Developmental Toxicity of Inhaled Methyl Ethyl Ketone in Swiss Mice

Developmental Toxicity of Inhaled Methyl Ethyl Ketone in SwissMice. Schwetz, B. A., Mast, T. J., Weigel, R. J., Dill, J. A.,and Morrissey, R. E. (1991). Fundam. Appl. Toxicol. 16, 742–748.Methyl ethyl ketone (MEK) is a widely used industrial solventto which there is considerable human exposure. To assess thepotential for MEK to cause developmental toxicity in rodents,groups of Swiss (CD-1) mice were exposed to 0, 400, 1000, or3000 ppm MEK vapors 7 hr/day on Days 6–15 of gestation.Groups consisted of about 30 bred females each. Exposure ofpregnant mice to these concentrations of MEK did not resultin overt maternal toxicity although there was a slight, treatment-relatedincrease in relative liver weight which was statistically significantin the 3000 ppm group. Mild developmental toxicity was observedin the 3000 ppm group in the form of a reduction in mean fetalbody weight. This reduction was statistically significant forthe males only, although the relative decrease from the controlvalues was the same for both sexes. There was no increase inthe incidence of resorptions or the number of litters with resorptionsamong mice exposed to MEK. There was no significant increasein the incidence of any single malformation, but several malformationswhich were not observed in the concurrent control group or thecontrols of contemporary studies were present at a low incidence—cleftpalate, fused ribs, missing vertebrae, and syndactyly. Therewas also a significant trend for increased incidence of misalignedsternebrae, a developmental variation. In summary, pregnantSwiss (CD-1) mice were relatively insensitive to the toxic effectsof MEK at the inhaled concentrations used in this study. However,the offspring of the mice exhibited significant signs of developmentaltoxicity at the 3000 ppm exposure level. Neither maternal nordevelopmental toxicity was observed at 1000 ppm MEK or below.