Mechanism of Lethal Interaction of Hazardous Chemicals at Subtoxic Doses

摘要

The possibility of unusual toxicity due to interaction of toxic chemicals uponenvironmental or occupational exposures to two or more chemicals, particularly when exposures involve levels ordinarily considered harmless individually is an important toxicological concern. Progress in this area of environmental toxicology has suffered for want of a model where the two interactants are individually nontoxic. Models, where toxic doses of chemicals are employed are not very representative of low level, environmental exposure. Prior exposure to nontoxic levels of the pesticide Kepone (chlordecone, CD) results in a 67-fold amplification of CCI4 lethality in experimental animals. This propensity for chlordecone to potentiate hepatotoxicity of halomethanes such as CCI4, CHCI3 and BrCCI3 has been the subject of this intense inquiry to unravel the underlying mechanism. The biological effects of this interaction include extensive hepatotoxicity characterized by histological alterations, hepatic dysfunction, and perturbation of related biochemical parameters.