Summary of Toxicological Studies on Cyproconazole

Cyproconazole technical was of low toxicity to rats, moderate toxicity to mice by oral administration. Its formulation was of low toxicity to rats and mice by oral administration. The technical and its formulation were of low acute dermal toxicity. The technical and its formulation were not skin irritant, although they were mildly irritating to eye. In a guinea pig skin sensitization study using the Maximization method no skin sensitization was induced by cyproconazole technical or its formulation. In subacute toxicity studies in rats and dogs, clinical biochemistry parameters at middle or high dose levels were affected by treatment of cyproconazole technical. Decreased body weight gains and increased liver weights were found in rats and dogs receiving high dose levels of cyproconazole technical. In a rat combined chronic toxicity/oncogenicity study, some parameters of haematology and clinical biochemistry mainly at high dose level were affected by treatment of cyproconazole technical. Decreased body weight gains and increased liver weights weree found at high dose level of cyproconazole technical. Histopathological examination revealed hepatocelluar fatty changes in male and hepatocellular hypertrophy in female at high dose. The incidence of neoplastic lesions was not affected by the treatment at the terminal or interim sacrifice. In mice oncogenicity study, reduced body weight gains and increased liver weight were seen at upper-middle and high dose levels of cyproconazole technical. An incidence of hepatocytic neoplasia was increased in male at upper-middle or high and female at high dose level of cyproconazole technical. The mechanism leading to the observed tumours is tumour promotion as a result of hepatic enzyme induction, a non-genotoxic event. In a dog chronic toxicity study, increased cytochrome P-450 activities were observed in both sexes at middle and high dose levels of cyproconazole technical. Reduced body weight gains in male and increased liver weight in both sexes were found at high dose level of cyproconazole technical. There were no treatment related findings in both sexes at low dose. In a two-generation rat reproduction study, there were no treatment-related effects on the reproduction parameters. The only treatment-related finding was an increased hepatocellular fatty changes in F0 males at the high dose level of cyproconazole technical. In a rat teratology study, reduced body weight gains and increased postimplantation losses were obs