title: Mutagenicity and cytotoxicity of N-methyl-2-pyrrolidinone and 4-(methylamino)butanoic acid in the Salmonella/microsome assay.
abstract: The industrial solvent N-methyl-2-pyrrolidinone (NMP) and its hydrolysis product, 4-(methylamino)butanoic acid (N-MeGABA), were examined for mutagenicity and cytotoxicity in the Ames Salmonella/microsome assay. In order to detect a broad range of possible mutagenic endpoints, the following strains were used in the assay: base-pair substitution strains TA100, TA102 and TA104; frameshift strains TA97 and TA98; and repair proficient strains TA2638, UTH8413 and UTH8414. In the standard plate incorporation assay, six log-linear doses of each compound were tested; doses ranged from 0.01 to 1000 mumol/plate for NMP, and 0.01 to 316 mumol/plate for N-MeGABA. Neither compound was detectably mutagenic when tested in the presence and absence of metabolic activation by Aroclor-induced rat liver S9. NMP did show significant responses with strains TA102 and TA104 that were less than two-fold over background, but no clear dose-response relationships were evident. A preincubation modification of the assay was also performed, using strains TA98 and TA104. Mutagenic activity was not observed for NMP, while N-MeGABA showed significant responses with TA104 but dose-related mutagenicity was not established. Preincubation testing revealed both NMP and N-MeGABA to be cytotoxic to the test population of Salmonella at the highest treatment doses.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington.
authors.forename: D A
authors.initials: DA
authors.lastname: Wells
authors.forename: H F
authors.initials: HF
authors.lastname: Thomas
authors.forename: G A
authors.initials: GA
authors.lastname: Digenis
mesh_terms: D000613:Aminobutyrates / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000613:Aminobutyrates; D009153:Mutagens; D011760:Pyrrolidinones; C056202:4-(methylamino)butanoic acid; C038678:N-methylpyrrolidone