Disposition of orally administered [14C]-nitrofurazone in broiler chickens

Authors: Singh, Anuradha; Smith, David

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/26/2024
Publication Date: 2/3/2025
Citation: Singh, A., Smith, D.J. 2025. Disposition of orally administered [14C]-nitrofurazone in broiler chickens. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.4c07931.
DOI: https://doi.org/10.1021/acs.jafc.4c07931

Interpretive Summary: Nitrofurazone possesses exceptional antimicrobial properties and has been used as a feed additive in livestock production to prevent disease since the 1950s. Its use in food animals, however, was prohibited in the US and other countries in the 1990s due to nitrofurazone’s mutagenicity and carcinogenicity. However, illegal use still occurs. The US and its trade partners currently monitor nitrofurazone residues in food animals using an assay which may falsely test positive for the presence of nitrofurazone. In an effort to identify a more suitable ‘marker’ for nitrofurazone use, nitrofurazone was dosed to broiler chickens and its fate (using a radiocarbon tracer) was determined. Nitrofurazone metabolites bound quickly to edible tissues of broilers and remained bound, mostly to proteins, for at least two weeks. Importantly, the study indicated that further study of protein fractions, especially in livers and muscles of chickens, may be productive in the isolation of a specific marker for illegal nitrofurazone use.

Technical Abstract: 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, identifying 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 (LSC). At WD 0, kidney was the major depot for total radioactive residues followed by 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 in liver. About 70% or higher of NFZ-related residues remained unextractable and bound to tissues, regardless of withdrawal day. Major portions of NFZ-residues were covalently bound to protein with smaller portions bound to DNA and RNA fractions.