Mechanism of nephrotoxic action due to organohalogenated compounds.
A number of organohalogenated chemicals cause nephrotoxicity in experimental animals and man. Studies in animals have shown that metabolic activation of the chemical is required to produce toxicity. Currently, two major pathways of metabolism, mediated either via cytochrome P-450 or glutathione conjugation, have been implicated. Chloroform is discussed as an example of cytochrome P-450-mediated activation and dihaloethanes and hexachloro-1,3-butadiene as examples of glutathione conjugation followed by activation. Acute human exposure to certain organohalogenated compounds can sometimes result in proximal tubular injury. These intoxications usually occur after either accidental or deliberate ingestion and are rarely occupational. Chronic low-level exposure can occur in the work place, and several biological tests have been developed to detect chronic nephrotoxicity. A few studies have been undertaken of workers exposed to organohalogenated chemicals; these have provided no indication that exposure to these chemicals causes chronic renal damage.
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Imperial Chemical Industries PLC, Central Toxicology Laboratory, Alderley Park, Nr Macclesfield, Cheshire, U.K.
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000378:metabolism
D006846:Hydrocarbons, Halogenated; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione