Fosfomycin (Veterinary Medicinal Products): Summary

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of fosfomycin (CAS No. 23155-02-4), using documents submitted for the ‟re-examination” of veterinary medicinal products. The data used for the assessment include ADME of fosfomycin Ca, residue of fosfomycin Ca and of fosfomycin Na, acute toxicity of fosfomycin Ca and fosfomycin Na. Data on subacute toxicity, reproductive and developmental toxicity, genotoxicity and microbiological effect are also included. The lowest-observed-adverse-effect level (LOAEL) in these toxicity studies was 175 mg (titer)/kg body weight (bw) per day based on adverse effects including diarrhea, autopsy findings such as erosion, hyperplasia, and exfoliation of glandular stomach mucosa, and histopathological findings such as erosion of the stomach and ileum mucosa observed as adverse effects in the 35-day subacute toxicity study in rats. Fosfomycin was not teratogenic in rats and rabbits. FSCJ considered that fosfomycin is not a genotoxic carcinogen. The toxicological ADI of fosfomycin was established to be 0.175 mg/kg bw per day by applying a safety factor of 1000 based on the LOAEL of 175 mg (titer)/kg bw per day. On the other hand, the microbiological ADI was calculated to be 0.019 mg/kg bw per day, which is lower than the toxicological ADI. Thus, FSCJ established the ADI for fosfomycin as 0.019 mg/kg bw per day.