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© 1984 Oxford University Press

research-article

Chronic Kidney Disease and Organic Chemical Exposures: Evaluations of Causal Relationships in Humans and Experimental Animals1

WILLIAM M. KLUWE2, KAMAL M. ABDO and JAMES HUFF

National Toxicology Program, National Institute of Environmental Health Sciences P.O. Box 12233, Research Triangle Park, North Carolina 27709

Chronic Kidney Disease and Organic Chemical Exposures: Evaluations of Causal Relationships in Humans and Experimental Animals. Kluwe, W. M., Abdo, K. M., and Huff, J. (1984). Fundam. Appl. Toxicol. 4, 889–901. Chronic renal failure is a serious health problem in the United States and other developed countries, and large amounts of public funds are being expended for what is essentially palliative treatment of this disease. Historical data also indicate increasing trends for urinary tract cancers of both sexes in the United States. Although the data on humans are not definitive, causal associations appear to exist between occupational exposures to some hydrocarbon solvents and chronic kidney disease, and there is preliminary evidence that suggests an association between organic chemical exposures and cancers of the urinary tract in humans. A review of more than 230 chemicals tested in two-year chronic toxicity studies by the National Toxicology Program (NTP)/National Cancer Institute (NCI) has identified two chemical classes that commonly produced nonneoplastic chronic renal disease in rodents: aromatic amines and organohalides. Tumors of the kidney were most frequently produced by alkyl or alkenyl halide compounds, while tumors of the bladder were caused by aromatic amines. Consistent with many literature reports, short-chain halogenated hydrocarbons appeared to have a propensity for causing a low incidence of renal tubular carcinoma in exposed rodents. Comparative analyses of the NTP/NCI studies did not indicate consistent sex or species differences in the nonneoplastic chronic toxic response, but chemically induced urinary tract cancers occurred more commonly in rats than in mice, and chemically induced cancers of the kidney occurred more commonly in males than in females. Viewed collectively, these data indicate a potential for organic chemicals, especially halogenated hydrocarbons and aromatic amines, to produce chronic kidney injury in humans and other mammalian species. Quantitative risk evaluations, however, require more detailed assessments of probable mechanisms of toxicity than those that are currently available for these chemicals


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