Toxicological evaluation of 4‐vinylcyclohexene. II. Induction of ovarian tumors in female B6C3F1mice by chronic oral administration of 4‐vinylcyclohexene

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Abstract
4‐Vinylcyclohexene (VCH), a dimer of 1,3‐butadiene present in the gases discharged during tire curing, was examined for its toxic and carcinogenic effects in Fischer 344 (F344) rats and 66C3F 1 mice by 2‐yr chronic testing. VCH was administered orally by gavage in corn oil at doses of 0 (vehicle control), 200, or 400 mg/kg body weight to groups of 50 F344 rats and B6C3F 1 mice of each sex for 103 wk (5 d/wk). Because the studies of VCH in male and female rats and in male mice were considered to be inadequate studies of carcinogenicity due to the extensive and early mortality at the high dose or both doses tested, as well as the lack of conclusive evidence of a carcinogenic effect, the present article focuses on the results of the 2‐yr study of VCH in female B6C3F 1 mice. Survival of high‐dose female mice was lower (p < 0.001) than that of the vehicle controls, whereas survival of low‐dose and survival of vehicle control female mice were comparable. Mean body weights of high‐dose female mice were generally slightly lower than those of the vehicle controls, whereas the mean body weights of low‐dose female mice were generally greater than or comparable to those of the vehicle controls. Oral administration of VCH by gavage to female B6C3F 1 mice was associated with an increased incidence of a number of nonneoplastic lesions, including mild acute inflammatory lesions and epithelial hyperplasia of the forestomach, congestion of the lungs and adrenal glands at the high dose, and cytologie alteration of the adrenal cortex at both doses. However, the most striking finding was the markedly increased (p < 0.01) incidences of uncommon ovarian neoplasms, including mixed benign tumors, granulosa‐cell tumors, and granulosa‐cell tumors or carcinomas (combined), in both groups of dosed female mice. In addition, the increased incidence of adrenal‐gland capsular adenomas in high‐dose female mice may have been compound‐related.