Chronic toxicity and oncogenicity study with vinyl acetate in the rat: in utero exposure in drinking water

The purpose of this study was to evaluate vinyl acetate for potential chronic toxicity and oncogenicity when given to rats in drinking water from the time of gestation. Target concentrations were 0, 200, 1000, and 5000 ppm (v/v). Drinking water solutions were prepared daily and analyzed at approximately 4-week intervals. F0 rats were given solutions of vinyl acetate for 10 weeks and then mated. Offspring (F1 rats) were culled to equal group sizes of 60 main study rats and 30 rats for satellite groups. F1 rats were treated for up to 104 weeks with interim kills of satellite groups at 52 and 78 weeks. Body weights and clinical signs of toxicity were monitored in F0 and F1 rats. Food and water consumption were measured in F1 rats. At Weeks 52 and 78 of the test, clinical pathology and urine analysis examinations were conducted on 10 rats per group from satellite animals. A complete gross and histopathological examination of F1 rats was conducted at the interim kills and on main study rats at Week 104. Average vinyl acetate consumption over the course of the study in male rats of the 200, 1000, and 5000 ppm groups was 10, 47, and 202 mg/kg/day, respectively. Female rats consumed an average of 16, 76, and 302 mg/kg/day, respectively. Compound-related effects observed during the study included a concentration-related decrease in water consumption among rats of the 1000 and 5000 ppm groups and a decrease in food consumption among rats of the 5000 ppm groups. Concurrent body weight decrement was observed only in the 5000 ppm groups.(ABSTRACT TRUNCATED AT 250 WORDS)