Picoxystrobin

摘要

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of picoxystrobin (CAS No. 117428-22-5), a strobilurin fungicide, based on results from various studies. Major adverse effects of picoxystrobin observed are decreased body weight gain, hepatocellular hypertrophy in mice, as well as mucosal hyperplasia and dilated mucosal gland of the duodenum in mice. No neurotoxicity, reproductive toxicity, teratogenicity, immunotoxicity or genotoxicity relevant to human health were observed. Although increased incidences of interstitial cell adenomas were observed in a two-year chronic toxicity/carcinogenicity study in rats, genotoxic mechanism was unlikely to be involved in the tumor induction, and therefore, FSCJ concluded that it is possible to establish a threshold dose in the assessment. Based on the above results, only picoxystrobin (parent compound) was identified as the residue definition for dietary risk assessment in agricultural products. The lowest no-observed-adverse-effect level (NOAEL) obtained was 4.6?mg/kg bw/day in a one-year chronic toxicity study in dogs. FSCJ specified the acceptable daily intake (ADI) of 0.046?mg/kg bw/day, applying a safety factor of 100 to the NOAEL. In an acute neurotoxicity study in rats, NOAEL was not obtained, but the lowest-observed-adverse-effect level (LOAEL) was 200?mg/kg bw. In developmental toxicity studies, NOAELs obtained for adverse effects possibly caused by a single oral administration of picoxystrobin were 25?mg/kg bw/day in rabbits and 30?mg/kg bw/day in rats. Considering those results comprehensively, FSCJ specified an acute reference dose (ARfD) of 0.2?mg/kg bw based on the LOAEL of 200?mg/kg bw obtained from an acute neurotoxicity study in rats, applying a safety factor of 1,000 (10 for species difference, 10 for individual difference, and 10 for the adopted LOAEL value).