Chirollo, Claudia (2010) Anthelmintics residues in milk and dairy products from cows treated with levamisole, oxyclozanide and nitroxynil at different administration doses. [Tesi di dottorato] (Unpublished)

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Anthelmintic drugs are widely used in veterinary medicine for protecting or treating animals mainly against gastrointestinal nematodes and trematodes. In general, they cause no human health risk if veterinary drugs are properly administered and the recommended doses are correctly adhered to. However, there may be a concern that if withdrawal periods are not adhered to or if products are administered to animals in unapproved applications (e.g. administration to lactating species) those levels may exceed MRLs in foods. In addiction, whenever chemicals are used, especially with long term low dose exposure, toxicological, teratological and carcinogenetic effects must be considered. Only a limited number of products are licensed for treatment of animals during the lactating period and have a MRL listed under European Commission Regulation 37/2010. The widespread availability of cheaper generic veterinary medicinal products and the development of drug resistance to the limited number of licensed products have increased the potential for off-label applications. SUMMARIES The aim of this study was to investigate the persistence of oxyclozanide and levamisole residues in bovine milk after treatment with a combination product and their subsequent fate during cheese production. Animals were milked twice daily up to 16 days post treatment. Soft (3 d ripening), hard (35 d ripening) and whey cheeses were produced from the milk samples collected from first two milkings. Milk and cheese samples were subsequently analysed by UPLC-MS/MS. Highest levels of levamisole (<600 µg/kg-1) and oxyclozanide (<25 µg/kg-1) were determinate at first and third milking respectively. Levamisole residues were found to concentrate in all cheese types. There was a three fold concentration effect for levamisole in mature cheese. Oxyclozanide residues were found to occur at lower levels in soft and hard cheese than milk with a 10-fold concentration in whey cheese compared to milk. Residues were found at higher levels in cheeses compared to the milk. The results of this study demonstrate that levamisole and oxyclozanide residues are rapidly excreted in dairy cows and milk is compliant after few days, but survive the fermentation process to persist in cheese. Nitroxynil is a halogenated phenol used to control fascioliasis in cattle and sheep. No.35 pregnant dairy cows were treated in this study with a nitroxynil 340 mg/ml solution for injection at the recommended dose of 10 mg/nitroxynil per kg body weight at the start of the dry period, and from 53 to 74 days before the expected calving. Calving occurred between 43 days and 79 days after treatment. Subsequently, the concentrations of nitroxynil in the milk were monitored for up to 120 days after calving. Nitroxynil was detected by UHPLC-MS/MS (ultra high performance liquid chromatography coupled to tandem mass spectrometry). The present study quantified the residue concentrations of nitroxynil in the milk of cows which were treated by subcutaneous administration at the recommended dose of 10 mg nitroxynil per kg body weight at the beginning of the dry period. The occurrence and the depletion of the residues in milk after calving were investigated.

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