Albendazole

Abstract

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of albendazole (CAS No. 54965–21–8), a parasiticide, based on the documents including assessment reports from the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the European Medicines Agency (EMEA), and the Australian Pesticides and Veterinary Medicines Authority (APVMA). Albendazole is considered to be of no concern for genotoxicity relevant to human health as long as used appropriately as a veterinary medicinal product, though this compound may have a genotoxic potential. The combined chronic toxicity/carcinogenicity study and carcinogenicity study in mice and rats showed no carcinogenicity. Therefore, a threshold level as acceptable daily intake (ADI) is possible to be established for the toxicity. FSCJ compared the no-observed-adverse-effect levels (NOAELs) from various toxicity studies, and adopted the NOAEL of 5 mg/kg bw/day obtained in a 6-month subacute toxicity study in dogs, and also in developmental toxicity studies in rats and in rabbits for ADI estimation. FSCJ concluded it appropriate to apply an additional safety factor of 5, and specified the ADI of 0.01 mg/kg bw/day, applying a safety factor of 500 to the NOAEL of 5 mg/kg bw/day. It has been evident that albendazole is metabolized to albendazole sulphoxide in vivo, and veterinary medicinal products containing albendazole sulphoxide as a main ingredient are used overseas. Therefore, FSCJ specified the group ADI of 0.01 mg/kg bw/day for the combined level of albendazole and albendazole sulphoxide (as albendazole eq.) considering the effect of albendazole sulphoxide.