Evaluation of the carcinogenic effects of furazolidone and its metabolites in two fish species

Abstract

The major metabolite from the use of furazolidone (FZD) in mammals, birds and fish is 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1alpha, 2-di(2-oxo-oxazolidin-3-yl)iminomethyl-furo [2,3-b]furan, also called 3-amine-2-oxazolidone (AOZ). A minor metabolite was identified as N-(5-amine-2-furfuryliden)-3-amine-2-oxazolidone (FOZ). To assess the potential carcinogenicity of FZD and the metabolic mixture of AOZ/FOZ, 11 mg FZD/ kg feed/day was fed for 12 weeks to mollies (Poecilia formosa), an ornamental fish species prone to develop tumors. The rate of tumors was quantified and defined both in mollies and their offspring. Then, some fish was made into fishmeal and incorporated into fish food at 500 g of meal/kg of food and fed to other mollies for 12 weeks. The rate of tumors was assessed. A similar trial design was carried out in tilapia fish (Oreochromis niloticus) by adding 50 mg FZD/kg to the feed for 90 days. All animals were placed in glass fishponds under controlled laboratory conditions. Each week, a significant biomass was collected from both groups to assess the macroscopic and histopathological changes. All mollies developed melanohistiocytomic tumors in the liver and other organs. Offspring from surviving mollie females stimulated to breed showed no changes compared to control animals. None of the mollies fed with the mollie-meal food contaminated with AOZ/FOZ developed tumors. Neither tilapia medicated with FZD nor tilapia fed with tilapia-meal contaminated with AOZ/FOZ developed tumors. These results do not support the established viewpoint that FZD must be banned from trophic chains based on its potential carcinogenic properties.

Development of an enzyme-linked immunosorbent assay for the detection of nitrofurantoin metabolite, 1-amino-hydantoin, in animal tissues

“…Since early 1990s, various experimental animal studies have shown that nitrofurans and their metabolites have potential carcinogenic and mutagenic effects (Auro et al, 2004;Jung, Le, Wengenmayer, Wolf, & Kramer, 1985;Westphal, Vetter, & Brogard, 1994). As a consequence, nitrofurans have been banned from using in animal husbandry in the European Union (EU) since 1995 (European Commission, 2005).…”

“…These metabolites are 3-amino-2-oxazolidinone (AOZ), semicarbazide (SEM), 1-amino-hydantoin (AHD) and 3-amino-5-morpolinomethyl-2-oxazolidone (AMOZ) derived from furazolidone, nitrofurazone, nitrofurantoin and furaltadone, respectively (Auro, Sumano, Ocampo, & Barragán, 2004). Several studies prove that the detection of the nitrofuran parent drugs is not a suitable monitoring technique Cooper, Samsonova, Plumpton, Elliott, & Kennedy, 2007;Pimpitak, Putong, Komolpis, Petsom, & Palaga, 2009).…”

A novel chemiluminescent ELISA for detecting furaltadone metabolite, 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ) in fish, egg, honey and shrimp samples

“…For many years, this class of broad-spectrum antibacterial drugs has been widely used as additives in livestock and aquaculture feed for treatment of certain bacterial infections (Ali, 1999). In addition, nitrofurans have also used as a growth promoter in farm animal feed and aquatic organism culture (Auro et al, 2004;McCracken and Kennedy, 2007). However, FTD, FZD, NZF, NFT and their metabolites have proven carcinogenic and mutagenic effects (van Koten-Vermeulen et al, 1993).…”

Direct detection of 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ) in food samples without derivatisation step by a sensitive and specific monoclonal antibody based ELISA

“…They are also being used in human medicine, as topical applications for skin burns and infections, and for the treatments of cholera and urinary infections (McCracken, Blanchflower, Rowan, Maurice, & Kennedy, 1995). Among the hundred listed nitrofurans, furaltadone (FTD), furazolidone (FZD), nitrofurazone (NFZ) and nitrofurantoin (NFT) are mostly used ones and have been banned in food-producing animals within the European Union (EU), Australia (1993), The Philippines (2001), Brazil (2002, Thailand (2002), and the United States (2002) because it was found by long-term studies with experimental animals that the parent drugs and their metabolites showed carcinogenic and mutagenic characteristics (Auro, Sumano, Ocampo, & Barragan, 2004;Commission Regulation (EC) 1442/95, 2005Khong et al, 2004;Van Koten-Vermeulen, 1993). Ministry of Agriculture of China also has prohibited the use of FTD, FZD, NZF, NFT, and nifurstyrenate sodium (NFSS) in animal husbandry since 2002 (Regulation of Department of Agriculture of China, 2002).…”