Mechanism of the Lethal Interaction of Chlordecone and CCl4 at Nontoxic Doses,

There is a significant interest in the possibility of unusual toxicity due to interaction of toxic chemicals upon environmental or occupational exposures even though such exposures may involve levels ordinarily considered harmless individually. While many laboratory and experimental models exist for such interactions, progress in this area of toxicology has suffered for want of a model where the two interactants are individually nontoxic. We developed such a model where prior exposure to nontoxic levels of the pesticide Kepone chlordecone results in a 67-fold amplification of carbon tetrachloride CC14 lethality in experimental animals. The mechanisms by which chlordecone amplifies the hepatotoxicity of halomethanes such as CC14, chloroform CHC13, and bromotrichloro BrCC13 has been a subject of intense study. The biological effects of this interaction include extensive hepatotoxicity characterized by histopathological alterations, hepatic dysfunction, and perturbation of related biochemical parameters. Close structural analogs of chlordecone such as mirex and photomirex do not share the propensity of chlordecone to potentiate halomethane toxicity.