Repeated dose toxicity study (28 days) in rats and mice with N-methylpyrrolidone (NMP).
Twenty-eight day feeding studies were conducted to evaluate the repeated dose toxicity of NMP, a widely used industrial solvent, in Crl:CD BR rats and B6C3F1 mice. Groups of 5 male and 5 female rats each were fed either 0, 2,000, 6,000, 18,000, or 30,000 ppm NMP; similar groups of mice were fed either 0, 500, 2,500, 7,500, or 10,000 ppm. In vivo parameters, hematology and clinical chemistry parameters, and complete pathology evaluations were conducted after approximately 28 days. Decrements in mean body weight gains, reflecting decreases in food consumption and efficiency, were seen in male rats fed 18,000 ppm and in both sexes fed 30,000 ppm. In rats, clinical chemical changes, indicating possible compound-related alterations in lipid, protein, and carbohydrate metabolism, occurred at 18,000 ppm in males and 30,000 ppm in both sexes. No histopathological changes in rats were judged to be directly related to NMP exposure. Hematological (mild to moderate leukopenia) and histopathological alterations (hypocellular bone marrow, testicular degeneration and atrophy, and thymic atrophy) were judged to be secondary to nutritional and body weight effects in male and/or female rats at 30,000 ppm. In mice, cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10,000 ppm and in 2 male mice at 7,500 ppm. For both rats and mice, abnormal urine coloration was observed (in mice at 2,500 ppm and above, and in rats at 18,000 ppm and above). The discoloration was interpreted as a sign of systemic availability of the test substance, but not as an adverse effect. The NOAEL was 6,000 ppm for male rats and 18,000 ppm for female rats. In mice, the NOAEL was 2,500 ppm based on the kidney histopathology.
Malek
D E
DE
DuPont Co., Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE, USA.
Malley
L A
LA
Slone
T W
TW
Elliott
G S
GS
Kennedy
G L
GL
Mellert
W
W
Deckardt
K
K
Gembardt
C
C
Hildebrand
B
B
Murphy
S R
SR
Bower
D B
DB
Wright
G A
GA
D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001774:Blood Chemical Analysis; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D050260:Carbohydrate Metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D007970:Leukopenia / Q000139:chemically induced; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013045:Species Specificity; D013723:Teratogens / Q000633:toxicity*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D014556:Urine / Q000737:chemistry
D015415:Biomarkers; D001798:Blood Proteins; D008055:Lipids; D011760:Pyrrolidinones; D013723:Teratogens; C038678:N-methylpyrrolidone