Treatment of Chlordecone (Kepone) Toxicity with Cholestyramine

Cohn, William; Boylan, James J.; Blanke, Robert V.; Fariss, Marc W.; Howell, John R.; Guzelian, Philip S.

doi:10.1056/nejm197802022980504

Cited by 202 publications

(103 citation statements)

References 15 publications

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“…In humans, chlordecone exposure in occupational circumstances has been associated with a well recognized clinical syndrome involving the nervous system, liver, and testes (Cannon et al, 1978;Cohn et al, 1978;Taylor et al, 1978). Experimental studies in animals confirm all of the toxic effects observed in humans (Faroon et al, 1995).…”

Section: Introductionmentioning

confidence: 94%

Pesticide exposure of pregnant women in Guadeloupe: Ability of a food frequency questionnaire to estimate blood concentration of chlordecone

Guldner

Multigner

Héraud

et al. 2010

Environmental Research

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Context: Chlordecone, an environmentally persistent organochlorine insecticide used intensively in banana culture in the French West Indies until 1993, has permanently polluted soils and contaminated foodstuffs. Consumption of contaminated food is the main source of exposure nowadays. We sought to identify main contributors to blood chlordecone concentration (BCC) and to validate an exposure indicator based on food intakes. Material and methods:We used a food frequency questionnaire (FFQ) completed by a sample of 194 pregnant women to estimate their dietary exposure to chlordecone and compared it to blood levels. In a first approach, chlordecone daily intake was estimated as the product of daily eaten quantity of 214 foodstuffs, multiplied by their chlordecone content, and summed over all items. We then predicted individual blood chlordecone concentration with empirical weight regression models based on frequency of food consumption, and without contamination data.Results: Among the 191 subjects who had BCC determination, 146 (76%) had detectable values and mean BCC was 0.86 ng/mL (range < LOD-13.2). Mean per capita dietary intake of chlordecone was estimated at 3.3 µg/day (range: 0.1-22.2). Blood chlordecone levels were significantly correlated with food exposure predicted from the empirical weight models (r=0.47, p < 0.0001) and, to a lesser extent, with chlordecone intake estimated from food consumption and food contamination data (r=0.20, p=0.007). Main contributors to chlordecone exposure included seafood, root vegetables, and Cucurbitaceous. Conclusion:These results show that the Timoun FFQ provides valid estimates of chlordecone exposure. Estimates from empirical weight models correlated better with blood levels of chlordecone than did estimates from the dietary intake assessment.

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Section: Introductionmentioning

confidence: 94%

Pesticide exposure of pregnant women in Guadeloupe: Ability of a food frequency questionnaire to estimate blood concentration of chlordecone

Guldner

Multigner

Héraud

et al. 2010

Environmental Research

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“…Some pesticides and congeners of PCBs can occupy thyroid hormone receptors, and other agents produce symptoms such as infertility in chlordecone (Cohn et al, 1978) and dibromochloropropane (Goldsmith et al, 1984) workers that are plausibly the result of interference with normal endocrine function, even if a hormonal basis is not established. Breast cancer is strongly related to hormone exposure, and has been studied extensively for an environmental hormonal etiology.…”

Section: Introductionmentioning

confidence: 99%

Some evidence of effects of environmental chemicals on the endocrine system in children

Rogan

Ragan

2007

International Journal of Hygiene and Environmental Health

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Pollutant chemicals that are widespread in the environment can affect endocrine function in laboratory experiments and in wildlife. Although human beings are commonly exposed to such pollutant chemicals, the exposures are generally low and clear effects on endocrine function from such exposures have been difficult to demonstrate. Human data including both exposure to the chemical agent and the endocrine outcome are reviewed here, including age at weaning, age at puberty, anogenital distance, and sex ratio at birth, and the strength of the evidence discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real.

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“…Among the most complete data for an environmental agent of this class are the results of studies of 32 workers exposed to high concentrations of the insecticide chlordecone, known more commonly as Kepone. Despite the fact that these workers had high concentrations of chlordecone in their serum, adipose tissue, and liver (20), standard chemical tests were in each case repeatedly negative (21). However, there was liver enlargement and tests for liver Despite the large numbers of people exposed to these chemicals there is surprisingly little information on human liver histopathology.…”

mentioning

confidence: 99%

“…Perhaps the reason that there is so little human liver biopsy material available is that physicians believe liver biopsy is unwarranted in cases of exposure to PCBs or other related chemicals when liver tests are at most only minimally abnormal. This is unfortunate, because liver biopsy performed by an experienced hepatologist carries little risk and in the case of the chlordecone workers provided essential information for diagnosis and management and, ultimately, for designing a rational approach to treatment (20,21).…”

mentioning

confidence: 99%

“…As seen in Figure 1, urinary excretion ofglucaric acid in workers was increased far above control values in the same range as three patients receiving inducing drugs for treatment of epilepsy. Moreover, after all the patients had been placed on cholestyramine, an orally administered anionic binding resin that stimulates the elimination of chlordecone from the body (20), the levels of chlordecone in the plasma fell to low or undetectable levels and the excretion of glucaric acid fell back into the normal range in each case. From these results we have estimated that the serum level of chlordecone associated with enzyme induction in the liver is in the range of 100 to 500 ng/ mL.…”

mentioning

confidence: 99%

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Clinical evaluation of liver structure and function in humans exposed to halogenated hydrocarbons.

Guzelian¹

1985

Environ Health Perspect

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An unresolved question is whether humans exposed to comparatively low doses of persistent environmental chemicals such as polyhalogenated biphenyls or organochlorine pesticides are at risk for injury to the liver. Cross-sectional epidemiologic studies suggest that these chemicals may produce statistically significant but clinically mild abnormalities in the commonly employed chemical tests of liver function. The few reports of human liver morphology reveal nonspecific changes reflecting effects of lipophilic chemicals. There is evidence that chemicals of this category in at least some doses cause induction of liver microsomal enzymes involved in biotransformation of foreign substances. This finding has been documented by measurements of the clearance of model drugs or the appearance in the urine of steroid metabolites or glucaric acid. Although a positive statistical correlation between the concentrations of these chemicals in serum and the serum gamma-glutamyltranspeptidase activity has been reported, the non-specificity of the latter enzyme precludes conclusion that this change is indicative of induction of liver microsomal enzymes. Although the effects of this type of environmental chemical are not indicative of progressive liver disease, only prospective clinical trials can resolve the issue of the risk for future development of liver malignancy.

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Treatment of Chlordecone (Kepone) Toxicity with Cholestyramine

Cited by 202 publications

References 15 publications

Pesticide exposure of pregnant women in Guadeloupe: Ability of a food frequency questionnaire to estimate blood concentration of chlordecone

Pesticide exposure of pregnant women in Guadeloupe: Ability of a food frequency questionnaire to estimate blood concentration of chlordecone

Some evidence of effects of environmental chemicals on the endocrine system in children

Clinical evaluation of liver structure and function in humans exposed to halogenated hydrocarbons.

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