Developmental toxicity of inhaled methyl ethyl ketone in Swiss mice

Methyl ethyl ketone (MEK) is a widely used industrial solvent to which there is considerable human exposure. To assess the potential for MEK to cause developmental toxicity in rodents, groups of Swiss (CD-1) mice were exposed to 0, 400, 1000, or 3000 ppm MEK vapors 7 hr/day on Days 6-15 of gestation. Groups consisted of about 30 bred females each. Exposure of pregnant mice to these concentrations of MEK did not result in overt maternal toxicity although there was a slight, treatment-related increase in relative liver weight which was statistically significant in the 3000 ppm group. Mild developmental toxicity was observed in the 3000 ppm group in the form of a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease from the control values was the same for both sexes. There was no increase in the incidence of resorptions or the number of litters with resorptions among mice exposed to MEK. There was no significant increase in the incidence of any single malformation, but several malformations which were not observed in the concurrent control group or the controls of contemporary studies were present at a low incidence--cleft palate, fused ribs, missing vertebrae, and syndactyly. There was also a significant trend for increased incidence of misaligned sternebrae, a developmental variation. In summary, pregnant Swiss (CD-1) mice were relatively insensitive to the toxic effects of MEK at the inhaled concentrations used in this study. However, the offspring of the mice exhibited significant signs of developmental toxicity at the 3000 ppm exposure level.(ABSTRACT TRUNCATED AT 250 WORDS)