Chemical Identification in Athletic Horses

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Guilty until Proven Innocent:
Preventing Inadvertent Chemical Identification in Athletic Horses

by Dr. Thomas Tobin

A racetrack groom leans next to his favorite horse's stall, eating his breakfast before the morning workout. The horse playfully nuzzles the groom until he finally turns to the horse and allows it to nibble at his bagel. Later on that week, the horse is disqualified from a race for a medication violation.
Because of the increased sensitivity in post-race urine testing, environmental and dietary substances can cause inadvertent chemical findings in racetrack urine tests. Managers and trainers can reduce the chance of sample contamination by understanding causes. A review developed by Dr. Thomas Tobin from the University of Kentucky's Gluck Equine Research Center evaluated possible sources that can result in administrative actions based on the chemical identification of environmental, dietary and enhorseenous substances in post-race samples.

To better understand a substance's impact on a horse's racing performance, the Association of Racing Commissioners International (ARCI) developed the following classification system;

Class 1 These are hard-core illegal narcotic opiates and stimulants with no place in racing. They also have the highest abuse potential. Substances in this class can have a profound affect on a horse's performance. Examples include morphine, etorphine and cocaine.

Class 2 This class has less abuse potential, but still includes illegal substances. Some agents in this class have legitimate therapeutic uses for horses in training. Examples include local anesthetics, reserpine, romipedine and barbiturates.

Class 3 Legitimate therapeutic agents with the potential to affect performance are included in this class. Such agents include antihistamines, bronchodilators and tranquilizers.

Class 4 These substances are legitimate and widely used therapeutic agents. They include phenylbutazone, corticosteroids and isoxsuprine.

Class 5 This class has negligible pharmacological effects, if any. Examples include dimethyl sulfoxide (DMSO) and polyethylene glycol (PEG).

Dietary Influences
Contaminating dietary substances can be found in normal, ordinary equine diet feedstuffs. According to Dr. Tobin, the following substances are agents that can give rise to inadvertent chemical identifications. Generally, these "food source" influences are clear-cut, geographic, and generally show seasonal occurrence.

Poppy Seed
Poppy seeds are a significant source of morphine. The poppy plant grows in certain parts of Australia, is cultivated in France and its seeds are common worldwide in baked products such as bagels and muffins. An ARCI Class 1 agent, morphine identifications can be associated with contaminated hay or inadvertent feeding of poppy seed products.

"Since codeine and heroine are metabolized to morphine, accidental contamination from prescription codeine — as well as heroine — can also result in a morphine identification," Dr. Tobin states.

Morphine administered intravenously at 0.1 mg/kg, a dose not associated with pharmacological responses in the horse, can be detected in the blood for up to 48 hours and for up to 144 hours in the urine. Horsemen in certain parts of the world should evaluate hay for possible contamination and be aware of poppy seed products around horses destined to race to avoid a morphine identification in post-race samples.

Alfalfa Hay
Alfalfa hay is a very common legume in equine diets. It can also cause high urinary concentrations of salicylate, an ARCI Class 4 agent. Salicylic acid (salicylate) is a prototype Non-steroidal Anti-Inflammatory Drug (NSAID) and has long been known as "normal" in horse urine. With one exception, Dr. Tobin is not aware of any recent administrative actions based on the substance. However, he noted that recently, an unusually large number of salicylate-based identifications have been made by a western testing laboratory. Salicylate administered topically, for example as methylsalicylate, can give rise to identifications of methylsalicylate in urine.

To help distinguish between naturally occurring and administered salicylate, some countries have set a urinary threshold.

"A threshold, also known as a No-Effect Threshold (NET), is the highest concentration of an agent that we are confident has no pharmacological effect," Dr. Tobin adds. "If a concentration in a urine sample goes above the threshold set, then the rule has been violated. If it goes under, then the rule has not been violated."

The current threshold of salicylate in some countries is 750 µg/ml in urine and this level has currently been adopted in California.

Lucerne hay
Lucerne hay, rainwater and many other feed ingredients contain dimethyl sulfoxide (DMSO) which, like salicylate, is a naturally occurring substance. DMSO, ARCI Class 5, is considered an agent with essentially no ability to affect the outcome of a race. Therefore, it is considered to be of little regulatory interest.

Managers, trainers and racing regulators, however, should be aware that the international threshold for DMSO is 15 µg/ml in urine. Lucerne hay, which contains relatively large amounts of DMSO, has yielded urinary concentrations as high as 5µg/ml of this agent. Caution should be exercised when using DMSO and lucerne hay concurrently.

Jimson Weed
Jimson weed, which grows wild across much of the United States, is a common source of scopolamine. It is occasionally abused by teenagers seeking a pharmaceutical high.

Within the past two years, a number of scopolamine identifications have been made in American racing. Scopolomine is an ARCI Class 3 agent and is very closely related to the alkaloid atropine. Unfortunately, it is not possible yet to confidently distinguish between plant sources and pharmacological sources of scopolamine; further research is needed in this area. Another plant source of both atropine and scopolamine is belladonna.

Environmental influences
Environmental contaminants may also give rise to chemical identifications in urine. Horses may be exposed to these materials pre-race which causes metabolites to be found in the post-race sample or the urine sample may become contaminated post-race.

Human Sweat
Most human skin and sweat commonly contain significant amounts of caffeine. Caffeine, an ARCI Class 2 agent, is the most widely used psychoactive (affecting the mental state) agent in the world. Humans consume an average of 125 mg of caffeine daily. Drinking coffee causes even more caffeine secretion in sweat. It is no wonder, then, that human sweat can possibly contaminate a post-race urine test.

"Finding caffeine in a blood or urine sample with associated metabolites generally means that the caffeine went through a horse," reports Dr. Tobin. "Finding caffeine in a urine sample with no associated metabolites most likely means that it did not go through a horse, with the implication that the chemical identification resulted from post-race contamination. If caffeine is detected in a post-race sample, it should be analyzed for metabolites or the corresponding blood sample should be checked to rule out post-race contamination."

Cocoa beans and husks
Theobromine, though a legitimate Class 4 therapeutic agent, is derived from caffeine in cocoa beans and husks. Chocolate candy bars, therefore, should not be used as a "snack" for horses intended to race. For two decades, theobromine was the most commonly identified material in horse urine in England.

Other influences
There are many other sources of contamination, yet they are by agents that are not classified by the ARCI. They include barley (hordenine), skin glands of toads or hay (bufotenine) and tobacco stalk bedding (nicotine). Managers and trainers should also be aware that ubiquitous agents such as cocaine, nicotine and arsenic are possible contaminants.
Biographical Information
Dr. Thomas Tobin is a professor of veterinary science and toxicology at the University of Kentucky's Gluck Equine Research Center in Lexington. He is a veterinarian, pharmacologist and toxicologist. He graduated from University College, Dublin in veterinary medicine, and holds a PhD in pharmacology and toxicology from the University of Toronto. Since 1975, Dr. Tobin has directed the Equine Pharmacology and Experimental Therapeutic Program at the University of Kentucky. He is the author of Drugs and the Performance Horse and about 300 other research publications. The current thrust of his research is on No-Effect Thresholds (NETS) for therapeutic medications.