Halogenated Hydrocarbon-Induced Nephrotoxicity and Carcinogenicity

Male Osborne-Mendel rats given a 10 per cent solution of CHCI3 in corn oil (gavaged five days each week) had a significant increase in renal epithelial neoplasms after 78 weeks, as compared with controls (Weisburger 1977). No increase in renal neoplasms was noted in C57BL, CBA, or CFl male mice (Roe et al. 1979). 

In male Sprague-Dawley rats, CCI4 (0.25 ml per 100 g body weight in an equal volume of mineral oil given by gastric tube) produced an early, reversible renal lesion limited to the proximal tubule (Striker et al. 1968). The first change occurred in the mitochondria, followed by cell swelling and proliferation of the smooth endoplasmic reticulum. 

Pre-treatment of rats with MFO inducers, such as polybrominated biphenyl, enhanced the nephrotoxicity of CCI4 (Kluwe et al. 1982). 

However, the kidney receives a high blood flow and possesses transport systems for S-conjugates, properties that also contribute to an accumulation of S-conjugates in this organ (Lash and Jones 1985). 

Trichloroethylene was acutely cytotoxic to proximal and distal tubular cells isolated by coUagenase perfusion from the kidneys of male Fischer 344 rats only at high concentrations, but, under conditions in which cytochrome P450 was not inhibited, S-(l,2-dichlorovinyl)glutathione formation was detected only in proximal tubular cells (Cummings etal. 2000). Inhibition of cytochrome P450 resulted in increases in both cytotoxicity and biotransformation of trichloroethylene. 

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