SUBCHRONIC TOXICITY OF 4-VINYLCYCLOHEXENE IN RATS AND MICE BY INHALATION EXPOSURE

This study was conducted to evaluate the subchronic toxicity of 4-viny lcyclohexene (VCH). Male and female Sprague-Dawley rats and B6C3F(1) m ice were exposed by inhalation to VCH 6 hr/ day, 5 days/week for 13 we eks. Rats were exposed to 0, 250, 1000, or 1500 ppm, and mice were exp osed to 0, 50, 250, or 1000 ppm. In addition, another group of rats an d 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. Th ree additional female mice exposed to 1000 ppm VCH died prior to study completion. The most notable compound-related clinical sign was letha rgy 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-expo sed animals or butadiene-exposed rats showed any compound-related hema tological effects. However, mice exposed to 1000 ppm butadiene exhibit ed mild macrocytic anemia. Clinical chemistry evaluation and urinalysi s 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 100 0 ppm butadiene had increased absolute and/or relative liver weights, and male rats in these same exposure groups had increased relative kid ney weights. Microscopically, increased accumulation of hyaline drople ts was observed in the kidneys of male rats from all VCH exposure grou ps. Although compound-related, the droplets were not accompanied by cy totoxicity. In mice, the most notable adverse histopathological effect was ovarian atrophy in females exposed to 1000 ppm VCH or 1000 ppm bu tadiene. The atrophy was slightly more severe in the VCH-exposed femal es than in the butadiene-exposed females. There were no other compound -related pathological effects in male or female mice exposed to VCH. A dditionally, butadiene-exposed male mice had decreased testicular weig hts, accompanied by slight testicular degeneration and atrophy. For VC H 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. (C) 1996 Society of Toxicology