Sporadic worldwide “clusters” of zilpaterol detection in racehorses appear to have been driven in large part by a worldwide cattle feed manufacturing process, according to the authors of a review.
Zilpaterol, a beta-adrenergic agonist medication, is approved in several countries as a cattle feed additive. It promotes weight gain and improves carcass quality.
The recent reporting of 18 or so feedstuff-related identifications of zilpaterol at low concentrations in the urine samples of racehorses by a French racing laboratory, together with previous zilpaterol clusters elsewhere, have raised questions around their origins, the possibility of performance effects, and any health consequences related to such low-concentration exposures.
Jacob Machin and his fellow researchers, writing in the Irish Veterinary Journal, said trace amounts of zilpaterol can transfer to horse feed, yielding equine urinary “identifications” of the additive.
These occur because zilpaterol is highly bioavailable in horses, resistant to biotransformation, and excreted as unchanged zilpaterol in urine, where it has a terminal half-life of about five days.
The first cluster, in April 2013, involved 48 racehorses in California; the second cluster, in July 2013, involved 15 to 80 racehorses in Hong Kong. The third cluster, in March of 2019, involved 24 racehorses in Mauritius. This cluster was traced to South African feedstuffs, triggering an alert concerning possible zilpaterol feed contamination in South African racing.
The fourth cluster, in September/October 2020, involved around 18 identifications in French racing, reported by the French Laboratories des Courses Hippiques, and in July 2021, a fifth cluster of 10 zilpaterol identifications occurred in South Africa.
“The regulatory approach to these identifications has been to alert horsemen and feed companies and penalties against horsemen are generally not implemented,” the review team noted.
They said a key driver in these events is that zilpaterol is dissolved in molasses for incorporation into cattle feed. “Inadvertent incorporation of Zilpaterol containing molasses into horse feed has apparently been the driving factor in each of these horse-racing-related clusters of zilpaterol identifications.”
A second factor in the 2019 Mauritius and 2020 French identifications was the sensitivity of the analysis work undertaken, with the French laboratory reportedly testing at a “more sensitive level for zilpaterol”.
As of January 1, 2021, a new FEI policy lists zilpaterol as a substance that can be treated as an atypical finding, allowing consideration of inadvertent feed contamination in the regulatory evaluation of zilpaterol identifications. The criteria for an atypical finding includes that there be identifications of the same substance in other samples taken at the relevant event(s).
“Given their minimal exposure to zilpaterol, there is little likelihood of Zilpaterol effects on racing performance or adverse health effects for exposed horses,” the review team found.
“Given the low daily microgram amounts of zilpaterol to which these horses have been exposed, in the order of 1/4000 or less than a pharmacologically effective dose, the likelihood of significant adverse health effects, either short or long term is, as a practical matter, indistinguishable from zero.”
In this regard, the European Union Joint Expert Committee on Food Additives derived an acceptable daily intake of zilpaterol for humans of 0.04 micrograms per kilogram body weight, or a total daily dose for a human of about 2.8 micrograms per day, or about 17 micrograms per day for a horse.
“These dosage levels, based on acceptable human exposure rates, are in the same order of the 15 micrograms per day or so total dose of zilpaterol to which the horses in the most recent 2020 French cluster of racing chemistry zilpaterol ‘positives’ have been exposed.
“There is therefore as a practical matter, essentially no likelihood of adverse effects on these animals related to the zilpaterol exposure.
“Similarly, there is also no significant possibility of an effect on the racing performance of horses exposed to these extremely small amounts of zilpaterol.”
The review team comprised Machin, Kimberly Brewer, Abelardo Morales-Briceno, Clara Fenger, George Maylin and Thomas Tobin.
Machin, J., Brewer, K., Morales-Briceno, A. et al. Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis. Ir Vet J 75, 11 (2022). https://doi.org/10.1186/s13620-022-00215-8