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Mutagenicity and cytotoxicity of n‐methyl‐2‐pyrrolidinone and 4‐(methylamino)butanoic acid in the Salmonella /microsome assay
Author(s) -
Wells David A.,
Thomas Harvey F.,
Digenis George A.
Publication year - 1988
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550080211
Subject(s) - chemistry , ames test , cytotoxicity , microsome , s9 fraction , salmonella , population , acid hydrolysis , biochemistry , in vitro , microbiology and biotechnology , hydrolysis , stereochemistry , biology , genetics , bacteria , demography , sociology
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 μmol/plate for NMP, and 0.01 to 316 μmol/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.