Differential ovotoxicity of 4-vinylcyclohexene and its analog, 4-phenylcyclohexene

Vinylcyclohexene (VCH) is an industrial byproduct that is known to cause the destruction of ovarian follicles in mice. Its analog, 4-phenylcyclohexene (4PC), is a volatile product from latex-backed carpeting. These studies were undertaken to assess the structure-activity relationships of these compounds and the potential for 4PC to cause ovotoxicity. Female B6C3F1 mice were dosed with VCH (6 mmol/kg/day, ip) or 4PC (3 or 6 mmol/kg/day, ip) daily for 30 days. Treatment with VCH caused dramatic reductions in small and growing follicles as compared to those of vehicle controls. No treatment-related ovarian lesions were associated with 4PC administration. Plasma FSH concentrations were unaltered by treatment with either compound. These results indicate that in mice, the substitution of the phenyl for the vinyl group in the 4 position eliminates the ovotoxicity caused by this class of compounds. Presumably, the ability of the vinyl group to form an epoxide (or dihydrodiol) and/or its smaller size accounts for this difference in ovarian toxicity.