2 Background, Miljøstyrelsen

Evaluation of Plasticisers for PVC for Medical Devices

2 Background

It is experienced that it is extremely complicated to find alternative materials to PVC in Medical device applications; reference to - among others - "Muligheder for substitution af PVC i udvalgte hospitalsartikler", Arbejdsrapport fra Miljøstyrelsen nr. 17/1991 ("Possibilities for substitution of PVC in selected hospital articles", Working report from the Danish Environmental Protection Agency No. 17/1991). Furthermore, according to the Danish EPA’s "Handlingsplan for at reducere anvendelsen af phthalater i blød plast" (Action Plan for reducing and phasing out phthalates in soft plastics, Ministry of Environment and Energy, June 1999), Medical Devices have been selected as a field of high priority requiring a particular effort to substitute phthalates as plasticising agents. According to the action plan, Medical Devices are a field of high priority, because of their migration from the plastic and subsequent exposure and possible adverse effects to patients.

The world market for plastics for the production of Medical Devices accounts for DKK 35 – 40 billions (ref. 1). Hereof PVC for disposable articles accounts for approximately one third. Every year approximately 150.000 tons of PVC is produced world wide for the Medical market (ref. 2) corresponding to 1 – 2 % of the total market for PVC.

In Denmark the turnover of Medical Devices in plastics accounts for approximately DKK 7 billions (ref. 3). Approximately 97 % hereof are being exported (ref. 3). The largest quantity is disposable articles mainly different sorts of catheters, suctions, drains and urine and colostomy bags.

These many types of relatively low-cost disposable articles have formed a basis for and made it possible to introduce many of the new treatments that are being used today. Generally, in each case of hospitalisation the patient will come into contact with some of these disposable articles. Due to the rich possibilities of variation, which can be achieved in e.g. properties like flexibility, strength, barrier properties and transparency, plasticised PVC has been proven to be particularly suitable for these applications. These properties are to a high extent conditional on the addition of Plasticisers to the PVC resins. In these types of Medical Devices the addition of Plasticisers typically varies from approximately 5 % by weight up to approximately 45 %; mainly 30 – 45 %. Totally dominating as plasticiser is di(2-ethylhexyl) phthalate (DEHP), with which one has more than 47 years of experience in Medical Devices (ref. 4). Furthermore, in the European Pharmacopoeia DEHP is the only plasticiser which is listed for use in those kind of products (ref. 8a, 8b and 9). As the European Pharmacopoeia is put on the same footing as the Directive for Medical Devices (ref. 10), which was put into force in July 1998 the manufactures of Medical Devices are left with a serious dilemma. This is because no other plasticiser is listed in the European Pharmacopoeia and using another plasticiser would mean that the device manufacturer would have to declare that such a device does not conform to the compositional requirements of this Pharmacopoeia. Therefore, a development study and an investigation regarding Plasticisers are highly needed. Any positive result is highly expected to form a basis for a decision in "Group 16 of the Council of Europe" to point out other Plasticisers for consideration and inclusion in future amendments of the Pharmacopoeia.

During recent years the environmental aspect by the use of phthalates has been studied in many relations (e.g. ref. 5, 11, 12 and 13). The Swedish government has proposed the European Commission to initiate a risk assessment of DEHP.

However, other aspects will be important regarding the use of phthalates in Medical Devices. It is known that the Plasticisers migrate to the surface of the plasticised PVC article, where it could cause a relative risk regarding the biocompatibility (ref. 6, 7, 14 and 15). Moreover, during recent years the potential for reprotoxic effects of DEHP has been observed in animal studies and whilst there is no knowledge in humans the fact that it has been observed in animals remains a significant concern (ref. 42).

Complicating the issue is that phthalates with different alkyl chain length behave differently in biological situations (like the case with different primary alcohols).