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Based on their performance-enhancing potential, caffeine and theophylline are prohibited substances in equine sports. Residues in horses can be caused by wilful application or by unintended uptake of contaminated feed. The International Federation of Horseracing Authorities recently introduced international residue limits (IRLs) to facilitate the discrimination between pharmacological relevant and irrelevant concentrations in doping samples. The objective of this study was to investigate the scientific validity of these IRLs. A systematic analysis was performed to assess the IRLs by different statistical approaches using published pharmacokinetic data. 31 out of 218 potentially relevant publications met the inclusion criteria. Thereby, both IRLs were found to be appropriate for the exclusion of the presence of a relevant pharmacological effect after a wilful application. The IRL of theophylline was also determined to be suitable for the prevention of positive doping tests caused by the ingestion of contaminated feed. In contrast, the IRL of caffeine is not suitable to prevent positive doping test caused by the ingestion of more than 10 mg caffeine per day per horse with contaminated feed. The lack of corresponding regulation for paraxanthine, a major active metabolite of caffeine and theophylline, was recognised as a substantial shortcoming of the current system, rendering both IRLs incomplete., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pyrrolizidine alkaloids are secondary plant metabolites with hepatotoxic effect in humans and several animal species. In recent studies, foods such as herbal teas and honey have been found to be contaminated with pyrrolizidine alkaloids., Objectives: The aim of this study was to identify and assess pyrrolizidine alkaloids in compound feeds manufactured for horses and containing either alfalfa or a blend of herbs., Methods: Forty-eight feed products for horses were included in the study. The feedstuffs were analysed for 28 selected pyrrolizidine alkaloids by liquid chromatography-mass spectrometry. The concentrations of the individual pyrrolizidine alkaloids were summed to calculate the total pyrrolizidine alkaloid content., Results: In 7 of 48 samples, pyrrolizidine alkaloid concentrations were below the limit of quantification of 1-5 μg/kg. The median of 41 out of 48 samples was 58 μg/kg, and the 25 and 75th percentiles were 8 and 151 μg/kg. The highest observed pyrrolizidine alkaloid concentrations, 1306 and 1222 μg/kg, were found in two alfalfa-based feed products, followed by 836 μg/kg in an herb-containing feed product. Lycopsamine, seneciphylline, seneciphylline-N-oxide, senecionine and senecionine-N-oxide were the most frequently detected alkaloids., Main Limitations: Risk assessment was based on no-observed-adverse-effect-level for pyrrolizidine alkaloids in rats and humans. The specific susceptibility of horses to pyrrolizidine alkaloids remains unknown., Conclusions: According to our risk assessment, pyrrolizidine alkaloid contamination should be limited to <90 μg/kg in equine compound feeds. We showed a high rate of pyrrolizidine alkaloids contamination in feed products for horses. In 43% of the analysed samples, pyrrolizidine alkaloid levels exceeded the calculated maximum tolerable levels. There is a need to introduce measures to reduce pyrrolizidine contamination in equine feedstuffs. The Summary is available in Portuguese - see Supporting Information., (© 2018 EVJ Ltd.)