A 90-day subchronic toxicity study of nivalenol, a trichothecene mycotoxin, in F344 rats

Abstract

A subchronic toxicity study of nivalenol (NIV), a trichothecene mycotoxin, was conducted in male and female F344 rats fed diet containing 0, 6.25, 25 or 100 ppm concentration for 90 days. Decrease of body weight and loose stools were observed at 100 ppm in both sexes from the start of the experiment, and body weight reduction was also observed at 25 ppm in males from week 6. At necropsy, many organs demonstrated reduced absolute weights at 100 ppm in both sexes, mostly due to the reduction in the body growth, with reduction of relative thymus weight also being evident in females. Hematologically, decrease of the white blood cell count was found at 100 ppm in males and from 6.25 ppm in females. In addition, decreased platelet counts in both sexes, red blood cell counts in males, and the hemoglobin concentration in females were detected at 100 ppm. Histopathologically, treatment-related changes were predominantly observed in the hematopoietic and immune organs and the anterior pituitary in both sexes and female reproductive organs at 100 ppm, such as thymic atrophy, hypocellularity in the bone marrow, diffuse hypertrophy of basophilic cells with increase of castration cells in the anterior pituitary, and increase of ovarian atretic follicles. Based on the hematological data, the no-observed-adverse-effect level of NIV was determined to be less than 6.25 ppm (0.4 mg/kg body weight/day for both males and females).