Developmental Toxicity of Oral and Inhaled Vinyl Acetate in the Rat

Vinyl acetate (VA) is used almost exclusively as an industrialchemical in polymerization, copolymerization, or as a chemicalintermediate. The present studies were undertaken as part ofa collaborative effort by the VA producers of Western Europe,Japan, and the United States to provide animal toxicology datafor risk assessment. To assess the potential of VA causing developmentaltoxicity in rodents, groups of 23 or 24 Crl:CD(SD)BR rats weregiven 0, 200, 1000, or 5000 ppm VA in drinking water or exposed6 hr/day to 0, 50, 200, or 1000 ppm VA vapors on Days 6–15of gestation (both routes approximating 0, 25, 100, or 500 mg/kg/day).Administration of VA in the drinking water produced no evidenceof maternal or developmental toxicity. A significantly loweredwater intake was observed in dams from the 5000 ppm VA groupand probably reflected unpalatability of the VA water solutionat the highest dose level. In the inhalation study, maternaltoxicity was evident by a marked reduction in weight gain ofdams exposed to 1000 but not 200 or 50 ppm VA. Fetal toxicitywas evident by a statistically significant decrease in meanfetal weight and mean crown-rump length in fetuses from the1000-ppm VA group. In addition, there was a statistically significantincrease in the incidence of minor skeletal alterations in fetusesfrom dams exposed to 1000 ppm VA. Delayed ossification was themain skeletal alteration. In summary, pregnant rats were relativelyinsensitive to the effects of VA administered in the drinkingwater at a concentration level as high as 5000 ppm. However,VA did adversely affect both the dam and the conceptus at aninhaled concentration of 1000 ppm, but not at lower exposurelevels. These results indicate that VA is not uniquely toxicto the conceptus. The no-observed-effect level for the dam andconceptus under these experimental conditions was greater than5000 ppm for the drinking water study and was 200 ppm for theinhalation study.