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1-Methyl-2-pyrrolidinone (NMP) does not induce structural and numerical chromosomal aberrations in vivo
1Department of Toxicology, BASF Aktiengesellschaft, Ludwigshafen, Germany.
Abstract:
1-Methyl-2-pyrrolidinone induces aneuploidy in yeast, but only under special treatment conditions. Other genotoxic effects have not been found in vitro, and in vivo no data are available in the literature. Therefore, NMP was investigated in the mouse micronucleus test and the Chinese hamster bone marrow test for structural and numerical chromosomal aberrations. These tests can detect both types of alterations as demonstrated by appropriate positive control substances (cyclophosphamide, vincristine sulfate and benomyl). NMP at single oral doses up to 3800 mg/kg body weight (approximately 80% of the LD50) did not lead to an increase either in micronucleated erythrocytes or in structural or numerical chromosomal aberrations when bone marrow was sampled 16, 24 and 48 h after treatment in the micronucleus test or after 24 and 48 h for karyotype analysis.
Insights
1-Methyl-2-pyrrolidinone (NMP) did not demonstrate genotoxicity in vivo. Studies showed NMP did not induce chromosomal aberrations or micronuclei in mice or hamsters, despite inducing aneuploidy in yeast under specific conditions.
Area of Science:
- Toxicology
- Genetics
- In vivo studies
Background:
- 1-Methyl-2-pyrrolidinone (NMP) has shown aneuploidy induction in yeast under specific conditions.
- Limited in vitro genotoxicity data exists for NMP, with no in vivo data available.
- The genotoxic potential of NMP requires further investigation in mammalian systems.
Purpose of the Study:
- To evaluate the in vivo genotoxic potential of 1-Methyl-2-pyrrolidinone (NMP).
- To assess NMP's ability to induce structural and numerical chromosomal aberrations in mammals.
- To investigate NMP's effects in established genotoxicity assays.
Main Methods:
- Mouse micronucleus test was performed to detect micronucleated erythrocytes.
- Chinese hamster bone marrow test was utilized for karyotype analysis.
- Animals were administered single oral doses of NMP up to 3800 mg/kg body weight.
Main Results:
- NMP did not increase the frequency of micronucleated erythrocytes in mice.
- No significant increase in structural or numerical chromosomal aberrations was observed in Chinese hamster bone marrow.
- These negative results were obtained at doses up to 3800 mg/kg body weight, approximately 80% of the LD50.
Conclusions:
- 1-Methyl-2-pyrrolidinone (NMP) does not appear to be genotoxic in vivo based on the conducted assays.
- NMP did not induce chromosomal damage or aneuploidy in mammalian test systems.
- The study provides evidence against the in vivo genotoxicity of NMP.