Inhalation toxicity studies of the alpha,beta-unsaturated ketones: Ethyl vinyl ketone

The National Toxicology Program is conducting a chemical class study to inv estigate the structure-activity relationships for the toxicity of alpha,bet a -unsaturated ketones. Ethyl vinyl ketone (EVK) was selected for study bec ause it is a representative straight-chain aliphatic alpha,beta -unsaturate d ketone with extensive use and widespread exposure. Short-term inhalation studies of EVK were conducted to provide toxicity data for comparison with the related alpha,beta -unsaturated ketones 2-cyclohexene-1-one (CHX) and m ethyl vinyl ketone (MVK). These data will be used in designing chronic toxi city and carcinogenicity studies of these ketones. Male and female F344 rat s and B6C3F1 mice were exposed to 0, 2, 4, or 8 ppm EVK 6 h/day, 5 days/wk for 13 wk. The nasal cavity was the major target organ of EVK in both rats and mice. Pathologic findings in both the olfactory and respiratory epithel ium were observed. Lesions consisted primarily of olfactory epithelial necr osis, atrophy and regeneration, and/or hyperplasia and squamous metaplasia of the respiratory epithelium. Squamous metaplasia of the respiratory epith elium was present in all rats and mice exposed to 4 and 8 ppm EVK, and thes e lesions were more severe in rats than in mice. Few systemic effects were observed in rats and mice exposed to EVK. A transient decrease in total leu kocytes due to decrements in lymphocyte and monocyte populations was presen t in male rats after exposure to 8 ppm for 3 and 21 days; however, this eff ect was not present after exposure for 13 wk. There were no chemical-relate d effects on micronucleus formation in mice, or on sperm motility and vagin al cytology in either species. EVK, like other alpha,beta -unsaturated keto nes, is a reactive, direct-acting gaseous irritant with toxicity limited pr imarily to the upper respiratory tract.