Tolfenamic Acid

摘要

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of tolfenamic acid (CAS No. 13170–19-5), an anti-inflammatory drug, based on the submitted documents including original research papers~(1)~(,)~(2)~(,)~(3)~()), together with reference to the reports from the European Medical Agency (EMEA) and the Australian government. No genotoxicity relevant to human health were suggested by the results from the various genotoxicity studies on tolfenamic acid. Therefore, an acceptable daily intake (ADI) is possible to be established for the toxicity. Major adverse effects of tolfenamic acid were observed on GI tract (erosions and ulcers). No carcinogenicity was observed in repeated dose toxicity studies in mice and rats. The lowest no-observed-adverse-effect level (NOAEL) was 1?mg/kg bw/day, based on the necrosis of GI mucosal epithelium in a one-month subacute toxicity study in rabbits, the adverse effect observed at the lowest dose among the toxicity studies. FSCJ thus specified the ADI of 0.01?mg/kg bw/day for tolfenamic acid by applying a safety factor of 100 to the NOAEL of 1?mg/kg bw/day in the one-month subacute toxicity study in rabbits.