1-Methyl-2-pyrrolidone (NMP): reproductive and developmental toxicity study by inhalation in the rat.

A two-generation reproduction study with a developmental toxicity component was conducted. For the reproduction phase, male and female rats inhaled 0, 10, 51, or 116 ppm NMP daily for 6 hr/day, 7 days/week from 34 days of age to the end of the mating period for the males (100 exposure days) and till weaning for the females (about 143 exposure days, but interrupted from Day 20 of gestation to Day 4 Postpartum). On Day 70 postpartum, one male and one female selected from each litter later mated with newly obtained, nonexposed adults of the opposite sex to produce an F2 generation. For the developmental phase, rats of both sexes inhaled 0 or 116 ppm NMP as outlined above, but euthanization of the females occurred on Day 21 of gestation followed by fetal examination for structural alterations. The indices of reproductive performance for the NMP-exposed rats did not differ significantly from those obtained for the control rats. Rats exposed to 116 ppm had a detectable decrease in response to sound. No other signs of NMP-related toxicity were detected among the parental rats. An exposure-related but slight decrease in fetal weight was detected only among the F1 offspring whose parents both inhaled NMP at 116 ppm. This slight effect also appeared at birth among the pups of the reproductive phase where it persisted till 21 days after birth when NMP inhalation by the mother ceased. Thereafter, the body weight of the offspring was comparable to the control values. No detectable or developmental effects appeared in the 10 or 51 ppm groups.