Toxicity of N-methyl-2-pyrrolidone (NMP): teratogenic, subchronic, and two-year inhalation studies.

ABSTRACT

Pregnant rats were exposed to N-methyl-2-pyrrolidone (NMP) at atmospheric concentrations of 0.1 and 0.36 mg/liter for 6 hr/day on Days 6 through 15 of gestation. Except for sporadic lethargy and irregular respiration in several rats the first 3 days of exposure, there were neither abnormal clinical signs nor pathological lesions in the maternal rats. Exposure did not affect either the outcome of pregnancy or embryonal growth rate. No abnormal development was detected in the vital organs and skeletons of the fetuses. Rats were exposed to an aerosol-vapor mixture of NMP at concentrations of 0, 0.1, 0.5, and 1.0 mg/liter for 6 hr/day, 5 days/week for 4 weeks. At 0.1 and 0.5 mg/liter exposure levels, rats did not show any significant clinical signs or pathological lesions. However, lethargy, respiratory difficulty, and excessive mortality were found in rats exposed to 1.0 mg/liter. These rats had focal pneumonia, bone marrow hypoplasia, and atrophy of lymphoid tissue in the spleen and thymus. These lesions were reversible in surviving rats following 2 weeks of recovery. Increases in the relative and absolute numbers of neutrophils were observed during exposure at 1.0 mg/liter, but returned to normal limits after 2 weeks of recovery. Rats were exposed to vapor of NMP at concentrations of 0, 0.04, or 0.4 mg/liter for 6 hr/day, 5 days/week for 2 years. Male rats at 0.4 mg/liter showed slightly reduced mean body weight. No life-shortening toxic or carcinogenic effects were observed in rats exposed for 2 years to 0.04 or 0.4 mg/liter of NMP.