Toxicity of anguidine in mice.

A characteristic of the trichothecene mycotoxin, anguidine, is its extreme toxicity to organs with populations of rapidly dividing cells. In preparation for evaluation of compounds that may protect against anguidine toxicity, we measured the LD50 of anguidine administered by gastric gavage (ig) or intraperitoneal injection (ip) and studied the dose- and time-dependent effects of anguidine on lymphohematopoietic organs, intestine, and testis, and measured hematocrit and peripheral blood leukocyte counts in male CD-1 mice. The ig LD50 at 96 hr was 15.5 mg/kg; after ip administration the LD50 at 96 hr was 20.0 mg/kg. Characteristic changes caused by sublethal doses of anguidine were cell depletion and necrosis in lymphohematopoietic organs, multifocal necrosis of intestinal epithelium, and diffuse necrosis of germinal epithelium followed by progressive tubule degeneration in the testes. There was leukocytosis due to both lymphocytosis and neutrophilia in the first few hours following anguidine exposure, followed by lymphopenia, neutropenia, and anemia by 3 days. After lethal doses, the intestinal necrosis was transmural, and there was extensive necrosis of lymphohematopoietic organs. There was rapid recovery after sublethal anguidine exposure of all anguidine-sensitive organs except for testis where decreased weights and abnormal spermatogenesis persisted for the 2-week observation period. Our results suggest that intestinal necrosis is an important cause of death following anguidine exposure. Atrophy of seminiferous tubules may have some value as an indicator of prior anguidine exposure, but the testicular changes are not unique to this compound.