Toxicological evaluation of 4‐vinylcyclohexene. I. Prechronic (14‐day) and subchronic (13‐week) gavage studies in fischer 344 rats and B6C3F1mice

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 B6C3F ₁ 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 B6C3F ₁ 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 ≥ 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 ≥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.