National Toxicology Program

Inhalation Developmental Toxicology Studies: Teratology Study of Methyl Ethyl Ketone (CAS No. 78-93-3) in Mice

NTP Study: TER88046

ABSTRACT

Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1^®) mice were exposed to 0, 400, 1000 or 3000 ppm MEK vapors, 7 hours per day, 7 days per week. Ten virgin females and ~30 plug-positive females per group were exposed concurrently for 10 consecutive days (6-15 gd for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on the 18th gestational day. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects.

Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppm group. Mild developmental toxicity was evident at 3000-ppm as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes.

There was no increase in the incidence of intrauterine death in the fetuses of mice exposed to MEK, but there was an increased incidence of misaligned sternebrae (a variation) which was correlated to increasing exposure concentration. The increase was statistically significant for the 3000-ppm group. Although there were no significant increases in the incidence of malformations, several malformations were present at a low incidence which were not observed in the O-ppm group or in the contemporary control data; cleft palate (1 fetus), fused ribs (2), missing vertebrae (1), and syndactyly (5 [all in the same litter]).

In summary, pregnant Swiss (CD-1^®) mice appear to be relatively insensitive to the toxic effects of MEK at the exposure levels employed in this study. However, the offspring of the mice exhibited significant signs of toxicity at the 3000-ppm exposure level. Neither maternal nor developmental toxicity were observed at 1000 ppm MEK or below.

Report Date: February 1989

NTIS# DE89-009563

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