Abstract
Food Safety Commission of Japan (FSCJ) conducted a risk assessment of isotianil (CAS No. 224049-04-1), an isothiazole agent for induced resistance to blast disease. This evaluation was requested from Ministry of Agriculture, Forestry and Fisheries (MAFF) on the reevaluation article of Agricultural Chemicals Regulation Act. Additional information including the fate in livestock (goats and chickens) and genotoxicity, and also the list of published scientific literature were newly submitted from the MAFF. The following data were used in the assessment; fate in plants (including paddy rice and potatoes), residues in crops, fate in livestock (goats and chickens), residues in livestock products, fate in animals (rats), subacute toxicity (rats, mice and dogs), chronic toxicity (rats and dogs), carcinogenicity (rats and mice), two-generation reproductive toxicity (rats), developmental toxicity (rats and rabbits), and genotoxicity. Major adverse effects of isotianil were observed in the stomach (mucosal epithelium hyperplasia of the forestomach limiting ridge in rats), the liver (including organ weight gain), and the kidney (including chronic nephropathy). No adverse effects were observed on carcinogenicity, fertility, teratogenicity, and genotoxicity. The lowest no-observed-adverse-effect level (NOAEL) obtained from the studies described above was 2.83 mg/kg bw per day in a one-year chronic toxicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.028 mg/kg bw per day based on the NOAEL after applying a safety factor of 100. An acute reference dose (ARfD) was judged unnecessary to be specified, based on the results of a single oral administration of isotianil and other related tests.