Assessment of reproductive toxicity and gonadotoxic potential of N-methyl-2-pyrrolidone in male rats.
OBJECTIVE
N-methyl-2-pyrrolidone (NMP) is a solvent used in petrochemical, electric and electronic industries, and in the production of paint removers, pesticides and veterinary drugs. The substance exhibits slight acute toxicity, and moderate irritant, embryotoxic and teratogenic effects. The aim of the study was to assess NMP reproductive toxicity and gonadotoxicity in male rats.


METHODS
The animals were exposed per os to NMP at daily doses of 0, 100, 300 and 1000 mg/kg. After 10 weeks of exposure, each male was mated with nonexposed female, then all the males were autopsied, and epididymis and testis were fixed for pathomorphological examination. Viability and development of offspring was observed to 28 days postbirth.


RESULTS
NMP at 1000 mg/kg was found to produce male infertility and extensive damage to the seminiferous epithelium in the seminal tubules of the testis. When administered at 100 mg/kg or 300 mg/kg, it did not significantly affect fertility or spermatogenesis. NMP exposure at 100 mg/kg did not influence either the viability or the development of their offspring in the first month of life, while exposure at 300 mg/kg resulted in a significantly lower viability of the offspring in the first four days of life.


CONCLUSIONS
This study has demonstrated that sub-chronic exposure of male rats to NMP at 1000 mg/kg/day produces gonadotoxic effect and brings about infertility. Administration at lower doses of 100 and 300 mg/kg did not impair male fertility, but only the lowest dose of 100 mg/kg was found to have no influence on the prenatal development of the progeny.
Sitarek
Krystyna
K
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lódź, Poland. ksitarek@imp.lodz.pl
Stetkiewicz
Jan
J
D000818:Animals; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006066:Gonads / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*
D011760:Pyrrolidinones; D012997:Solvents; C038678:N-methylpyrrolidone