90-day subchronic toxicity study in rats and mice fed N-methylpyrrolidone (NMP) including neurotoxicity evaluation in rats.
In mice, there were no effects on body weight or food consumption. As observed in rats, mice fed 2,500 or 7,500 ppm exhibited a change in urine coloration which was not associated with morphological changes in cholesterol, triglycerides, calcium, and alkaline phosphatase occurred at 28 days but not 90 days. These changes are thus assessed as being of minor toxicological relevance. Liver weights were elevated in males fed 2,500 or 7,500 ppm and centrilobular hypertrophy was seen in both sexes fed 7,500 ppm. These changes may be regarded as an adaptation process but are clearly related to NMP exposure. Other toxicological endpoints examined were unaffected by NMP. The NOAEL was 3,000 ppm for both sexes of rats based on body weight effects and changes in 3 neurobehavioral parameters (males only) at higher feeding levels. In mice, the NOAEL was 1,000 ppm based on liver responses to higher concentrations.
Malley
L A
LA
DuPont Co., Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE, USA.
Kennedy
G L
GL
Elliott
G S
GS
Slone
T W
TW
Mellert
W
W
Deckardt
K
K
Gembardt
C
C
Hildebrand
B
B
Parod
R J
RJ
McCarthy
T J
TJ
Griffiths
J C
JC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011760:Pyrrolidinones / Q000633:toxicity*; D051381:Rats
D011760:Pyrrolidinones; C038678:N-methylpyrrolidone