The Acute and Chronic Toxicities of Nivalenol in Mice

The Acute and Chronic Toxicities of Nivalenol in Mice. Ryu,J.-C, Ohtsubo, K., Izumiy-ama, N., Nakamura, JL, Tanaka, T.,Yamamura, H., and Ueno, Y. (1988). Fundam. Appl Toxicol. 11,38–47. In an attempt to ascertain precisely the toxiceffects of nivalenol (N1V), we conducted the determination ofLD50 values, and interim kills during the carcinogenic studyin mice. LD50 values (mg/kg) of NIV in 6-week-old male ddY micewere determined as 38.9 (po), 7.4 (ip), 7.2 (sc), and 7.3 (iv).Seven-week-old female C57BL/6CrSlc SPF mice were fed diets containing0, 6, 12, and 30 ppm (mg/kg) NIV over 1 year, and were assessedfor effects on body weight gain, feed efficiency, terminai organweights, hematology, and histopathology. The rates of body weightgain and feed efficiency showed a good dose-dependent correlationin all experimental periods. Gross and histopathological evaluationof the liver, thymus, spleen, kidneys, stomach, adrenal glands,pituitary gland, ovaries, sternum, bone marrow, lymph node,brain, and small intestines with or without Peyer's patch portionfrom control and all NIV-exposed mice revealed that these tissueswere normal in appearance and in histopathological structure.Also, no changes were observed in the ultrastructural studieson the bone marrow. Dietary NIV did, however, cause dose-dependentdecreases of absolute organ weights (mg) and increases of relativeorgan weights (mg/g body weight) in the terminal organ weightsrecorded. A significant leukopenia was observed in the 30 ppmgroup at 6 months and in all NIV-treated groups at 1 year. Nomarked changes were observed in the other hematological parameters.These results indicated that 6 ppm or more of dietary NIV for1 year showed a characteristic toxic effect of trichothecenemycotoxins in mice.