Effect of 4-vinylcyclohexene on micronucleus formation in the bone marrow of rats and mice.

This study was conducted to evaluate the potential of 4-vinylcyclohexene (VCH) to induce micronuclei in the bone marrow of mice and rats. Male and female Crl:CD BR (Sprague-Dawley) rats and B6C3F1/CrBR mice were exposed to VCH 6 hr/day for 2 days or for 13 weeks. In the 2-day study, mice were exposed by inhalation to 0, 250, 500, or 1000 ppm, and rats were exposed to 0, 500, 1000, or 2000 ppm. In the 13-week study, mice were exposed to 0, 50, 250, or 1000 ppm, and rats were exposed to 0, 250, 1000, or 1500 ppm. In each study, a separate group of mice was exposed to 1000 ppm 1,3-butadiene (BD) so that a comparison could be made between the two compounds. Likewise, cyclophosphamide was also included for rats as a positive control. Bone marrow was collected from VCH-exposed animals approximately 24 h and 48 h after the final exposure. There were no statistically significant increases in micronucleatedpolychromatic erythrocytes (MN-PCEs) among VCH-treated mice and rats at any dose level or sampling interval at either 2-days or 13-weeks. Also, no statistically significant differences in the polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) ratios were observed in any of the VCH-treated mice and rats compared to air-exposed animals. As expected, both the butadiene-treated mice and the cyclophosphamide-treated rats showed significantly more MN-PCEs than the control animals.

Subchronic toxicity of 4-vinylcyclohexene in rats and mice by inhalation exposure.

This study was conducted to evaluate the subchronic toxicity of 4-vinylcyclohexene (VCH). Male and female Sprague-Dawley rats and B6C3F1 mice were exposed by inhalation to VCH 6 hr/day, 5 days/week for 13 weeks. Rats were exposed to 0, 250, 1000, or 1500 ppm, and mice were exposed to 0, 50, 250, or 1000 ppm. In addition, another group of rats and mice was exposed to 1000 ppm butadiene so that a comparison could be made between the two compounds. Exposure to 1000 ppm VCH resulted in deaths of all male mice and 5/10 female mice on Test Days 11 or 12. Three additional female mice exposed to 1000 ppm VCH died prior to study completion. The most notable compound-related clinical sign was lethargy observed in the 1500 ppm VCH-exposed rats and 1000 ppm VCH-exposed mice. Male rats exposed to 1500 ppm VCH had significantly lower body weights compared to controls, and male and female rats in the 1500 ppm group had significantly lower body weight gains. None of the VCH-exposed animals or butadiene-exposed rats showed any compound-related hematological effects. However, mice exposed to 1000 ppm butadiene exhibited mild macrocytic anemia. Clinical chemistry evaluation and urinalysis showed no compound-related effects in rats exposed to either VCH or butadiene. Male and female rats exposed to 1000 or 1500 ppm VCH or 1000 ppm butadiene had increased absolute and/or relative liver weights, and male rats in these same exposure groups had increased relative kidney weights. Microscopically, increased accumulation of hyaline droplets was observed in the kidneys of male rats from all VCH exposure groups. Although compound-related, the droplets were not accompanied by cytotoxicity. In mice, the most notable adverse histopathological effect was ovarian atrophy in females exposed to 1000 ppm VCH or 1000 ppm butadiene. The atrophy was slightly more severe in the VCH-exposed females than in the butadiene-exposed females. There were no other compound-related pathological effects in male or female mice exposed to VCH. Additionally, butadiene-exposed male mice had decreased testicular weights, accompanied by slight testicular degeneration and atrophy. For VCH exposure, the no-observed-adverse-effect-level is 1000 ppm for rats based on lethargy and lowered body weights and 250 ppm for mice based on mortality and ovarian atrophy.