Mounting evidence against a chemical we are exposed to daily is being ignored. What more do regulators need, ask David Melzer and Tamara Galloway
© Image Source/Rex FeaturesContains more than just water
Three letters lie at the heart of our modern world: BPA. Short for bisphenol A, a synthetic oestrogen
, a staggering 3 billion kilograms of the stuff is produced annually, with an estimated value of $500,000 per hour to the global economy.
BPA is used in the production of a hard and transparent form of polycarbonate plastic used to create food and drink containers and other consumer goods. It is also used in the epoxy resins that line metal food cans, and as an ingredient in dental sealants.
In fact, we are so consistently exposed to BPA that over 90 per cent of us excrete BPA metabolites in our urine at any given time
. How exactly BPA enters the human body is not yet clear, although eating food kept in BPA-containing packaging, breathing household dust and handling plastics that contain BPA may all contribute to our daily exposure. Currently, BPA is not listed on food or drink labels so millions of people have no way of knowing their daily exposure.
BPA was first reported in the scientific literature in the 1930s as a synthetic oestrogen, and it is this property that has led to most of the subsequent controversy. Laboratory studies show that, at the right dose, BPA can act as a hormone mimic, binding not only to oestrogen receptors but to other related receptors, too. However, this "active" dose has been furiously contested in what has become an intense scientific dispute.
A large number of lab studies using rats and mice exposed to high doses of BPA failed to show measurable effects on key aspects of reproductive development, function and behaviour. But other studies of rodents continue to be published that do show developmental and functional abnormalities at low doses, including at doses significantly below those found in humans.
Given the near ubiquitous presence of BPA in our bodies and its recognised activity as a hormone disrupter, you might expect regulators to take a precautionary approach. The European Food Standards Agency (EFSA) has just had a chance to revise its safety level for BPA, or its Tolerable Daily Intake (TDI). However, in its latest opinion paper, published at the end of last month, the EFSA wrote that "no new study could be identified, which would call for a revision of the current TDI", seemingly discounting much recent science.
Current recommendations by the EFSA and the US Food and Drug Administration (FDA) have remained unchanged for several years, with the TDI set at 50 micrograms of BPA per kilogram of body weight per day. This equates to a "safe" dose for an average person weighing 70 kilograms of 3.5 milligrams of BPA per day. For comparison, the daily contraceptive pill contains around 50 micrograms of oestrogen, though the synthetic oestrogens in most modern pills are much more potent than BPA.
Why the apparent generosity of the TDI limit? Some regulators have argued that since BPA appears to have a very short half-life in humans, it has little time to circulate in the body and cause any effects. Also, they point to the fact that BPA is just one compound with weak oestrogenic activity. By contrast, soya products may be ingested in far higher amounts and typically contain a whole array of plant-derived "natural" oestrogens.
Not only that, but average exposure to BPA is thought to be well below 100 micrograms per day, orders of magnitude lower than the level required to exceed the TDI.
Despite these arguments, doubts remain about BPA's safety. BPA is a synthetic chemical not found in nature. It doesn't just bind to the main oestrogen receptor, but also to poorly understood variants of it, and has an anti-androgen effect. Most reports of low-dose effects have come from animal studies. The focus is now beginning to shift to looking for direct evidence of BPA effects in humans. Our own human epidemiological studies have reported associations with cardiovascular disease, liver enzyme abnormalities and, recently, raised testosterone concentrations in men (Environmental Health Perspective
, DOI: link
If these associations turn out to be causal, then BPA may be anything but inert at everyday exposure levels. However, while epidemiological studies are excellent at identifying things worth investigating, hard proof can only come from a controlled experiment. In 2009, the US National Institute for Environmental Health Sciences set out a $30 million research programme to look into the effects of BPA. Most of this effort has been concentrated on lab studies. We believe this will not be enough, and that human studies are also required to settle the argument.
Of course we can't just give people BPA and wait for them to develop disease. Instead, we should harness the power of modern molecular biology to establish whether BPA at everyday exposure levels is biologically active in humans. A controlled experiment where subjects would avoid known sources of BPA, followed by measured exposures at realistic everyday intakes - far below the official safe limit - for a limited period should be practicable. Such a study could only be done with the consent of well-informed volunteers.
This approach could also help us discover what BPA does to sex hormones and other potential molecular targets. These crucial questions are currently being ignored. While experimental exposure of humans to BPA raises ethical concerns, we should consider that it could be profoundly unethical to forcibly expose millions to a chemical that we cannot yet say with certainty causes no harm - as we may be doing right now.David Melzer is professor of epidemiology and public health at Peninsula Medical School in Exeter, UK.
Tamara Galloway is professor of ecotoxicology at the University of Exeter