Chlordecone toxicity

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,... 

Bansal SK, Desaiah D. 1985. Chlordecone toxicity Effect of withdrawal of treatment on ATPase inhibition. Neurotoxicology 6(3) 103-107. 

Cannon SB, Kimbrough RD. 1979. Short-term chlordecone toxicity in rat including effects on reproduction, pathological organ changes and their reversibility. Toxicol Appl Pharmacol 47 469-476. 

Ho IK, Fujimori K, Huang TP, et al. 1981. Neurochemical evaluation of chlordecone toxicity in the mouse. J Toxicol Environ Health 8 701-706. 

Jordan JE, Grice T, Mishra SK, et al. 1981. Acute chlordecone toxicity in rats A relationship between tremor and ATPase activities. Neurotoxicology 2 355-364. 

There are no reports of death in humans exposed to chlordecone. The major target organs of chlordecone toxicity are the nervous system, the liver, and the testes. 

Tvede KG, Loft S, Poulsen HE, et al. 1989. Methyl parathion toxicity in rats is changed by pretreatment with the pesticides chlordecone, mirex and linuron. Arch Toxicol Suppl 13 446-447. 

The selection of these compounds was made on the grounds of their toxicity, environmental stability, and tendency to undergo biomagnification the intention was to move toward their removal from the natural environment. In the REACH proposals of the European Commission (EC published in 2003), a similar list of 12 POPs was drawn up, the only differences being the inclusion of hexachlorobiphenyl and chlordecone, and the exclusion of the by-products, dioxins, and furans. The objective of the EC directive is to ban the manufacture or marketing of these substances. It is interesting that no fewer than eight of these compounds, which are featured on both lists, are insecticides. 

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. 

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. Flowever, 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. 

It is unclear whether the myopathy was a direct toxic effect of chlordecone on the muscle or whether the myopathy was a consequence of neuronal dysfunction. 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 hepatic toxicity in animals following inhalation exposure to mirex or chlordecone. 

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. 

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. 

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 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. 

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. 

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. 

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. 

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