Evaluation of N-ethyl-2-pyrrolidone-induced liver effects in rats

N-ethyl-2-pyrrolidone (NEP) is an industrial solvent used in association or in replacement of N-methyl-2-pyrrolidone. Both are teratogenic in rats and are categorized as reproductive toxicants 1B by the European Commission. Nevertheless, there is currently limited data available on the general toxic potential of NEP.
We have performed sub-acute toxicity study in Sprague-Dawley rats to determine whether NEP induced adverse liver effects. Animals received NEP by gavage at the doses of 0, 5, 50 and 250 mg/kg/day (n=5/group/sex) for 28 days. At the end of the study, the animals were euthanized and evaluated for the effects of NEP on hepatic clinical, biochemical, and histopathological parameters.
Plasma levels of hepatic leakage enzymes (i.e. alanine aminotransferase, aspartate aminotransferase), alkaline phosphatase, total bilirubin and cholesterol were comparable across groups and there were no substantial or dose-related changes in liver weight. Both sexes showed a moderate increase in P4502E1 activity in liver microsomes at the high dose, which was accompanied by slight centrilobular hypertrophy of hepatocytes in males. There were no other findings at histological examination. These changes may indicate an adaptative response of the liver to NEP repeated oral exposures.
In conclusion, NEP stimulated P450 enzyme system in the liver but produced no overt hepatotoxicity up to 250 mg/kg/day.