TCS Daily

Using the Most Vulnerable

By Sandy Szwarc - June 27, 2005 12:00 AM

Headlines recently exclaimed: "Hormone-altering chemical puts ICU newborns at risk-Babies treated with plastics have high levels of a toxic substance, a study finds." The basis for this disturbing news was a study from Harvard School of Public Health published in the on-line issue of Environmental Health Perspectives which detected phthalates in the urine of critically-ill and premature babies in neonatal intensive care units. The amounts correlated with how many medical treatments and procedures were being used to save their lives -- babies with the highest levels of intervention had levels 5.1 times higher than those with the least.

But before emotions, fears and uncertainties get the better of us, let's turn to the scientific evidence. Are "detectible" amounts of a chemical -- in billionths of a gram -- "high"? Does its mere presence make it dangerous? And is this chemical even considered a danger to humans in the first place? No, no and no.

Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer used in various medical devices from IV tubing and blood containers to feeding tubes. It serves a number of critical purposes: it gives plastic tubing and products strength so they don't become distorted and are able to withstand pressure; it helps resist kinks or deformation; it minimizes breakdown when exposed to fluids; it helps withstand the heat of hospital machinery and sterilization; it enhances clarity to allow for close monitoring by nurses and medical workers; and makes tubing soft and flexible so that it doesn't damage the fragile veins and airways of tiny infants. . These DEHP-plasticized materials have "demonstrated superiority to other materials for specific applications; in certain situations no acceptable or approved alternatives exist, and its functional performance is often critical in life-saving and medical-intervention measures," concluded the consensus statement of a 1999 independent expert panel, chaired by C. Everett Koop, which reviewed the international scientific evidence.

DEHP in plastic products is widespread and the release of tiny amounts during medical usage has been known and exhaustively studied for more than 30 years. This isn't the first study of hospitalized babies, either.

The Harvard researchers looked at 54 babies admitted for at least three days to two Boston area NICUs. They tested their urine for mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP. Eleven of the babies had undetectable levels. The median urinary MEHP levels for low, medium and high exposures for all babies were 4, 28, and 86 ng/ml. That's billionths of a gram.

While they detected the substance, they didn't determine if it resulted in any health problems or harm. They didn't have any of the medical records for the babies. Despite this shortcoming, press releases from both Harvard and Health Care Without Harm, a coalition of more than 435 environmental groups and allied organizations, were quick to say the babies had been "dosed with toxic phthalates" and that DEHP was a known toxin that alters male reproductive development and function.

Principles of Toxicology

DEHP exemplifies two major principles of toxicology: "rats are not people" and "the dose makes the poison." Potential dangers of DEHP were first seen in rat studies. But tumors, hormonal and reproductive problems have only appeared in rodents at extremely high, daily doses -- in several grams per kilogram, not billionths of grams.

Multiple studies have also shown that primates absorb far less DEHP, eliminate it differently and are much less sensitive to it than rats. The marmoset monkey is believed to more accurately reflect responses in humans. When researchers gave monkeys 2.5 grams per kilogram - about 3,500 times higher than the highest level found in the babies' urine -- orally every day for months, they still didn't detect any effects on testes, liver or kidneys.1

Not only the amount of the dose, but the type of exposure also determines how much of these phthalates are absorbed. For example, multiple rat studies published in Toxicology and Applied Pharmacology have found no effect on health or reproductive development through blood or inhalation exposure. DEHP directly entering the blood stream (as hospital patients with IVs would experience) or through the airways ( as hospital patients on ventilators would experience) is not readily metabolized or available to the body. All available research has shown that phthalates are broken down and excreted within 24 hours and that there is no concern that they accumulate in our bodies at all.2

In a 2002 scientific report, the European Commission stated:

        "There are no concerns over carcinogenicity in humans on the basis of 
        animal studies.... mechanisms for adverse effects do exist in rodents, but 
        these do not appear to be of great significance in non-human primates and 
        that the evidence that such mechanisms could be operative in humans is 

And the Koop expert panel concluded:

        "human risk assessments should not, by default, be based on carcinogenicity 
        in rodents... because evidence shows that humans are less sensitive."

But if you're a parent worried about your fragile newborn, or a healthcare professional trying to give that baby the best chance for survival, you're most interested in what studies have been done on people, especially babies and children, exposed to DEHP in the hospital. The highest observed levels in humans from medical device or procedure exposures -- 20 to 70 times that of any other -- have been found in those receiving "extracorporeal membrane oxygenation" (ECMO), a life-saving procedure in which blood is run continuously via tubing through oxygenating equipment. Researchers have not found any short-term toxicity to heart, lung or liver function from ECMO in babies.4 And several studies of both male and female adolescents who'd had ECMO as infants have shown no effects on their reproductive development, growth or hormones even 14 to 16 years later.5 Several studies of patients who've received long-term high exposures through dialysis have also failed to find increased risks for any form of cancer.6,7

The Center for Devices and Radiological Health at the Food and Drug Administration conducted an extensive safety assessment of DEHP in medical devices and in their September 2001 report they estimated that the total exposures of an infant receiving all of the procedures that might expose them to DEHP would still be below the level that caused effects in animal studies. They concluded there was little to no risk imposed by patient exposures.

The scientific expert panels and government health agencies that have examined the evidence have, except for the U.S. EPA, negated DEHP as being a threat to human health. Health Canada, for example, has classified DEHP as "unlikely to be carcinogenic to humans."8 And the International Agency for Research on Cancer, part of the World Health Organization, took the rare step of downgrading DEHP from a possible carcinogen to one "not classifiable as to carcinogenicity to humans"9

The Koop scientific panel concluded:

        "DEHP in medical devices is not harmful to even highly exposed people....
        There is no evidence indicating that DEHP exposure in humans is associated 
        with kidney, liver, lung, reproductive, developmental, or cardiovascular 
        toxicity. DEHP-containing medical devices should not be taken off the market, 
        because the weight of scientific evidence indicates that they pose no 
        significant health risk to humans..... The outdated U.S. EPA cancer 
        classification for DEHP is based on ... rodents, a mechanism for which there 
        is scientific consensus to support its irrelevance to humans. As such, DEHP 
        should be reclassified by the US EPA as unlikely to be carcinogenic 
        to humans."

The overwhelming body of evidence is in sharp contrast to the spin in press releases issued by Harvard and Health Care Without Harm, which call for the removal of DEHP products from hospitals. "This new evidence of toxic chemical exposure to the most vulnerable sick infants is alarming, and adds urgency to the need to pass the Safer Alternatives bill that is currently before the state legislature," said Bill Ravenesi, Boston campaign director of Health Care Without Harm. He is also with the Alliance for a Healthy Tomorrow, the coalition sponsoring the Safer Alternative Bill (H.1286 - S.553). This bill is coming up for public hearing this month and mandates DEHP and nine other chemicals be removed from common household products. The Harvard study was funded in part by Health Care Without Harm and the environmental Rasmussen Foundation.


1. Toxicology Science; 1998;42:49-56
2. Environmental Health Perspectives; 2000;108:979-982
3. Health and Consumer Protection Directorate-General, September 26, 2002
4. Critical Care Medicine; 1997; 25:696-703
5. Environmental Health Perspectives; 2004;112(13):1339-1340
6. Medscape General Medicine; 1999;1(1)
7. Critical Reviews in Toxicology; 1996; 26(4):365-481
8. Health Canada 26, February 19, 1999
9. IARC, February 15-22, 2000



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