2019 Volume 7 Issue 1 Pages 15-19
The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of flubendiamide (CAS No. 272451-65-7), an iodophthalimide insecticide for the setting of an acceptable daily intake (ADI) in 2006. FSCJ now has assessed this insecticide for the setting of an acute reference dose (ARfD). Data including fate in animals (rats and mice) and residues in crops (burdock roots, pumpkins and others) were newly submitted. Major adverse effects of flubendiamide include hepatocellular hypertrophy, fatty changes in hepatocytes, follicular epithelial cell hypertrophy in thyroid and ocular enlarged eye in rats. No neurotoxicity, carcinogenicity, reproductive toxicity, teratogenicity, neurodevelopmental toxicity and genotoxicity were observed. The lowest no-observed-adverse-effect level (NOAEL) in the toxicological studies was 1.70 mg/kg body weight/day in a two-year carcinogenicity study in rats. FSCJ confirmed an ADI of 0.017 mg/kg bw/day after applying a safety factor of 100 to the NOAEL. Adverse effects elicited by a single oral administration of flubendiamide would be abnormalities in eyes such as ocular hypertrophy and iris adhesion in offspring, which were obtained in a two-generation reproductive toxicity study, a one-generation reproductive toxicity study and a neurodevelopmental toxicity study in rats. FSCJ judged that these studies may be applicable to set the ARfD for lactating women in relation to the exposure of flubendiamide to offspring after the birth through breast milk. By taking into account the overall evaluations of the two-generation reproductive toxicity study, one-generation reproductive toxicity study and neurodevelopmental toxicity study in rats, FSCJ judged NOAEL of 15.0 mg/kg bw/day as for an overall NOAEL, and consequently specified an ARfD of 0.15 mg/kg bw/day for lactating women by applying a safety factor of 100 to the NOAEL.