Metoclopramide

Summary

Abstract

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of metoclopramide (CAS No. 364-62-5) as a veterinary medicinal product used to gastrointestinal motility disorder, based on the documents submitted from the Ministry of Health, Labour and Welfare (MHLW). Various in vivo and in vitro genotoxicity studies suggested no apparent genotoxicity of metoclopramide relevant to human health. No carcinogenicity study nor the detail of chronic toxicity study was available, but metoclopramide is unlikely a genotoxic carcinogen. FSCJ concluded, therefore, that the acceptable daily intake (ADI) for metoclopramide can be specified. The lowest value among no-observed-adverse-effect levels (NOAELs) and lowest-observed-adverse-effect levels (LOAELs) in various toxicological studies was 0.5 mg/kg bw/day in a 6-month subacute toxicity study in dogs (LOAEL), as a toxic indicator of clinical signs including restlessness. FSCJ considered it appropriate to apply an additional safety factor of 10 on the specification of the ADI based on the LOAEL, taking into account of the lack of carcinogenicity tests, reproductive toxicity tests and neurotoxicity tests, and insufficient data of chronic toxicity tests. Accordingly, the specified ADI is 0.0005 mg/kg bw/day for metoclopramide, applying a safety factor of 1,000 (10 for species difference, 10 for individual difference and 10 for the additional factor) to the LOAEL of 0.5 mg/kg bw/day in a 6-month subacute toxicity study in dogs.