Disposition of Orally Administered [14C]-Nitrofurazone in Broiler Chickens

Nitrofurazone (NFZ), a synthetic antibiotic, is banned from use in food animals because of its potential carcinogenicity and mutagenicity. Regulatory agencies regularly surveil illegal use of NFZ in animal-derived products by measuring a marker metabolite, semicarbazide (SEM). However, SEM is not specific for NFZ exposure, and its detection has proven to return false positive results in unexposed animals. Therefore, the identification of a NFZ-specific marker is a pressing need for detecting illicit NFZ use. To this end, disposition and depletion studies in broiler chickens were performed using ¹⁴C-NFZ test articles containing radiocarbon at the furaldehyde carbon (NFZ-A) or the carbonyl carbon of SEM (NFZ-B). Birds were fed complete rations containing [¹⁴C]-NFZ-A (n = 12, Group A) or ¹⁴C-NFZ-B (n = 12, Group B) at 5 mg NFZ/kg feed for 7 consecutive days. Control birds (n = 6) were fed NFZ-free feed. Birds were euthanized on withdrawal days (WD) 0, 4, 7, and 14. Total radioactive residues in plasma, liver, kidney, muscle, gizzard, lung, and heart were determined by oxidation, followed by liquid scintillation counting. At WD 0, the kidney was the major depot for total radioactive residues followed by the liver. Depletion rates of radioactive residues in tissues were not different (P > 0.20) between the NFZ-A and NFZ-B treated groups, suggesting that the SEM moiety remained intact during biotransformation of both nitrofurazone test articles. Estimated half-life of radioactive residues was longer in muscle than that in the liver. About 70% or higher of NFZ-related residues remained unextractable and bound to tissues, regardless of the withdrawal day. Major portions of NFZ-residues were covalently bound to protein, with smaller portions bound to DNA and RNA fractions.