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Widespread Plasticizer Clouds Doping Tests of Cyclists

Cyclists get dinged for finding phthalates in their blood but argue that the chemicals are ubiquitous in all people these days



Wikimedia Commons/Kallenovsky

In the race to catch drug cheats, sports officials are turning to more sophisticated tests. Since cheaters are rarely caught red-handed, scientists devised a plan to catch them with the packaging — inside their bodies. But a plasticizer is so ubiquitous in people that it has clouded the results of these blood doping tests in the world of professional cycling.

Alberto Contador, a three-time Tour de France champion from Spain, was found guilty of doping Monday after he tested positive in 2010 for a performance-enhancing drug. A plasticizer, typically used to soften plastic bags or tubes, was also found in his system, which prompted allegations of an illegal blood transfusion.

Doping in the world of elite sports has grown so high-tech that officials began testing athletes like Contador not only for banned substances and illegal medical procedures, but also for trace evidence of cheating, such as the residues of IV bags.

Experts — and Contador — say that these chemical residues are so widespread that there is too much doubt about how they got into an athlete's body. But others say that spikes of these chemicals, at levels much higher than normal, are a red flag for doping. Due to the controversy, funding for the test to detect these chemicals was discontinued in November 2011.

In a preliminary test in 2010, Contador's urine sample showed a spike in plasticizers that are found in IV bags used to store blood, according to the ruling by an international sport arbitration panel.

The theory is that a cyclist with plasticizers in his urine was using the IV bags for blood doping — illegally boosting one's red blood cell count to carry more oxygen to the lungs and muscles. But Contador's case has been controversial since the beginning, and he has vowed to appeal the ruling, saying that the widespread use of plasticizers in the environment has clouded the testing efforts of the sport's doping police.

The World Anti-Doping Agency funded research to develop a plasticizer test that would catch cheating cyclists, but so far it's not the smoking gun that many have hoped for. Plasticizers known as phthalates are used in everyday products, with possible toxic effects. The goal is to one day be able to prove that a plasticizer spike in a cyclist's urine was due to blood doping paraphernalia, and not, say, an accidental exposure from food.

The plasticizer in question is called bis(2-ethylhexyl)phthalate, or DEHP, which is "ubiquitous" in the environment, said Shanna Swan, a reproductive epidemiologist at the Mount Sinai School of Medicine in New York who has studied the effects of phthalates on infant boys.

"Ninety-eight percent of people in the U.S.A. have measurable levels," Swan said.

DEHP is only one of many phthalates in that are common in the environment. Phthalates can mimic estrogen or disrupt testosterone, and exposure of fetuses and infants is the major concern. In infant boys, prenatal exposure to dibutyl phthalate has been linked to feminization of the reproductive tract. In men, phthalate exposure has been linked to sperm defects and altered thyroid hormones.

DEHP is the primary plasticizer in many medical supplies such as IV blood bags, which are about 40 percent DEHP. But it's also in food, and diet is the largest source of DEHP exposure, said Joe Braun, an epidemiologist at Harvard University. It apparently gets into food from use of some plastic food wraps and containers.

Since 2000, blood doping tests have been able to detect whenever blood from more than one person is present in a cyclist's sample (called a homologous blood transfusion). But these same tests cannot detect when a rider is doping with his own blood (autologous blood transfusion), so markers such as DEHP or its metabolites are needed to indicate foul play.

Contador's 2010 test showed a spike in phthalates in his system near the end of that summer's Tour de France, the first time the plasticizer test was used. His samples also tested positive at that time for clenbuterol, a performance enhancing drug that riders have been known to use illegally in off-season workouts.

Contador claims that the clenbuterol got into his system when he ate tainted steaks. The WADA and the International Cycling Union said that the drug most likely came from an illegal blood transfusion, because the plasticizer spike was detected the day before he tested positive for clenbuterol. The Court of Arbitration for Sport in Lausanne, Switzerland, agreed, overturning an earlier ruling by the Spanish cycling federation. Contador is now banned from racing for two years. [Full PDF of the report here]

He has said he will appeal the ruling and that he never underwent any kind of transfusion. His argument, as summarized in the ruling, is that "the transfusion theory is scientifically impossible" and that "a spike of phthalates can be attributed to any number of legitimate reasons." Yet research has linked blood transfusions to spikes in DEHP.

"Although you can not directly know of the source of DEHP in the system, research has reported extremely high levels of DEHP on the day of blood reinfusion compared to the previous day," said Steven Neese, who studies endocrine disrupting chemicals at the University of Illinois. "These levels remain high even a day later."

The tainted steaks theory could not be easily dismissed because DEHP can be absorbed by food and water from their packaging. The regulatory panel, however, decided the evidence did not support this theory, and said in a statement that "it was more likely that the adverse analytical finding of the Athlete was caused by a blood transfusion or by the ingestion of a contaminated food supplement than by the consumption of contaminated meat."

A study published on Feb. 6 in the journal Environmental Health Perspectives found that many prescription and over-the-counter drugs and supplements may use phthalates as in active ingredients, but DEHP was not among them.

"I have not found DEHP listed in any currently marketed medication and/or supplement formulations that can be orally ingested," said Kathy Kelley, a research pharmacist at Boston University and the lead author of the study.

A typical person in the U.S. is exposed to 1 to 30 micrograms of DEHP per kilogram body weight per day from eating, breathing or through the skin, Neese said. Due to daily exposures, athletes submit several biological samples during a race and during the off-season so that doping officials can look for spikes in chemicals.

"So long as [baseline] exposure levels were established in the athlete prior to retest, and the DEHP levels were significantly elevated upon retest, it would be difficult for this to be from any normal exposure," Neese said.

Contador's DEHP levels spiked to 10 times higher than found in his other urine samples, according to the panel's report. The DEHP levels were "much higher" than maximum levels found in transfusion studies accredited by the WADA. Contador's phthalate concentrations were not listed in the panel's report, and representatives from the WADA and the U.S. Anti-Doping Agency were unavailable for comment.

A national survey by the U.S. Centers for Disease Control and Prevention from 2001 to 2001 found that DEHP's first metabolite is present at 37.9 micrograms per liter in the 95th percentile of men, which means that just "5 percent of U.S. men had a value higher than this," Swan said.

It is possible, however, that a rare acute exposure from occupational or diet sources can significantly elevate levels, Neese said.

In cyclists, things get even more complicated because many things might cause their levels to spike.

"DEHP metabolite concentrations can vary because of a variety of factors including hydration status, time since least meal or urine void, and time since last exposure to DEHP," Braun said. "The high levels of activity in professional cyclists may also change how quickly DEHP is processed by the body."

Based on these complicating factors and the widespread DEHP exposure, the WADA discontinued funding for the plasticizer test in November, a year after Contador was implicated in blood doping. The developer of the test, Jordi Segura, the head of the International Olympic Committee-accredited laboratory in Barcelona, did not return requests for comment.

The cancellation of the test could be a moot point as a push for DEHP-free supplies has begun.

The American Academy of Pediatrics and the FDA have both expressed concerns about medical products containing DEHP, particularly for infants.

"Some exposures, like the environment in the neonatal intensive care nursery, convey very high exposures," Swan said. "A growing body of data suggests that the absence of these chemicals in the environment would have positive health consequences."

Brett Israel is a researcher, writer and former intern at Environmental Health News.

This article originally ran at Environmental Health News, a news source published by Environmental Health Sciences, a nonprofit media company.

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