Kinetics of<sup>14</sup>C‐furazolidone in piglets upon oral administration during 10 days and its interaction with tissue macro‐molecules

Vroomen, L.H.M.; Berghmans, M.C.J.; Leeuwen, Pim van; Struijs, T.D.B. van der; Vries, P.H.U. de; Kuiper, H.A.

doi:10.1080/02652038609373600

Cited by 59 publications

(41 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Residual control was based on the measurement of furazolidone concentration in blood and tissues. However, studies concerning the metabolism and toxicity of furazolidone and other nitrofurans revealed that the monitoring of residues based only on the detection of parent nitrofuran structures did not provide adequate data for the evaluation of real tissue contamination and their health risk (Vroomen et al, 1986(Vroomen et al, , 1990. Due to fears of the carcinogenic effects on humans, nitrofurans were banned from use in livestock production in the European Union (Commission Regulation, 1995).…”

Section: Introductionmentioning

confidence: 99%

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

Vass¹,

Hruška²,

Fránek³

2008

Vet. Med.

229

130

View full text Add to dashboard Cite

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

show abstract

Section: Introductionmentioning

confidence: 99%

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

Vass¹,

Hruška²,

Fránek³

2008

Vet. Med.

229

130

View full text Add to dashboard Cite

show abstract

“…However, it was unusual to find any residues of nitrofurans using these methods directed at the parent compounds. Studies on furazolidone showed that residues of the parent compound are highly unstable in treated animals (Nouws and Laurensen, 1990;McCracken et al, 1995), but that metabolites containing AOZ are covalently bound to tissue protein (Vroomen et al, 1986;Hoogenboom et al, 1991c) and that these metabolites persist for much longer than the parent compound (Hoogenboom et al, 1992a). Nitrofuran drugs contain a side-chain connected via an azomethine bond to the nitrofuran moiety.…”

Section: Determination Of Nitrofurans and Their Marker Metabolitesmentioning

confidence: 99%

“…Initially, testing for residues of nitrofurans in animal tissues was conducted using methods directed at the parent compounds, using high-performance liquid chromatography-ultraviolet (HPLC-UV) (Vroomen et al, 1986;Degroodt et al, 1992;Bellomonte et al, 1993) and later using liquid chromatography-mass spectrometry (LC-MS) (McCracken et al, 1995) techniques. However, it was unusual to find any residues of nitrofurans using these methods directed at the parent compounds.…”

Section: Determination Of Nitrofurans and Their Marker Metabolitesmentioning

confidence: 99%

“…Instead, an approach based on marker metabolites has been adopted for monitoring purposes, with the particular marker metabolites chosen to reflect residues of nitrofurans which persist in treated animals. The nitroreduction results in the formation of reactive metabolites able to bind covalently to tissue macromolecules, including proteins, which, in food-producing animals, have relatively long half-lives, persisting for several weeks in edible tissues (Vroomen et al, 1986;Hoogenboom et al, 1991cHoogenboom et al, , 1992aVass et al, 2008c). Side-chains may be released from these protein-bound metabolites, namely AOZ, AMOZ, AHD, SEM and DNSH in the case of furazolidone, furaltadone, nitrofurantoin, nitrofurazone and nifursol, respectively.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Scientific Opinion on nitrofurans and their metabolites in food

Panel¹

2015

EFS2

View full text Add to dashboard Cite

Nitrofurans are antimicrobial agents not authorised for use in food-producing animals in the European Union. Nitrofurans are rapidly metabolised, occurring in animal tissues as protein-bound metabolites. The European Commission requested EFSA to provide a scientific opinion on the risks to human health related to the presence of nitrofurans in food and whether a reference point for action (RPA) of 1.0 µg/kg for the marker metabolites is adequate to protect public health. Data on occurrence of nitrofuran marker metabolites in food were extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF). The CONTAM Panel concluded that these data were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which a single nitrofuran marker metabolite is present at 1.0 µg/kg in foods of animal origin, excluding milk and dairy products. The mean chronic dietary exposure for this worst-case scenario would range from 3.3 to 8.0 and 1.9 to 4.3 ng/kg b.w. per day for toddlers and adults, respectively. Nitrofurans and their marker metabolites, generally, are genotoxic and carcinogenic and, also, have non-neoplastic effects in animals. Margins of exposure (MOEs) were calculated at 2.0 × 10 5 or greater for carcinogenicity and at 2.5 × 10 3 or greater for non-neoplastic effects. The CONTAM Panel concluded that it is unlikely that exposure to food contaminated with nitrofuran marker metabolites at or below 1.0 µg/kg is a health concern. A scenario in which foods are considered to be contaminated with semicarbazide, from use of carrageenan as a food additive, at 1 µg/kg was used to assess whether it is appropriate to apply the RPA to foods of non-animal origin; MOEs of greater than 10 4 calculated for nonneoplastic effects do not indicate a health concern.© European Food Safety Authority, 2015 However, the opinion also identified certain categories of non-allowed pharmacologically active substances that are considered to be outside the scope of the procedure, including substances that are high potency carcinogens, such as nitrofurans. As nitrofurans are excluded from that opinion, and taking into account that the presence of SEM in food may be from sources other than use of nitrofurazone, the European Commission (EC) requested the European Food Safety Authority (EFSA) for a scientific opinion on the risks to human health related to the presence of nitrofurans and their metabolites in food. The opinion should include (a) an evaluation of the toxicity of nitrofurans and their metabolites for humans, considering all relevant toxicological endpoints and identification of the toxicological relevance of nitrofurans and their metabolites present in food, and (b) an exposure assessment of the EU population to nitrofurans and their metabolites from food, including the consumption patterns of specific (vulnerable) groups of the population. In addition, the opinion should assess the appropriateness of...

show abstract

“…In veterinary practice, pharmacotherapy with this drug often fails to be effective in the treatment of such infections, although the causative bacteria may be proven to be susceptible to furazolidone. One of the possible reasons for this frequently observed therapeutic failure in pigs and calves is that the drug is readily absorbed from the gastrointestinal tract after oral application (4,5), so that in the more distal parts of the alimentary tract, no effective furazolidone concentrations are reached.…”

Section: Introductionmentioning

confidence: 99%

The absorption of a new sustained release furazolidone formulation from the digestive tract of piglets and calves

Hekman¹,

Rietveld

1988

Veterinary Quarterly

View full text Add to dashboard Cite

SUMMARY Chyme concentrations and total recoveries of furazolidone (5 mg/kg bodyweight) were determined by a HPLC-method, after oral administration of two different furazolidone formulations to piglets (n = 6) and pre-ruminant calves (n = 8), provided with an ileal re-entrant canula. Additional blood samples were taken from the calves to measure the time dependent plasma levels of furazolidone.In the case of the normal crystalline preparation, the results indicate an almost complete absorption of the drug from the upper parts of the digestive tract. In both species, 96-99% of the dose had been absorbed by the time it reached the end of the ileum. The mean ileal recovery of the newly developed furazolidone formulation in calves and piglets was 14% and 38%, respectively. In calves the observed maximum plasma concentrations of furazolidone after oral application of the sustained release formulation were 14 times lower than with the normal crystalline preparation.

show abstract

Kinetics of¹⁴C‐furazolidone in piglets upon oral administration during 10 days and its interaction with tissue macro‐molecules

Cited by 59 publications

References 22 publications

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

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

Scientific Opinion on nitrofurans and their metabolites in food

The absorption of a new sustained release furazolidone formulation from the digestive tract of piglets and calves

Contact Info

Product

Resources

About

Kinetics of14C‐furazolidone in piglets upon oral administration during 10 days and its interaction with tissue macro‐molecules

Cited by 59 publications

References 22 publications

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

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

Scientific Opinion on nitrofurans and their metabolites in food

The absorption of a new sustained release furazolidone formulation from the digestive tract of piglets and calves

Contact Info

Product

Resources

About

Kinetics of¹⁴C‐furazolidone in piglets upon oral administration during 10 days and its interaction with tissue macro‐molecules