Nitrofuran antibiotics: a review on the application, prohibition and residual analysis

Abstract

Nitrofuran antibiotics, employed for the treatment of bacterial diseases in livestock production, were banned from use in the European Union (EU) in 1995 due to concerns about the carcinogenicity of their residues in edible tissue. This review provides an overview of nitrofuran toxicity, metabolism, and also specific aspects of legislation surrounding their prohibition. Special attention is devoted to semicarbazide -a nitrofuran metabolite and food contaminant. Analytical procedures for nitrofuran analysis in various matrices and validation requirements for screening and confirmation methods with respect to EU regulations are also reviewed.Keywords: nitrofurans; tissue bound metabolites; semicarbazide; bioavailability; mutagenicity; legislation; sample preparation; validation; detection methods List of abbreviations AHD = 1-aminohydantoin; AOZ = 3-amino-2-oxazolidinone; AMOZ = 3-amino-5-morpholino-methyl-1,3-oxazolidinone; CC α = decision limit; CC β = detection capability; EC = European Commission; EFSA = European Food Safety Authority; ELISA = enzyme linked immuno-adsorbent assay; ESI = electro-spray ionisation; EU = European Union; FTD = furaltadone; FZD = furazolidone; HPLC = high performance liquid chromatography; IC = inhibition concentration; LC = liquid chromatography; LOD = limit of detection; MS = mass spectrometry; NFT = nitrofurantoin; NFZ = nitrofurazone; NP = nitrophenyl; NPAHD = 3-(2-nitrobenzylidenamino)-2,4-imidazolidinedione); NPAMOZ = 5-(morpholinomethyl)-3-(2-nitrobenzylidenamino)-2-oxazolidinone); NPAOZ = [3-(2-nitrobenzylidenamino)-2-oxazolidinone]; NPSEM = 3[(2-nitrophenyl)methylene]-hydrazinecarboxamide; o-NBA = ortho-nitrobenzaldehyde; RASFF = Rapid Alert System for Food and Feed; SE = solvent extraction; SEM = semicarbazide; SPE = solid phase extraction; UV = ultraviolet

Novel hapten synthesis for antibody production and development of an enzyme-linked immunosorbent assay for determination of furaltadone metabolite 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ)

“…However, since the early 1990s, various experimental animal studies have shown that nitrofurans and their metabolites have potential mutagenicity and genotoxicity [2]. As a consequence, nitrofurans have been banned for use in animal husbandry in the European Union (EU) and other countries [2]. The EU has set the minimum required performance limits (MRPLs) to be 1 μg kg -1 for each nitrofuran metabolite in food of animal origin [3].…”

“…Instrumental analytical methods such as liquid chromatography with ultraviolet (UV) or UV photodiode array detection and the coupling of high performance liquid chromatography and liquid chromatography electro-spray ionisation to tandem mass spectrometry (HPLC-MS/MS and LC-ESI MS/MS, respectively) are well established for the determination of nitrofuran antibiotics and their metabolites. A detailed review on the residual analysis of nitrofurans and their metabolites was recently published by Vass et al [2]. The instrumental methods can offer high sensitivity and specificity and have the potential for simultaneous determination of several nitrofurans, but the associated highcosts, time-consuming labour requirements and practicalities of the instrumentation have inhibited broadening the scope of monitoring particularly to field-screening scenarios.…”

“…As an alternative, immunoassays based on the interaction of antibody and antigen provide a low cost, portable and high throughput screening method capable of the sensitive determination of nitrofuran metabolites. The first enzyme-linked immunosorbent assay (ELISA) capable of detecting the furazolidone metabolite (AOZ) was developed by Cooper et al [6] under the support of a multi-national EU research project "FoodBRAND" [2]. Since then, immunoassays for the determination of AOZ [7][8][9], SEM [10][11][12], AHD [13,14] and AMOZ [15] were reported in succession.…”

Response of antimicrobial nitrofurazone-degrading biocathode communities to different cathode potentials

“…Due to its potential carcinogenicity, genotoxicity and mutagenicity to human health, the European Union and U.S. Food and Drug Administration have banned the utility of NFZ in foodproducing animals. However, in some developing countries including China, it is still widely used in the livestock and fishery aquaculture owing to its low production cost, easy availability and high efficiency (Hong et al, 2015;Kwon, 2017;Vass et al, 2008). As a result, NFZ residues and its toxic biological metabolite semicarbazide are often detected in diverse aquatic species and products as well as aquaculture pond water and sediments (Vass et al, 2008;Yu et al, 2013).…”

“…However, in some developing countries including China, it is still widely used in the livestock and fishery aquaculture owing to its low production cost, easy availability and high efficiency (Hong et al, 2015;Kwon, 2017;Vass et al, 2008). As a result, NFZ residues and its toxic biological metabolite semicarbazide are often detected in diverse aquatic species and products as well as aquaculture pond water and sediments (Vass et al, 2008;Yu et al, 2013). In order to eliminate the ecological impact of NFZ on water environment, the efficient degradation of NFZ and elimination of its antibacterial activity are very important during livestock wastewater treatment and aquaculture pond water remediation.…”