Pyraziflumid (Pesticides)

Food Safety Commission of Japan (FSCJ) conducted a risk assessment of pyraziflumid (CAS No.942515-63-1), a carboxamide fungicide of pyrazine-biphenyl type, based on results from various studies. Major adverse effects of pyraziflumid observed were of single-cell necrosis hepatocytes and hypertrophy of follicular epithelial cell in the thyroid. No adverse effects were detected in fertility, teratogenicity and genotoxicity relevant to human health. Increased incidences of thyroid follicular cell adenomas and carcinomas in males, and also of hepatocellular adenomas in females were identified in a two-year combined chronic toxicity/carcinogenicity study in rats. Genotoxic mechanisms were, however, unlikely involved in the tumor developments, and these enabled FSCJ to establish a threshold in the assessment. Based on various studies, pyraziflumid (parent compound only) was the residue definition for dietary risk assessment in agricultural products. The lowest no-observed-effect level (NOAEL) obtained from all the studies was 2.15 mg/kg bw/day in a two-year combined chronic toxicity/carcinogenicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.021 mg/kg bw/day by applying a safety factor of 100 to the NOAEL. FSCJ considered it unnecessary to specify an acute reference dose (ARfD) in view of the absence of adverse effects that would be likely to be elicited by a single oral administration of pyraziflumid.