2,4-D (Pesticides)

Food Safety Commission of Japan (FSCJ) conducted a risk assessment of 2,4-D¹⁾ (CAS No. 94-75-7), a phenoxy herbicide, based on results from various studies. Major adverse effects of 2,4-D observed were suppressed body weight, renal tubular degeneration, hypertrophy of hepatocytes, reduced weight of testis and retinal degeneration in rats. No adverse effects were detected in carcinogenicity, reproductive toxicity, teratogenicity and genotoxicity relevant to human health. The relevant substance to the residue definition for dietary risk assessment was identified as 2,4-D and metabolite C²⁾ in agricultural products and 2,4-D (parent compound only) in livestock products. The lowest no-observed-effect level (NOAEL) obtained from all the studies was 0.99 mg/kg bw/day in a two-year combined chronic toxicity/carcinogenicity study (the 1^st study in Table 1) in rats. FSCJ specified an acceptable daily intake (ADI) of 0.0099 mg/kg bw/day by applying a safety factor of 100 to the NOAEL. The lowest NOAEL for adverse effects likely to be elicited by a single oral administration of 2,4-D was 15 mg/kg bw/day obtained from the acute neurotoxicity study in rats. Consequently, FSCJ specified an acute reference dose (ARfD) of 0.15 mg/kg bw by applying a safety factor of 100 to the NOAEL.