CHRONIC TOXICITY AND ONCOGENICITY OF N-METHYLPYRROLIDONE (NMP) IN RATS AND MICE BY DIETARY ADMINISTRATION.

Autor: Malley, L. A., Kennedy, G. L., Elliott, G. S., Slone, T. W., Mellert, W., Deckardt, K., Kuttler, K., Hildebrand, B., Banton, M. I., Parod, R. J., Griffiths, J. C.
Předmět:
Zdroj: Drug & Chemical Toxicology; 2001, Vol. 24 Issue 4, pN-338, 1p, 8 Charts
Abstrakt: A two-year feeding study in rats and an 18-month feeding study in mice were conducted to evaluate the potential chronic toxicity and oncogenicity of NMP in Crl:CD® (SD)BR rats and B6C3F1/CrlBR mice. Groups of 62 male and female rats were administered diets containing 0, 1600, 5000, or 15000ppm of NMP for approximately 2 years. Groups of 50 male and female mice were administered diets containing 0, 600, 1200, or 7200ppm NMP for approximately 18 months. In vivo parameters were evaluated weekly during the first 3 months of the study, and every other week or monthly during the remainder of the study. For rats, an ophthalmoscopic examination was conducted prior to study start and near the end of the study. Periodically, blood samples were collected from rats and mice for determination of leukocyte differential counts, and from mice for red blood cell morphology. After approximately 2 years of dietary administration in rats and 18 months in mice, all surviving animals were sacrificed. Selected tissues were processed for morphological evaluation. Over the course of the two-year study in rats, test substance-related decrements in body weight and weight gain occurred in 15000ppm males and females, which correlated with decreased food consumption and food efficiency. A toxicologically significant, test substance-related increase in the incidence of severe chronic progressive nephropathy occurred in 15000ppm males. Several morphological changes noted grossly and/or microscopically were secondary to the increased severity of chronic progressive nephropathy. NMP was not oncogenic in male or female rats at dietary concentrations of 15000ppm and below. A test substance-related decrease in the percentage of 15000ppm males surviving to the end of the two-year study compared to the control group resulted from the higher incidence of severe chronic progressive nephropathy. However, a sufficient population of 15 000 ppm rats were at risk for potential oncogenicity, so the... [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje