Safety evaluation of ractopamine

Abstract

SUMMARYRactopamine hydrochloride is pharmacologically classified as a phenethanolamine β-adrenoceptor agonist. The use of the substance as a feed additive is authorised in different countries (USA, Canada, Japan and Mexico) for growth promotion of fattening pigs and cattle. Ractopamine has not been assessed in the EU so far.Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to provide an opinion on the JECFA evaluation for ractopamine hydrochloride, having consulted and closely co-operated with other organisations such as EMEA and the Community Reference Laboratory responsible for β-agonists (BVL in Berlin).The metabolic fate of ractopamine hydrochloride is similar in the target species (pig and cattle), laboratory animals and humans.The FEEDAP Panel concluded from an acute study in dogs that tachycardia and peripheral vasodilatation observed are in line with the expected pharmacological action. From another acute study in dogs, with limited statistical power, a pharmacological NOAEL of 2 µg kg -1 bw could be derived.Comparing dog and monkey data it appeared that the dog could be considered as more sensitive to ractopamine (β-adrenergic substances). However, the FEEDAP Panel considered that there was not enough data to support this conclusion.NOAEL's derived from pharmacological repeated dose studies should not be regarded as a meaningful basis for an ADI because of the observed down regulation of lung β-adrenergic Opinion on safety evaluation of ractopamineThe EFSA Journal (2009) 1041, 2-52 receptors, at least as long as dose-and time-dependency and β-adrenoceptors speciation is not established. When evaluating hypothetical risks for the consumer, data from acute pharmacological studies would better reflect the consumer situation after intake of a single meal containing ractopamine residues.The NOAELs derived from toxicological end points were considerably higher than those from pharmacological end points. Effects observed in toxicity studies were mostly related to the pharmacological action.Although a series of mutation studies in prokaryotes and eukaryotic systems were negative, several in vitro tests were positive. The FEEDAP Panel considered that some positive genotoxicity studies in vitro are a possible cause of concern. However, these results have to be considered in conjunction with the carcinogenicity studies provided.The FEEDAP Panel concluded that all treatment-related effects observed in the long-term studies in mice and rats were attributable to the β-adrenergic activity of ractopamine. It shares the JECFA and FDA opinion, considering that the induction of leiomyomas is a non-genotoxic event with a threshold and ractopamine is not a direct carcinogen. Considering all studies, the FEEDAP Panel concluded that ractopamine is not mutagenic and is not likely to present a carcinogenic risk to consumers.Since data in laboratory animals gave a wide range of NOAELs, the available human data was considered pivotal by JECFA as it was by the FEEDAP Panel when ...

Evaluation of public and animal health risks in case of a delayed post‐mortem inspection in ungulates

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Presence of β2‐agonist growth promoters in human urine samples: GC‐MS/MS evaluation of the excretion profiles of ractopamine administered in microdoses

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