemical in 1958 under the trade names 

Kepone® and GC-1189 (Epstein 1978; Huff and Gerstner 1978). The technical grade of chlordecone, 

which typically contained 94.5% chlordecone, was available in the United States until 1976 (IARC 

1979a). Chlordecone was also found to be present in technical grade mirex at concentrations of up to 

2.58 mg/kg and in mirex bait formulations at concentrations of up to 0.25 mg/kg (EPA 1978b; IARC 

1979a). 

Approximately 55 different commercial formulations of chlordecone have been prepared since its 

introduction in 1958 (Epstein 1978). The major form of chlordecone, which was used as a pesticide 

on food products, was a wettable powder (50% chlordecone) (Epstein 1978). Formulations of 

chlordecone commonly used for nonfood products were in the form of granules and dusts containing 

5% or 10% active ingredient (Epstein 1978). Other formulations of chlordecone contained the 

following percentages of active ingredient: 0.125% (used in the United States in ant and roach traps), 

5% (exported for banana and potato dusting), 25% (used in the United States in ant and roach bait), 

50% (used to control mole crickets in Florida), and 90% (exported to Europe for conversion to kelevan 

for use on Colorado potato beetles in eastern European countries) (Epstein 1978). 

Chlordecone is no longer produced commercially in the United States. Between 1951 and 1975, 

approximately 3.6 million pounds (1.6 million kg) of chlordecone were produced in the United States 

(Epstein 1978). During this period, Allied Chemical Company produced approximately 1.8 million 

pounds (816,500 kg) of chlordecone at plants in Claymont, Delaware; Marcus Hook, Pennsylvania; 

and Hopewell, Virginia. In 1974, because of increasing demand for chlordecone and a need to use 

their facility in Hopewell, Virginia, for other purposes, Allied Chemical transferred its chlordecone 

manufacturing to Life Sciences Products Company (EPA 1978b). Life Sciences Products produced an 

estimated 1.7 million pounds (771,000 kg) of chlordecone from November 1974 through July 1975 in 

Hopewell, Virginia (Epstein 1978). Hooker Chemical Company also produced approximately 49,680 

(22,500 kg) pounds of chlordecone in the period from 1965 to 1967 at a plant at Niagara Falls, New 

York. Nease Chemical Company produced approximately 65,780 pounds (30,000 kg) of chlordecone 

between 1959 and 1966 at a plant in State College, Pennsylvania (Epstein 1978). 
 

 

MIREX AND CHLORDECONE 191 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

4.2 IMPORT/EXPORT 

No current data are available regarding import volumes of mirex. Mirex has reportedly been imported 

to the United States from Brazil, but data on the amounts of mirex imported are not available (DHHS 

1985; IARC 1979c). 

No current data are available regarding import volumes of chlordecone. 

Technical mirex and technical chlordecone are not exported since these substances are no longer 

produced in the United States. 

Over 90% of the mirex produced from the 1950s until 1975 was exported to Latin America, Europe, 

and Africa (Sterret and Boss 1977). No other historic data regarding the export of mirex were located. 

Diluted technical grade chlordecone (80% active ingredient) was exported to Europe, particularly 

Germany, in great quantities from 1951 to 1975 by the Allied Chemical Company (Epstein 1978) 

where the diluted technical product was converted to an adduct, kelevan. Approximately 90-99% of 

the total volume of chlordecone produced during this time was exported to Europe, Asia, Latin 

America, and Africa (DHHS 1985; EPA 1978b). 

4.3 USE 

Because it is nonflammable, mirex was marketed primarily as a flame retardant additive in the United 

States from 1959 to 1972 under the trade name Dechlorane® for use in various coatings, plastics, 

rubber, paint, paper, and electrical goods (EPA 1978b; IARC 1979c; Kutz et al. 1985; Merck 1989; 

Verschueren 1983). Mirex was most commonly used in the 1960s as an insecticide to control the 

imported fire ants (Solenopsis invicta and S. richteri) in Alabama, Arkansas, Florida, Georgia, 

Louisiana, Mississippi, North Carolina, South Carolina, and Texas (Carlson et al. 1976; EPA 1978b; 

IARC 1979c; Waters et al. 1977a, 1977b). From 1962 to 1976, approximately 132 million acres 

(53.4 million hectares) in 9 states were treated with approximately 485,000 pounds (226,000 kg) of 

mirex at a rate of 4.2 g/hectare (later reduced to 1.16 g/hectare) (IARC 1979c). Mirex was chosen for 

fire ant eradication programs because of its effectiveness and selectiveness for ants (Carlson et al. 

1976; Waters et al. 1977a, 1977b). It was onginally applied aerially at concentrations of 0.3-0.5%. 
MIREX AND CHLORDECONE 192 

4.PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

However, aerial application of mirex was replaced by mound application because of suspected toxicity 

to estuarine species and because the goal of the fire ant program was changed from eradication to 

selective control. Mirex was also used successfully in controlling populations of leaf cutter ants in 

South America, harvester termites in South Africa, Western harvester ants in the United States, 

mealybugs in pineapples in Hawaii, and yellowjacket wasps in the United States (EPA 1978b; IARC 

1979c; Waters et al. 1977b). All registered products containing mirex were effectively canceled on 

December 1, 1977 (Sittig 1980). However, selected ground application was allowed until June 30 

1978, at which time the product was banned in the United States with the exception of continued use 

in Hawaii on pineapples until stocks on hand were exhausted (EPA 1976; Holden 1976; Sittig 1980; 

Waters et al. 1977a). 

Until August 1, 1976, chlordecone was registered in the United States for use on banana root borer (in 

the U.S. territory of Puerto Rico); this was its only registered food use. Additional registered 

formulations included non-food use on non-fruit bearing citrus trees to control rust mites; on tobacco 

to control tobacco and potato wireworms; and for control of the grass mole cricket, and various slugs, 

snails, and fire ants in buildings, lawns, and on ornamental shrubs (EPA 1978b; Epstein 1978; IARC 

1979a). The highest reported concentration of chlordecone in a commercial product was 50%, which 

was used to control the grass mole cricket in Florida (Epstein 1978). Chlordecone has also been used 

in household products such as ant and roach traps at concentrations of approximately 0.125% (IARC 

1979a). The concentration used in ant and roach bait was approximately 25% (Epstein 1978). All 

registered products containing chlordecone were effectively canceled as of May 1, 1978 (Sittig 1980). 

4.4 DISPOSAL 

Since mirex and chlordecone are not flammable and are very stable in the environment, many disposal 

methods investigated for these chemicals have proven unsuccessful (Sullivan and Krieger 1992; 

Tabaeiet al. 1991; Waters et al. 1977b). 

Mirex is unaffected by hydrochloric, sulfuric, and nitric acids, and would be expected to be extremely 

resistant to oxidation except at the high temperatures of an efficient incinerator (EPA 1978b; Sittig 

1980; WHO 1984a). Mirex is not identified as an EPA hazardous substance under SARA Title III 

(EPA 1993). A recommended method of disposal for mirex is incineration or long-term storage 

(Holloman et al. 1975; IARC 1979c). Polyethylene glycol or tetraethylene glycol and potassium 
MIREX AND CHLORDECONE 193 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

hydroxide when used in combination with sodium borohydride or alkoxyborohydrides, produce a 

powerful reducing media which quantitatively destroys mirex at 70 oC. The reduction rate is further 

increased by using tetrahydrofuran and catalytic quantities of Bu3SnH/AlBN which produce 100% 

destruction of mirex to hexahydromirex within 1 hour at 58 oC (Tabaei et al. 1991). 

Chlordecone is considered an EPA hazardous waste and must be disposed of according to EPA 

regulations (EPA 1980c). For more information on disposal regulations applicable to chlordecone, see 

Chapter 7. Degradation of chlordecone has been evaluated in the presence of molten sodium (Greer 

and Griwatz 1980). Addition of chlordecone to molten sodium at a temperature of 250 oC resulted in 

significant degradation of chlordecone with small quantities of <12 ppm observed in the reaction 

products. Microwave plasma has also been investigated as a potential disposal mechanism for 

chlordecone (DeZearn and Oberacker 1980). An estimated 99% decomposition was observed in a 

5-kw microwave plasma system for 80% chlordecone solution, slurry, or solid. Another recommended 

disposal method for chlordecone is destruction in an incinerator at approximately 850 oC followed by 

off-gas scrubbing to absorb hydrogen chloride (IRPTC 1985). 

Activated carbon adsorption has been investigated for the treatment of waste waters contaminated with 

chlordecone (EPA 1982b). The discharge of chlordecone in sewage disposal systems is not 

recommended, as it may destroy the bacteriological system (IRPTC 1985). Chlordecone as a waste 

product in water may be dehalogenated by a process involving ultraviolet light and hydrogen as a 

reductant. The reaction is pH dependent, and degradation is best when the system contains 5% sodium 

hydroxide. Using this method, 95-99% of chlordecone is removed within 90 minutes. The 

degradation products are the mono-, di-, tri-, tetra-, and pentahydro derivatives of chlordecone. This 

degradation method is applicable to chlordecone in hazardous wastes at concentrations in the ppm 

(mg/L) range and lower (Reimers et al. 1989; Sittig 1980). 

MIREX AND CHLORDECONE 195 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

As a result of human health concerns, production of mirex ceased in 1976, at which time industrial 

releases of this chemical to surface waters were also curtailed. However, releases from waste disposal 

sites continue to add mirex to the environment. Virtually all industrial releases of mirex were to 

surface waters, principally Lake Ontario via contamination of the Niagara and Oswego Rivers. About 

75% of the mirex produced was used as a fire retardant additive, while 25% was used as a pesticide. 

As a pesticide, mirex was widely dispersed throughout the southern United States where it was used in 

the fire ant eradication program for over 10 years. 

Adsorption and volatilization are the more important environmental fate processes for mirex, which 

strongly binds to organic matter in water, sediment, and soil. When bound to organic-rich soil, mirex 

is highly immobile; however, when adsorbed to particulate matter in water it can be transported great 

distances before partitioning out to sediment. Atmospheric transport of mirex has been reported based 

on its detection in remote areas without anthropogenic sources, although this is not a major source of 

mirex in the environment. Given the lipophilic nature of this compound (high octanol-water partition 

coefficient), mirex is both bioaccumulated and biomagnified in aquatic and terrestrial food chains. 

Mirex is a very persistent compound in the environment and is highly resistant to both chemical and 

biological degradation. The primary process for the degradation of mirex is photolysis in water or on 

soil surfaces; photomirex is the major transformation product of photolysis. In soil or sediments, 

anaerobic biodegradation is also a major removal mechanism whereby mirex is slowly dechlorinated to 

the lo-monohydro derivative. Aerobic biodegradation on soil is a very slow and minor degradation 

process. Twelve years after the application of mirex to soil, 50% of the mirex and mirex-related 

compounds remained on the soil. Between 65-73% of the residues recovered were mirex and 3-6% 

were chlordecone, a transformation product (Carlson et al. 1976). 

Mirex has been detected at low concentrations in ambient air (mean 0.35 pg/m3

) and rainfall samples 

(<0.5 ng/L) from polluted areas of the Great Lakes region. In addition, the compound has been 

detected in drinking water samples from the Great Lakes area of Ontario, Canada. Mirex has also 

been detected in groundwater samples from agricultural areas of New Jersey and South Carolina. 
MIREX AND CHLORDECONE 196 

5. POTENTIAL FOR HUMAN EXPOSURE 

Mirex has been monitored in surface waters, particularly during the period it was still being produced. 

Concentrations of mirex in Lake Ontario, the Niagara River, and the St. Lawrence River were in 

the ng/L (ppt) range. The highest concentrations of mirex, 1,700 μg/kg (ppb), were found in 

sediments in Lake Ontario where they accumulated after the deposition of particulate matter to which 

the mirex was bound. A recent dynamic mass balance for mirex in Lake Ontario and the Gulf of St. 

Lawrence estimated that approximately 2,700 kg (6,000 lb) of mirex have entered Lake Ontario over 

the past 40 years, of which 550 kg (1,200 lb) have been removed (exclusive of sedimentation and 

burial) mainly by transport on sediment particles via outflowing water and migrating biota 

contaminated with mirex. 

The high bioconcentration factor (BCF) values (up to 15,000 for rainbow trout) observed for mirex 

indicate that this compound will be found in high concentrations in aquatic organisms that inhabit 

areas where the water and sediments are contaminated with mirex. Fish taken from Lake Ontario, the 

St. Lawrence River, and the southeastern United States (areas where mirex was manufactured or used 

as a pesticide) had the highest mirex levels. There are currently eight fish consumption advisories in 

effect in three states (New York, Pennsylvania, and Ohio) that were tnggered by mirex contamination 

in fish. Waterfowl and game animals have also been found to accumulate mirex in their tissues. Data 

on mirex residues in foods do not show a consistent trend with regard to contaminant levels or 

frequency of detection. Mirex has been irregularly detected in Food and Drug Administration (FDA) 

Pesticide Residue Monitoring Studies since 1978. Little information on the specific foods in which 

residues were found or levels detected was located. 

General population exposure to mirex has been determined as a result of several monitoring studies 

(EPA 1986b; Kutz et al. 1979; Stehr-Green 1989). Levels of mirex in most tissues are very low (at or 

near the detection limit). Examination of the 1982 National Adipose Tissue Survey failed to detect 

mirex in the adipose tissues of children less than 14 years old although mirex residues were detected 

in adults. People who live in areas where mirex was manufactured or used have higher levels in their 

tissues. Women who live in these areas were found to have detectable levels of mirex in their milk 

that could be passed on to their infants. Since mirex is no longer manufactured, occupational exposure 

currently is limited to workers at waste disposal sites or those involved in remediation activities 

involving the clean-up and removal of contaminated soils or sediments. 
 

MIREX AND CHLORDECONE 197 

5. POTENTIAL FOR HUMAN EXPOSURE 

Mirex has been identified in at least 7 of the 1,408 hazardous waste sites on the NPL (HazDat 1994). 

However, the number of sites evaluated for mirex is not known. The frequency of these sites within 

the United States can be seen in Figure 5-1. 

Production of chlordecone ceased in 1975 as a result of human health concerns; at that time industrial 

releases of this chemical to surface waters via a municipal sewage system were curtailed. However, 

releases from waste disposal sites may continue to add chlordecone to the environment. Major 

releases of chlordecone occurred to the air, surface waters, and soil surrounding a major manufacturing 

site in Hopewell, Virginia. Releases from this plant ultimately contaminated the water, sediment, and 

biota of the James River, a tributary to the Chesapeake Bay. 

Atmospheric transport of chlordecone particles was reported during production years based on results 

from high volume air samplers installed at the site and up to 15.6 miles away. Chlordecone is not 

expected to be subject to direct photodegradation in the atmosphere. Chlordecone is very persistent in 

the environment. Chlordecone, like mirex, will strongly bind to organic matter in water, sediment, and 

soil. When bound to organic-rich soil, chlordecone is highly immobile; however, when adsorbed to 

particulate matter in surface water chlordecone can be transported great distances before partitioning 

out to sediment. Sediment in extensive areas of the James River currently serves as a sink or reservoir 

for this compound. The primary process for the degradation of chlordecone in soil or sediments is 

anaerobic biodegradation. Based on the lipophilic nature of this compound (high octanol-water 

partition coefficient), chlordecone has a tendency to both bioaccumulate and biomagnify in aquatic 

food chains. BCF values of over 60,000 have been measured in Atlantic silversides, an estuarine fish 

species. 

No information was found on atmospheric concentrations of chlordecone other than historic monitoring 

data from samples collected in the vicinity of the manufacturing site. Chlordecone has been monitored 

in surface waters, particularly during the period shortly before and after production was terminated. In 

1977, chlordecone was detected in surface water samples from the James River at low concentrations 

(less than 10 ng/L [ppt]), although it was not detected in more recent monitoring studies. The highest 

concentrations of this compound are found in sediments, principally in the James River where it had 

accumulated after the deposition of particulate matter to which the chlordecone was bound. In 1978, 

chlordecone was detected in sediments from the James River below its production site at 

concentrations in the mg/kg (ppm) range. 

MIREX AND CHLORDECONE 199 

5. POTENTIAL FOR HUMAN EXPOSURE 

The high BCF values observed for chlordecone (>60,000) indicate that the compound will be found in 

high concentrations in aquatic organisms that dwell in waters or sediments contaminated with 

chlordecone. Chlordecone has been detected in fish and shellfish from the James River, which empties 

into the Chesapeake Bay, at levels in the μg/g (ppm) range. There is currently a fish consumption 

advisory in effect for the lower 113 miles of the James River. Chlordecone residues were detected in 

foods analyzed from 1978-1982 and 1982-1986 as part of the Food and Drug Administration (FDA) 

Pesticide Residue Monitoring Studies. Chlordecone was detected in one of 27,065 food samples 

analyzed by 10 state laboratories, but was not detected in the more recent FDA Pesticide Residue 

Monitoring Studies from 1986 to 1991. No information on the specific foods in which residues were 

found or levels detected was located. 

General population exposure to chlordecone has not been determined because this compound has not 

been monitored in any national program (EPA 1986b; Kutz et al. 1979; Phillips and Birchard 1991a; 

Stehr-Green 1989). Levels of chlordecone were detected in 9 of 298 samples of human milk collected 

from women in the southern United States. Residues were detected only in residents of areas that had 

been extensively treated with the pesticide mirex for fire ant control. People who lived in the area 

where chlordecone was manufactured had higher levels in their blood during production years. 

Women who lived in these areas could pass chlordecone in their milk on to their infants. Workers 

who manufactured chlordecone developed an occupationally-related illness. However, chlordecone is 

no longer manufactured, so occupational exposure is limited to workers at waste disposal sites or those 

involved in remediation activities involving the clean-up and removal of contaminated soils or 

sediments. 

Chlordecone has been identified at 2 of the 1,408 hazardous waste sites on the NPL (HazDat 1994). 

However, the number of sites at which chlordecone has been evaluated is not known. The frequency 

of these sites within the United States can be seen in Figure 5-2. 

5.2 RELEASES TO THE ENVIRONMENT 

Mirex has been detected in air, surface water, soil and sediment, aquatic organisms, and foodstuffs. 

Historically, mirex was released to the environment primarily during its production or formulation for 

use as a fire retardant and as a pesticide. There are no known natural sources of mirex and production 

of the compound was terminated in 1976. Currently, hazardous waste disposal sites and contaminated 

 

MIREX AND CHLORDECONE 201 

5. POTENTIAL FOR HUMAN EXPOSURE 

sediment sinks in Lake Ontario are the major sources for mirex releases to the environment (Brower 

and Ramkrishnadas 1982; Comba et al. 1993). 

Chlordecone has been detected in the air, surface water, soil and sediment, aquatic organisms and 

foodstuffs. Historically chlordecone was released to the environment primarily during its production at 

a manufacturing facility in Hopewell, Virginia. There are no known natural sources of chlordecone 

and production of the compound was terminated in 1975. Currently, hazardous waste disposal sites 

and contaminated sediment sinks in the James River are the major sources for chlordecone release to 

the environment (EPA 1978c; Huggett and Bender 1980; Lunsford et al. 1987). 

Releases of mirex and chlordecone are not required to be reported under the Super-fund Amendments 

and Reauthorization Act (SARA) Section 313 (EPA 1993a); consequently, there are no data for these 

compounds in the 1992 Toxics Release Inventory Database. 

5.2.2 Air 

Little information on historic releases of mirex to the air was located. Some atmospheric 

contamination may have occurred due to releases from manufacturing facilities, which were primarily 

located near Niagara Falls, New York, and State College, Pennsylvania; however, no quantitative 

sampling data were located (EPA 1978c). Atmospheric releases of mirex could result from airborne 

dust from the production and processing of mirex or Dechlorane®, combustion of products containing 

Dechlorane®, or volatilization of mirex applied as a pesticide (WHO 1984a). Because mirex was 

principally dispersed as a pesticide in a bait form associated with corn cob grit particles that settle 

rapidly, the amount of mirex remaining airborne should have been insignificant. Furthermore, 

volatilization of mirex after application should also have been insignificant because of the high melting 

point and low vapor pressure of the bait (EPA 1978c). 

Although release of mirex to the atmosphere was probably small in comparison to amounts released to 

surface water, soil, and sediment, infrequent detections of minute concentrations of mirex in air (mean 

concentration 0.35 pg/m3

) and rainfall (<0.5 ng/L [ppt]) samples have been reported many years after 

production ceased (Hoff et al. 1992; Strachan 1990; Wania and MacKay 1993). Arimoto (1989) 

estimated that 5% of the total input of mirex to Lake Ontario was attributed to atmospheric deposition. 
 

MIREX AND CHLORDECONE 202 

5. POTENTIAL FOR HUMAN EXPOSURE 

Large amounts of chlordecone were released into the air from a chemical manufacturing plant in 

Hopewell, Virginia, from April 1974 through June 1975. Throughout the manufacturing period, 

extensive areas of the environment were contaminated with the chlordecone because of improper 

manufacturing and disposal processes (Lewis and Lee 1976). Concentrations of chlordecone in the air 

surrounding the plant ranged from 0.18 ng/m3

 to a maximum of 54.8 μg/m3 which was found in a 

sample collected 200 meters from the plant (Epstein 1978). High-volume air samplers in operation 

200 meters from the plant were found to contain this chlordecone level, which constituted over 50% of 

the total particulate loading. Chlordecone concentrations at more distant sites (up to 15.6 miles away) 

ranged from 1.4 to 20.7 ng/m3 (Epstein 1978). The long-range transport properties of chlordecone 

indicate that at least a small portion of the chlordecone emissions were of a fine particle size having a 

relatively long residence time in the atmosphere (Lewis and Lee 1976). 

5.2.2 Water 

Mirex has been released to surface waters via waste waters discharged from manufacturing and 

formulation plants, in activities associated with the disposition of residual pesticides, and as a result of 

its direct use as a pesticide, particularly in the fire ant eradication program conducted in several 

southern states. 

Releases of mirex in industrial wastes were greatest during the manufacture of this chemical between 

1957 and 1976 by the Hooker Chemical and Plastics Corporation in Niagara Falls, New York. 

Releases to the Niagara River peaked between 1960 and 1962 at 200 kg/year (440 lb/year), but 

subsequently declined to 13.3 kg/year (29 lb/year) in 1979, and 8 kg/year (18 lb/year) in 1981 

(Durham and Oliver 1983; Lewis and Makarewicz 1988). Releases to the Oswego River occurred as a 

result of discharges from Armstrong World Industries Inc. in Volney, New York (Lum et al. 1987; 

Mudambi et al. 1992). Since production of mirex was discontinued in 1976 (Kaiser 1978), releases 

after 1976 were, and continue to be, the result of leaching from dump sites adjacent to the Niagara and 

Oswego Rivers, both of which feed into Lake Ontario (Kaminsky et al. 1983) and releases of mirex 

from sediment sinks in Lake Ontario. Total loading of mirex to Lake Ontario has been estimated to 

be 688 kg (1,517 lb) with half of this incorporated into the sediments (Holdrinet et al. 1978; Lewis 

and Makarewicz 1988). A more recent study by Comba et al. (1993), however, estimated total loading 

of mirex to Lake Ontario to be 2,700 kg (6,000 lb) over the last 40 years of which 550 kg (1,200 lb) 

has been removed mainly by transport via outflowing water into the St. Lawrence River. 
MIREX AND CHLORDECONE 203 

5. POTENTIAL FOR HUMAN EXPOSURE 

In addition to direct releases of mirex to surface waters that occurred at the manufacturing plant in 

Niagara Falls, New York, an estimated 226,000 kg (498,000 lb) of mirex was used as a pesticide to 

treat 132 million acres (53.4 million hectares) in 9 southern states from 1962-1976 as part of the fire 

ant eradication program conducted by the Department of Agriculture (IARC 1979c). Mirex insecticide 

baits were dispersed by aerial applications, and mirex could be released into surface water directly or 

could reach surface waters via runoff. Because mirex binds tightly to organic-rich soils, leaching is 

not generally expected to occur. However, mirex residues have been detected (concentration 

unspecified) in groundwater well samples collected in proximity to agricultural land in New Jersey 

(Greenburg et al. 1982). In a South Carolina study, mirex was also detected in potable water supplies 

in two rural counties. Mirex was detected in 12.5% of water samples at a mean concentration of 

2 ng/L (ppt) (range from not detectable to 30 ng/L) in Chesterfield County and was detected in 72.7% 

of the water samples at a mean concentration of 83 ng/L (range of not detectable to 437 ng/L) in rural 

Hampton County. The authors attributed the higher mirex residues in the potable water of Hampton 

County to the extensive use of mirex in this county for fire ant control (Sandhu et al. 1978). 

Chlordecone has been primarily released to surface waters in waste waters from a manufacturing plant 

in Hopewell, Virginia, and may be released in activities associated with the disposal of residual 

pesticide stocks, and as a result of the direct use of mirex. Chlordecone has been released directly as 

a contaminant of mirex and indirectly from the degradation of mirex. 

Production of chlordecone at a manufacturing plant in Hopewell, Virginia, from 1966 to 1975, resulted 

in the release of the compound, primarily through industrial discharge of waste water into the 

Hopewell municipal sewage system, which discharged into Baileys Creek, and ultimately flowed into 

the James River. Leaching and erosion of contaminated soils from the plant site and direct discharge 

of solid wastes also contributed to the chlordecone content in the James River estuary (Colwell et al. 

1981; Nichols 1990). Effluent from the manufacturing plant contained 0.1-l .0 mg/L (ppm) 

chlordecone, and water from the plant’s holding ponds contained 2 to 3 mg/L (ppm) chlordecone 

(Epstein 1978). It has been estimated that 7,500-45,000 kg (16,500-100,000 lb) of the 1,500,000 kg 

(3.3 million pounds) of chlordecone produced at the plant entered the estuary in industrial effluent or 

runoff (Colwell et al. 1981; Nichols 1990). 

Another source of chlordecone release to water may result from the application of mirex containing 

chlordecone as a contaminant and by the degradation of mirex which was used extensively in several 
MIREX AND CHLORDECONE 204 

5. POTENTIAL FOR HUMAN EXPOSURE 

southern states. Carlson et al. (1976) reported that dechlorinated products including chlordecone were 

formed when mirex bait, or mirex deposited on soil after leaching from the bait, was exposed to 

sunlight, other forms of weathering, and microbial degradation over a period of 12 years. Chlordecone 

residues in the soil could find their way to surface waters via runoff. 

5.2.3 Soil 

Mirex is not currently registered for use in the United States so release of mirex to soil from pesticide 

applications is no longer of concern. However, use of mirex as a pesticide for fire ant control required 

the spraying of this chemical on soils of an estimated 132 million acres in the southern United States 

(IARC 1979c). An estimated 226,000 kg (498,000 lb) of mirex was used in 9 states from 1962-1976 

as part of the fire ant eradication program conducted by the Department of Agriculture (IARC 1979c). 

Releases of mirex to sediment as a result of industrial waste water discharges were noted in Lake 

Ontario near the mouth of the Niagara River. Lake Ontario sediment concentrations were correlated 

with the years of peak production and use, and were found to decrease in the upper sediments as use 

was restricted in the late 1970s (Durham and Oliver 1983). Total loading of mirex to Lake Ontario 

has been estimated to be 688 kg (1,517 lb), with half of this amount incorporated into the sediments 

(Holdrinet et al. 1978; Lewis and Makarewicz 1988). However, a more recent study by Comba et al. 

(1993) involving development of a mass balance for mirex in Lake Ontario and the Gulf of St. 

Lawrence estimated that over the past 40 years approximately 2,700 kg (6,000 lb) of mirex has entered 

Lake Ontario of which 550 kg (1,200 lb) has been removed via transport to the St. Lawrence estuary. 

Removal of mirex from Lake Ontario, has resulted primarily by outflowing water containing 

suspended sediment. 

Although mirex was identified at 7 of the 1,408 NPL waste sites (HazDat 1994), it is not known at 

how many of the sites environment samples were analyzed for this compound. Currently, hazardous 

wastes sites may still be potential sources for release of this compound to soil. 

Chlordecone is not currently registered for use in the United States. However, use of chlordecone as a 

pesticide to control banana borers on bananas, tobacco wireworms on tobacco, mole crickets on turf, 

and various slugs, snails, and ants in buildings, lawns, and ornamental shrubs, required the application 

of this chemical to soils (Epstein 1978; IARC 1979a). No estimate of the amount of chlordecone 
 

 

MIREX AND CHLORDECONE 205 

5. POTENTIAL FOR HUMAN EXPOSURE 

released from these uses was found. Chlordecone releases to soils may also occur as a result of the 

application of mirex containing chlordecone as a contaminant and by the degradation of mirex which 

was used extensively in a regional fire ant eradication program. As stated in Section 5.2.2, Carlson et 

al. (1976) reported that dechlorinated products, including chlordecone, were formed when mirex bait, 

or mirex deposited on soil after leaching from the bait, was exposed to sunlight, other forms of 

weathering, and microbial degradation over a period of 12 years. No estimates of the amount of 

chlordecone released from the application and degradation of mirex are available. 

Chlordecone releases to soil occurred at a production facility in Hopewell, Virginia. Soil samples 

adjacent to the site contained l-2% chlordecone (l0,000-20,000 mg/kg [ppm]), and surface soils up to 

3,000 feet from the site contained concentrations of 2-6 mg/kg (ppm) (Epstein 1978). 

The major release of chlordecone to sediments, however, occurred indirectly as a result of waste water 

discharges, runoff of contaminated soil, and direct disposal of solid wastes at a production facility in 

Hopewell, Virginia. An estimated l0,000-30,000 kg (22,000-66,100 lb) of chlordecone is associated 

with bottom sediment in the James River estuary (Huggett and Bender 1980; Nichols 1990). This 

sediment serves as a reservoir for future release of chlordecone via resuspension of sediments resulting 

from storms or dredging activities (Lunsford et al. 1987). 

Although chlordecone was identified at 2 of the 1,408 NPL waste sites (HazDat 1994), it is not known 

at how many of the sites environment samples were analyzed for this compound. Currently, hazardous 

wastes sites may still be potential sources for releases of this compound to soil. 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

Because mirex is a very hydrophobic compound with a low vapor pressure, atmospheric transport is 

unlikely (Hoff et al. 1992). These authors reported detecting mirex in only 5 of 143 samples at a 

maximum and mean concentration of 22 pg/m3

 and 0.35 pg/m3, respectively. Based on a vapor 

pressure of <3x10-7 mm Hg at 25oC, mirex is expected to exist mainly in the particulate phase with a 

small proportion existing in the vapor phase in the ambient atmosphere (IARC 1979c). A mass 

balance approach to the movement of mirex within Lake Ontario indicates that 5% of the total input of 
 

 

 

MIREX AND CHLORDECONE 206 

5. POTENTIAL FOR HUMAN EXPOSURE 

mirex to the lake can be attributed to atmospheric deposition compared with 72% of benzo(a)pyrene 

(Arimoto 1989). 

Based on a calculated soil sorption coefficient (Koc) of 1,200 (5,800 experimental) for mirex, this 

compound will tightly bind to organic matter in soil and, therefore, will be highly immobile. Thus, 

mirex is most likely to enter surface waters as a result of soil runoff (Kenaga 1980). In addition, most 

land applications of mirex to soils containing high organic content would result in very little leaching 

through soil to groundwater. However, leaching of mirex from some agricultural soils can occur as 

mirex has been detected in groundwater wells near agricultural areas (Greenburg et al. 1982; Sandhu et 

al. 1978). 

When released to surface waters, mirex will bind primarily (80-90%) to the dissolved organic matter 

in the water with a small amount (10-20%) remaining in the dissolved fraction, because mirex is a 

highly hydrophobic compound (Yin and Hassett 1989). Mean mirex concentrations in sediments, 

collected at four basins in Lake Ontario between 1982 and 1986, ranged from 30 to 38 μg/kg in three 

of the basins within the water circulation pattern of the lake. A fourth basin outside the pattern 

showed much lower concentrations (6.4 μg/kg), indicating that mirex was being transported with the 

lake water (Oliver et al. 1989). The residence time for mirex in Lake Ontario water was estimated to 

be 0.3 years. This indicated that mirex was either scavenged by particles or was chemically reactive 

and, therefore, was rapidly removed from the water column (Arimoto 1989). 

Since the only sources of mirex in Lake Ontario are contaminated sediments, mirex in the water 

column is assumed to have come from resuspended sediments (Oliver et al. 1989). The source of the 

mirex in Lake Ontario surficial sediments was determined to be suspended sediments from the Niagara 

River, which were found to contain 8-15 and 55 μg/g (ppm) mirex in the upper and lower river 

sections, respectively. The surficial sediments contained 3 μg/g in the upper river (above the 

manufacturing and dump sites), 86 μg/g in the lower river (below the sites), and 10 μg/g in the 

western basin of Lake Ontario, indicating that mirex-containing sediments were being carried down the 

river with the current and deposited in Lake Ontario (Mudroch and Williams 1989). Kaminsky et al. 

(1983), reported a range of 8.2-62 ppb (μg/kg) in sediment from the eastern and central basins of Lake 

Ontario. Over 94% of the suspended particulate matter entering the lake is eventually deposited in 

lake sediments (Lum et al. 1987). Mirex concentrations in sediments of Lake Ontario show a strong 

correlation with peak production years (Durham and Oliver 1983; Eisenreich et al. 1989). Although 
 

MIREX AND CHLORDECONE 207

5. POTENTIAL FOR HUMAN EXPOSURE 

there was evidence of sediment bioturbation by deposit-feeding worms and burrowing organisms, the 

sediment profiles for mirex and other chlorinated hydrocarbons were not destroyed (Eisenreich et al. 

1989). Between the 1960s when mirex production began, and the early 1980s after production 

ceased, levels of mirex in bottom sediments increased in Lake Ontario, with the Niagara River being 

the major source of this compound (Allan and Ball 1990). 

Mirex may be removed from Lake Ontario by several mechanisms, including the transport of 

contaminated suspended particulate material via water outflow into the St. Lawrence River), biomass 

removal through fishing and migration (e.g., migrating eels contaminated with mirex), volatilization, 

and photolysis (Comba et al. 1993; Lum et al. 1987). Transport of mirex accumulated in body tissues 

by eels has been estimated to be 2,270 grams annually or twice the amount of mirex removed by 

transport of suspended particulates (1,370 grams annually) (Lum et al. 1987). 

The transport of mirex out of Lake Ontario, (a known reservoir), to its tributaries is also possible as a 

result of migrating fish which move from the lake into the tributary streams to spawn. Fish, such as 

Pacific salmon, become contaminated with mirex while in the lake. These fish then swim upstream in 

the tributaries to their spawning grounds, spawn, and die. A direct transfer of mirex may then occur 

when resident stream fish feed on the decomposing carcasses and/or eggs, both of which contain mirex 

residues. Indirect transfer can occur as a result of the release of mirex from the salmon into the water 

or sediments and subsequent movement up the food chain. Movement of mirex back into Lake 

Ontario is also possible when the contaminated eggs hatch and surviving juvenile salmon return to the 

lake (Lewis and Makarewicz 1988). 

Algae are known to bioaccumulate mirex with BCFs in the range of 3,200-7,300, while bacteria have 

a BCF of 40,000 with an octanol-water partition coefficient of 7.8 million (Baughman and Paris 1981). 

Based on a water solubility of 0.6 mg/L, a bioconcentration factor of 820 was calculated for mirex 

(Kenaga 1980). Bioaccumulation of mirex also occurred in invertebrates exposed to 0.001-2.0 μg/g 

mirex in water; tissue residues ranged from 1.06 to 92.2 μg/g (de la Cruz and Naqui 1973). After 

28 days exposure, the BCF values for the amphipod (Hyallelu azteca) and crayfish (Orconectes 

mississippiensis) were 2,530 and 1,060 respectively. Fathead minnows exposed to 33 μg/L (ppb) 

mirex for 56 days accumulated 122 μg/g (ppm) mirex tissue residues (BCF of 3,700), with no other 

evident metabolic products. Residues decreased to 88.6 μg/g 28 days after mirex was removed from 

the water (Huckins et al. 1982). The half-life of mirex in rainbow trout was greater than 1,000 days in 
 

MIREX AND CHLORDECONE 208 

5. POTENTIAL FOR HUMAN EXPOSURE 

fish exposed for 96 days to a mean concentration of 4.1 ng/L, although equilibrium was not reached 

during the test period. A subsequent analysis comparing a laboratory BCF for mirex in rainbow trout 

(1,200) with an actual BCF found in rainbow trout in Lake Ontario (15,000), indicated that ingestion 

of contaminated food (as would occur in the lake), rather than absorption across the gills, is the 

primary exposure route for trout (Oliver and Niimi 1985). 

Biomagnification of mirex is supported by a study of various aquatic organisms that comprise an 

aquatic food chain in Lake Ontario (Oliver and Niimi 1988). The following concentrations (+ standard 

deviation) of mirex were found: 

Sample Mirex concentration* 

Watera 31 + 12 

Bottom sedimentb 3.9 + 1.9 

Suspended sedimentb 15 + 4.4 

Plankton 1.3 + 0.1 

Mysids 8 + 2.8 

Amphipods 12 + 6.7 

Oligochaetes 6.9 + 2.9 

Sculpins 57 

Alewives 45 

Small smelts 26 + 3.6 

Large smelts 53 

Average fish 180 + 150 

*μg/kg wet weight unless otherwise noted
 a

 pg/L wet weight
 b

μg/kg dry weight
 

In these food chains, alewives feed primarily on mysids and to a lesser extent on amphipods; sculpins 

feed on amphipods, then mysids; smelt feed on mysids. Mysids feed on zooplankton, with amphipods 

and oligochaetes consuming detrital matter. The alewives and smelt are preyed upon by salmonids, 

such as trout (Oliver and Niimi 1988). A comparison of concentrations of mirex in lake trout, a 

predator species, with those in smelt, a prey species, gives a ratio of 1.26, indicating that 

biomagnification is occurring (Thomann 1989). 

Mirex can also bioaccumulate in terrestrial plants. Azalea leaves, exposed to 0.023 μg/kg of mirex in 

greenhouse air, had significant uptake of the pesticide resulting in a BCF of 1.18x107

 (log BCF=7.07) 

(Bacci et al. 1990b). Mirex residues ranging from 10-l,710 μg/kg (ppb) were detected in soybeans, 
 

MIREX AND CHLORDECONE 209 

5. POTENTIAL FOR HUMAN EXPOSURE 

garden beans, sorghum, and wheat seedlings grown on substrates containing 0.3-3.5 mg/kg (ppm) 

mirex (de la Cruz and Rajanna 1975). Based on these data and known soil concentrations, it has been 

estimated that plants grown on contaminated soil could contain 0.0002-2 μg/kg (ppb) mirex (EPA 

1978c). No information on the uptake of mirex by plants under field conditions was located. 

In a 1972 residue study conducted in Mississippi during the time when mirex was being used 

extensively in fire ant control programs, Naqui and de la Cruz (1973) reported mirex accumulation in 

grassland invertebrates (e.g., spiders and grasshoppers) ranging from 100 to 700 μg/kg (ppb) (mean 

280 μg/kg). More recently, Hebert et al. (1994) studied organochlorine pesticides in a terrestrial food 

web on the Niagara Peninsula in Ontario, Canada, from 1987 to 1989. These authors reported mirex 

concentrations in the various food web compartments as follows: soil (not detectable), plants (not 

detectable), earthworms (not detectable to 0.4 μg/kg), mammals (not detectable to 0.5 μg/kg), starlings 

(0.9-1.6 μg/kg), robins (4.7-18.9 μg/kg), and kestrels (4.7-22.2 μg/kg) which suggests that 

biomagnification of mirex is occurring. The earthworm appeared to be a particularly important species 

for organochlorine transfer from the soil to organisms occupying higher trophic levels. Connell and 

Markwell (1990) reported transfer of lipophilic compounds (such as mirex) through a three-phase 

system involving soil to soil water to earthworm partitioning. The transfer is a passive process and is 

principally dependent on the lipid content of the worms and the organic content of the soil. 

The fate and transport of chlordecone is very similar to mirex. Based on its low vapor pressure and 

high Koc, chlordecone in the air may be expected to be associated primarily with particulate matter 

(Kenaga 1980). However, only small amounts of chlordecone may volatilize into the air. 

Chlordecone volatilizes more slowly from water (0.024% applied amount/mL of evaporated water) 

than from sand, loam, or humus soil (0.036%, 0.035%, and 0.032%, respectively) (Kilzer et al. 1979). 

Atmospheric transport of chlordecone particles was reported as a result of emissions from a production 

facility in Virginia. Chlordecone concentrations at up to 15.6 miles away ranged from 1.4 to 

20.7 ng/m3

 (Epstein 1978). The long-range transport properties of chlordecone indicate that at least a 

portion of the emissions were of a fine particle size having a relatively long residence time in the 

atmosphere (Lewis and Lee 1976). 

The major industrial release of chlordecone occurred to surface waters of the James River. 

Chlordecone, because of its relatively low solubility in water and lipophilic nature, is readily absorbed 
 

MIREX AND CHLORDECONE 210 

5. POTENTIAL FOR HUMAN EXPOSURE 

to particulate matter in water and is ultimately deposited in sediments (EPA 1978; Lunsford et al. 

1987). Once adsorbed to sediments, chlordecone remains relatively immobile in the normal range of 

pH (7-8) and salinity (0.06-19.5 %) encountered in an estuary. While chlordecone is associated 

mainly with the organic portion of bottom sediments, sediment areas with high percentages of 

inorganic mineral grains are relatively clean of contamination. The greatest mass of chlordecone (an 

estimated 6,260 pounds [2,840 kg]) was found in a sink where the sedimentation was relatively rapid. 

Transport is primarily through adsorption of chlordecone to fine organic particles in the water column. 

Its movement and deposition follow estuarine circulation, which is seaward from the freshwater 

reaches and upper estuarine water layer, and reflux downward for suspended materials (Nichols 1990). 

While much of the chlordecone that was present in contaminated sediments in 1976 is still in the 

sediment, it is continuously being buried under several centimeters of new sediment each year 

(Huggett and Bender 1980). Storm activities and dredging are of concern because they would result in 

reenrichment of the surface sediments in areas with chlordecone contaminated sediment previously 

buried by natural ongoing sedimentation processes in the estuary (Huggett and Bender 1980; Lunsford 

et al. 1987). 

Chlordecone has been found to have a very high bioaccumulation potential in fish and other aquatic 

organisms. Atlantic menhaden (Brevoortia lyrunnus) and Atlantic silver-sides (Menidia menidiu) had 

28-day BCFs of 2,300-9,750 and 21,700-60,200, respectively (Roberts and Fisher 1985). Based on a 

water solubility of 3 mg/L, a BCF of 333 was estimated for chlordecone. However, the measured 

value was 8,400 (Kenaga 1980). Using a log octanol-water partition coefficient for chlordecone of 

6.08, a BCF of 6,918 was estimated for the oyster (Hawker and Connell 1986). However, an oyster 

BCF of 10,000 has been reported with tissue concentrations at equilibrium within 8-17 days (Bahner 

et al. 1977). For estuarine organisms such as mysids, grass shrimp, sheepshead minnows, and spot, 

BCFs were measured to be 13,000, 11,000, 7,000, and 3,000, respectively (Bahner et al. 1977). Shad 

roe taken from the James River contained chlordecone levels that were 140% higher than muscle tissue 

residues, indicating a partitioning of the chemical into the lipid-rich eggs (Bender and Huggett 1984). 

The accumulation of chlordecone was studied in a terrestrial/aquatic laboratory model ecosystem by 

Metcalf et al. (1984). Radiolabeled chlordecone was applied to sorghum seedlings grown on the 

terrestrial portion of the aquarium. The treated seedlings were eaten by salt marsh caterpillars. In the 

aquatic portion, chlordecone was transferred through several species-an algae, snail, water flea 
 

MIREX AND CHLORDECONE 211 

5. POTENTIAL FOR HUMAN EXPOSURE 

mosquito larvae, and mosquito fish. After 33 days, the BCFs were 0.35 for the algae, 637.4 for the 

snails, 506.9 for the mosquito larvae, and 117.9 for the mosquito fish. A biomagnification factor for 

chlordecone of approximately 2.1 was determined for a water-algae-oyster food chain; however, a 

biomagnification factor of greater than 10.5 was measured for a water-brine shrimp-mysid-spot food 

chain with a water concentration of 0.1 mg/L (ppm) chlordecone (Bahner et al. 1977). 

Plant uptake of chlordecone from the soil via the roots, and volatilization of chlordecone from soil 

with plant uptake via the leaves were found to be negligible in a closed laboratory system using barley 

seedlings. This indicates that bioaccumulation of chlordecone by plants (lowest on the terrestrial food 

chain) is very unlikely based on its log soil adsorption coefficient of almost 4.0 (Topp et al. 1986). 

No information on the uptake of chlordecone by plants under field conditions was located. 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

Little information was found on the degradation of mirex in the atmosphere. Mirex is expected to be 

stable against photogenerated hydroxyl radicals in the atmosphere (Eisenreich et al. 1981). 

Photolysis of chlordecone in the atmosphere does not appear to be an important degradation pathway 

for this compound. While nonvolatile products of photolysis were not monitored, only 1.8% of the 

chlordecone adsorbed on silica gel and exposed to ultraviolet light (wavelength >290 nm) was 

photolyzed to carbon dioxide or other volatile compounds (Freitag et al. 1985). 

5.3.2.2 Water 

The degradation of mirex in water occurs primarily by photolysis. During the photodecomposition of 

mirex, the chlorine atoms are replaced by hydrogen atoms. The primary photoreduction product of 

mirex in water is photomirex (Andrade et al. 1975); the rate of this reaction can be increased by the 

presence of dissolved organic matter (such as humic acids) and was greatest at 265 nm in Lake 

Ontario water (Mudami and Hassett 1988). In Lake Ontario, Mudambi et al. (1992) reported that the 

ratio of photomirex to mirex (P/M) increased in the stratified surface layer of the lake from spring 

until autumn and in water from Oswego Harbor. P/M ratios in the mirex source sediments (the Niagara 
MIREX AND CHLORDECONE 212 

5. POTENTIAL FOR HUMAN EXPOSURE 

and Oswego Rivers) were very low (<0.07), whereas higher P/M ratios were seen in the lake bottom 

sediments (>0.10) and surface waters (>0.30). These findings suggest that photomirex in Lake Ontario 

is produced by photolysis of mirex present in the surface waters and it is then partitioned between 

water, sediment, and biota. 

Degradation of chlordecone to an unidentified compound was studied in water in a terrestrial/aquatic 

laboratory model ecosystem. Degradation occurred to some extent during the 33-day exposure period, 

and unidentified metabolites were detected in all organisms in the system-algae, snail, mosquito, and 

mosquito fish (Francis and Metcalf 1984). An earlier laboratory study in which fathead minnows were 

exposed to chlordecone in a flow-through diluter system for 56 days found that chlordecone was 

bioconcentrated 16,600 times by the minnows; however, only l-5% of these residues were 

chlordecone (Huckins et al. 1982). Several observations suggested that some of the chlordecone 

residues present in the minnows were chemically bound to biogenic compounds. 

Pseudomonas aeruginosa strain K03 and a mixed aerobic enrichment culture isolated from sewage 

sludge lagoon water were found to aerobically transform chlordecone to monohydrochlordecone in 

8 weeks. Monohydrochlordecone constituted 14.2 and 14.5% of the chlordecone transformation 

products for the P. aeruginosa and mixed aerobic enrichment culture, respectively. The P. aeruginosa 

K03 strain and the mixed culture also produced 15.6 and 4.2% dihydrochlordecone, respectively 

(Orndorff and Colwell 1980). None of the bacterial strains were able to use chlordecone as a sole 

carbon source; therefore, co-metabolism appeared to be the only degradation process. Complete 

mineralization of chlordecone by bacteria is unlikely (Orndorff and Colwell 1980). Degradation of 

chlordecone can occur via microbial action, but the rate and extent of transformation are such that 

microbial action will not cause rapid removal of chlordecone from the environment except under 

highly enriched and selected conditions. Aerobic degradation of chlordecone by activated sludge from 

a municipal sewage plant showed that <0.1% of the applied chlordecone was degraded in 5 days, and 

the sludge showed a bioaccumulation factor of 9,900 compared with the concentration in the water 

(Freitag et al. 1985). 

5.3.2.3 Sediment and Soil 

Degradation of mirex in soil may occur by photolysis or anaerobic biodegradation, both of which are 

very slow removal processes. Mirex is highly resistant to aerobic biodegradation and, as such, is 
 

 

MIREX AND CHLORDECONE 213 

5. POTENTIAL FOR HUMAN EXPOSURE 

extremely persistent in soils (estimated half-life of 10 years) (Carlson et al. 1976; La1 and Saxena 

1982), although it appears to have no adverse effect on resident microbial communities (Jones and 

Hodges 1974). Upon exposure to ultraviolet light, mirex is known to degrade to chlordecone, 

photomirex, and/or dihydromirex (Francis and Metcalf 1984). Detectable levels of mirex 

photodegradation products (monohydro derivative and chlordecone hydrate) occur within 3 days after 

exposure of mirex to sunlight, although after 28 days of exposure, approximately 90% of the mirex 

was unchanged (Ivie et al. 1974a). Anaerobic degradation relies on iron(II) porphyrin as the reductant 

for the dehalogenation reaction (Kuhn and Suflita 1989). 

Under anaerobic conditions, mirex was slowly dechlorinated to the 10-monohydro derivative by 

incubation with sewage sludge bacteria for two months (Andrade and Wheeler 1974; Andrade et al. 

197.5; Williams 1977). The primary removal mechanism for mirex was anaerobic degradation as 

demonstrated by the 6-month stability of the compound in nine aerobic soils and lake sediments (Jones 

and Hodges 1974). 

Aerobic degradation of mirex is a very slow and minor degradation process. Twelve years after the 

application of mirex to soil at one pound per acre, 50% of the mirex and mirex-related organochlorine 

compounds remained in the soil; 65-73% of the residues consisted of mirex and 3-6% consisted of 

chlordecone. Although concentrations were slightly higher, similar ratios of mirex (76-81%) and 

chlordecone (l-6%) residues were seen five years after an accidental spill of mirex bait on soil. Mirex 

underwent photolysis to form four dechlorination products: two monohydro and two dihydro 

compounds (Carlson et al. 1976). Two soil microbes, Bacillus sphaericus and Streptomyces albus, 

isolated from a field previously treated with mirex, were able to utilize 1% mirex as a sole carbon 

source. However, the rate of degradation, as demonstrated by carbon dioxide evolution, was slow and 

only about 10-20% greater than the controls after 20 hours (Aslanzadeh and Hedrick 1985). 

No evidence of microbial degradation was detected for mirex exposed to hydrosoils from a reservoir 

(not previously contaminated with chlordecone) and from chlordecone-contaminated hydrosoils from 

the James River area of Virginia under either anaerobic or aerobic conditions for 56 days (Huckins et 

al. 1982). The concentrations of chlordecone in the anaerobic and aerobic hydrosoils averaged 0.38 

and 0.54 uglg respectively. Some photodegradation of mirex to photomirex was seen in an artificial 

salt marsh ecosystem; the photomirex was subsequently photodegraded to the 2,8- or 3,8-dihydro 

derivative. Most mirex loss occurred during the first 7 days after application (from 2.65 to 2.13 mg/g) 
MIREX AND CHLORDECONE 214 

5. POTENTIAL FOR HUMAN EXPOSURE 

with a steady accumulation of photomirex (610 ppb/day [μg/kg/day]) through day 21, accumulation of 

17 μg/kg/day of 2,8- or 3,8-dihydro derivative through day 35, and an accumulation rate of 

206 μg/kg/day for the 10-monohydro photoproduct that is formed in the presence of amines. The 

8-monohydro derivative (photomirex) was found to accumulate in the salt marsh organisms and 

sediment (Cripe and Livingston 1977). 

Application of radiolabeled mirex to plants grown in a terrestrial/aquatic laboratory model ecosystem 

indicated that when the plant leaves were eaten by caterpillars, the aquatic system became 

contaminated. Mirex was detected in all segments of two aquatic food chains (alga > snail and 

plankton > daphnia > mosquito > fish) within 33 days. Undegraded mirex contributed to over 98.6, 

99.4, 99.6, and 97.9% of the radiolabel in fish, snails, mosquitoes, and algae, respectively. No 

metabolites of mirex were found in any of the organisms (Francis and Metcalf 1984; Metcalf et al. 

1973). 

Chlordecone is similar to mirex in structure and is also highly persistent in soils and sediments (halflife 

expected to be analogous to 10 years duration for mirex) because of its resistance to 

biodegradation, although some microbial metabolism of chlordecone has been reported (La1 and 

Saxena 1982; Omdorff and Colwell 1980). No evidence of microbial degradation was detected for 

chlordecone exposed to hydrosoils from a reservoir (not previously contaminated with chlordecone) 

and from Bailey Creek (contaminated with chlordecone) under either anaerobic or aerobic conditions 

for 56 days (Huckins et al. 1982). 

Three Pseudomonas species extracted from soil samples to which chlordecone was added (1 mg/ml) 

were found to utilize chlordecone, as a sole carbon source, with quantifiable degradation (67-84%) in 

14 days. Among the degradation products of chlordecone, only hydrochlordecone and 

dihydrochlordecone were identified (George and Claxton 1988; George et al. 1986). Sewage sludge 

bacteria and sediment bacteria, primarily Pseudomonas aeruginosa strain KO3, were able to aerobically 

degrade chlordecone by 10-14% to monohydrochlordecone and, to a lesser extent, dihydrochlordecone 

in 8 weeks. None of the bacterial strains was able to use chlordecone as a sole carbon source; 

therefore, co-metabolism appeared to be the only degradation process. Complete mineralization of 

chlordecone by bacteria is unlikely (Omdorff and Colwell 1980). Concentrations of chlordecone 

greater than 0.2 mg/L are likely to inhibit microbial activity, whereas concentrations of less than 
MIREX AND CHLORDECONE 215 

5. POTENTIAL FOR HUMAN EXPOSURE 

0.01 mg/L had no effects on cell count or uptake of amino acids. Bacteria in James River sediment 

did not produce significant concentrations of chlordecone metabolites (Colwell et al. 1981). 

Degradation of chlordecone in a terrestrial ecosystem was studied by applying the compound to soil, 

growing plants on the soil; and then determining the amount of chlordecone in each compartment after 

1 week. During this time only 0.1% of the applied chlordecone (2 mg/kg) was decomposed to carbon 

dioxide from the soil, and 0.3 mg/kg (approximately 15% of the applied concentration) was 

accumulated by the barley plants. Less than 10% of the applied chlordecone was degraded in the soil 

or converted by the barley plants, and there was no volatilization of the compound from the soil to the 

air (Kloskowski et al. 1981). A laboratory soil-plant system showed that degradation of chlordecone, 

as determined by soil residues remaining after volatilization and mineralization, was l-3% after 

1 week; this compared favorably with the residues remaining in soil in the field after one growing 

season (Scheunert et al. 1983). Analysis of soil contaminated with chlordecone collected in the 

vicinity of the chlordecone production facility showed some photolytic degradation of the compound 

with the production of small amounts of monohydro isomers of chlordecone (Borsetti and Roach 

1978). 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

5.4.1 Air 

Mirex has been detected in wet precipitation over rural areas at concentrations of less than 1 ng/L 

(ppt) (EPA 1981b). Rain fall samples collected at several sites in 1985-1986 as part of the Great 

Lakes Organics Rain Sampling Network contained from >0.2 to <0.5 ng/L (ppt) of mirex. Mirex was 

not detected consistently at many stations throughout the sampling period; therefore, quantitative 

results for mirex were not presented (Strachan 1990). Air samples taken over southern Ontario in 

1988 showed mirex in 5 of 143 samples, at an annual mean concentration of 0.35 pg/m3

 (range, 

0.1-22 pg/m3

) with all of the positive samples detected in polluted environments (Hoff et al. 1992). 

Information on atmospheric concentrations of chlordecone is limited to air sampling results obtained at 

the Life Sciences Products Company production site in Hopewell, Virginia. High volume air filter 

samples collected 200 meters from the plant in March 1974 prior to initiation of production at the site 

contained only 0.18 to 0.35 ng/m3

 of chlordecone. Subsequent air sampling after production was 
MIREX AND CHLORDECONE 216 

5. POTENTIAL FOR HUMAN EXPOSURE 

initiated ranged from 3 to 55 μg/m3. During production years 1974 and 1975, air concentrations at 

more distant sites up to 15.6 miles from Hopewell, Virginia, ranged from 1.4 to 20.7 ng/m3

 (Epstein 

1978). 

5.4.2 Water 

Mirex was detected in rural drinking water samples at concentrations ranging from not detectable to 

437 ng/L (ppt) (Sandhu et al. 1978). Finished drinking water samples from Niagara Falls, New York, 

taken in 1978-1979, had a maximum mirex concentration of 0.03 μg/L (ppt) (Kim and Stone 1982); 

however, in a more recent survey in 1987, mirex was detected in only 5 of 1,147 drinking water 

samples from Ontario, Canada, (maximum concentration of 5 ng/L [ppt]) (Environment Canada 1992). 

The pollution of the Niagara River from chemical manufacturing effluents and leachates from chemical 

manufacturing waste dumps has been well documented. Between 1975 and 1982, mirex was detected 

in the aqueous phase of 6 of 22 samples in the Niagara River at levels between 0.0005 and 

0.0075 ng/L (ppt) (Allan and Ball 1990). Twelve percent of 104 whole water samples, collected from 

the Niagara River between 1981 and 1983, had mirex concentrations that ranged from below the 

detection limit (0.06 ng/L[ppt]) to 2.6 ng/L, with a median concentration of 0.06 ng/L (Oliver and 

Nicol 1984). Mirex was detected in the suspended particulate phase of 42 Niagara River water 

samples taken at the mouth of the river in 1986-1987; 17% of the samples had a mean mirex 

concentration of 0.022 ng/L (ppt) (Allan and Ball 1990). 

In 1982, Mudambi et al. (1992) reported the mean mirex concentrations in the Lake Ontario system 

ranging from 1.85 to 30 pg/L. An intralake comparison of chemicals found in the Great Lakes during 

the 1986 spring turnover did not detect mirex in any of the lakes (Stevens and Neilson 1989), nor in 

the dissolved or particulate fractions of water from the St. Lawrence River between 1981 and 1987 

(Germain and Langlois 1988). In 1986, low levels of mirex were found in 8 of 14 water samples 

taken at various locations along the St. Lawrence River (Kaiser et al. 1990a). The highest 

concentration observed was 0.013 ng/L (ppt). Sergeant et al. (1993) reported mirex concentrations in 

Lake Ontario water samples declined from 0.0015 μg/L (1.5 ng/L) in 1986 to <0.0004 μg/L (0.4 ng/L) 

in 1988. 
MIREX AND CHLORDECONE 217 

5. POTENTIAL FOR HUMAN EXPOSURE 

Mirex was detected in water samples taken in 1972 from areas in Mississippi that had been aerially 

treated with mirex to control the imported red fire ant (Spence and Markin 1974). Water samples 

taken from the bottom of a pond showed residue values that remained higher and more constant than 

those taken from the surface of the pond. Water showed the highest residues immediately after 

treatment (bottom, 0.53 μg/L [ppb]; surface, 0.02 μg/L [ppb]), and detectable levels were still present 

as long as 3 months after treatment (bottom, 0.005 μg/L [ppb]; surface, 0.003 μg/L [ppb]) (Spence and 

Markin 1974). 

The solubility of chlordecone in water is low (l-3 mg/L) and as with mirex, contamination is more 

likely to be associated with the particulate matter in the water rather than the water itself. 

Chlordecone was detected primarily in water samples collected in and around the production facility 

site in Hopewell, Virginia, and in adjacent waters of the James River estuary. Effluent from the Life 

Sciences Products Company facility contained 0. l-l.0 mg/L (ppm) chlordecone, while water in 

holding ponds at the site contained 2-3 mg/L (ppm) chlordecone (Epstein 1978). Levels of 

chlordecone in river water in August 1975 ranged from not detectable (<50 ng/L [ppt]) in the York 

River and Swift Creek areas, to levels of 1-4 μg/L (ppb) in Baileys Creek which received direct 

effluent discharges from the Hopewell Sewage Treatment Plant. Water concentrations of up to 

0.3 μg/L (ppb) were detected in the James River at the mouth of Bailey Creek and in the Appomattox 

River (upstream from Hopewell) at 0.1 μg/L (ppb) (Epstein 1978). Hopewell drinking water drawn 

from the James River contained no detectable chlordecone levels (EPA 1978c; Epstein 1978). In 

1977, 12 years after production of chlordecone began and 2 years after production ceased, average 

concentrations of chlordecone in estuarine water (dissolved) were <l0 ng/L (ppt) (Nichols 1990). In 

October 1981, 6 years after production at the plant ceased, chlordecone water concentrations ranged 

from not detectable to 0.02 μg/L (ppb) (Lunsford et al. 1987). 

5.4.3 Sediment and Soil 

Mirex was identified in sediment samples collected in 1979 from Bloody Run Creek, which is a 

drainage ditch for the Hyde Park landfill in Niagara Falls, New York. Mirex levels in the sediment 

ranged from 0.5 to 2 mg/kg (ppm) (detection limit, 0.5 mg/kg [ppm]) (Elder et al. 1981). 

Between 1979 and 1981, mirex concentrations in suspended sediments of the Niagara River declined 

from a mean concentration of 12 ng/L to 1 ng/L (ppt); concentrations in bottom sediments were 
MIREX AND CHLORDECONE 218 

5. POTENTIAL FOR HUMAN EXPOSURE 

generally low, ranging from less than 1 μg/kg (ppb) to a maximum value of 890 μg/kg (ppb), at a site 

believed to be the source of mirex to the river (Allan and Ball 1990). In 1981, mirex was detected in 

sediments of Lake Ontario near the mouth of the Niagara River at increasing concentrations to a 

maximum of 1,700 μg/kg (ppb) at a sediment depth of 9 cm. Concentrations decreased between 9 and 

13 cm and were not detected in sediments below a depth of 13 cm. Concentrations were 

chronologically correlated with mirex production and peak sales periods and were reduced when its 

use was restricted (Durham and Oliver 1983). In 1982, mirex was detected in settling particulates 

from sediment traps in the Niagara River (average, 7 μg/kg [ppb]; range, 3.9-18 μg/kg [ppb]), 

resuspended bottom sediments from the Niagara Basin of Lake Ontario (average, 9.45 μg/kg [ppb], 

range 5.2−16 μg/kg [ppb]), and bottom sediments from Lake Ontario (average, 48 μg/kg [ppb]) (Oliver 

and Charlton 1984). 

An analysis of urban runoff and sediment runoff collected between 1979 and 1983 from 12 urban 

areas in the Canadian Great Lakes Basin showed that mirex was not detected in any runoff waters, 

although it was found in 10% of 129 runoff sediment samples at a mean concentration of 1.3 μg/kg 

(ppb) (Marsalek and Schroeter 1988). Sediment samples collected from the St. Lawrence River 

between 1979 and 1981 contained low concentrations of mirex (median, <0.l μg/kg; range, 

<0.1-3.3 μg/kg), indicating that Lake Ontario is the source of the contamination to the river (Sloterdijk 

1991). Low levels of mirex were found in bottom sediment core samples taken from the riverine lakes 

in the St. Lawrence River in October 1985; the average concentration of mirex was 0.43 μg/kg (range, 

<0.0l-0.95 μg/kg) (Kaiser et al. 1990a). In 1987, mirex was detected in suspended sediments 

throughout the St. Lawrence River. At the St. Lawrence River stations near Kingston, the mirex 

concentration was approximately 5 μg/kg (ppb), but declined to about 1 μg/kg (ppb) near Quebec City 

(Kaiser et al. 1990a). 

In 1971 and 1972, mirex was detected in soil and sediment samples taken from areas in Louisiana and 

Mississippi that had been aerially treated with mirex to control the imported red fire ant (Spence and 

Markin 1974). In Louisiana, samples were collected throughout the first year after spraying. Soil and 

sediment residues in the Louisiana study peaked after 1 month (soil, 2.5 μg/kg [ppb]; sediment, 

0.7 μg/kg [ppb]) and gradually declined over the remainder of the year. In Mississippi, samples were 

collected for 4 months following spraying. Sediment residues in Mississippi also peaked about 

1 month after spraying (1.1 μg/kg [ppb]) and gradually declined over the next couple of months. The 
 

MIREX AND CHLORDECONE 219 

5. POTENTIAL FOR HUMAN EXPOSURE 

residue levels found in soil in Mississippi were much more variable and showed no distinctive pattern 

(Spence and Markin 1974). 

Less than 10% of the sediment samples taken from the San Joaquin River and its tributaries in 

California (an area of heavy organochloride pesticide use) in 1985 contained mirex residues; all 

samples contained less than 0.1 μg/kg (ppb) (Gilliom and Clifton 1990). 

Studies of sediment from seven sampling stations in the Upper Rockaway River, New Jersey, showed 

that sediment quality corresponded to the land-use data for the area (Smith et al. 1987). The two 

upstream stations, which drain primarily forested areas of the Upper Rockaway Basin, had low mirex 

concentrations in the sediments (<0.1 μg/kg). The remaining stations, which drained an area consisting 

of residential, commercial, and industrial land including six EPA Super-fund sites, had mirex 

concentrations ranging from 8.2 to 80 μg/kg (ppb) (Smith et al. 1987). 

Sediment samples taken from 51 sampling locations in the Gulf of Mexico for the National Oceanic 

and Atmospheric Administration (NOAA) Status and Trends Mussel Watch Program were analyzed for 

mirex contamination (Sericano et al. 1990; Wade et al. 1988). Average mirex concentrations of 

0.07 μg/kg (ppb) (range, <0.0l-0.67) and 0.18 μg/kg (ppb) (range, <0.02-3.58) were found in 

sediments in 1986 and 1987, respectively. The sampling sites represent the contaminant loading for 

the Gulf of Mexico estuaries removed from known point-sources of contamination (Sericano et al. 

1990; Wade et al. 1988). 

With the exception of the James River area of Virginia, very little information is available on 

chlordecone residues in soil and sediment. Chlordecone was detected in soil immediately surrounding 

the Life Sciences Products Company in Hopewell, Virginia, at levels of l-2% (10,000-20,000 mg/kg) 

and contamination extended to 1,000 m at concentrations of 2-6 mg/kg (ppm) (Huggett and Bender 

1980). 

Assessment of sediment cores taken from the James River below Hopewell, Virginia, indicated that 

chlordecone concentrations were greatest nearest the release site. Sediment concentrations of 

chlordecone in Baileys Creek, the waterbody into which effluent from the Hopewell municipal sewage 

treatment facility was discharged, were 2.2 mg/kg (ppm) (Omdorff and Colwell 1980). Chlordecone 

concentrations of 0.44-0.74 mg/kg were found at sediment depths of 55-58 cm in the main channel of 
 

 

 

MIREX AND CHLORDECONE 220 

5. POTENTIAL FOR HUMAN EXPOSURE 

the James River. This area had the highest sedimentation rate (>19 cm/year). Further downriver, 

(80 kilometers from Hopewell) in the James River estuary, chlordecone concentrations decreased and 

maximum concentrations were found closer to the sediment surface. The highest chlordecone 

concentration of 0.18 mg/kg (ppm) was from a sediment depth of 46-48 cm in an area with a 

sedimentation rate of 10 cm/year (Cutshall et al. 1981). 

5.4.4 Other Environmental Media 

In general, because releases of mirex from its production and use as a pesticide were terminated almost 

20 years ago, mirex residues in various biological organisms are much lower than those reported 

during or shortly after its peak years of production and use. This trend is supported by both regional 

and national studies. 

In areas where mirex was historically used for fire ant control, it has been detected in fish and other 

aquatic biota from contaminated rivers. An analysis of mirex residues in primary, secondary, and 

tertiary consumers in ox-bow lakes in Louisiana in 1980 indicated that although mirex was not 

detected in any water or sediment samples, or in the tissues of primary consumers (some fish), it was 

detected in the tissues of secondary consumers (fish and birds that consume invertebrates and insects), 

and in all tertiary consumers (fish-eating fish, birds, and snakes). The highest mean mirex 

concentrations were found in cottonmouth snakes (0.11 mg/kg [ppm]) (Niethammer et al. 1984). Fish 

taken from the lower Savannah River during 1985 had mirex residues in their tissues that ranged from 

nondetectable to 1 mg/kg (ppm) wet weight, although most residues were near 0.02 mg/kg (Winger et 

al. 1990). 

Of all the Coho salmon collected from all of the Great Lakes in 1980, only fish taken from Lake 

Ontario contained detectable mirex residues at an average concentration of 0.14 μg/g (ppm) (Clark et 

al. 1984). The mean concentration of mirex residues in rainbow trout taken from Lake Ontario was 

0.11 μg/g (ppm), while the mean water concentration in the lake was 0.008 ng/L (ppt) (Oliver and 

Niimi 1985). Borgmann and Whittle (1991) studied the contaminant concentration trends in Lake 

Ontario lake trout from 1977 to 1988. Mirex concentrations generally declined from 0.38 μg/g (ppm) 

in 1977 to 0.17 μg/g (ppm) in 1988, although there was considerable variability in the mirex residue 

data. The concentrations of mirex also showed a distinct east-west gradient across the lake. The 

highest mirex residues were detected in fish collected at the western side of the basin and were 70% 
 

 

 

MIREX AND CHLORDECONE 221 

5. POTENTIAL FOR HUMAN EXPOSURE 

above those detected in fish collected at the eastern portion of the basin. Suns et al. (1993) conducted 

a similar study of spatial and temporal trends of organochlorine contaminants in spottail shiners from 

selected sites in the Great Lakes. These authors reported that mirex was only detected in fish from the 

Niagara River, the Credit River in western Lake Ontario, and in the St. Lawrence River at Cornwall. 

Mirex concentrations in spottail shiners collected during the late 1980s were generally lower than 

mirex residues found in spottail shiner samples collected during the 1970s. Considerable fluctuation in 

mirex residues in spottail shiners was observed, which precluded proper trend assessment. Based on 

the fish data, mirex inputs to Lake Ontario appeared to be continuing on an intermittent basis. Most 

recently, Newsome and Andrews (1993) analyzed mirex in fillet samples of 11 commercial fish 

species from the Great Lakes. The highest mirex concentrations were found in carp from a closed 

fishery area (120 μg/kg [ppb]), eel (56.8 μg/kg), carp from an open fishery area (5.24 μg/kg), bullhead 

(3.63 μg/kg), and trout (2.38 μg/kg). 

Burbot, a bottom-feeding fish, taken from remote lakes in Canada in 1985-1986, contained liver 

concentrations of mirex ranging between 3.7 and 17.4 μg/kg (ppb) lipid weight (detection limit, 

0.5 μg/kg), while photomirex was not detected. The lowest mirex values were seen in fish from the 

most remote locations, suggesting that atmospheric transport of this compound was occurring (Muir et 

al. 1990). 

Ninety percent of the mussels collected in 1985 at various points along the St. Lawrence River 

contained mirex at levels up to 1.6 μg/kg (ppb). The only source of mirex was contaminated particles 

entering the river from Lake Ontario; mussels collected from the Ottawa River, which does not receive 

its water from Lake Ontario, did not contain any mirex. The mirex concentrations in the mussels 

decreased with distance from the lake (Metcalf and Charlton 1990). 

Mirex concentrations were measured in 78 snapping turtles collected from 16 sites in southern Ontario, 

Canada, during 1988-1989 to evaluate the risk to human health (Herbert et al. 1993). Mean 

concentrations of mirex in the muscle tissue were below fish consumption guidelines for mirex 

(100 μg/kg [ppb]) and ranged from not detectable to 3.95 μg/kg (ppb). However, mirex concentrations 

in older turtles from some sites were as high as 9.3 μg/kg (ppb). 

Freshwater fish sampled (as part of the U.S. Fish and Wildlife Service National Contaminant 

Biomonitoring Program) between 1980 and 1984 contained detectable concentrations of mirex. Mirex 
 

 

MIREX AND CHLORDECONE 222 

5. POTENTIAL FOR HUMAN EXPOSURE 

was detected in 18% of the 1980 samples (maximum concentration, 210 μg/kg [ppb]; mean 

concentration, 0.01 μg/g) and in 13% of the 1984 samples (maximum concentration, 440 μg/kg [ppb]; 

mean concentration, 10 μg/kg). The highest mirex concentrations were detected in whole fish taken 

from Lake Ontario, the St. Lawrence River, and the southeastern United States, all areas where mirex 

had been manufactured or used (Schmitt et al. 1990). In the recent EPA National Study of Chemical 

Contaminants in Fish, mirex was detected at 38% of 362 sites sampled. The mean mirex 

concentration was 3.86 μg/kg (ppb) and the maximum concentration was 225 μg/kg (ppb). The 

highest concentrations of mirex were detected in fish collected in the Lake Ontario area of New York 

State (EPA 1992a). 

Of oysters (Crassostrea virginica) sampled throughout the United States between 1965 and 1972 for 

the National Pesticide Monitoring Program, only those from South Carolina locations had detectable 

mirex residues (maximum concentration, 540 μg/kg [ppb]) with most residues being less than 38 μg/kg 

(ppb) (Butler 1973). Oysters taken from 49 sampling locations in the Gulf of Mexico for the NOAA 

Status and Trends Mussel Watch Program 1986-1987 were analyzed for mirex contamination 

(Sericano et al. 1990; Wade et al. 1988). Average mirex concentrations of 1.40 μg/kg (ppb) (range, 

<0.25-15.8 μg/kg) and 1.38 μg/kg (ppb) (range, <0.25-16.1) were found in oysters in 1986 and 1987, 

respectively (Sericano et al. 1990). The sampling sites represent the contaminant loading for the Gulf 

of Mexico estuaries removed from known point-sources of contamination (Wade et al. 1988). 

Mirex was also detected in the muscle and liver tissues of seven species of aquatic and terrestrial 

mammals collected in areas of Alabama and Georgia that had been repeatedly treated with mirex to 

suppress fire ant populations from March 1973 through July 1976. At 6 months post-treatment, skunk 

and opossum muscle tissue contained the highest mean mirex concentrations of 3.50 and 1.5 1 μg/g 

(ppm), respectively (Hill and Dent 1985). Two years post-treatment, muscle residues declined in all 

species except the mink, which increased from 0.14 μg/g at 6 months post-treatment to a mean muscle 

residue of 0.28 μg/g at 1 year post-treatment and 0.53 μg/g at 2 years post-treatment. 

Mirex was detected in the subcutaneous fat and breast muscle of 55 waterfowl collected in New York 

State during 1981 and 1982. Average mirex levels were 280 μg/kg (ppb) in fat and 2.0 μg/kg in 

breast muscle (Kim et al. 1985). Mirex was detected at a concentration of >500 μg/kg (ppb) in 24 of 

164 samples of subcutaneous fat of six species of waterfowl (mallard, black duck, scaup, wood duck, 

bufflehead, and Canada goose) harvested by hunters in 1983-1984 (Foley 1992). More recently, mirex 
 

 

MIREX AND CHLORDECONE 223 

5. POTENTIAL FOR HUMAN EXPOSURE 

was detected in fat samples from 5 of 26 goldeneyes shot by hunters in December 1988 in New York 

State; however, no quantitative information on mirex residues was provided (Swift et al. 1993). 

Gebauer and Weseloh (1993) used farm-raised mallards as sentinels for accumulation of pollutants at 

three sites in southern Ontario, Canada. The sites included the Hamilton Harbor Confined Disposal 

Facility designated as an “Area of Concern” because of high pollutant concentrations of sediment; the 

Winona Sewage Lagoons, which contained high concentrations of metals; and Big Creek Marsh, which 

served as a reference area. The geometric mean concentrations of mirex detected in muscle tissue at 

each site were: 7.1 μg/kg (ppb) at the Hamilton Harbor site after 115 days; 0.07 μg/kg at the sewage 

lagoon site after 112 days; and 0.14 μg/kg at the reference site after 30 days. 

Mirex residues were detected in food samples analyzed as part of the FDA Pesticide Residue 

Monitoring Studies conducted from 1978-1982 of 49,877 food samples and from 1982-1986 of 

49,055 food samples; however, the frequency of detection was unspecified but was <l and 2% 

respectively (Yess et al. 1991a, 1991b). A similar 1985 analysis of foods grown in Ontario, Canada, 

failed to detect any mirex or photomirex in any of the vegetable, fruit, milk, egg, or meat products 

tested (Davies 1988). Mirex was also detected in the FDA Pesticide Residue Monitoring Study from 

1986-1987; however, the frequency of detection was unspecified but less than 1% (FDA 1988). 

Mirex was not detected in 27,065 samples of food collected in 10 state food laboratories from 1988 

and 1989 (Minyard and Roberts 1991). Mirex was also not detected in domestically produced or 

imported foods sampled as part of the FDA Pesticide Residue Monitoring Study during 1988-1989 

(FDA 1990), was detected (at less than 1% occurrence) in foods sampled in 1989-1990 (FDA 1991), 

and was not detected in foods sampled in 1990-1991 and 1992-1992 (FDA 1992, 1993). Mirex 

residues were detected in one sample of 806 cornposited milk samples collected through the 

Pasteurized Milk Program by the EPA in 1990-1991 (Trotter and Dickerson 1993). The milk was 

sampled at 63 stations that provide an estimated 80% of the milk delivered to U.S. population centers. 

At each station, milk from selected sources was cornposited to represent milk routinely consumed in 

the station’s metropolitan area. The detection of mirex occurred in milk samples from Cristobal, 

Panama. 

Because releases of chlordecone from its production and use ceased almost 20 years ago, current 

chlordecone residues in various biological organisms are generally lower than those reported during its 

peak production years (1974-1975). Releases of chlordecone from the manufacturing plant in 

Hopewell, Virginia, severely contaminated the James River estuary in Virginia from 1966 through 
 

 

MIREX AND CHLORDECONE 224 

5. POTENTIAL FOR HUMAN EXPOSURE 

1975. In 1977, 12 years after production of chlordecone began and 2 years after it ceased, average 

chlordecone concentrations in various biological organisms in the estuary were as follows (Nichols 

1990): phytoplankton, 1.30 μg/g; zooplankton, 4.80 μg/g; freshwater fish, 2.50 μg/g; migratory fish, 

0.40 μg/g; and benthic fauna (molluscs), 1.50 μg/g. Considerable variations in chlordecone 

concentrations detected in fish species in the James River were in part associated with different life 

histories and residence times of each species in the estuary (Huggett and Bender 1980). Freshwater 

species which were permanent residents in the upper estuary exhibited the highest range in tissue 

residues varying from <0.1 μg/g (ppm) for channel catfish to >2 μg/g for largemouth bass. Residues 

in marine fish increased with length of exposure time in the James River. American shad that 

inhabited the estuary only briefly showed average chlordecone residues of <0.l μg/g. Longer-term 

residents that spent 6-9 months in the estuary, such as spot and croaker, contained 1 μg/g. 

Concentrations in resident estuarine species ranged from 0.7 μg/g for the bay anchovy to 2.7 μg/g for 

white perch. 

Dredging of the James River in Virginia increased the chlordecone levels in resident clams (Rangia 

cuneatu). The river has contaminated sediments containing up to 3.5 μg/g (ppm) chlordecone. Prior 

to the 2-week dredging period, chlordecone concentrations in the water column ranged from 

nondetectable to 0.02 μg/L (ppb); background concentrations in the clams ranged from 0.06 to 

0.14 μg/g. During the dredging, body burdens of chlordecone in clams increased by 0.01-0.04 μg/g 

(ppm). Two weeks after the dredging was completed, residues in the clams had not returned to predredging 

levels (Lunsford et al. 1987). 

In addition to the James River area, chlordecone residues of 0.025 and 0.23 mg/kg (ppm) were 

detected in trout and suckers, respectively, collected from Spring Creek 18 miles downstream of the 

Nease Chemical Plant in Pennsylvania (EPA 1978c). This plant produced small quantities of 

chlordecone from 1966-1974 (Epstein 1978). 

Because chlordecone contamination of the James River in Virginia and Spring Creek in Pennsylvania 

represented relatively isolated incidents resulting from industrial negligence and because the compound 

was not used extensively on agricultural crops in the United States, monitoring for this compound has 

not been included as part of the U.S. Fish and Wildlife Service National Contaminant Biomonitoring 

Program (Schmitt et al. 1990) or the EPA National Study of Chemical Residues in Fish (EPA 1992a). 
MIREX AND CHLORDECONE 225 

5. POTENTIAL FOR HUMAN EXPOSURE 

Chlordecone residues were detected in the FDA Pesticide Residue Monitoring Studies of 49,877 food 

samples from 1978-1982 and of 49,055 food samples from 1982-1986; however, the frequency of 

detection was unspecified but was less than 1 and 2% respectively (Yess et al. 1991a; 1991b). 

Chlordecone was also detected in 1 of 27,065 samples of food collected from 10 state laboratories 

during 1988 and 1989 (Minyard and Roberts 1991). Chlordecone was not detected in any 

domestically produced or imported foods analyzed as part of the FDA Pesticide Residue Monitoring 

Studies during 1986-1987, 1988-1989, 1989-1990, 1990-1991, and 1991-1992 (FDA 1988, 1990, 

1991, 1992, 1993). 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Mirex has not been produced since 1976 and has not been used in the United States since 1977, when 

all registered uses of the product were canceled. The potential for exposure of the general population, 

therefore, is relatively small and should continue to diminish over time. Members of the general 

population may be exposed to low concentrations of mirex primarily through consumption of 

contaminated food stuffs, in particular contaminated fish and shellfish from Lake Ontario, the St. 

Lawrence River, and Spring Creek in Pennsylvania, which were all contaminated by industrial 

discharges, and areas of the southern United States that were extensively treated with mirex for fire ant 

control. No dietary intake estimates are available (FDA 1990, 1991, 1992) since mirex has been so 

infrequently found in foodstuffs in recent years. Mirex exposure from drinking water has not been 

found to constitute significant human exposure since mirex is relatively insoluble in water and rapidly 

adsorbs to sediment (EPA 1978c). 

Mirex has been detected in the general U.S. population. The National Human Monitoring Program for 

Pesticides detected mirex at low frequencies in human adipose tissue collected nationwide. In 1972, 

mirex was detected in 0.05% of all samples and in 1973, mirex was detected in 0.09% of all samples; 

however, by 1974, the percentage of positive samples had increased to 0.11% (Kutz et al. 1979). 

Mirex was detected in 13% of samples collected as part of the 1982 National Adipose Tissue Survey 

(EPA 1986b). Concentrations of mirex ranged from 0.008 to 0.39 μg/g (ppm) (mean concentration 

0.025 μg/g). Further analysis of adipose tissue samples collected as part of the 1982 National Adipose 

Tissue Survey failed to detect mirex in any tissues from children (newborn infants to 14-year-olds); 

however, tissue samples from adults aged 15-44 and 45 years or older were found to contain mirex 

residues. The greatest concentrations (values not provided) for 15-44-year-old adults were found in 
 

MIREX AND CHLORDECONE 226 

5. POTENTIAL FOR HUMAN EXPOSURE 

the Northeast and South Atlantic States, while the greatest concentrations for >45-year-old adults were 

found in the West South Central States and Northeast States (Phillips and Birchard 1991a). 

In a survey of human adipose tissue from residents of southwestern Ontario between 1976 and 1979, 

mirex was detected in 32.8% of the samples at mean concentrations of <0.01 mg/kg (ppm). In 

1980-1981, it was detected in more samples (64.8%) at greater concentrations (mean concentration, 

0.04 mg/kg); however, in 1983-1984, it was detected in only 6.2% of the samples at an average 

concentration of 0.06 mg/kg. Adipose tissue collected from 13 infants during this time contained less 

than 0.01 mg/kg mirex except for one sample that contained 0.02 mg/kg. Mirex was not detected in 

any blood or human milk samples collected for this survey (Frank et al. 1988). A 1985 nationwide 

study of chlorinated hydrocarbons in the adipose tissue of Canadians found mirex to be present in all 

108 samples collected nationwide at a mean concentration of 7 ng/g (ppb) (maximum concentration, 

72 ng/g). The high rate of detection was a result of improved analytical procedures and lower limits 

of detection than those used in earlier studies. Residues were evenly distributed throughout the 

country and did not differ significantly between the sexes or by age (Mes et al. 1990). In a 

1990-1991 survey of human adipose tissue from residents of British Columbia, Canada, mirex was 

detected at a minimum, mean and maximum concentration of 1.15, 6.10, and 33.3 ng/g (ppb) lipid 

respectively (Teschke et al. 1993). 

Mirex residues in human blood serum were measured as part of the Second National Health and 

Nutrition Examination Survey (NHANES II), conducted between 1976 and 1980. Of the 4,038 

samples analyzed, mirex concentrations ranged from not detectable to detected but below quantifiable 

levels (10 μg/L [ppb]) (Stehr-Green 1989). 

Mirex was detected (mean detection limit 3 pg/g [ppt]) in 62% of 412 breast milk samples collected 

from women in all Canadian provinces (Mes et al. 1993). The mean, median, and maximum mirex 

concentrations detected in whole milk were 0.14, 0.08, and 6.56 ng/g (ppb), respectively, and for milk 

fat were 4.2, 2.3, and 124.5 ng/g, respectively. In previous studies, mirex residues were not detected. 

None of the 1,436 human milk samples collected in the United States in the late 1970s as part of the 

National Human Milk Study contained identifiable levels of mirex (Savage et al. 1981). A similar 

national study of nursing mothers in Canada (Mes et al. 1986) also failed to detect mirex in any 

human milk samples. The high rate of detection in the Mes et al. (1993) study was a result of 

improved analytical procedures and lower limits of detection. 
 

 

MIREX AND CHLORDECONE 227 

5. POTENTIAL FOR HUMAN EXPOSURE 

An analysis of potential human exposure to contaminants in drinking water and foods was conducted 

in Ontario, Canada, in 1980. Mirex was detected only in edible fish taken from Toronto Harbor on 

Lake Ontario. The average mirex concentrations were 0.001 mg/kg (ppm) wet weight for white 

sucker, 0.01 mg/kg wet weight for rainbow trout, and 0.033 mg/kg wet weight for northern pike. 

Estimated human exposure levels, based on an average fish consumption of 0.53 kg/year for each fish 

species, were 0.0005 for white sucker, 0.005 for rainbow trout, and 0.017 mg/year for northern pike, 

respectively (Davies 1990). 

Mirex is no longer manufactured, formulated, or used in the United States. Therefore, there is 

currently no occupational exposure to this chemical associated with its production or application as a 

pesticide. Current occupational exposure is most likely to occur for workers employed at waste 

disposal sites or those engaged in remediation activities including removal of soils and sediments 

contaminated with mirex. There is a slight possibility of exposure for workers involved in dredging 

activities (e.g., sediment remediation work performed by the Corps of Engineers). 

Chlordecone has not been produced since 1975 or used in the United States since 1978 when all 

registered uses of the product were canceled. The potential for exposure of the general population, 

therefore, is relatively small and should continue to diminish over time. Members of the general 

population may be exposed to low concentrations of chlordecone primarily through consumption of 

contaminated foodstuffs, in particular contaminated fish and shellfish from the James River in Virginia. 

No dietary intake estimates are available (FDA 1990, 1991, 1992) since chlordecone has been so 

infrequently found in foodstuffs in recent years. Chlordecone exposure from drinking water has not 

been found to constitute significant human exposure since chlordecone is relatively insoluble in water 

and rapidly adsorbs to sediment (EPA 1978c). 

No information was located for the general population on chlordecone concentrations in human 

adipose tissue or blood as this compound was not included in any major national study (e.g., National 

Human Adipose Study). 

Chlordecone was detected in 9 of 298 samples of human milk collected in the southern United States; 

however, the detection limit was relatively high (1 μg/kg). Residues were detected only in women 

living in areas that had received mirex bait treatment for fire ant control (EPA 1978c). 
 

MIREX AND CHLORDECONE 228 

5. POTENTIAL FOR HUMAN EXPOSURE 

With regard to occupational exposures, chlordecone was detected in blood samples from workers at the 

Life Sciences Products Company in Hopewell, Virginia. Chlordecone levels in the blood of 32 

workers at the manufacturing plant ranged from 0.165-26.0 μg/mL (ppm) (Epstein 1978). The mean 

blood level of workers exhibiting symptoms of nervousness and tremors was 8.48 μg/mL compared to 

a mean of 1.57 μg/mL in workers exhibiting no symptoms (Epstein 1978). In another occupational 

study, Cannon et al. (1978) reported maximum chlordecone blood levels in workers at the Hopewell 

facility of 11.8 μg/rnL. Chlordecone blood levels of workers who reported illness averaged 

2.53 μg/mL, while blood levels for workers reporting no illness averaged 0.6 μg/rnL. 

In 1975, when chlordecone was still being produced, over half of the workers at a manufacturing plant 

developed clinical illness characterized by nervousness, tremor, weight loss, opsoclonus, pleuritic and 

joint pain, and oligospermia (Cannon et al. 1978). During the years of production, chlordecone was 

also detected in family members of the plant workers at the Life Sciences Products Company in 

Hopewell, Virginia. Although half of the workers at the plant had clinical signs of chlordecone 

poisoning, such signs were detected in only two family members who washed contaminated clothes 

(Cannon et al. 1978). Another study also found higher chlordecone levels in members of chlordecone 

workers’ families compared with families of workers at other local industries or other community 

residents (Taylor et al. 1978). Such illness could have been mitigated by appropriate occupational 

health measures that would prevent the transport of contaminated materials from the workplace, such 

as not bringing work clothes home (Knishkowy and Baker 1986). 

Current occupational exposure is most likely to occur for workers employed at waste disposal sites or 

those engaged in remediation activities associated with the clean-up or removal of soils or sediments 

that are contaminated with chlordecone. 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Members of the general population who currently have potentially high exposures to mirex include 

recreational and subsistence fishers who may consume large quantities of fish and shellfish from 

waterbodies with mirex contamination, hunters who consume game species that may be contaminated 

with mirex, populations living near sites where mirex was manufactured or waste disposal sites 

contaminated with mirex, or populations living in areas where mirex was used extensively for fire ant 

control. 
 

MIREX AND CHLORDECONE 229 

5. POTENTIAL FOR HUMAN EXPOSURE 

Mirex contamination has tnggered the issuance of several human health advisories nationwide. As of 

September 1993, mirex was identified as the causative pollutant in eight fish consumption advisories in 

three different states. This information is summarized below (RTI 1993): 

State Waterbody Extent 

Ohio Middle Fork/Little Beaver Creek SR Alternate 14 and Allen Road to SR 11, 

South of Lisbon 

Pennsylvania Spring Creek SR 3010 bridge at Oak Hall to mouth, 

New York Irondequoit Bay Monroe County 

Lake Ontario Below the Falls 

Lake Ontario Below the Falls, west of Point Breeze 

Lake Ontario Below the Falls, east of Point Breeze 

Niagara River Below the Falls 

St. Lawrence River Entire River 

EPA Office of Water has recently identified mirex as a target analyte and recommended that this 

chemical be monitored in fish and shellfish tissue samples collected as part of state toxics monitoring 

programs. EPA recommends that residue data obtained from these monitoring programs should then 

be used by states to conduct risk assessments to determine the need for issuing fish and shellfish 

consumption advisories for the protection of the general public as well as recreational and subsistence 

fishermen (EPA 1993a). Recreational and subsistence fishers that consume appreciably larger amounts 

of locally caught fish from contaminated waterbodies may be exposed to higher levels of mirex 

associated with dietary intake (EPA 1993a). 

Persons living in areas where mirex has been used for fire ant control or near where it was 

manufactured may be at increased risk of exposure. Human tissue samples (unspecified) taken from 

186 people at sites treated with mirex over the previous 10 years had mirex residues in the range of 

<l-l.32 μg/g (ppm) (mean concentration, 0.38 μg/g) (Holleman and Hammons 1980). A 1975-1976 

survey of 624 human adipose tissue samples from subjects living in eight southern states where mirex 

had been used for fire ant control indicated that 10.2% of the population in the area had detectable 

levels of mirex at a geometric mean concentration of 0.286 μg/g (ppm). Populations living in two 

states, Texas and North Carolina, had no detectable mirex residues in their tissues, whereas 51.1% of 

the samples from populations in Mississippi had detectable levels (mean concentration, 0.290 μg/g) 

(Kutz et al. 1985). Mirex was detected in human adipose tissue samples from residents of northeast 
 

MIREX AND CHLORDECONE 230 

5. POTENTIAL FOR HUMAN EXPOSURE 

Louisiana during the late 1970s (Greer et al. 1980). Concentrations of mirex in adipose tissue 

collected during surgery and during post-mortem examinations ranged from 0.01 μg/g to 0.60 μg/g 

(ppm) with a mean mirex concentration of 0.14 μg/g. Human adipose tissue samples from 

northeastern Louisiana, an agricultural area, contained detectable amounts of mirex in 20 of 22 

samples in 1977 at a mean concentration of approximately 0.15 μg/g (ppm), 10 of 10 samples in 1980 

at a mean concentration of 0.25 μg/g, and only 2 of 10 samples in 1984 at a mean concentration of 

0.15 μg/g (Holt et al. 1986). 

A comparison of mirex residues in adipose tissue samples collected between 1979 and 1981 from 

residents of Kingston, Ontario (a city located on Lake Ontario), and residents of Ottawa, Ontario, 

indicated that persons living in Kingston had significantly higher mirex and photomirex residues than 

those in Ottawa (27 and 9 ng/g (ppb), respectively, in Kingston versus 11 and 6 ng/g, respectively, in 

Ottawa). Males from Kingston had significantly higher levels of mirex (38 ng/g) than females from 

the area (12 ng/g); this gender difference was not explained or seen in the Ottawa samples (Williams 

et al. 1984). A subsequent 1984 study examined mirex levels in six additional cities on the Canadian 

portion of Lake Ontario. The overall mean mirex residue in human adipose tissue was 11±13 ng/g 

(ppb) (males, 12±15 ng/g; females, 9.6±10 ng/g) (Williams et al. 1988). 

Mirex levels in the blood of pregnant women in Jackson, Mississippi, and the Mississippi Delta area 

where mirex was extensively used were correlated with the health of the infants they bore. The mean 

mirex level in maternal blood was 0.54 μg/L (ppb) for 106 samples; however, mirex levels in the 

blood of the infants were not correlated with differences in gestation times, Apgar score, or other 

problems at birth. Only three children with neurological problems had mothers with pesticide levels, 

including mirex, above the mean levels (Lloyd et al. 1974). 

In 1977, mirex was detected in human milk and colostrum samples of women living in upstate New 

York. Milk from women in Oswego and Rochester, areas adjacent to Lake Ontario (known to be 

contaminated with mirex), was compared with milk from women in Albany (considered to be free 

from mirex contamination). Mean mirex concentrations from women in each area were as follows: 

Area Colostrum (ng/g) Mild (ng/g) 

Albany 0.057 (n=24) 0.07 (n=6)
 

Oswego 0.51 (n=18) 0.120 (n=16)
 

Rochester 0.035 (n=4) 0.162 (n=6)
 
 

MIREX AND CHLORDECONE 231 

5. POTENTIAL FOR HUMAN EXPOSURE 

Only two of the 28 milk samples (both from Oswego) were below the detection limit of 0.01 ng/g 

(ppb), while 16 of 24 colostrum samples in Albany, 10 of 18 colostrum samples from Oswego, and 

2 of 4 colostrum samples from Rochester were below the detection limit. None of the women 

reported eating freshwater fish, a possible source of the mirex contamination (Bush et al. 1983a). 

Members of the general population currently having potentially higher exposure to chlordecone include 

recreational and subsistence fishers who may consume large quantities of fish and shellfish from 

waterbodies with chlordecone contamination, populations living near sites where chlordecone was 

manufactured or waste disposal sites contaminated with chlordecone. 

Chlordecone contamination has tnggered the issuance of one human health advisory. As of September 

1993, chlordecone was identified as the causative pollutant in an advisory issued by the State of 

Virginia for the 113 miles of the James River Estuary. The advisory extends from Richmond, 

Virginia, downstream to the Hampton-Norfolk Bridge Tunnel including all tributaries to the James 

River (RTI 1993). 

The only data on chlordecone residues in populations living near a production site are historic and 

were collected almost 20 years ago. The EPA initiated a community survey in August 1975 shortly 

after production of chlordecone was halted to determine chlordecone levels in blood of persons living 

in the vicinity of the Hopewell manufacturing plant. Two hundred nine community residents, none of 

whom had ever been employed at the Allied Chemical plant or Life Sciences Products Company 

(LSPC) were surveyed. Chlordecone blood levels were greater than 5 ppb in 39% of residents living 

0.25 miles south of the LSPC plant, in 7.7% of residents living 0.25 miles north of the LSPC plant, in 

5.9% of residents living 0.5 miles from the site, in 2.6% of residents living 0.75 miles from the site, 

and in 3.3% of residents living 1 mile from the site. Chlordecone blood levels were approximately 

linear as a function of proximity to the LSPC site (Epstein 1978). No additional information was 

located on current chlordecone levels in residents of the Hopewell, Virginia, area. 

5.7 ADEQUACYOFTHEDATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of mirex and chlordecone is available. Where adequate 
 

MIREX AND CHLORDECONE 232 

5. POTENTIAL FOR HUMAN EXPOSURE 

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 mirex and chlordecone. 

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. 

5.7.1 Identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of mirex and 

chlordecone are sufficiently documented to permit estimation of their environmental fate (Howard et 

al. 1981; HSDB 1994b; IARC 1979c; Kenaga 1980; Merck 1989; Sax and Lewis 1987). No further 

information is necessary. 

Production, Import/Export, Use, Release, and Disposal. Mirex and chlordecone are no 

longer being produced or used in this country (IARC 1979a, 1979c; Sittig 1980). Mirex was most 

commonly used from 1962-1976 as an insecticide to control fire ants (IARC 1979c). Between 1962 

and 1976, 132 million acres were treated with approximately 485,000 pounds of mirex at a rate of 

4.2 g/hectare. Mirex was also used as a flame retardant from 1959 to 1972 in various coatings, 

plastics, rubber, paint, paper, and electrical goods (IARC 1979c). Until 1976, chlordecone was used as 

an insecticide on bananas, non-bearing citrus trees, tobacco, and ornamental shrubs (Epstein 1978; . 

IARC 1979a). It was also used in household products such as ant and roach traps (IARC 1979a). 

However, all registered products containing mirex and chlordecone were canceled in 1977 and 1978, 

respectively (Sittig 1980). Since mirex and chlordecone are not flammable and are very stable in the 

environment, many disposal methods have proven unsuccessful. Since mirex is not identified by EPA 

as a hazardous waste under SARA Title III, no regulatory information is available for the disposal of 

mirex. However, the recommended method of disposal for mirex is incineration (HSDB 1994b). 

Efficient disposal methods exist for chlordecone (DeZeam and Oberacker 1980; Greer and Griwatz 

1980). Chlordecone is considered an EPA hazardous waste and must be disposed of according to EPA 

regulations (EPA 1980c). 
MIREX AND CHLORDECONE 233 

5. POTENTIAL FOR HUMAN EXPOSURE 

Environmental Fate. Mirex and chlordecone released to the environment partition to soil and 

sediment. Small amounts may remain dissolved in water (Yin and Hassett 1989). Mirex and 

chlordecone released to the atmosphere are eventually deposited on soil or surface waters. On the 

surface of soil or water, mirex undergoes photolysis with the subsequent loss of a chlorine atom (Alley 

et al. 1974; Francis and Metcalf 1984; Reimer et al. 1989). Both compounds are resistant to aerobic 

degradation, although some anaerobic biodegradation does occur (Andrade and Wheeler 1974; Andrade 

et al. 1975; Carlson et al. 1976; Huckins et al. 1982). When not exposed to sunlight or anaerobic 

conditions, mirex and chlordecone persist in soil, particularly sediments, for many years. Data on the 

atmospheric transport and degradation of these compounds are minimal; additional information would 

be helpful in identifying potential mechanisms and sources of atmospheric releases and the potential 

for contamination of surface waters and soils. Information on the persistence of mirex and 

chlordecone in water would also be useful. 

Bioavailability from Environmental Media. Both mirex and chlordecone can be absorbed 

following oral exposure in animals, although chlordecone is more readily absorbed than mirex (Byrd et 

al. 1982; Egle et al. 1978; Gibson et al. 1972; Kavlock et al. 1980; Mehendale et al. 1972). Very 

limited data indicate that mirex is absorbed by rats following inhalation exposure in cigarette smoke 

(Atallah and Dorough 1975). No data were located regarding absorption of mirex following dermal 

exposure in animals. Limited human data concerning the presence of mirex in adipose tissue and the 

excretion of mirex in human milk, and occupational studies concerning chlordecone indicate that mirex 

and chlordecone can be absorbed, although the exact route of exposure (inhalation, oral, dermal) was 

not specified in these cases (Burse et al. 1989; Cannon et al. 1978; Cohn et al. 1978; Kutz et al. 1974; 

Mes et al. 1978; Taylor 1982, 1985). Limited animal data indicate that dermal absorption of 

chlordecone is low. Information regarding the bioavailability of mirex and chlordecone from dermal 

contact of contaminated soils would be helpful, particularly for populations living near hazardous 

waste sites. 

Food Chain Bioaccumulation. Both mirex and chlordecone are highly lipophilic and, therefore, 

have high bioconcentration potentials. They are bioaccumulated in aquatic food chains with virtually 

no degradation of the compounds by exposed organisms (de la Cruz and Naqui 1973; Epstein 1978; 

Huckins et al. 1982; Huggett and Bender 1980; Kenaga 1980; Lunsford et al. 1987; Naqvi and de la 

Cruz 1973; Nichols 1990; Oliver and Niimi 1985, 1988; Roberts and Fisher 1985). Uptake and 

bioaccumulation of mirex in terrestrial food chains have also been shown to occur (Bacci et a1.1990b; 
 

 

 

MIREX AND CHLORDECONE 234 

5. POTENTIAL FOR HUMAN EXPOSURE 

Connell and Markwell 1990; de la Cruz and Rajanna 1975; Hebert et al. 1994; Naqvi and de la Cruz 

1973). No further information is necessary. Only limited information is available on uptake and 

bioaccumulation of chlordecone in terrestrial food chains (Naqvi and de la Cruz 1973), and little 

uptake of chlordecone by plants was observed (Topp et al. 1986). Additional information on uptake of 

chlordecone in plants under field conditions would be helpful. 

Exposure Levels in Environmental Media. Environmental monitoring data are available for 

mirex levels in air, water, soil, and sediment (Durham and Oliver 1983; Hoff et al. 1992; Kaiser et al. 

1990a; Oliver and Nicol 1984). Limited information on mirex concentrations in groundwater is 

available (Greenburg et al. 1982; Sandhu et al. 1978); however, because mirex binds tightly to organic 

matter in soil, additional leaching data are not necessary. Data on atmospheric releases and levels of 

chlordecone are available only for two years (1974-l 975) of its production at the Hopewell, Virginia 

facility (Epstein 1978); however, since chlordecone production in the United States ceased in 1975 and 

because most of the chlordecone produced was exported or was used in insect bait traps so that it was 

not widely dispersed in the environment, no additional current information on chlordecone in the 

atmosphere is required. Historic chlordecone levels in surface waters, soils, and sediments in the 

vicinity of the Hopewell, Virginia facility have been well characterized (Cutshall et al. 1981; Epstein 

1978; Huggett and Bender 1980; Nichols 1990), but no recent information was found. Groundwater 

monitoring data are lacking, but because chlordecone binds tightly to organic matter in soil, leaching 

into groundwater is not anticipated to occur extensively. Minimal information was found on the 

uptake of mirex and chlordecone by plants grown under field conditions. Adequate information on 

mirex and chlordecone levels in fish and shellfish are available (Borgmann and Whittle 1991; Clark et 

al. 1984; EPA 1992a; Huggett and Bender 1980; Metcalf and Charlton 1990; Muir et al. 1990; 

Newsome and Andrews 1993; Nichols 1990; Oliver and Niimi 1985; Schmitt et al. 1990; Sericano et 

al. 1990). Further information on foods other than fish and shell fish, particularly in foods grown in 

areas where mirex has been used as a pesticide, would be helpful in estimating current human and 

animal intake. 

Reliable monitoring data for the levels of mirex and chlordecone in contaminated media at hazardous 

waste sites are needed so that the information obtained on levels of mirex and chlordecone in the 

environment can be used in combination with the known body burden of mirex and chlordecone to 

assess the potential risk of adverse health effects in populations living in the vicinity of hazardous 

waste sites. 
 

MIREX AND CHLORDECONE 235 

5. POTENTIAL FOR HUMAN EXPOSURE 

Exposure Levels in Humans. Mirex has been detected in human adipose tissue, blood, and milk 

(Phillips and Birchard 1991a; Stehr-Green 1989). Because of the lipophilic nature of mirex, most 

determinations of exposure are based on residues found in adipose tissue. Higher levels in tissue have 

been correlated with areas of mirex usage, manufacture, or disposal at waste sites (Bush et al. 1983a; 

Holleman and Hammons 1980; Taylor et al. 1978). Chlordecone has not been detected in human 

adipose tissue or in blood samples from the general population, although historically it was detected in 

human milk samples collected in the southeastern United States (EPA 1978c). Adequate information 

is available regarding chlordecone levels in blood of occupationally exposed workers and their families 

during 1974-1975 employed at the Hopewell, Virginia site. (Cannon et al. 1978; Epstein 1978; 

Knishkowy and Baker 1986; Taylor et al. 1978). More recent information for mirex and chlordecone 

would be helpful in determining where human exposure is of greatest concern. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposure Registries. No exposure registries for mirex and chlordecone were located. These 

substances are not currently compounds for which subregistries have been established in the National 

Exposure Registry. These substances 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 these substances. 

5.7.2 Ongoing Studies 

No ongoing studies were located (FEDRIP 1994). 

MIREX AND CHLORDECONE 237 

6. ANALYTICAL METHODS
 

The purpose of this chapter is to describe the analytical methods that are available for detecting, and/or 

measuring, and/or monitoring mirex and chlordecone, their metabolites, and other biomarkers of 

exposure and effect to mirex and chlordecone. 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. 

6.1 BIOLOGICAL SAMPLES 

The most commonly used methods for measuring mirex in blood, tissues (including adipose tissue), 

milk, and feces are gas chromatography (GC) or capillary GC combined with electron capture 

detection (ECD) or mass spectrometry (MS). Tables 6-l and 6-2 summarize the applicable analytical 

methods for determining mirex and chlordecone, respectively, in biological fluids and tissues. Sample 

preparation for biological matrices involves solvent extraction followed by clean-up steps. Biological 

samples are often contaminated with other compounds such as polychlorinated biphenyls (PCBs); 

therefore, additional clean-up steps and/or confirmation techniques are employed to assure reliable 

results. 

Mirex can be extracted from blood using hexane, acetone-hexane, hexane-ethyl ether, or petroleum 

ether and acetone (Bristol et al. 1982; Caille et al. 1987; Korver et al. 1991; Stahr et al. 1980; 

Waliszewski and Szymczynski 1991). Blood samples are often contaminated with other compounds 

such as PCBs. The use of adsorption chromatography as a clean-up step is effective in achieving 

separation of PCBs from mirex in blood (Korver et al. 1991). Other clean-up methods for blood and 

tissue samples include concentrated sulfuric acid wash (Waliszewski and Szymczynski 1991), and 

Florisil column clean-up (Mes 1992). For measuring mirex in blood, sensitivity of GC/ECD is in the 

sub-parts per billion (ppb) range (Korver et al. 1991). Recovery of mirex from blood is generally 




MIREX AND CHLORDECONE 242 

6. ANALYTICAL METHODS 

good (≥70%) (Caille et al. 1987; Korver et al. 1991; Stahr et al. 1980; Waliszewski and Szymczynski 

1991). Precision is generally very good for blood samples (≤10% relative standard of deviation 

[RSD]) (Korver et al. 1991; Stahr et al. 1980). The low RSDs indicate good repeatability of the 

procedures (Waliszewski and Szymczynski 1991). Sample storage may adversely affect recovery 

(Bristol et al. 1982) and precision (Bristol et al. 1982; Stahr et al. 1980). Confirmation of mirex in 

blood can be accomplished by using GC/MS (Korver et al. 1991; Mes 1992). 

Mirex can be extracted from tissues using hexane, hexane-acetone, hexane-ethyl ether, or petroleum 

ether (Caille et al. 1987; EPA 1980e; Head and Burse 1987; Kutz et al. 1985; LeBel and Williams 

1986). Clean-up methods include liquid-liquid partitioning (adipose tissue) (Kutz et al. 1985), gel 

permeation chromatography (GPC) (adipose tissue) (LeBel and Williams 1986; Macleod et al. 1982), 

and Florisil column clean-up (liver and adipose tissue) (EPA 1980e; Kutz et al. 1985; Mes 1992; 

Macleod et al. 1982; Stein and Pittman 1979). For measuring mirex in tissues, sensitivity of GC/ECD 

is in the sub-ppm to sub-ppb range (Kutz et al. 1985; LeBel and Williams 1986; Mes 1992; Stein and 

Pittman 1979). Recovery of mirex from tissues is generally good (≥70%) (Caille et al. 1987; EPA 

1980d; LeBel and Williams 1986; Macleod et al. 1982), as is precision (<20% RSD) (EPA 1980d; 

Caille et al. 1987; LeBel and Williams 1986). Confirmation of mirex in adipose tissue can be 

accomplished using GC/MS (Kutz et al. 1985; LeBel and Williams 1986; Mes 1992). Photomirex has 

been measured in adipose tissue by GC/MS (LeBel and Williams 1986). 

Capillary GC/ECD, dual column capillary GC/ECD, and capillary GC/MS have been used for 

quantitation of mirex in milk with sensitivity in the low to sub-ppb range (Bush et al. 1983b; Mes et 

al. 1986; Mussalo-Rauhamaa et al. 1993; Rahman et al. 1993). Recovery data for milk are generally 

very good (>70%) (Mes et al. 1993; Mussalo-Rauhamaa et al. 1993; Rahman et al. 1993), but 

precision data were not reported. 

Mirex can be extracted from feces with hexane-acetonitrile and the extract cleaned up on 

alumina/Florisil columns, then analyzed using GCYECD. Sensitivity, precision, and accuracy data for 

feces were not reported (Gibson et al. 1972). 

The most commonly used method for measuring chlordecone in blood is GC combined with ECD 

(Blanke et al. 1977; Caille et al. 1987; Caplan et al. 1979; Waliszewski and Szymczynski 1991). 
MIREX AND CHLORDECONE 243 

6. ANALYTICAL METHODS 

Sample preparation involves an extraction procedure. Chlordecone is unique among the chlorinated 

pesticides since it has a ketone functional group that readily forms a hydrate in the presence of water 

(Caplan et al. 1979). This hydrate formation permits selective extraction of chlordecone from all other 

chlorinated pesticides (Caplan et al. 1979). Although recoveries for the selective extraction procedure 

were low (<50%) because multiple extractions were not performed, sensitivity was maintained and 

precision was good (<7% RSD) (Caplan et al. 1979). Another preparation step that allowed better 

recovery (>80%) of chlordecone from blood involved extraction with petroleum ether and acetone 

followed by a sulfuric acid clean-up step (Waliszewski and Szymczynski 1991). Results of this 

method were reproducible, with precision being <7% RSD (Waliszewski and Szymczynski 1991). 

Sensitivity was not reported for this method (Waliszewski and Szymczynski 1991). Extraction of 

plasma and tissues with hexane-acetone gave low-to-adequate recoveries (58.5-87.4%), but again, 

reproducibility was good, with precision being <6% RSD (Caille et al. 1987). Method detection limits 

for measuring chlordecone in blood samples are in the low ppb range (Caille et al. 1987; Caplan et al. 

1979). Confirmation techniques for chlordecone include GC/MS and GC with microcoulometric 

detection (Blanke et al. 1977), and for chlordecone and its breakdown products, GC/chemical 

ionization (CI) MS (Harless et al. 1978). 

Chlordecone can be extracted from tissues with hexane-acetone, then analyzed by GC/ECD. 

Sensitivity is 1 ppm, and recoveries of 73.2% (liver) and 58.5% (kidney) were reported (Caille et al. 

1987). No methods for measuring chlordecone in human milk were located. 

GC/ECD is the most commonly used method to measure chlordecone in urine and saliva, and 

chlordecone and its metabolites (chlordecone alcohol and the glucuronide conjugates) in feces and bile 

(Blanke et al. 1977; Fariss et al. 1980). For the liquid samples, using acetone in hexane to extract 

chlordecone from acidified samples gave good recoveries (95%) and required no clean-up step (Blanke 

et al. 1977). Stool and bile samples required a clean-up procedure prior to analysis. Sensitivity was 

5 ppb. For the bile samples, precision was adequate (<20% RSD) (Blanke et al. 1977). No other data 

were reported. Chlordecone and its metabolites (chlordecone alcohol and the glucuronide conjugates) 

were detected by GC/ECD in feces and bile (Blanke et al. 1978; Fariss et al. 1980). Chlordecone 

alcohol was isolated from feces (Wilson and Zehr 1979). 
 

MIREX AND CHLORDECONE 244 

6. ANALYTICAL METHODS 

6.2 ENVIRONMENTAL SAMPLES 

Methods exist for determining mirex and chlordecone in air (ambient and occupational), water, 

sediment and soil, biota and fish, and foods. Most involve separation by GC with detection by ECD 

or MS. Tables 6-3 and 6-4 summarize some of the applicable analytical methods used for determining 

mirex and chlordecone, respectively, in environmental samples. 

The most commonly used methods for measuring mirex or its degradation products in air are packed 

column or capillary GC/ECD. Air samples are collected using polyurethane foam (PUF), then the 

PUF plugs are Soxhlet-extracted (Durrell and Sauer 1990; ASTM 1991; Lewis et al. 1977). For air 

samples, sensitivity of GC/ECD is in the sub-ppb range (Durrell and Sauer 1990). Recovery is 

excellent (>98%), although precision was not reported (Lewis et al. 1977). Confirmation of mirex 

may be accomplished using GC/MS (ASTM 1991) or dual capillary column GC/dual detector (Durrell 

and Sauer 1990). 

Mirex has been measured in water samples using GC and capillary GC coupled with ECD or MS 

detection (Driscoll et al. 1991; Durrell and Sauer 1990; Hargesheimer 1984; Sandhu et al. 1978). 

Samples are extracted with dichloromethane (Hargesheimer 1984) or hexane (Driscoll et al. 1991; 

Sandhu et al. 1979). Clean-up methodologies which have been applied to water samples are chromic 

acid treatment (Driscoll et al. 1991) and Florisil column fractionation (Sandhu et al. 1978). For water 

samples, sensitivity is in the low ppb (Durrell and Sauer 1990) to low parts per trillion (ppt) range 

(Hargesheimer 1984; Sandhu et al. 1978). Precision is acceptable (<20% RSD) (Driscoll et al. 1991; 

Dun-e11 and Sauer 1990; Sandhu et al. 1978). The sensitivity of GC/MS analysis is in the sub-ppb 

range (Hargesheimer 1984); recovery and precision data were not reported (Hargesheimer 1984). A 

chromic acid digestion extraction technique was compared to conventional solvent extraction for 

recovery of mirex and photomirex from river water samples (Driscoll et al. 1991). The digestion 

technique was more efficient than conventional solvent extraction, with better recoveries and superior 

precision (Driscoll et al. 1991). The better precision obtained with sample digestion may be due to 

lack of emulsions, which allowed better phase separation and, therefore, more reproducible recoveries 

(Driscoll et al. 1991). Sensitivity data were not reported. Confirmation can be accomplished using 

dual capillary GC/dual detector system (ECD and electrolytic conductivity detector, ELCD) (Durrell 

and Sauer 1990). 






 

 

MIREX AND CHLORDECONE 251 

6. ANALYTICAL METHODS 

Mirex and photomirex have been measured in soil and sediment samples using GC and capillary 

GC/ECD. Soil and sediment samples are usually solvent extracted, then cleaned up using Florisil 

columns and GPC. Recovery of mirex and photomirex from sediment samples is generally excellent 

(>90%) (Chau and Babjak 1979; Norstrom et al. 1980a; Onuska et al. 1980; Sergeant et al. 1993) with 

very good precision (<20 %RSD) (Norstrom et al. 1980a; Onuska et al. 1980). Sensitivity is in the 

low ppb to low ppt range (Norstrom et al. 1980a; Sergeant et al. 1993). 

Mirex and its degradation products have been measured in biota using GC/ECD, capillary GC/ECD 

and capillary GC/MS techniques (Bush and Barnard 1982; Hellou et al. 1993; Norstrom et al. 1980a; 

Onuska et al. 1980; Quintanilla-Lopez et al. 1992). Samples are homogenized and most commonly 

extracted with solvent shake-out (Hellou et al. 1993; Norstrom et al. 1980a) or Soxhlet extraction 

(Quintanilla-Lopez et al. 1992). The clean-up techniques that are most commonly used are Florisil 

columns (Bush and Barnard 1982: Hellou et al. 1993; Norstrom et al. 1980a) and GPC (Hellou et al. 

1993; Norstrom et al. 1980a). An additional nitration step has been used to separate mirex and 

photomirex from PCBs (Norstrom et al. 1980a). Sensitivity of GC/ECD analysis is in the low to subppb 

range. Recoveries are excellent (>90%), and precision is good (<20% RSD). Mirex and its 

degradation products have been measured in gull eggs using GC/ECD with capillary GC/MS 

confirmation (Norstrom et al. 1980b). 

Packed and capillary GC/ECD or GC/MS have been used to measure mirex in foods, including fruits, 

vegetables, and fatty foods (Bong 1977; de la Riva and Anadon 1991; Di Muccio et al. 1991; Krause 

1973; Liao et al. 1991; Manes et al. 1993; Stan 1989; Trotter and Dickerson 1993). Food samples are 

most commonly homogenized and extracted with solvent, then cleaned up using GPC (Stan 1989; 

Trotter and Dickerson 1993), Florisil columns (de la Riva and Anadon 1991; Krause 1973), or SPE 

columns (Di Muccio et al. 1993; Manes et al. 1993). Sensitivity is in the low to sub-ppb range for 

both GC/ECD and GC/MS techniques (de la Riva and Anadon 1991; Liao et al. 1991; Manes et al. 

1993; Trotter and Dickerson 1993). Good to excellent recovery (>85% to >90%) and good precision 

(<20% RSD) were obtained for most methods (Bong 1977; Di Muccio et al. 1991; Trotter and 

Dickerson 1993). Confirmation was accomplished using a different capillary column (Manes et al. 

1993; Trotter and Dickerson 1993). GC/ECD has been used to measure mirex in fatty foods with 

excellent recovery and good precision; however, the method is not suitable when PCBs are present 

(Ault and Spurgeon 1984). 
 

MIREX AND CHLORDECONE 252 

6. ANALYTICAL METHODS 

The major analytical problem in the measurement of mirex and photomirex in environmental samples 

is co-elution with interferents. Confirmation techniques have been developed to assure reliable results. 

A dual-column, dual-detector GC analysis has been used to prevent false-positive identifications due to 

interfering compounds and to avoid misidentification (Durrell and Sauer 1990). The two detectors 

used were ECD and ELCD. MS techniques have been used to assure correct identification 

(Hargesheimer 1984; Hellou et al. 1993; Liao et al. 1993; Onuska et al. 1980; Stan 1989) and also to 

confirm GC/ECD measurements (Sergeant et al. 1993). Chemical procedures have been used as well. 

Perchlorination (Hallett et al. 1978) and nitration (Norstrom et al. 1980a, 1980b) have been used to 

convert co-eluting PCBs to compounds easily separable from mirex. 

The most commonly used methods for measuring chlordecone and its degradation products in air, 

water, soil, sediment, fish, shellfish, and animal fat are similar to those used for mirex (i.e., GC/ECD 

techniques and confirmation by GC/MS). Because of the polar nature of chlordecone, the removal of 

chlordecone from the different types of environmental samples was accomplished using extraction with 

polar solvents (Moseman et al. 1977). The clean-up steps generally used for the environmental 

samples include Florisil column chromatography and GPC. 

Air samples are collected using filters, or filters and impingers, and extracted with benzene and 

methanol (Hodgson et al. 1978; NIOSH 1984). Sensitivity is in the low ppb range for GC/ECD. 

Recovery is very good (>85%); precision is acceptable (<25% RSD) (Hodgson et al. 1978; NIOSH 

1984). Confirmation of the identity of chlordecone in air was accomplished using both GC/MS and 

GC/ELCD (Hodgson et al. 1978). 

Water samples are usually solvent extracted and may be analyzed directly by GC/MS (Spingam et al. 

1982). Sensitivity is in the low ppb range, but recovery is low (7-11%) and precision is poor (48% 

RSD). Extracts may be cleaned up on Florisil columns and analyzed by GC/ECD (Garman et al. 

1987; Moseman et al. 1977; Saleh and Lee 1978). Recoveries were very good (>90%) with sensitivity 

of GC/ECD being in the low to sub-ppt range (Harris et al. 1980; Moseman et al. 1977; Saleh and Lee 

1978); precision data were not reported. Detection limits were lowered to sub-ppt levels by passing 

large volumes of water through XAD-2 resin, then extracting the resin (Harris et al. 1980). Recovery 

was very good (91%) as was precision (4% RSD). 
MIREX AND CHLORDECONE 253 

6. ANALYTICAL METHODS 

Sediment and soil samples are homogenized and extracted. Clean-up procedures are required prior to 

analysis by GC/ECD or GC/MS techniques (Lopez-Avila et al. 1992; Moseman et al. 1977; Saleh and 

Lee 1978; Tieman et al. 1990). For sediment, soil, and sludge, recoveries were good (>85%) with 

sensitivity in the low ppb range (Moseman et al. 1977; Saleh and Lee 1978). Precision is good (<6% 

RSD) (Saleh and Lee 1978). Analytical difficulties (unacceptable recovery; not detectable using 

second capillary GC column) were reported (Lopez-Avila et al. 1992; Tieman et al. 1990). 

Fish samples are extracted and cleaned up using liquid-liquid partitioning or Florisil columns prior to 

analysis by GC/ECD (Carver and Griffith; Hodgson et al. 1978; Mady et al. 1979; Moseman et al. 

1977). Recoveries are good for chlordecone (> 80%) (Carver and Griffith 1979; Hodgson et al. 1978; 

Mady et al. 1979) and the monohydro and dihydro degradation products (Carver and Griffith 1979). 

Precision is good (Carver and Griffith 1979; Mady et al. 1979) and sensitivity is in the low ppb range 

(Carver and Griffith 1979; Mady et al. 1979). 

Few methods for measuring chlordecone in foods are available. Lower recoveries (58-81%) were 

obtained with GC/ECD for beef, pork, and poultry fat samples using GPC clean-up before analysis 

(Goodspeed and Chestnut 1991). Precision varied greatly (7.1-47.7% RSD) because of the lower 

recoveries; sensitivity was not reported. 

6.3 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 mirex and chlordecone 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 mirex and chlordecone. 

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. 
 

 

MIREX AND CHLORDECONE 254 

6. ANALYTICAL METHODS 

6.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. There are reliable methods 

for detecting, quantifying, and identifying mirex and chlordecone in biological samples. These include 

packed column and capillary GC/ECD and packed column and capillary GC/MS. These methods are 

sensitive enough to measure background levels in the population and levels at which biological effects 

occur. These methods are accurate and reliable for measuring mirex in blood (Korver et al. 1991; Mes 

1992) and chlordecone in blood (Caille et al. 1987). Sensitivity for these methods is in the low to 

sub-ppb range. Sensitive (low to sub-ppb range) and accurate methods are available to measure mirex 

in tissues (Caille et al. 1987; LeBel and Williams 1986; Mes 1992). Improved recovery data and 

greater sensitivity for measuring chlordecone in tissues are needed (Caille et al. 1987). For milk, 

fecal, bile, urine, and saliva samples, sensitivity, recovery, and precision data are needed to more fully 

evaluate the reliability of these methods as predictors of environmental exposure to both mirex and 

chlordecone (Blanke et al. 1977; Bush et al. 1983b; Gibson et al. 1972). 

Biochemical indicators of renal dysfunction (increased urinary protein and/or histopathological changes 

of the kidneys) have been associated with exposure to both mirex (NTP 1990) and chlordecone 

(Larson et al. 1979b). Microsomal enzyme induction as shown by changes in urinary D-glucaric acid 

has also been associated with exposure to both mirex and chlordecone (Guzelian 1985; Morgan and 

Roan 1974). Although these changes are not specific for mirex or chlordecone, these parameters may 

provide information about renal damage and hepatic effects in exposed populations. Tremorgrams 

have been used to assess tremors associated with chlordecone exposure in humans (Taylor et al. 1978). 

An infrared reflection technique and oculography have been used to assess the oculomotor disturbances 

caused by chlordecone (Taylor et al. 1978). Standard tests for memory and intelligence can be used to 

determine the presence of encephalopathy, but in the absence of baseline pre-exposure levels for 

individuals, subtle changes may be difficult to detect. Decreased sperm count has been observed 

following exposure to mirex or chlordecone (Chu et al. 1981a; Yarborough et al. 1981). The existing 

analytical methods that are discussed for exposure can reliably measure mirex or chlordecone in blood, 

urine, and tissues at the levels at which these effects occur. 
MIREX AND CHLORDECONE 255 

6. ANALYTICAL METHODS 

Methods for Determining Parent Compounds and Degradation Products in 

Environmental Media. Reliable methods for detecting mirex and chlordecone in environmental 

media include GC/ECD, capillary GC/ECD and capillary GC/MS. In general, the methods are 

sensitive and accurate enough to measure background levels of mirex and chlordecone in the 

environment and levels at which health effects occur. Methods of adequate sensitivity (low ppb to 

sub-ppb), accuracy, and specificity are available for determining levels of mirex in air (Dun-e11 and 

Sauer 1990; Hoff et al. 1992; Lewis et al. 1977), water (Durrell and Sauer 1990; Hargesheimer 1984; 

Sandhu et al. 1978), and soils and sediment (Norstrom et al. 1980a; Sergeant et al. 1993; Seidel and 

Lindner 1993). Sensitive, accurate methods are also available for measuring chlordecone in air 

(NIOSH 1984), water (Garman et al. 1987; Harris et al. 1980; Saleh and Lee 1978: Spingarn et al. 

1982), and soil and sediment (Moseman et al. 1977; Saleh and Lee 1978). Methods for measuring 

mirex and chlordecone in aquatic species and food are reliable and accurate and provide detection 

limits in the low ppm to ppb range. These include methods for determining mirex in fish and other 

aquatic species (Bush and Barnard 1982; Hellou et al. 1993; Norstrom et al. 1980a; Quintanilla-Lopez 

et al. 1992; Rahman et al. 1993) and food (Ault and Spurgeon 1984; Liao et al. 1991; Manes et al. 

1993; Trotter and Dickerson 1993). Similarly, there are acceptable methods for determining 

chlordecone in fish and other aquatic species (Carver and Griffith 1979; Mady et al. 1979) and food 

(Goodspeed and Chestnut 1991; Posyniak and Stec 1980). More information on the precision of these 

methods for measuring mirex and chlordecone in water and improved sensitivity, recovery, and 

precision data in foodstuffs are needed to better assess the risk of exposure for these media. Research 

investigating the relationship between levels of mirex and chlordecone measured in air, water, soil, and 

food and observed health effects could increase our confidence in existing methods and/or indicate 

where improvements are needed. No data were located regarding measurement of mirex in soil 

samples. 

6.3.2 Ongoing Studies 

Research is being conducted at the State University of New York at Albany, sponsored by the 

National Institute of Environmental Health Sciences, to improve chemical analysis of environmental 

media for PCBs and selected pesticides, including mirex. No other studies involving rnirex or 

chlordecone were located in the FEDRIP database. 

MIREX AND CHLORDECONE 257 

7. REGULATIONS AND ADVISORIES
 

The international, national, and state regulations and guidelines pertaining to mirex and chlordecone in 

air, water, and food are summarized in Tables 7-l and 7-2, respectively. 

ATSDR has derived an acute oral minimal risk level (MRL) of 0.01 mg/kg/day for chlordecone based 

on a NOAEL of 1.25 mg/kg for neurological effects (increased startle response) in Fischer 344 rats in 

a 10-day study conducted by EPA (1986c). 

An MRL of 0.0005 mg/kg/day has been derived for intermediate-duration oral exposure to chlordecone 

based on a NOAEL of 0.05 mg/kg/day for renal effects in rats at a LOAEL of 0.25 mg/kg/day in a 

study by Larson et al. (1979b). 

An MRL of 0.0008 mg/kg/day has been derived for chronic-duration oral exposure to mirex based on 

a NOAEL of 0.075 mg/kg/day for dose-dependent hepatic changes from a study by NTP (1990). 

An MRL of 0.0005 mg/kg/day has been derived for chronic-duration oral exposure to chlordecone 

based on a NOAEL of 0.05 mg/kg/day for renal effects in rats at a LOAEL of 0.25 mg/kg/day in a 

study by Larson et al. (1979b). 

The EPA has derived an oral reference dose (RfD) of 2.00x10-4 mg/kg/day for mirex (IRIS 1994). 

The RfD is based on liver cytomegaly, fatty metamorphosis, angiectasis, and thyroid toxicity in rats 

(NTP 1990). No reference concentration is available for mirex. Neither a reference dose nor a 

reference concentration exist for chlordecone. 

Mirex is regulated by the Clean Water Effluent Guidelines as stated in Title 40, Sections 400-475, of 

the Code of Federal Regulations. Mirex has a specific effluent limitation for the pesticide chemicals 

point source category (EPA 1978f). No effluent guidelines exist for chlordecone. 

EPA canceled the registration of mirex in 1976 (EPA 1976). 

The Food and Dmg Administration set an action level of 0.1 ppm mirex in fish tissue (EPA 1978a). 
MIREX AND CHLORDECONE 258 

7. REGULATIONS AND ADVISORIES 

Under the Resource Conservation and Recovery Act (RCRA), chlordecone is listed as a hazardous 

waste when it is a discarded commercial chemical product off-specification species, container residue, 

and spill residue thereof (EPA 1980b). 






 

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MIREX AND CHLORDECONE 265 

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*Williams DT, LeBel GL, Junkins E. 1988b. Organohalogen residues in human adipose autopsy 

samples from six Ontario municipalities. J Assoc Off Anal Chem 71:410-414. 

*Williams GM. 1980. Classification of genotoxic and epigenetic hepatocarcinogens using liver 

culture assays. Ann N Y Acad Sci 349:273-282. 

Williams GM. 198 1. Liver carcinogenesis: The role for some chemicals of an epigenetic 

mechanisms of liver-tumor promotion involving modification of the cell membrane. Food Cosmet 

Toxicol 19(5):577-583. 

*Williams GM, Mori H, McQueen CA. 1989a. Structure-activity relationships in the rat hepatocytes 

DNA-repair test for 300 chemicals. Mutat Res 221(3):263-286. 

*Williams J, Eckols K, Stewart G, et al. 1988a. Proestrous effects of chlordecone on the serotonin 

system. Neurotoxicology 9597-610. 

*Williams J, Eckols K, Uphouse L. 1989b. Estradiol and chlordecone interactions with the estradiol 

receptor. Toxicol Appl Pharmacol 98:413-421. 

*Williams J, Montanez S, Uphouse L. 1992. Effects of chlordecone on food intake and body weight 

in the male rat. Neurotoxicology 13(2):453-462. 

*Williams J, Uphouse L. 1991. Vaginal cyclicity, sexual receptivity, and eating behavior of the 

female rat following treatment with chlordecone. Reprod Toxicol 5(1):65-71 

*Williams JD, Yarbrough JD. 1983. The relationship between mirex-induced liver enlargement and 

the adrenal glands. Pestic Biochem Physiol 19:15-22. 

Williams PP. 1977. Metabolism of synthetic organic pesticides by anaerobic microorganisms. 

Residue Rev 66:63-135. 

Wilson D, Yarbrough JD. 1988. Autoradiographic analysis of hepatocytes in mirex-induced adaptive 

liver growth. Am J Physiol 255:G132-G139. 

*Wilson NK, Zehr RD. 1993. Structures of some Kepone photoproducts and related chlorinated 

pentacyclodecanes by carbon-13 and proton nuclear magnetic resonance. J Org Chem 

44(8):1278-1282. 

*Winger PV, Schultz DP, Johnson WW. 1990. Environmental contaminant concentrations in biota 

from the lower Savannah River, Georgia and South Carolina. Arch Environ Contam Toxicol 

19(1):101-17. 

Winters CJ, Molowa DT, Guzelian PS. 1990. Isolation and characterizaiton of cloned cDNAs 

encoding human liver chlordecone reductase. Biochemistry 29(4):1080-1087. 
MIREX AND CHLORDECONE 328 

8. REFERENCES 

*Wolfe JL, Esher RJ, Robinson KM, et al. 1979. Lethal and reproductive effects of dietary mirex 

and DDT on old-field mice, Peromyscus polionotus. Bull Environ Contam Toxicol 21:397-402. 

Yang RS, Coulston F, Goldberg L. 1975. Binding of hexachlorobenzene to erythrocytes: Species 

variation. Life Sci 17(4):545-549. 

Yarbrough J, Cunningham M, Yamanaka H, et al. 1991. Carbohydrate and oxygen metabolism 

during hepatocellular proliferation: A study in perfused livers from mirex-treated rats. Hepatology 

13(6) 1229-1234. 

*Yarbrough JD, Brown LD, Grimley JM. 1984. Mirex-induced adaptive liver growth: A 

corticosterone-mediated response. Cell Tissue Kinet 17:465-473. 

*Yarbrough JD, Chambers JE, Grimley JM, et al. 1981. Comparative study of 8monohydromirex 

and mirex toxicity in male rats. Toxicol Appl Pharmacol 58:105-117. 

Yarbrough JD, Chambers JE, Robinson KM. 1982. Alterations in liver structure and function 

resulting from chronic insecticide exposure. In: Chambers JE, Yarbrough JD, eds. Effects of chronic 

exposures to pesticides on animal systems. New York, NY: Raven Press, 25-59. 

*Yarbrough JD, Grimley JM, Alley EG. 1986a. Induction of the hepatic cytochrome P-450 

dependent monooxygenase system by cis- and trans-5,10-dihydrogen mirex. Toxicol Lett 32:65-71. 

*Yarbrough JD, Grimley JM, Karl PI. 1986b. Relationship of ornithine decarboxylase and thymidine 

kinase to mirex-induced liver growth. Am J Physiol 251:G859-G865. 

Yarbrough JD, Grimley JM, Karl PI, et al. 1983. Tissue disposition, metabolism, and excretion of 

cis- and trans-5,10-dihydrogen mirex. Drug Metab Dipos 11:611-614. 

*Yarbrough JD, Grimley JM, Thottassery JV. 1992. Mirex-induced adaptive liver growth in rats 

subjected to thyroidectomy. Hepatology 15(5):923-927. 

*Yess NJ. 1988. FDA pesticide program residues in foods 1987. J Assoc Off Anal Chem 

71(6):156A-174A. 

*Yess NJ, et al. 1991b. Residues in food, 1990. FDA pesticide program. J AOAC 

74(5):121A-141A. 

*Yess NJ, Houston MG, Gunderson EL. 1991a. Food and drug administration pesticide residue 

monitoring of foods: 1978-1982. J Assoc Off Anal Chem 74:265-272. 

*Yin C, Hassett JP. 1989. Fugacity and phase distribution of mirex in Oswego River and Lake 

Ontario waters. Chemosphere 19(8-9):1289-1296. 

*Young RA, Mehendale HM. 1989. Carbon tetrachloride metabolism in partially hepatectomized and 

sham-operated rats preexposed to chlordecone (Kepone). J Biochem Toxicol 4(4):211-219. 

Young S, Clower M Jr, Roach JAG. 1984. Method for determination of organohalogen pesticide 

residues in vegetable oil refinery by-products. J Assoc Off Anal Chem 67(1):95-106. 
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8. REFERENCES 

Zeiger E. 1987. Carcinogenicity of mutagens: Predictive capability of the Salmonella mutagenesis
 

assay for rodent carcinogenicity. Cancer Res 47(5):1287-1296.
 

Zeiger E, Pagan0 DA. 1984. Suppressive effects of chemicals in mixture on the Salmonella plate test
 

response in the absence of apparent toxicity. Environ Mutagen 6(5):683-694
 

Zenick H. 1984. Mechanisms of environmental agents by class associated with adverse male
 

reproductive outcomes. In: Reproduction: The new frontier in occupational and environmental health
 

research. Prog Clin Biol Res 160:335-361.
 

Zweig G, McCutcheon RS. 1981. American Society for Pharmacology and Experimental
 

Therapeutics Symposium on Molecular Mechanisms of Toxicity of Chlordecone (Kepone), Rochester,
 

MN, August 20, 1980. J Toxicol Environ Health 8(5-6): 701-1040.
 

MIREX AND CHLORDECONE 331 

9. GLOSSARY 

Acute Exposure - Exposure to a chemical for a duration of 14 days or less, as specified in the
 

Toxicological Profiles.
 

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.
 

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.
 

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.
 

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.
 

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.
 

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 occurred. The terms, as used here, include malformations and variations,
 

altered growth, and in utero death.
 

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.
 

Immediately Dangerous to Life or Health (IDLH) - The maximum environmental concentration
 

of a contaminant from which one could escape within 30 min without any escape-impairing symptoms
 

or irreversible health effects.
 

Intermediate Exposure - Exposure to a chemical for a duration of 15-364 days, as specified in the
 

Toxicological Profiles.
 
 

MIREX AND CHLORDECONE 332 

9. GLOSSARY 

Immunologic Toxicity - The occurrence of adverse effects on the immune system that may result 

from exposure to environmental agents such as chemicals. 

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 is expected 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 dose 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. 

Malformations - Permanent structural changes that may adversely affect survivol, development, or 

function. 

Minimal Risk Level - An estimate of daily human exposure to a dose of a chemical that is likely to 

be without an appreciable risk of adverse noncancerous effects over a specified duration of exposure. 

Mutagen - A substance that causes mutations. A mutation is a change in the genetic material in a 

body cell. Mutations can lead to birth defects, miscarriages, or cancer. 

Neurotoxicity - The occurrence of adverse effects on the nervous system following exposure to 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL) - The dose of 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. 

Permissible Exposure Limit (PEL) - An allowable exposure level in workplace air averaged over 

an 8-hour shift. 
 

 

 

 

MIREX AND CHLORDECONE 333 

9. GLOSSARY 

q1* - The upper-bound estimate of the low-dose slope of the dose-response curve as determined by 

the multistage procedure. The ql* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually yg/L for water, mg/kg/day for food, 

and μg/m3

 for air). 

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 effects during a lifetime. The RfD is operationally derived from the 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. 

Reportable Quantity (RQ) - The quantity of a hazardous substance that is considered reportable 

under CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an 

amount established by regulation either under CERCLA or under Sect. 3 11 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. 

Short-Term Exposure Limit (STEL) - The 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 TLV-TWA may not be exceeded. 

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) - A concentration of a substance to which most workers can be 

exposed without adverse effect. The TLV may be expressed as a TWA, as a STEL, or as a CL. 

Time-Weighted Average (TWA) - An allowable exposure concentration averaged over a normal 8­

hour workday or 40-hour workweek. 

Toxic Dose (TD,,) - 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. 

Uncertainty Factor (UF) - A factor used in operationally deriving the RfD 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 LOAEL data rather than NOAEL data. Usually each of these factors is set equal 

to 10. 
 

 

 

MIREX AND CHLORDECONE A-l 

APPENDIX A 

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 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-l) 2-2, and 2-3) and figures (2-l and 2-2) 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 endpoints, 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-AdverseEffect Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels 

(CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 2-l and Figure 2-l 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 2-1 

(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 2-1, 2-2, and 2-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 2-l) and oral (LSE Figure 2-2) routes. Not all substances will have data on each 

route of exposure and will not therefore have all five of the tables and figures. 
MIREX AND CHLORDECONE A-2 

APPENDIX A 

(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 ” 1%” data points in Figure 2-l). 

(5) Species The test species, whether animal or human, are identified in this column. Section 2.4, 

“Relevance to Public Health,” covers the relevance of animal data to human toxicity and Section 

2.3, “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 toxaphene 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 onginal 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. 

(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 endpoint 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 8 of the profile. 
MIREX AND CHLORDECONE A-3 

APPENDIX A 

(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 2-1 

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 endpoint 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. 

(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 (qi*). 

(19) Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 


 

 

MIREX AND CHLORDECONE A-6 

APPENDIX A 

Chapter 2 (Section 2.4) 

Relevance to Public Health 

The Relevance to Public Health section 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 endpoints by addressing the 

following questions. 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3 . What exposure conditions are likely to be of concern to humans, especially around hazardous

 waste sites? 

The section covers endpoints 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 section. 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 endpoints (if 

derived) and the endpoints 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 Data Needs section. 

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 2.4, “Relevance to Public Health,” contains basic information known about the substance. 

Other sections such as 2.6, “Interactions with Other Substances,” and 2.7, “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). 
MIREX AND CHLORDECONE A-7 

APPENDIX A 

To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is 

available for all potential systemic, neurological, and developmental effects. If this information and 

reliable quantitative data on the chosen endpoint are available, ATSDR derives an MRL using the 

most sensitive species (when information from multiple species is available) with the highest 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.