Repeated dose oral toxicity of N-ethyl-2-pyrrolidone in Sprague Dawley rats

The solvent N-ethyl-2-pyrrolidone was evaluated in a 4-week repeated dose study in rats. NEP diluted in distilled water was administered by gavage to male and female Sprague-Dawley rats at doses of 0 (vehicle control), 5, 50, and 250 mg/kg/day for 28 consecutive days. Transient decreases in the body weight and in the body weight gain of the males was observed during the first days of treatment at the 50 and 250 mg/kg/day doses. There was a marked increase in urine volume at the beginning of treatment in males and female rats at doses of 50 and 250 mg/kg/day. No biologically significant differences were observed in hematological and clinical chemistry in males and females at necropsy. Histological examination revealed an increase in hyaline droplets in the kidneys and centrilobular hypertrophy in the liver of males at 250 mg/kg/day. Cytochrome P450 2E1 activity in liver microsomes was slightly increased at 250 mg/kg/day in males and females. The results of this study demonstrate that NEP has mild effects at doses up to 250 mg/kg/day when administered orally to rats for 28 days, males being more susceptible than females.