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Toxicological Sciences 58, 386-398 (2000)
Copyright © 2000 by the Society of Toxicology

Safety Evaluation

trans-Nonachlor and cis-Nonachlor Toxicity in Sprague-Dawley Rats: Comparison with Technical Chlordane

G. S. Bondy*,1, W. H. Newsome{dagger}, C. L. Armstrong*, C. A. M. Suzuki*, J. Doucet{dagger}, S. Fernie*, S. L. Hierlihy*, M. M. Feeley{ddagger} and M. G. Barker*

* Toxicology Research Division, {dagger} Food Research Division and {ddagger} Chemical Health Hazard Assessment Division, Food Directorate, Health Protection Branch, Health Canada, Ottawa, Ontario K1A 0L2, Canada

cis-Nonachlor and trans-nonachlor are bioaccumulating components of the pesticide chlordane, which can be detected in various environmental biota and in humans. Existing studies have focused on the potential adverse health effects of the parent chlordane mixture. Comparable toxicity data are nonexistent for individual chlordane constituents such as trans-nonachlor, cis-nonachlor, or oxychlordane, which are among the most common chlordane-related environmental contaminants and tissue residues. In this study, rats were administered cis-nonachlor, trans-nonachlor, or technical chlordane by gavage for 28 days at doses of 0.25 to 25 mg/kg body weight. Residue analyses indicated that trans-nonachlor accumulation in adipose was greater than cis-nonachlor when rats were administered each chemical under identical conditions of dose and exposure. For all test chemicals, the major metabolite oxychlordane accumulated in adipose tissue. Adipose tissue residue levels of all test chemicals and the major metabolite were higher in female rats. The liver was a target organ in male and female rats, indicated by increased liver weight and histopathological changes consistent with microsomal enzyme induction. Hepatic changes were most pronounced in rats treated with trans-nonachlor. Elevated kidney weights and depressed organic ion transport were observed in males treated with trans-nonachlor and chlordane. Although in general, changes in target organs and clinical chemistry endpoints were similar for all 3 test chemicals, the approximate toxicity ranking from most to least toxic was trans-nonachlor > technical chlordane > cis-nonachlor.

Key Words: trans-nonachlor; cis-nonachlor; chlordane; oxychlordane; toxicity.


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