Developmental toxicity of oral and inhaled vinyl acetate in the rat

Vinyl acetate (VA) is used almost exclusively as an industrial chemical in polymerization, copolymerization, or as a chemical intermediate. The present studies were undertaken as part of a collaborative effort by the VA producers of Western Europe, Japan, and the United States to provide animal toxicology data for risk assessment. To assess the potential of VA causing developmental toxicity in rodents, groups of 23 or 24 Crl:CD(SD)BR rats were given 0, 200, 1000, or 5000 ppm VA in drinking water or exposed 6 hr/day to 0, 50, 200, or 1000 ppm VA vapors on Days 6-15 of gestation (both routes approximately 0, 25, 100, or 500 mg/kg/day). Administration of VA in the drinking water produced no evidence of maternal or developmental toxicity. A significantly lowered water intake was observed in dams from the 5000 ppm VA group and probably reflected unpalatability of the VA water solution at the highest dose level. In the inhalation study, maternal toxicity was evident by a marked reduction in weight gain of dams exposed to 1000 but not 200 or 50 ppm VA. Fetal toxicity was evident by a statistically significant decrease in mean fetal weight and mean crown-rump length in fetuses from the 1000-ppm VA group. In addition, there was a statistically significant increase in the incidence of minor skeletal alterations in fetuses from dams exposed to 1000 ppm VA. Delayed ossification was the main skeletal alteration. In summary, pregnant rats were relatively insensitive to the effects of VA administered in the drinking water at a concentration level as high as 5000 ppm. However, VA did adversely affect both the dam and the conceptus at an inhaled concentration of 1000 ppm, but not at lower exposure levels. These results indicate that VA is not uniquely toxic to the conceptus. The no-observed-effect level for the dam and conceptus under these experimental conditions was greater than 5000 ppm for the drinking water study and was 200 ppm for the inhalation study.