Abstract
The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of malathion (CAS No. 121–75-5), an organophosphorus pesticide, based on summary reports made by applicants and documents from JMPR, the governments of the US, EU and others. A major adverse effect of malathion observed is inhibition of ChE activity in the brain and red blood cells. None of the reproductive toxicity, teratogenicity, developmental neurotoxicity or genotoxicity relevant to human health was observed. No carcinogenicity was observed in rats. In an 18-month carcinogenicity study in mice, an increased incidence of hepatocellular adenomas was observed. However, a genotoxic mechanism was not likely to be involved in the tumor development, therefore it is reasonable to establish a threshold in the assessment. FSCJ specified the acceptable daily intake (ADI) for malathion at 0.29 mg/kg bw/day, applying a safety factor of 100 to the no-observed-adverse-effect level (NOAEL) of 29 mg/kg bw/day obtained in the two-year chronic toxicity study and two-year combined chronic toxicity/carcinogenicity study in rats. Since the lowest NOAEL after a single oral dose was 15 mg/kg bw observed in the randomized double-blind study in humans, FSCJ specified the acute reference dose (ARfD) of 1.5 mg/kg bw applying a safety factor of 10 (1 for a clinical single oral dosing study in humans and 10 for individual difference) to the NOAEL.
