Mutagenicity and cytotoxicity of N-methyl-2-pyrrolidinone and 4-(methylamino)butanoic acid in the Salmonella/microsome assay

J Appl Toxicol. 1988 Apr;8(2):135-9. doi: 10.1002/jat.2550080211.

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.

MeSH terms

  • Aminobutyrates / pharmacokinetics
  • Aminobutyrates / toxicity*
  • Animals
  • Biotransformation
  • Cell Survival / drug effects*
  • Microsomes, Liver / metabolism*
  • Mutagenicity Tests
  • Mutagens* / pharmacokinetics
  • Pyrrolidinones / pharmacokinetics
  • Pyrrolidinones / toxicity*
  • Rats
  • Rats, Inbred Strains
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics*
  • Subcellular Fractions / metabolism

Substances

  • Aminobutyrates
  • Mutagens
  • Pyrrolidinones
  • 4-(methylamino)butanoic acid
  • N-methylpyrrolidone