The Long, Winding Road to Market Reform: A Case Study of a Phthalate
by Ted Schettler, SEHN science director
The California State Legislature is considering a bill that would ban the use of one chemical in the phthalate family from use in intravenous (IV) fluid bags and tubing, after a phase-out period of several years. The bill, which concerns di-ethylhexyl phthalate (DEHP), passed the Assembly overwhelmingly and is now in the Senate. If it passes there and is signed by Governor Newsom, California will be the first state to limit exposure to this toxic chemical during medical care—a step that the Food and Drug Administration (FDA) and medical device manufacturers have failed to take despite being urged to act for over 25 years.
DEHP is added to the polymer polyvinylchloride (PVC) to add flexibility to what is otherwise a rigid plastic. Plasticized PVC has many applications, from shower curtains to raincoats to IV bags and tubing. The chemical does not covalently bind to the plastic polymer which means it can leach out during use. Since DEHP can comprise 40 percent or more of the final product, exposures can be high enough to be of concern. In the case of IV bags and tubing, DEHP flows directly into patients’ bloodstreams.
Multiple interventions with plastic devices in a newborn child. Mattman4698, https://creativecommons.org/licenses/by-nc/2.0/
DEHP is an endocrine disrupting chemical. Extensive laboratory animal testing shows that it has anti-androgenic effects, particularly when exposures occur during fetal and neonatal development, resulting in abnormalities in reproductive tract development and long-term lower sperm counts. Similar findings have been reported in humans.
In 2006, a panel of scientists convened by the National Toxicology Program systematically reviewed the literature and concluded:
There is serious concern that certain intensive medical treatments of male infants may result in DEHP exposure levels that adversely affect development of the male reproductive tract. ….There is concern for adverse effects on development of the reproductive tract in male offspring of pregnant and breastfeeding women undergoing certain medical procedures that may result in exposure to high levels of DEHP… There is concern for effects of DEHP exposure on development of the male reproductive tract for infants less than one year old.
DEHP also interacts with the estrogen receptor, and in vitro laboratory studies suggest that the chemical can promote resistance to tamoxifen, a drug used to treat some kinds of breast cancer and to lower the risk of breast cancer in women at high risk.
Forty years of concern. Intravenous bags and tubing made of plasticized PVC became increasingly popular mid-20th century, replacing glass bottles and other kinds of plastic. In the 1970s, however, concerns about potential adverse impacts from direct patient exposure to DEHP were raised, particularly after intensive medical therapies, eventually leading to some calls for alternative plasticizers in medical devices.
Meanwhile, alternative flexible polymers came onto the market, which did not require any plasticizers. In the late-1990s, Health Care Without Harm and others encouraged the FDA to begin more vigorously regulating uses of DEHP in PVC medical devices where exposures to the plasticizer could be excessive and alternatives were available. This corresponded to the time of the growing evidence of reproductive and developmental impacts of DEHP at relatively low doses of exposure. Major medical device manufacturers, including Baxter and Abbott, came under increasing pressure to switch to alternative polymers without sacrificing quality of care.
Shareholder action, FDA draft guidance. Twenty-six years ago, in 1998, a group of shareholders of Baxter—including health care institutions which were not only Baxter investors but also purchasers of medical devices—initiated a dialogue with Baxter regarding concerns about the use of PVC and DEHP in medical devices.
This led the shareholders to draft and prepare to file a shareholder resolution which asked the company to phase out the use of PVC in medical devices. The flexible PVC devices contained DEHP as a plasticizer, so that a phase out of PVC devices would not only reduce exposures to DEHP but also result in transitions to polymers with life-cycle impacts less hazardous than PVC.
In response, Baxter came to an agreement with the shareholders in return for their willingness to withdraw the proposed shareholder resolution. The agreement took the form of a memorandum of understanding (MOU).
The terms of the MOU stated that Baxter was “committed to developing alternatives to PVC products and is developing and implementing proposed timetables for substituting its current containers for IV solutions with containers that do not contain PVC.” The MOU called for a timetable that would include measurable and verifiable benchmarks. That was in 1999.
In 2002, following a safety assessment, the FDA issued a public health notification, warning about the potential for excessive exposures to DEHP from medical devices in vulnerable infants and children receiving intensive medical care. The agency suggested switching to alternative products when that could be accomplished without compromising patient safety or care. The notification was not followed by further regulation.
Baxter’s action/non-action. Seven years after Baxter’s MOU with the shareholders, in 2006, Baxter announced that “it had received approval from the FDA on its new AVIVA premium line of intravenous solutions.” Baxter said, “While providing similar functionality and benefits of the company's VIAFLEX flexible container systems, AVIVA containers are made of non-PVC (non-polyvinyl chloride) film, contain no latex and offer a DEHP-free fluid pathway to patients.”
Baxter had a DEHP alternative 18 years ago but continued to promote their line of PVC/DEHP IV bags vigorously. Subsequently, the company reported that their new AVIVA line of products had proven unpopular.
Today, Baxter says they have a portfolio of IV sets that are FDA approved and do not contain DEHP. Nevertheless, the company remains opposed to the proposed California legislation and insists that they will need ten years to fully comply with the ban, if it becomes law. I have no insight into their production plans, but guess that they aim to develop PVC IV bags and tubing with an alternative plasticizer. Meanwhile safer alternatives are already available from other companies.
California steps in, with potential national consequences. More than forty years after the first concerns about exposure to DEHP from medical devices were raised and 18 years after a National Toxicology Program panel of scientists expressed their serious concern about impacts in some patients, California may be on the brink of forcing a change in the market, with national consequences. Baxter and other companies that chose to dismiss these concerns may soon be forced to make changes in the production of their IV fluid bags and tubing, based on now well-established evidence that DEHP is a hazardous chemical that should have been replaced years ago.