REPEATED DOSE TOXICITY STUDY (28 DAYS) IN RATS AND MICE WITH N-METHYLPYRROLIDONE (NMP)

Twenty-eight day feeding studies were conducted to evaluate the repeat ed dose toxicity of NMP, a widely used industrial solvent, in Crl:CD(R )BR rats and B6C3F1 mice. Groups of 5 male and 5 female rats each were fed either 0, 2,000, 6,000, 18,000, or 30,000 ppm NMP; similar groups of mice were fed either 0, 500, 2,500, 7,500, or 10,000 ppm. In vivo parameters, hematology and clinical chemistry parameters, and complete pathology evaluations were conducted after approximately 28 days. Dec rements in mean body weight gains, reflecting decreases in food consum ption and efficiency, were seen in male rats fed 18,000 ppm and in bot h sexes fed 30,000 ppm: in rats, clinical chemical changes, indicating possible compound-related alterations in lipid, protein, and carbohyd rate metabolism, occurred at 18,000 ppm in males and 30,000 ppm in bot h sexes. No histopathological changes in rats were judged to be direct ly related to NMP exposure. Hematological (mild to moderate leukopenia ) and histopathological alterations (hypocellular bone marrow, testicu lar degeneration and atrophy, and thymic atrophy) were judged to be se condary to nutritional and body weight effects in male and/or female r ats at 30,000 ppm. In mice, cloudy swelling of the epithelia of the di stal parts of the renal tubuli was observed in 4 males and 3 females a t 10,000 ppm and in 2 male mice at 7,500 ppm. For both rats and mice, abnormal urine coloration was observed (in mice at 2,500 ppm and above , and in rats at 18,000 ppm and above). This discoloration was interpr eted as a sign of systemic availability of the test substance, but not as an adverse effect. The NOAEL was 6,000 ppm for male rats and 18,00 0 ppm for female rats. In mice, the NOAEL was 2,500 ppm based on the k idney histopathology.