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Science looks again at DEHP

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A previous article addressed political developments that resulted in new labelling rules for medical devices containing di(2-ethylhexyl) phthalate (DEHP).¹ More or less at the same time that the members of the European Parliament were debating the use of DEHP in medical devices, a scientific discussion on the same issue, which was about to materialise in a long awaited report, was taking place between European Union (EU) toxicologists. This report has now been published and some of its conclusions are examined in this article.²

Scientific discussion within the EU about the possible risks related to the use of DEHP as a plasticiser in poly(vinyl chloride)(PVC) based medical devices is not new. In 2002, a scientific committee was asked by the European Commission to evaluate the risks. A scientific committee is a group of independent experts within the European system who provide the European Commission with the scientific advice it needs when preparing policy and proposals relating to consumer safety, public health and the environment. In 2002, the Scientific Committee on Medical Products and Medical Devices (SCMPMD) published its opinion on medical devices containing DEHP.³ In that opinion, it stated that there were no reports of any adverse effects in humans following exposure to medical devices containing DEHP, not even in neonates or in other patient groups of relatively high exposure.

In light of new information on exposure to DEHP that has become available since 2002, the European Commission found it appropriate to ask a new scientific committee to look into the issue once more. This committee, the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), has after years of work and public consultation published its Opinion on the issue.² Its conclusions differ in many ways from those in the 2002 Opinion.

Although the new Opinion of 2008 states clearly that “there is limited evidence suggesting a relation between DEHP exposure and some effects in humans” and “so far, there is no conclusive scientific evidence that DEHP exposure via medical treatments has harmful effects in humans,” it expresses some concerns. The Opinion states that even in the absence of clinical or epidemiological evidence of harmful effects in humans, “there is a reason for some concern for prematurely born male neonates for which the DEHP exposure may be transiently above the dose inducing reproductive toxicity in animal studies.” According to the Opinion other patient groups besides neonates are also at risk, namely, male foetuses and male infants of pregnant women, lactating women exposed to DEHP and trauma patients who undergo massive infusion of blood. The reason for the concern for these patient groups is that the level of DEHP exposure can exceed the exposure limits determined (with an appropriate safety margin) from doses that result in reproductive effects observed during animal studies.

The European Commission also wanted to know about possible alternative plasticisers that can be used to replace DEHP. Consequently, eight alternative plasticisers were evaluated and among these were nonphthalate plasticisers, as well as certain citrates and adipates. It was difficult for SCENIHR to conclude anything decisive about the alternatives. For some of the alternatives “a complete evaluation could not be performed due to lack of data on either toxicity or exposure;” some alternatives “could be suitable to replace DEHP in certain medical devices;” and for others “it may be difficult to achieve the same functionality as for PVC plasticised with DEHP.” Its overall conclusion on the possible alternatives to DEHP was that “the risk and benefit should be carefully evaluated according to established protocols, for each individual medical device and each medical procedure in which the alternatives are intended to be used.”

If manufacturers of medical devices had expected definitive answers in the Opinion, then they will be deeply disappointed. The Opinion gives no clear answer to the question of whether or not DEHP in medical devices poses a risk: “further studies are required to confirm or reject the suggestions of adverse effects of DEHP in humans.” Regarding which plasticisers could be used as alternatives, the SCENIHR Opinion does not give a clear answer on this either, but asks manufacturers to make a case- by-case evaluation of the risks and benefits of using a certain alternative.

There is no doubt that the scientific and public debate about the possible risks associated with the use of DEHP in medical devices will continue in the years to come. The SCENIHR Opinion has not put an end to that at all. New generations of scientists will look into the matter and will hopefully find out whether or not DEHP does pose a risk to humans and if so, what alternatives the medical device industry should use.

Positive life cycle analysis

In a report published by the European Commission in 2004, “Life Cycle Assessment of PVC and Principal Competing Materials,”⁴ it is mentioned that no comparative studies have been undertaken so far to compare PVC with possible competing materials within the medical sector. That report considered this to be a significant information gap. In 2008, the first steps have been taken to fill that gap. The Swedish Life Cycle Assessment (LCA) expert, Håkan Stripple, of the Swedish Environmental Research Institute, tries in an article to compare catheters manufactured in PVC, thermoplastic polyurethane (TPU) and in a newly developed polyolefin based elastomer.⁵ From a PVC point of view, some interesting conclusions are drawn. The evaluation of the LCA results showed that the newly developed polyolefin based elastomer catheter had in general low environmental impact. Important in relation to PVC, his article says that, “the impact is significantly lower than the TPU catheter material and in the same level as the existing PVC bulk plastic material.” Later on in the article, it is reported that “compared with the PVC plastic material the new polyolefin based elastomer showed an almost equivalent environmental performance.” For the first time, there is now a LCA analysis that compares examples of PVC medical devices with alternatives and shows that PVC is actually among the most favourable with regard to environmental performance.

Good PVC on show

Normally, when the use of PVC in medical devices is on the agenda in the public domain, the discussion is about environmental and health issues. Seldom is any comment made about the improvement provided by the use of PVC based medical devices in modern day treatment of patients. The most recent permanent exhibition at the Thackray Medical Museum in Leeds, UK, (www.thackraymuseum.org) adjusts this situation. The museum, which is one of the largest medical history museums in Europe, has recently opened an exhibition called “Fantastic Plastic, The Story of Modern Day Surgery told through PVC and Plastics.”

“For a medical museum to show medical devices from the present day is quite unusual. Normally medical museums concentrate on the past,” says the museum’s Chief Executive, Almut Grüner. “The visitors like the goriness of the nineteenth century … patients having holes cut into their heads and older treatments. I think we are missing a trick if we do not take people into the present day and say, look how it has developed and look what we have now.”

PVC as a material is at the centre stage of the exhibition and this is a new approach for the museum. Grüner continues, “What we have learned by making this exhibition is that by concentrating on a material you can actually look at a much wider range of issues. Starting from the early use of a material, to its present day use, you can cover … a lot of different areas of surgery, which have one thing in common and that is the kind of material that has been used to alleviate an illness.”

One medical device on display at the exhibition demonstrates well the improvement that has been achieved during the past 60 years in medical device technology. It is an old blood transfusion set made of rubber and glass. A new blood transfusion set is displayed alongside it. The advantages of the blood transfusion set made from today’s PVC compared with the set made 60 years ago is obvious to the visitor; it is smaller, lighter, cheaper, less fragile and for single use.

A lack of decisiveness

The latest report from the EU scientific committee does not help medical device manufacturers much with regard to the use of DEHP in medical devices. It does not give a clear answer on whether or not DEHP poses a risk, nor does it say anything decisive on the alternatives to DEHP. The only clear recommendation is that a case-by-case evaluation should be conducted if a company wishes to switch to another plasticiser.

In terms of the use of PVC in medical devices in general, there have been some positive developments. For the first time, an LCA study on medical devices exists, which reports that PVC compared with some alternatives has a good environmental performance. Within environmental science the use of LCA is regarded as the best tool if you want to evaluate environmental performance.

Ole Grøndahl Hansen is General Manager at the PVC Information Council, Nørre Voldgade 48, DK-1358, Copenhagen, Denmark, tel. +45 33 30 86 30, e-mail: pgh@pvc.dk, www.pvc.dk