2017 Volume 5 Issue 3 Pages 110-113
Food Safety Commission of Japan (FSCJ) conducted a risk assessment of fenquinotrione (CAS No. 1342891-70-6), a triketone herbicide, based on results from various studies. A major adverse effect of fenquinotrione was observed in ocular toxicity characterized as keratitis in rats, which is often observed with other 4-hydroxyphenylpyruvate dioxygenase (4-HPDDase) inhibitors in this species. Other effects included were centrilobular hepatocytes hypertrophy, and also cholecystolithiasis in mice. No effects were observed on neurotoxicity, fertility, teratogenicity and genotoxicity. A corneal squamous cell carcinoma found in a male rat, at a sub-highest dose in a two-year carcinogenicity study, was judged to be treatment-related, because this tumor is rare in rats. The occurrence was considered to be attributed to persistent stimulation of inflammation including keratitis. In addition, negative results were obtained from all of the genotoxicity studies. Therefore, a genotoxic mechanism was unlikely involved in the tumor development, and it enabled FSCJ to establish a threshold in the assessment. Fenquinotrione (parent compound only) was the residue definition for dietary risk assessment in agricultural products. The lowest no-observed-adverse-effect level (NOAEL) obtained from all the studies was 0.166 mg/kg bw/day in a two-generation reproductive toxicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.0016 mg/kg bw/day by applying a safety factor of 100 to the NOAEL. The lowest-observed-adverse-effect-level (LOAEL) for potential adverse effects of a single oral administration of fenquinotrione was 2,000 mg/kg bw based on soft feces and staining of perianal fur observed within one day after the oral administration in an acute toxicity study in rats. Thus the acute reference dose (ARfD) is not necessary, since the LOAEL was adequately above the cut off level (500 mg/kg bw).