Dicyclanil (Veterinary Medicinal Products)

摘要

Food Safety Commission of Japan (FSCJ) conducted a risk assessment of dicycranil(CAS No. 112636-83-6), a pyrimidine-derived insect growth regulator, using theevaluation reports from the Joint FAO/WHO Expert Committee on Food Additives(JECFA), the European Medicines Agency (EMEA), and also the Australiangovernment. In an 18-month chronic toxicity/carcinogenicity study in mice,increased incidences of hepatocellular adenomas and carcinomas were observed infemales in the 500 ppm group. In spite of a recent experiment implying thepossible indirect genotoxicity of dicyclanil on the carcinogenicity, dicyclanilis unlikely to exert the carcinogenicity through thegenotoxic mechanism judging from other studies. FSCJ recognized it as feasibleto set the threshold value. Adverse effects detected at the lowest dose invarious toxicological studies were the increased plasma levels of cholesteroland phospholipid at 100 ppm (equivalent to 2.7 mg/kg bw/day in males and 3.5mg/kg bw/day in females) in a 90-day subacute toxicity study in dogs.No-observed-adverse-effect level (NOAEL) of this study was 20 ppm (equivalent to0.61 mg/kg bw/day in males and 0.71 mg/kg bw/day in females). On the other hand,the NOAEL in a long term study, a 12-month chronic toxicity study in dogs was 25ppm (equivalent to 0.71 mg/kg bw/day in males) based on increased level ofplasma cholesterol observed only in males at 150 ppm (equivalent to 4.4 mg/kgbw/day in males and 5.1 mg/kg bw/day in females). The increased cholesterollevels in plasma were common in both studies in dogs. It was appropriate tochoose the NOAEL for the effect on cholesterol in the longer term treatment, andthus FSCJ adopted the NOAEL of 0.71 mg/kg bw/day. Consequently, FSCJ specifiedthe ADI of 0.0071 mg/kg bw/day for dicyclanil based on the NOAEL of 0.71 mg/kgbw/day in the 12-month chronic toxicity study in dogs, by applying a safetyfactor of 100.