Food Safety Commission of Japan (FSCJ) conducted a risk assessment of
captan (CAS No. 133-06-2), a
phthalimide fungicide, based on results from various studies. Major adverse effects of
captan were observed in suppressed
body weight, and also in duodenal mucosal
hyperplasia in mice. No adverse effect on fertility was detected. Increases in incidence of duodenal
adenoma and
adenocarcinoma were identified in mice. Negative results were however obtained from a gene mutation assay of the target in transgenic mice. No genotoxicity relevant to human health of
captan was recognized in spite of the positive results in vitro. Therefore, a genotoxic mechanism was unlikely involved in the
tumor development, and it enabled us to establish a threshold in the assessment. In developmental toxicity studies,
captan, at the doses causing maternal toxicity, increased external alterations as well as skeletal and soft tissue alterations in the fetus of rabbits and hamsters. No
captan-induced teratogenicity was detected in rats.
Captan (parent compound only) was identified as the residue definition for dietary risk assessment in agricultural and livestock products. The lowest no-observed-adverse-effect level (NOAEL) obtained from all the studies was 10 mg/kg bw/day. FSCJ specified an acceptable daily intake (ADI) of 0.1 mg/kg bw/day by applying a safety factor of 100 to the NOAEL. The lowest NOAEL for potential adverse effects of a single
oral administration of
captan was 30 mg/kg bw/day in a developmental toxicity study in rabbits. FSCJ specified an acute reference dose (ARfD) of 0.3 mg/kg bw, for women who are or may be pregnant, by applying a safety factor of 100 to the NOAEL. In addition, FSCJ specified an ARfD of 3 mg/kg bw, for general population, by applying a safety factor of 100 to the no-observed-effect level (NOEL) of 300 mg/kg bw obtained from a general pharmacology study in mice.