Journal Article

Upper Respiratory Tract Toxicity of Inhaled Methylvinyl Ketone in F344 Rats and B6C3F1 Mice

Daniel L. Morgan, Herman C. Price, Robert W. O'Connor, John C. Seely, Sandra M. Ward, Ralph E. Wilson and Michael C. Cunningham

in Toxicological Sciences

Volume 58, issue 1, pages 182-194
Published in print November 2000 | ISSN: 1096-6080
Published online November 2000 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/58.1.182
Upper Respiratory Tract Toxicity of Inhaled Methylvinyl Ketone in F344 Rats and B6C3F1 Mice

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The National Toxicology Program is conducting a chemical class study to investigate the structure-activity relationships for the toxicity of α,β-unsaturated ketones. Methylvinyl ketone (MVK) was selected for study because it is a representative straight-chain aliphatic α,β-unsaturated ketone and because of its extensive use and widespread exposure. Short-term inhalation studies of MVK were conducted to provide toxicity data for comparison with other α,β-unsaturated ketones and for use in designing chronic toxicity and carcinogenicity studies. In 2-week studies, rats and mice were exposed to 0, 0.25, 0.5, 1, 2, 4, or 8 ppm MVK 6 h/day, 5 days/week for 12 exposures. Morbidity and early deaths occurred in all male and female rats after 1 exposure and in 2 male mice after 10 exposures to 8 ppm. Rats exhibited nasal cavity toxicity and lung necrosis at 4 ppm. No toxicity was observed in animals exposed to less than 2 ppm. Based on these results a 13-week study was conducted at 0, 0.5, 1, and 2 ppm MVK. As observed in the 2-week study, the nasal cavity was the main target organ and rats were more sensitive than mice. Respiratory and olfactory epithelial necrosis were prominent by day 21 in the rat. At study termination these lesions were still evident but not as severe as noted earlier. Additionally, changes such as olfactory epithelial regeneration and metaplasia (respiratory) as well as respiratory epithelial hyperplasia and metaplasia (squamous) were clearly evident. Nasal lesions in mice were limited to a subtle squamous metaplasia of transitional and/or respiratory epithelium covering predominantly the tips of naso- and maxilloturbinates in Levels I and II. A transient, leukopenia was observed in rats exposed to 2 ppm, however, this effect was not present after 13 weeks of exposure. In mice, leukocyte counts were significantly decreased at all exposure concentrations after 13 weeks of exposure. Absolute testicular and epididymal weights and sperm counts were decreased at the high dose only. MVK can be characterized as a reactive, direct-acting gaseous irritant. MVK exposure causes the same nasal cavity lesions as the cyclic α,β-unsaturated ketone, 2-cyclohexen-1-one, although at lower exposure concentrations.

Keywords: Methylvinyl ketone; 3-buten-2-one; α,β-unsaturated ketones; inhalation; upper respiratory tract; nasal cavity; gaseous irritant

Journal Article.  7855 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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