By Marla Cone
Editor in Chief
Environmental Health News
November 10, 2008
Every day for three months, the patient took a prescription drug called Asacol to treat his inflamed colon. Unbeknownst to him, every pill he swallowed also delivered a dose of a hormone-altering, industrial chemical.
The man, who lived in the Boston area, was contaminated with about 100 times more dibutyl phthalate than ever recorded before in a human being. His daily dose of the chemical was double the amount that the U.S. Environmental Protection Agency considers safe.
At least 47 prescription medications – including the colitis drug Asacol, an antacid and an HIV drug – contain phthalates, according to scientists at the Harvard School of Public Health and U.S. Centers for Disease Control and Prevention.
Widely used as plasticizers, phthalates have been linked to abnormal reproductive tracts, sperm damage and reduced testosterone in animal tests as well as some human studies.
Russ Hauser, a Harvard professor ofenvironmental epidemiology, called pharmaceuticals “an unrecognized source of potential high exposure.” A thin layer of a phthalate-containing polymer, designed to slow the release of medication, coats many timed-release drugs.
Phthalates are found in virtually every human body. But for people taking medications coated with the compounds, their exposure exceeds other, well-known sources, such as plastics, perfumes and lotions, by ten to 1,000-fold, Hauser said.
Phthalates are ingredients in vinyl, as well as some building materials, paints, adhesives and personal care products, including fragrances, shampoos and nail polishes.
Congress enacted a law in August banning the chemicals in toys and other children’s products. But their use in prescription drugs and over-the-counter medications is approved by the U.S. Food and Drug Administration.
New data showing high levels of phthalates in people taking some medications “raise concern about potential human health risks,” Hauser and his colleagues reported in a study published in October in Environmental Health Perspectives online.
The scientists warned “of the potential for high delivered doses of phthalates to vulnerable segments of the population, particularly pregnant women or young children.”
In one case, the man taking Asacol for his ulcerative colitis, an inflammatory bowel disease, had a concentration of a dibutyl phthalate (DBP) metabolite in his urine measuring nearly 17,000 parts per billion, according to a case study reported by the Harvard/CDC team. The average for the general population was 46.
The unidentified man, in his early 30s, was tested for phthalates as part of a visit to a Boston infertility clinic. He and his wife were unable to conceive a child.
The effects of phthalates on male fertility remain unknown, but some scientists theorize that exposure, especially in the womb, could contribute to an increase in men’s reproductive disorders, such as reduced sperm quality, testicular cancer and undescended testicles.
Representatives of the plastics industry say the levels of phthalates used in consumer products are safe. They say human studies are small and inconclusive, and that the animals in studies showing effects were exposed to high doses.
The FDA has not put restrictions on use of phthalates except for a 2001 guideline that warned hospitals that phthalate-containing intravenous tubing and other plastic medical devices exposes infants to large doses of the chemicals.
Dr. Shanna Swan, a professor of obstetrics and gynecology and of environmental medicine at University of Rochester, called DBP, used in Asacol, “one of the most toxic” phthalates. It was associated with feminization of newborn boys – a shortened distance between the genitals and the anus – in a study that Swan and her colleagues published in 2005.
About 20 million prescriptions for Asacol have been written in the United States since it was approved by the FDA in 1992, according to Procter & Gamble Pharmaceuticals, the drug’s manufacturer.
“DBP is an important component of our enteric coating, which ensures that Asacol is delivered to the site of inflammation in the colon and/or rectum,” said Scott Docherty, external relations manager for Procter & Gamble Pharmaceuticals.
Without the phthalate coating, which dissolves when it reaches a certain pH, the drug would be released in the stomach. Because DBP has been approved by the FDA, the company is not looking for alternatives, Docherty said.
P&G’s surveillance of patients “has not identified any adverse events or effects” caused by the DBP, he said.
The Boston area man was prescribed an extraordinary dosage of Asacol – 12 pills a day, which is double the highest recommended dose on the manufacturer’s label. He took it for three months, twice as long as recommended.
Docherty said for patients taking the recommended doses of Asacol, their DBP exposure is far below the EPA’s “no observed effects level.”
“If the patient follows the labeled dose, even the highest dose on the label, they would be taking six tablets per day and there would still be a safety margin 100-fold below” the EPA’s guideline, Docherty said.
But Hauser’s team recently found other examples of high exposure, although not as extreme as that man’s.
The scientists analyzed a national database of 8,000 people, and found six, including a pregnant woman, who took mesalamine, the active ingredient in Asacol. They averaged 50 times more DBP metabolite in their urine than people who did not take the drug, and two exceeded the EPA’s no-effects level, the October report said.
Another 121 people who took three other medications – omeprazole, used in Prilosec antacids; didanosine, which is sold under the name Videx EC and treats HIV patients; and theophylline, a pulmonary disease medicine – also had above-average levels of another phthalate, up to eight times higher than people who did not take the drugs.
Swan cautioned that the Harvard/CDC study included small numbers of people taking the drugs so the averages may be distorted by a few highly exposed ones. Nevertheless, Swan, who did not participate in the study, said the data suggest that millions of people could be at risk.
Baby boys exposed in the womb may be the most vulnerable, Hauser and Swan said.
At least three women in the study with above-average phthalate levels were pregnant – one was taking mesalamine and two were taking the antacids, said Sonia Hernandez-Diaz, a Harvard associate professor of epidemiology who was the study’s lead author.
Another woman of childbearing age who took the colitis drug had a daily dose of DBP exceeding the EPA’s guideline.
“We know that high doses of DBP given to pregnant rats can lead to reproductive tract anomalies in the male offspring. Therefore, I would be concerned about high DBP exposure in pregnant women,” Hauser said.
When prescribing medications to pregnant women, doctors should seek formulations free of the compounds, he said.
Many people who take the medicines have a serious disease that may make them more susceptible to chemicals. HIV patients, for example, have a suppressed immune system.
The authors reported that their study “probably underestimates the true impact of exposure to phthalates in medications.”
Most notably, they did not study over-the-counter medications and vitamins, which often have timed-release coatings.
“I think there are likely other medications that also contribute to very high human exposure,” Hauser said, adding that the number of problematic medications “is likely to change, up or down, depending on what we learn in the coming months.”