Abamectin (Avermectin)

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of an insecticide, abamectin (CAS No. 71751-41-2), based on results from various studies. The insecticide is consisted of avermectin B1a (CAS No. 65195-55-3) and avermectin B1b (CAS No. 65195-56-4), both macrolides having a structure of 16-membered ring. Major adverse effects of abamectin observed are neurological symptoms such as tremor/convulsion and mydriasis. FSCJ considered that abamectin causes tremor/convulsion through the GABA-ergic action with hyperpolarization of nerve/muscle cells. Neither carcinogenicity, reproductive toxicity, developmental neurotoxicity nor genotoxicity was observed. Based on the above results, abamectin and its isomeric 8,9-Z avermectin B1a, a photolytic product of avermectin B1a, were identified as chemicals for the residue definition for dietary risk assessment in agricultural products. The lowest value among the no-observed-adverse-effect levels (NOAELs) and the lowest-observed-adverse-effect levels (LOAELs) obtained in all the studies was the LOAEL of 0.12 mg/kg bw/day in a developmental neurotoxicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.0006 mg/kg bw/day, applying a safety factor of 200 (10 for species difference, 10 for individual difference, and additional 2 for the use of LOAEL). The lowest NOAEL for adverse effects that would be likely to be elicited by a single oral administration of abamectin was 0.5 mg/kg bw/day consistently obtained in the acute neurotoxicity study in rats, and in the 18-week subacute toxicity study, the 85-day subacute toxicity study and the one-year chronic toxicity study in dogs. FSCJ specified an acute reference dose (ARfD) of 0.005 mg/kg bw, applying a safety factor of 100 to the NOAEL.