Tissue distribution and excretion of N-methyl-2-pyrrolidone in male and female rats.
OBJECTIVE
N-methyl-2-pyrrolidone (NMP) belongs to solvents widely used in the petrochemical industry a well as in the production of pesticides, veterinary drugs and paint removers. NMP is easily absorbed from the respiratory tract, digestive system and through the skin. It is a compound of slight acute toxicity that also displays moderate irritating activity. The aim of this study was to assess tissue distribution and excretion following a single intraperitoneal NMP administration.


METHODS
Tissue distribution and excretion of NMP following administration of a single dose of 250 mg/kg body weight (350 kBq/rat) was investigated using 14C. Blood plasma (6 rats per time point) were sampled up to 72 h after administration and determination of radioactivity. Male and female rats (4 animals per time point) were decapitated at appropriate time intervals and examined tissues were removed for determination of radioactivity. Excretion of 14C in urine and feces were also measured. All radioactivity measurements were carried out using a Rackbetta 1209 (LKB, Sweden) liquid scintillation counter.


RESULTS
The highest 14C activity in tissues and internal organs of female and male rats was observed 4 h after administration of the compound. The highest accumulation was detected in the muscles and fat tissue as well as in the liver and testicles. During 72 h following administration, approximately 80% of the dose was excreted in urine. Elimination of the compound in feces was far less significant: only about 5% of the dose was excreted at once.


CONCLUSIONS
The results of the study indicate that there are no significant differences in 14C-NMP tissue distribution between male and female rats; NMP absorption from the peritoneal cavity to blood is rapid, disappearance from plasma is monophase and kidneys are the main route of excretion of NMP and/or its metabolites from the rat body after administration of a dose equal to 10% of LD50. The ability to accumulate NMP and/or its metabolites in testes and seminal vesicles may be the reason for fertility impairment in male rats observed after repeated exposure to this compound.
Sitarek
Krystyna
K
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lódź, Poland. ksitarek@imp.lodz.pl
Kilanowicz
Anna
A
D000818:Animals; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D011760:Pyrrolidinones / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D051381:Rats; D014018:Tissue Distribution
D011760:Pyrrolidinones; C038678:N-methylpyrrolidone