1-methyl-2-pyrrolidone (nmp): reproductive and developmental toxicity study by inhalation in the rat

Abstract

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.

Toxicokinetics and Metabolism ofN-[14C]Methylpyrrolidone in Male Sprague-Dawley Rats. A Saturable NMP Elimination Process

“…Studies on reproductive toxicity have shown that NMP causes developmental toxicity at doses causing no or mild maternal toxicity (Hass et al, 1994;Solomon et al, 1995). Cases of stillbirth after occupational exposure to NMP have been reported (Solomon et al, 1996;Bower, 1997).…”

Characterization of the Polyurethanolytic Activity of Two Alicycliphilus sp. Strains Able To Degrade Polyurethane and N -Methylpyrrolidone

“…However, recent findings indicate that NMP has aquatic toxicity for Daphnia magna, with a 50% lethal concentration at 24 h of 1.23 mg ⅐ liter Ϫ1 , and only certain pesticides have greater toxicity than this compound (23). NMP has been reported to be teratogenic in rats when administered orally (38) but not by inhalation (16,25,37), although a reduction in fetal weight has been observed to occur in the absence of obvious maternal effects at certain doses (37,43). It has also been correlated with stillbirth in a woman working in a laboratory where NMP was used routinely (42) and with the poisoning of an agricultural worker by an insecticide in which it was a major component (44).…”

Time to pregnancy among partners of men exposed to di(2-ethylhexyl)phthalate

“…of the NOAEL (no observed adverse effect level) of reproduction toxicity in rodents (19). In the other processing plant, thin film was calendered from PVC, with DEHP as the main plasticizer.…”