Toxicity of 4-vinyl-1-cyclohexene diepoxide after 13 weeks of dermal or oral exposure in rats and mice.

4-Vinyl-1-cyclohexene diepoxide (VCHD) is used as a chemical intermediate and as a reactive diluent for diepoxides and epoxy resins. Toxicology studies were conducted by administering VCHD in acetone by dermal application or in corn oil by gavage to F344/N rats and B6C3F1 mice for 13 weeks. In the 13-week dermal studies, groups of 10 rats of each sex received 0.3 ml of VCHD in acetone at concentrations ranging from 6.25 to 200 mg/ml, and mice received 0.1 ml at concentrations ranging from 6.25 to 100 mg/ml. Skin lesions were observed at the site of application at the top two dose levels for both species and sexes, and consisted of acanthosis, parakeratosis, and hyperkeratosis of the epidermis and sebaceous gland hyperplasia. In mice, follicular atrophy of the ovary, characterized by decreased numbers of primary and secondary follicles, occurred at the 50- and 100-mg dose levels. In 13-week oral studies, groups of 10 rats and mice of each sex were administered VCHD at dose levels ranging from 62.5 to 1000 mg/kg in corn oil. In rats and mice, there were body weight decreases in the groups given the two highest doses. The major target organs in rats were forestomach (hyperplasia and hyperkeratosis) and kidney (tubular cell degeneration/necrosis and regeneration). In mice the target organs included forestomach (hyperplasia and hyperkeratosis), ovary (follicular atrophy), and testis (degeneration of germinal epithelium).