A 14-Week Vapor Inhalation Toxicity Study of Methyl Isobutyl Ketone

In a 2-week probe study male and female Fischer- 344 rats andB6C3F1 mice were exposed 6 hr/day to 2000, 500, 100, or 0 ppmmethyl isobutyl ketone (MIBK). At 2000 ppm there was a slightincrease in male rat liver weight (absolute and relative). Theonly changes observed histologically were increases in regenerativetubular epithelia and hyalin droplets in kidneys of male ratsexposed to 2000 or 500 ppm. Exposure levels for a subchronicstudy were 0, 50, 250, or 1000 ppm methyl isobutyl ketone vapors6 hr/day, 5 days per week, for 14 weeks. The 14 weeks of exposurehad no adverse effect on the clinical health or growth of ratsor mice. Male rats and male mice exposed to 1000 ppm MIBK hada slight but statistically significant increase in liver weightand the liver weight/body weight ratio. Liver weight was alsoincreased slightly in male mice exposed to 250 ppm. No grossor microscopic hepatic lesions related to MIBK exposure wereobserved. Furthermore, the only microscopic change observedwas an increase in the incidence and extent of hyahin dropletswithin proximal tubular cells of the kidneys of male rats exposedto 250 and 1000 ppm of MIBK. The relevance of the male rat kidneytubular effect to humans is not known. In conclusion, otherthan the male rat kidney effect, exposure of male and femalerats and mice to MIBK at levels up to 1000 ppm for 14 weekswas without significant toxicological effect.