IMIZOL

Pivotal Study:

90-day non-GLP-compliant oral dog study (Reynolds et al., 1977): Beagles (4/sex/dose) were dosed with 0, 5, 20, or 80 mg/kg bw/d imidocarb dipropionate (expressed as base) in gelatin capsules for 90 days. All males and two females at 80 mg/kg bw died or were killed in extremis after having reduced food intake and weight loss for 2 weeks before death. Signs of toxicity at the high dose included weakness, recumbency, salivation, muscle fasiculation, ataxia, and splayed hind legs, probably indicating an anticholinesterase effect. The food intake of dogs at 20 mg/kg bw was transiently reduced. Eosinophilia was observed in some dogs given 20 or 80 mg/kg, and there was a trend towards increased serum alanine and aspartate aminotransferase & bilirubin at the high dose, with occasional, transient increases at 20 mg/kg bw. Significant increases in the absolute and relative weights of the kidney, adrenal, and thyroid occurred at 80 mg/kg. Histological changes at the high dose included: pyknosis and karyorrhexis in the thymus, spleen, lymph nodes, and stroma of small intestine villi; and fatty changes in the thick section of the loop of Henle and the distal convoluted tubules. The livers of high & mid-dose dogs showed haemorrhagic necrosis, fatty changes, granularity, or vacuolation of the hepatocytes. The NOEL was 5 mg/kg bw/d.

Animal Specie:

Dog

Effect:

Transient reducting in food intake & histopathology in the liver

NOEL:

5 mg/kg bw/day

Point of departure:

5 mg/kg bw/day