Latest Review of Evidence Suggests BiSphenol A is Safe

Many ill people dream of being able to live in familiar surroundings and not be forced to frequently visit the doctor or stay in hospital. Yet many medicines have to be taken regularly and with high accuracy. In order to apply them at home or on the way, small devices that patients can wear on their body or in their clothing have been developed.

One innovation is a small injection pump that fits comfortably into one’s breast pocket, enabling patients to administer their own medicines very precisely. The device, which has regulatory approval pending, is to be shown at the K 2013, the world’s largest plastics fair being held in Düsseldorf, Germany in mid-October.

And it is a good example of how useful high-tech plastics are for the medical technology industry: all housing components of the mechanical pump are made of polycarbonate. A combination of good properties make the material the preferred choice for this application, according to Bayer, one of the world’s leading polycarbonate producers.

It was at Bayer where this kind of plastic was invented in 1953—exactly six decades ago. The transparent, light and easy to shape polycarbonate was put on the market only a few years later. Since then global consumption has reached 3.7 million metric tonnes and is expected to grow further.

Part of Daily Life

The high-performance plastic has become part of daily life and is used in many key industries—in the automotive business and in consumer electronics as well as in the construction sector. As the producers—represented by the Polycarbonate/Bisphenol A Group under the industry association Plastics Europe—point out, polycarbonate makes big roof constructions and razor-thin laptop shells possible, or it helps making cars lighter by replacing components from glass and steel, so reducing fuel consumption.

And, of course, polycarbonate is commonplace in medical technology, particularly when other materials are unable to meet all the stringent requirements for the devices. So far, so good. But now a political discussion casts a shadow over the success story.

The reason is that the chemical Bisphenol A (BPA), the essential building block for polycarbonate, is becoming increasingly prominent in a public debate on suspected hormone-like substances. The controversy is focused on the substance’s use in materials in contact with food. And many are concerned of a possible spill-over to other areas—such as medical technology.

At the time of going to press, stakeholders are waiting for another milestone in the debate. In the European Union, the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) is expected to issue a draft opinion on the safety of the use of BPA in medical devices for public consultation, taking into account all scientific evidence.

Thoroughly examined

“BPA is one of the most thoroughly tested chemicals today,” says Jasmin Bird, BPA spokesperson of Plastics Europe. “Also in the medical sector the responsible authorities have assessed potential risks and confirmed the safety of devices made of polycarbonate.” However, a plastic made from a building block different to BPA would no longer be polycarbonate, but another material with a completely different property profile, she says.

According to plastics producers as well as medical device manufactures, it is a unique combination of various properties that makes polycarbonate one of the most popular engineering resins on the market. It is light, crystal clear, unbreakable and durable, as well as being easy to process, shape and recycle.

In addition, polycarbonate is able to withstand high temperatures of up to 140 degrees Celsius, and can be sterilised by all commonly used methods. And its biocompatibility is essential for many medical devices that are in direct or indirect contact with patients.

All these seem to be reasons enough for the high-tech plastic to have been in use in the medical sector for more than 50 years. In the 1960s, the first polycarbonate housings of “artificial kidneys” for people suffering from renal disease came on the market, and in the following decade the first blood oxygenators for cardiac surgery based on the material were launched.

According to the World Health Organization (WHO), cardiovascular disease is the leading cause of death globally. Often only seconds matter and can mean the difference between staying alive and dying. And many times automated external defibrillators (AEDs) can help when the heart suddenly stops beating.

One of the global leaders in this field is Cardiac Science Corporation, based in Wisconsin, USA. For their next-generation device presented earlier this year at MD&M West, the world’s largest medical device defibrillator and manufacturing event, they chose a special polycarbonate blend offering superior impact performance, overall strength and flame resistance.

“Many of our emergency service and military customers use AEDs in rugged conditions that require our Powerheart AEDs to be durable without sacrificing life-saving features,” explains Mike Fry, General Manager of Resuscitation, Cardiac Science.

When invasive cardiac surgery is needed, for example during a coronary artery bypass or replacing a valve, plastic devices are also beneficial. During such operations, the heart is stopped and a blood oxygenator takes over the function of the heart and lungs.

Multiple applications

Polycarbonate is the material of choice for the oxygenator shells as well as for blood reservoirs. The material’s glasslike clarity is highly desirable for visual evaluation of blood flow and conditions during the procedure, while the toughness provides a high level of security, the plastics industry says.

Key properties such as mechanical strength are also required for other applications—the housings of membrane cartridges for example, which are used in haemodialysis to filter patient’s blood and remove excess water and toxins. Polycarbonate can also be easily sterilised through the use of high-temperature steam as well as by irradiation and with ethylene oxide.

The material not only provides advantages in renal care but also in the operating suite—especially when it comes to minimally invasive surgery, which reduces the length of operations, is less stressful and allows for faster healing.

Most recently, the material was chosen for a new access cannula body to help with fluid management during arthroscopic surgery. As Ted Kucklick, CEO of device producer Cannuflow from California, USA, says: “This made it possible for us to make a two-layer cannula with significant added functionality without an increase in the outer diameter compared with the generic cannulas surgeons previously used.”

Surgery also requires precision. For example, when it comes to knee replacements, doctors until now had to subjectively determine the amount of pressure to apply to an implant. But a new intelligent device from OrthoSensor, based in Florida, USA uses sensors and wireless technology to provide real-time, evidenced-based data to the surgeon to optimise the positioning and balance of implants.

OrthoSensor had several criteria for choosing a material for this innovative product, including biocompatibility, lubricity and superior strength. They chose a special polycarbonate grade which is available in various translucent colours. “The OrthoSensor Knee Balancer is a revolutionary, intelligent orthopaedic device, so using a high quality, reliable material was of paramount importance to us,” said Erik Herrmann, the company’s Director of Product Development, Surgical Balancing.

The use of polycarbonate is not limited to hospitals and doctors’ offices, however. It is also utilised in rehabilitation—for example for the housing of HAL^®, a “robot suit” developed in Japan. Its artificial arms and legs help patients to move and rebuild muscles.   

Polycarbonate: Meeting strict requirements

To put it in a nutshell: polycarbonate helps bring innovative devices to the healthcare market. And its resins and blends are especially able to meet the rigorous challenges and requirements these applications and the medical authorities demand.

But in spite of the repeated safety confirmations from authorities around the world and the obvious benefits of the material, the polycarbonate market is threatened with erosion by the debate on Bisphenol A, its essential component. The debate is occurring within the European Union and focused on applications with food contacts, for example water bottles and cans with synthetic resin coatings.

In Belgium, for example, a law has been in force since the beginning of 2013 that no longer permits BPA-based food packaging for children under the age of three. A similar ban was applied at the same time in France. In addition, products of this type are to be subject to a general ban in the country beginning in January 2015.

In contrast, the European Food Safety Authority (EFSA), one of the organisations responsible for the risk assessment of BPA, has repeatedly confirmed that products based on this intermediate—which is firmly bound in the plastic matrix—can be used safely in food contact. Its most recent opinion on this subject came in late 2011.

According to the EFSA, an official French report on BPA failed to consider several key points required for a comprehensive and scientific assessment. Currently, the authority is undertaking a full re-evaluation of the human risks associated with exposure to BPA through the diet. It considers also the contribution of non-dietary sources to the overall exposure to Bisphenol A.

The first part of this re-evaluation has been made available as draft in July—it reconfirmed that diet is the main source of BPA exposure. Exposure is extremely low and was even found to be far lower than previously estimated by the EFSA.

Safety confirmed

“Numerous other authorities, including those in Germany, Switzerland, the United Kingdom, Japan and Australia, share the view that BPA poses no health risk when used as intended in materials in contact with food,” says Jasmin Bird from Plastics Europe. In addition, the Food and Drug Administration (FDA) in the United States has confirmed the safety of the chemical in the currently approved uses in food containers and packaging.

However, a ban on baby bottles made with polycarbonate has been in place in the European Union since June 2011. Through this step the European Commission had wanted to create a uniform legal position in the Union following corresponding ventures in the Member States Denmark and France. “It sees the ban as strictly a precautionary measure and has continuously underscored that there is no scientifically sound basis for broader restrictions,” says Bird.

The driving factor behind such measures is fear that BPA could interfere with hormone levels in the human body. But humans are exposed to only extremely low quantities of BPA. And these trace amounts are not only well below the safety thresholds defined by the regulatory authorities and scientific committees around the world, they are also excreted from the body very rapidly.

Threshold for intake

In the European Union the daily intake limit is 0.05 milligrams BPA per kilogram of body weight.  “An average adult consumer would have to ingest more than 600 kilograms of food and beverages in contact with polycarbonate containers every day to exceed that level—which is impossible,” says Bird.

However, some researchers maintain that the chemical can produce harmful effects in humans in small quantities and not at higher doses. This is referred to as the low-dose hypothesis. But multiple studies conducted according to protocols established for human health assessment by regulatory agencies have not confirmed these low dose observations. So this hypothesis remains unproven. 

Multiple studies have already been published on BPA, and there is a constant stream of new ones. “Yet it is not the number of studies that is decisive, but rather their quality,” says Dr Melanie Möthrath, a chemist and BPA expert at Bayer MaterialScience.

Scientific studies often arrive at different conclusions, and the reasons often lie far back at the study's concept phase. Möthrath explains: “For example, there are differences in the test system selected—cell culture or live animal. Or the studies differ in the uptake pathway for the substance being examined. They can be applied via the food, injected into tissue or via small pumps under the skin.”

Robust science is key, not scaremongering

Another important factor is the amount of a substance to which a test animal is exposed. The question is whether the dose of the substance reflects normal human exposure or is so high that it is not realistic.

In addition to the validity of each individual study, the consistency of all data from various studies plays a major role. “The key concept here which looks into the consistency of the data across multiple studies is the so-called weight of scientific evidence,” Möthrath explains.

Another measure of quality is the use of Good Laboratory Practices (GLP). This is a system of research management practice guidelines designed to ensure the generation of high quality reliable data. These guidelines, recognised by authorities and scientists the world over, stipulate that all recordkeeping must be complete, the data and methodology transparent and the conclusions are expected to be replicable. 

Nevertheless, according to the experts, results from small exploratory studies often dominate the media headlines. “This fuels public fear, which is then picked up and reinforced by politicians,” Plastics Europe’s Jasmin Bird says.

But stakeholders hope that scientific principles and reason eventually gain the upper hand in the debate. Not the least because any other intermediate than BPA would of course have to be as well safety-tested and the medical end use application would have to prove to be as reliable as a device made of polycarbonate. But such a precursor is not in sight.

With the help of polycarbonate however, innovative products can be created which are the size of a credit card and thinner than a typical cell phone. For example, an auto-injector for people who are at risk from allergic shocks was introduced last year by US-based pharmaceutical company Intelliject.

"As someone who has suffered severe allergic reactions myself, I know it is critical to have an epinephrine auto-injector that can be taken anywhere and cope with rough and tumble situations and still perform,” says Evan Edwards, the company’s co-founder. Its novel device e-cue (trademarked) meets these requirements—thanks to polycarbonate.