Toxicological evaluation of 4-vinylcyclohexene. I. Prechronic (14-day) and subchronic (13-week) gavage studies in Fischer 344 rats and B6C3F1 mice.

Abstract

4-Vinylcyclohexene (VCH), a dimer of 1,3-butadiene present in the gases discharged during tire curing, was examined for its toxic effects in Fischer 344 (F344) rats and B6C3F1 mice by 14-d prechronic and 13-wk subchronic testing. In the 14-d studies, VCH was administered orally by gavage in corn oil at doses of 0 (vehicle control), 300, 600, 1250, 2500, or 5000 mg/kg body weight to groups of five F344 rats and B6C3F1 mice of each sex, while the doses for the 13-wk studies (10 animals/group; 5 d/wk) were 0 (vehicle control), 50, 100, 200, 400, or 800 mg/kg body weight for rats and 0 (vehicle control), 75, 150, 300, 600, or 1200 mg/kg body weight for mice. All rats and most mice in the 14-d studies died when administered doses greater than or equal to 1250 mg/kg, although no compound-related gross or histopathologic effects were observed. In the 13-wk studies, extensive mortality was observed only in mice dosed at 1200 mg/kg. Final body weights were reduced in the 13-wk studies in male rats receiving doses greater than or equal to 400 mg VCH/kg, in female rats receiving 800 mg/kg, and in female mice receiving 600 mg/kg. Compound-related histopathologic effects in the 13-wk studies included hyaline droplet degeneration of the proximal convoluted tubules of the kidney in dosed male rats, the severity of which was dose-related, and a reduction in the number of primary follicles and mature graafian follicles in the ovaries of female mice receiving 1200 mg VCH/kg. No compound-related gross or histopathologic effects were evident in dosed female rats or male mice in the 13-wk studies.