DEVELOPMENTAL TOXICITY OF ORAL AND INHALED VINYL-ACETATE IN THE RAT

Vinyl acetate (VA) is used almost exclusively as an industrial chemica l 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 pot ential of VA causing developmental toxicity in rodents, groups of 23 o r 24 Crl:CD(SD)BR rats were given 0, 200, 1000, or 5000 ppm VA in drin king water or exposed 6 hr/day to 0, 50, 200, or 1000 ppm VA vapors on Days 6-15 of gestation (both routes approximating 0, 25, 100, or 500 mg/kg/day), Administration of VA in the drinking water produced no evi dence of maternal or developmental toxicity. A significantly lowered w ater intake was observed in dams from the 5000 ppm VA group and probab ly reflected unpalatability of the VA water solution at the highest do se 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 fr om the 1000-ppm VA group. In addition, there was a statistically signi ficant increase in the incidence of minor skeletal alterations in fetu ses from dams exposed to 1000 ppm VA, Delayed ossification was the mai n skeletal alteration, In summary, pregnant rats were relatively insen sitive to the effects of VA administered in the drinking water at a co ncentration level as high as 5000 ppm, However, VA did adversely affec t both the dam and the conceptus at an inhaled concentration of 1000 p pm, but not at lower exposure levels, These results indicate that VA i s not uniquely toxic to the conceptus, The no-observed-effect level fo r the dam and conceptus under these experimental conditions was greate r than 5000 ppm for the drinking water study and was 200 ppm for the i nhalation study. (C) 1995 Society of Toxicology.