Predictable BPA opinion released by EFSA

In mid December 2014 when the European Food Safety Authority (EFSA) flagged that they had finalised the bisphenol A (BPA) opinion and only some editorial work remained, I predicted in a blog that the EFSA Panel would once again clear the use of BPA in food contact materials. On 21 January 2015 EFSA published the new opinion, and surprise, surprise, BPA is considered harmless at current exposure levels. This is the summary wording of EFSA:

EFSA’s comprehensive re-evaluation of bisphenol A (BPA) exposure and toxicity concludes that BPA poses no health risk to consumers of any age group (including unborn children, infants and adolescents) at current exposure levels. Exposure from the diet or from a combination of sources (diet, dust, cosmetics and thermal paper) is considerably under the safe level (the “tolerable daily intake” or TDI).

This conclusion comes despite the fact that EFSA further firmed up the TDI to 4 µg/kg of body weight per day, more than 12 times lower than the previously recommended TDI of 50 µg/kg of body weight per day. The highest estimates for exposure from a combination of dietary, inhalation and dermal routes (called “aggregated exposure” in EFSA’s opinion) are three to five times lower than the new TDI when using a deterministic method (see comparison with probabilistic method further down). All clear then?

New BPA opinion published by EFSA

New BPA opinion published by EFSA.

Not so fast, there are still uncertainties as EFSA points out. Effects on the reproductive, nervous, immune, metabolic and cardiovascular systems, as well as in the development of cancer are not considered likely at present, but they could not be excluded on the available evidence the Panel concluded. The new TDI is thus temporary pending the outcome of a long-term study in rats by the US National Toxicology Program, which will help to reduce these uncertainties.

So what to believe?

EFSA and the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) have divergent views on the safety of BPA in food contact and other materials. If there are different views on the safety of a compound between a national food safety organisation and EFSA, it is compulsory to discuss and if possible reconcile their respective assessments. Such a discussion took place in December 2014. From the minutes of the meeting it is possible to deduce that the differences relate to:

  • results from two key toxicological studies selected by ANSES on the effects of BPA on brain and behaviour, and on the mammary gland;
  • on an extra safety factor of 3 added by ANSES to the normal safety factor of 100, while EFSA applied an extra safety factor of 1.5  to address uncertainties; and
  • on the use of a probabilistic method to determine exposure used by ANSES as opposed to the deterministic method used by EFSA.

Looking first at the selected toxicological studies it seems as if ANSES trusted the negative results from the two studies more than EFSA. EFSA on the other hand balanced the negative findings against similar studies showing no negative effects in the two areas in question. To be fair EFSA also included a study that was published after the ANSES opinion that showed no negative effects on the mammary gland, but still the opinions of the two organisations differed in relation to the validity of several of the studies.

Adding an extra safety factor of 3 makes sense in light of the remaining uncertainties and could have been adopted also by EFSA. EFSA instead selected to use a weight of evidence approach to cater for the remaining uncertainties, but such an approach relies solely on subjective expert judgement. You might be interested to know that EFSA involved an unprecedented 26 experts in the working group that developed the initial draft BPA opinion to arrive at the best possible balanced view, but still the extra safety factor used by ANSES might provide greater certainty.

Mother and child sensitive to oxidative stress pre birth (Photo: Nina Matthews)

Mother and child sensitive to prenatal oxidative stress caused by BPA exposure (Photo: Nina Matthews).

Finally, the differences in exposure methodology used between the two organisations might also cause some differences in the final result. ANSES has long used probabilistic methods to calculate exposure, while EFSA has stubbornly stuck to the simpler deterministic methods. To EFSA’s advantage is access to extensive Europe wide data for the input parameters for the calculations, BPA occurrence and food consumption. However, the use of probabilistic techniques will better cater for unusual occurrence and consumption patterns and thus cover a larger range of the population.

Considering the two latter points, combined they would probably take the highest estimates of exposure closer to the temporary TDI since the EFSA margin was three to five times lower than the new TDI. Adding the toxicological results that ANSES used we could have a problem. On the other hand, the might of EFSA’s scientific expertise very clearly concluded that there is no problem of any kind that they could identify using the present scientific knowledge.

More research results on BPA

However, already new toxicological results are piling up. In a first multispecies study combining human association and animal causal studies assessing the risk posed by prenatal BPA exposure to metabolic health, evidence was provided of the induction of nitrosative stress by prenatal BPA in both the mother and foetus at time of birth. The researchers concluded that:

Whether or not BPA is harmful to human health has been vigorously debated. These findings demonstrate that more studies like this one are needed to determine the disease risk of exposure to BPA. In the interim, these results indicate that pregnant women should minimize their exposure to BPA to safeguard their babies and themselves from oxidant injury.

I can safely predict that the EFSA opinion will not be the last word on potential human harm caused by BPA.

Red hot findings indicate new dangers with bisphenol A

Hormon disturbing chemicals (Photo: Sooz)

Hormon disturbing chemicals can be dangerous (Photo: Sooz).

Endocrine disruptors interfere with our bodies’ finely tuned hormonal regulation systems. Unfortunately, human exposure to endocrine disruptors, and particularly to bisphenol A commonly found in food packaging materials, is omnipresent in our daily lives. The potential risks to consumer health of such chemical contaminants have been the subject of many contradictory reports with science divided over how to handle the findings. Now there seems to be a link between bisphenol A exposure and food intolerance. More than 20% of the global population suffer from food allergy or intolerance making this an important issue.

Scientific controversy

The French are hellbent on proving that bisphenol A is a dangerous chemical that should not even come close to food of any sort. And they might be right. In the USA it is the opposite situation with federal agencies protecting the use of bisphenol A in food applications at any cost. They cannot both be right though. The arbiter is sitting on the fence. This is the European Food Safety Authority that recently completed a new draft assessment of bisphenol A but decided to consult extensively with external stakeholders before making a final decision. It is not going to be easy.

To start in France,  the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on bisphenol A in April 2013 which recommended limiting exposure to this substance and lowering the toxicological thresholds on which risk evaluations were based. This resulted in the French government deciding to ban the use of bisphenol A in all food packaging from 2015. And new research findings are accumulating showing new dangers.

New scientific results published

Using female rats exposed to bisphenol A at low doses during pregnancy and early suckling, scientists at INRA’s Joint Research Unit for Food Toxicology in Toulouse demonstrated that it affected development of the immune system in the off-spring of the exposed rats and predisposed their progeny to food intolerance in adulthood. The scientists tested different doses (0, 0.5, 5 and 50 μg/kg body weight per day) and demonstrated a non-linear relationship between the bisphenol A doses and the undesirable effects observed. In particular, the most marked disturbances were observed at a dose of 5 μg/kg body weight per day. This is of course confusing but in line with the low dose hypothesis suggesting that there can be different reactions at different dose levels. At the low-dose level the scientists found that when challenged with ovalbumin, an egg white protein not previously included in their diet, an immune reaction was seen directed against ovalbumin which induced colonic inflammation that testified to a food intolerance. However, rats descending from the control group developed a food tolerance to ovalbumin, which resulted in a lack of immune response.

This is the same dose of 5 µg/kg body weight per day that is proposed by EFSA to be safe. The new findings highlight the problem of determining a safe and tolerable dose for bisphenol A. EFSA is still to make up their mind but has so far used the expression “as likely as not” for many negative findings to indicate an uncertainty around the real health impact of current human exposure levels.

Laboratory findings questioned

Laboratory findings questioned because of contamination.

Americans have been more gung ho about the safety of bisphenol A. To be fair there is an ambitious ongoing U.S. research project known as “CLARITY-BPA” into the safety of bisphenol A funded to the tune of US$32 million. But scientists from the National Center for Toxicological Research in Arkansas preempted this research by publishing interim findings in Oxford Journals’ Toxicological Sciences claiming that only very high doses of bisphenol A are dangerous, and that the “low levels” in common circulation through plastic bottles, thermal paper receipts, tin can linings and other sources are not a threat. These findings have since been heavily criticised because of bisphenol A contamination also of the control group.

Is there a safe level?

So what to believe? It seems pretty clear that not even 5 µg/kg body weight per day is a safe level. But actual exposure might be much less than this according to EFSA’s new exposure calculations as long as you don’t live exclusively on canned food. We have to wait until the end of 2014 until we can get access to EFSA’s conclusions. Agony for us and for the scientists grappling with the final opinion.

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Bisphenol A – half of the story

Bisphenol A might be contributing to obesity (Photo: Malingering)

Bisphenol A might be contributing to obesity (Photo: Malingering)

We have written about bisphenol A before. Bisphenol A is mainly used in combination with other chemicals to manufacture polycarbonate plastics and resins used as food contact materials but can also be found in carbonless copy paper and thermal point-of-sale receipt paper. It is clear that bisphenol A is an endocrine disruptor at high doses but there are also some indications that it might be equally effective at very low doses. It has been proposed that the latter might even be one explanation of many to the obesity epidemic. According to this theory exposure to bisphenol A might induce epigenetic changes turning on obesity genes. Question is do we need to take action to remove bisphenol A from the food supply?

Let’s look at the process to arrive at a plausible answer to that question.

When assessing potential risks to public health posed by a food hazard it is necessary to have detailed knowledge of the expected toxicological effects of the hazard, the amount needed to be consumed to cause such effects and the expected population exposure to the hazard. There might also be other sources than the diet to be considered when calculating exposure. It might sound a bit complex and of course in most cases a lot of scientific data need to be gathered and assessed to draw reliable conclusions. But at the end it is still only a straight forward mathematical calculation using the critical dose and the estimated exposure as inputs.

But what inputs to use? Scientific facts evolve over time both on the toxicological side and the exposure side. A range of new scientific findings have been or are about to be published covering low-dose effects of bisphenol A. They are currently being evaluated by the European Food Safety Authority (EFSA) so this side of the equation is still uncertain. In the meantime, EFSA has published a revised exposure assessment providing half of the story needed to complete a risk assessment of bisphenol A.

EFSA previously calculated exposure to bisphenol A in 2006 using rough estimates of its presence in food and very basic food consumption information. This might be acceptable in case such conservative estimates are far lower than the expected dose of  toxicological concern. However, it didn’t include attempts to estimate exposure from non-food sources that could have been considerable. Now EFSA has published a refined exposure assessment using accurate data on the amount of bisphenol A present in food and detailed food consumption information provided by many European Union member countries. On top of that, EFSA also included exposure from non-food sources, thus combining data from oral, inhalation and dermal routes in the final results. Exposure modelling involved the assessment of chronic exposure to bisphenol A through diet, thermal paper, air, dust, toys, cosmetics, and dental sealants.

The new exposure estimates were much lower than the estimates of 2006. In the previous assessment, high exposure was up to 5,300 ng/kg bodyweight per day in toddlers and up to 11,000 ng/kg bodyweight per day in infants aged 3 months. This should be compared with the current estimates of up to 857 ng/kg bodyweight per day for toddlers and up to 495 ng/kg bodyweight per day for infants of 1-5 days.

Thermal paper not considered before was the second highest contributor to exposure in all population groups above 3 years of age. However, diet was found to be the major source of bisphenol A exposure in all population groups so this was not an important shortcoming of the previous exposure assessment.

Cashier a risk group still to be considered (Photo: Dan Goorevitch)

Cashiers a risk group still to be considered (Photo: Dan Goorevitch)

To check the accuracy of the calculations, total exposure to bisphenol A was also estimated using urinary biomonitoring data. Biomonitoring estimates based on urinary bisphenol A concentrations were in good agreement with modelled bisphenol A exposures from all sources, suggesting that no major exposure sources had been missed for the modelled exposure assessment.

There is a slight caveat in the presented data. Estimates of dermal exposure to bisphenol A were associated with considerable uncertainty and didn’t include cashiers as a particular group at risk because of lack of data. This might be rectified when an ongoing study on dermal exposure in cashiers sponsored by the National Institute of Environmental Health Sciences in the USA under the National Toxicology Program is published.

And of course, despite the considerable lowering of the exposure estimates for bisphenol A, we will not know if those levels still pose a risk to public health until the toxicological evaluation has been completed.

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Big issue – hormone disrupting chemicals

Make no mistake, you will soon hear more about hormone disrupting chemicals, or endocrine disruptors as they are also called since hormones constitute the body’s endocrine system. So we thought that now is a good time to give you a brief introduction to this growing problem issue for public health and the environment.

World Health Organization changes its mind on endocrine disruptors (Photo: Wikimedia)

World Health Organization changes its mind on endocrine disruptors (Photo: Wikimedia)

If we first go back about ten years in time international organisations had a rather cavalier attitude to endocrine disrupting chemicals. Scientists had started to sound warning bells, but there was yet no critical mass of information. Thus, in 2002 a report published by the International Programme on Chemical Safety (IPCS), which is a joint programme of such esteemed authorities like the World Health Organization (WHO), the United Nations Environment Programme (UNEP) and the International Labour Organization, raised the problem. However, they basically dismissed it due to lack of evidence of causal links between observed changes and actual levels of the chemicals.

The tone is different in a new report published in 2012. In the intervening period, organisations like the Endocrine Society, the European Commission and the European Environment Agency have published scientific reviews drawing renewed attention to concerns to public and wildlife health. Further, the European Society for Paediatric Endocrinology and the Pediatric Endocrine Society have called for action on endocrine disruptors and their effects. In an update to the initial IPCS report, it is now claimed that increasing scientific evidence suggests that endocrine disrupting chemicals actually are a cause for global concern, and that more research is critically needed to understand these chemicals and their human health effects in more depth. It is also stated that their environmental health impacts could be of similar concern with negative effects on organisms like fish in polluted water and plants living near industrial sites. Effects on early development of both humans and wildlife are highlighted as special concerns, as these effects are often irreversible and may not become evident until later in life.

Endocrine disrupting chemicals mimic hormones in the human body and have the capacity to interfere with tissue and organ development and function. This effect may alter susceptibility to different types of diseases throughout life. It can cause pregnancy complications, cancers, thyroid disorders and metabolic problems in adults. In infants and young children the impact of such chemicals is more severe because their bodies and brains are developing so quickly that endocrine disturbances have a disproportionate impact. It is clear that a large number of non-communicable diseases have their origin during development with exposure to endocrine disrupting chemicals one of a number of important risk factors for disease. Included are some of the major human diseases that are increasing in incidence and prevalence around the world.

Around 800 chemicals are expected endocrine disruptors (Photo: tk-link)

Around 800 chemicals are suspected endocrine disruptors (Photo: tk-link)

This sounds like doom and gloom as we are exposed to perhaps hundreds of environmental chemicals at any one time. Potential endocrine disrupting chemicals can be found in a huge range of consumer products as well as pesticides, herbicides, industrial pollution and more. Close to 800 chemicals are known or suspected to be capable of interfering with hormone receptors, hormone synthesis or hormone conversion. However, only a small fraction of these chemicals have been investigated in tests capable of identifying overt endocrine effects in intact organisms. That makes addressing their presence in the environment difficult. The United Nations is suggesting tighter regulations on the use of such chemicals, reminiscent of bans on compounds like PCBs in the past. These bans were used to limit new emissions of compounds known to be harmful to human or environmental health, and could be used again to prevent exposure to hormone disruptors and protect the environment.

But they would take time and energy to implement. Even as some companies have chosen voluntarily to start refraining from use of chemicals like bisphenol A and phthalates, others have lagged behind, and eliminating them from the environment could be a lengthy process. The United Nations report points to the simultaneous need for more action to address immediate known issues, and more research to uncover issues that haven’t been identified yet, in the hopes of staying one step ahead.

This is a global threat that needs to be resolved. The European Food Safety Authority was given a mandate in 2012 to define scientific criteria to identify endocrine disruptions in humans and the ecosystem. It is providing its contribution to this area in a soon to be published opinion and a stakeholder meeting. The opinion will feed into the current review of the European Union’s strategy on endocrine disruptors as well as EFSA’s ongoing and future scientific work in assessing substances such as food contact materials, pesticides and contaminants in food and feed.

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Judgement day for bisphenol A

Judgement (Photo: walknboston)

Judgement over bisphenol A (Photo: walknboston)

Scientific efforts to prove or disprove harmful effects of bisphenol A, a chemical that is mainly used in combination with other chemicals to manufacture plastics and resins used as food contact materials, are gathering momentum. But have we reached the critical mass yet to draw the right conclusions. Let me explain.

Science is all about the exciting exploration of new findings or the more mundane task of other scientists trying to verify the new findings so that they can become established truths, or is it? To be honest, scientists can be a very conservative lot sticking to what they already believe they know. The more revolutionary the findings, the less is the likelihood that they will be accepted. Deviating from accepted thinking can be a dangerous thing and risk your career.

Here are three examples of how the scientific community initially refused to listen.

Environment influencing the genetic make-up

In a previous blog, the importance of epigenetics in understanding gene expression was covered. It was the heretic proposal that environmental factors could influence your genetic make-up and become hereditary. This was revolution and not easily accepted by the scientific community. During the 1940s and 1950s, Barbara McClintock discovered transposition and used it to show how genes are responsible for turning physical characteristics on or off. She developed theories to explain the repression or expression of genetic information from one generation of maize plants to the next. Encountering skepticism of her research and its implications, she stopped publishing her data in 1953.

Barbara McClintock was a dogged scientist believing that her findings were true despite ridicule from other scientists. It took her close to 40 years to prove the concept under constant threat to her position. It is now the hottest topic in biology and will have a major impact on future toxicological research. Barbara McClintock finally got full vindication by being awarded the Nobel Prize in Physiology or Medicine in 1983.

The low-dose theory

Equally important is the low-dose theory of chemical interaction with our bodily processes. According to conventional thinking the dose makes the poison and this is the basis for current chemical risk assessments. The higher the dose the more severe the effect is the accepted mantra, which makes sense to most of us. And here some scientists proposed that low doses of certain chemicals can have different and more pronounced effects than high doses, can that really be trusted?

Actually, there is an extensive body of research that purports to demonstrate such a phenomenon. Recently Edward Calabrese revived the theory through his research on peppermint plants giving rise to a scientific debate that has been gaining prominence over the last 20 years. Much research has focused on endocrine active substances or endocrine disruptors where the conventional relationship (more exposure equals higher risk) has been particularly challenged. Such substances have been shown to have fundamentally different (and harmful) effects on the body at low doses than at high doses. As seems to be the case for most scientific findings that challenge conventional thinking it took a long time for the scientific community to accept the low-dose theory and still there are some lingering doubts. In 2009, Calabrese was awarded the Marie Curie Prize for “outstanding achievements in research on the effects of low and very low doses of ionizing radiation on human health and biotopes”.

The contagious protein

Who has not heard about mad cow disease? It is the animal equivalent of Creutzfeldt-Jakobs Disease in humans, a debilitating brain disorder, the cause of which long was a mystery. And along came scientists proposing that the culprit was a misfolding protein that was contagious and thus could spread between individuals. Stanley Prusiner called it a prion, just a simple protein without any genetic material. The scientific community was astonished. This was just not possible.

It took years of experimentation to prove the theory. Now, of course, with the publicity of the mad cow disease many of us have heard about the prion. Whether prions are the agent which causes disease or merely a symptom caused by a different agent is still debated by a minority of researchers. However, the matter should be considered settled when Prusiner won the Nobel Prize in Physiology or Medicine in 1997 for his research into prions.

And what about new findings for bisphenol A?

The lesson from all of this? It is simply that it takes a lot of time and convincing arguments for scientists to change their mind. And now we have 21 scientists in the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids pondering about the fate of bisphenol A for the sixth time. Will the judgement be different on this occasion? One panel member already previously expressed a dissenting view, an unusual event in the short history of EFSA. But the peer pressure from the scientific community is high for status quo.

Yes, there are indications that bisphenol A might be an endocrine disruptor effective at very low doses. The effect might even be one explanation of many to the obesity epidemic. According to this theory exposure to bisphenol A might induce epigenetic changes turning on obesity genes. Changes that will be inherited by your off-spring. We will see in May 2013 when the new opinion is published if the new scientific findings are convincing enough. French scientists already believe they are and politicians in several countries have bowed for public pressure and as a precautionary measure banned bisphenol A from baby bottles. Endocrine disruptors are particularly dangerous during early life with rapid development easily influenced.

EFSA preparing the ground work for a decision

EFSA preparing the groundwork for a decision

EFSA has been doing the groundwork by organising a scientific meeting to discuss low-dose effects. It met with French scientists in 2011 to discuss their conclusions. It further organised a Member State meeting in 2012 to air the views of European scientists. Finally, in co-operation with other European scientific advisory bodies, EFSA’s Scientific Committee is undertaking a review of all the current scientific information on endocrine active substances with the view of publishing an opinion in March 2013.

The pot is being stirred.

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BPA-induced juvenile anxiety

BPA-induced behavioural changes

A scientific report published in September 2012 noted that emerging studies had associated prenatal bisphenol A (BPA) exposure with elevated hyperactivity and anxiety in young girls. This suggested a possibility that developmental exposure to endocrine disruptors like BPA might contribute to the growing prevalence of behavioural and mood-related disorders in children. To explore this further the scientists used rodents as an experimental model in trying to establish how chronic, low dose oral exposure to BPA throughout development might impact affective behaviour during adolescence and adulthood. They further studied the underlying molecular changes to the nervous system related to such effects and looked at the potential for dietary intervention with a soy-rich diet to mitigate BPA effects.

Assessment of serum BPA confirmed that the internal dose was within the human range of 2 ng/ml of unconjugated BPA reported in several studies. At this level BPA was shown to induce anxiogenic behaviour in juveniles and loss of sexual dimorphisms in adult exploratory behaviour, but only in the animals reared on the soy-free diet. Changes were identified in the amygdala region of the brain. Expression analysis revealed a number of genes associated with BPA-induced juvenile anxiety in rats, including a subset known to mediate sociosexual behaviour. Overall, the results showed that behavioural impacts of BPA can manifest during adolescence, but wane in adulthood, and may be mitigated by diet. The data also revealed that receptors linked to oxytocin/vasopressin signalling pathways, previously associated with human affective disorders, might have been involved in the behavioural changes.


Patisaul et al. (2012). Anxiogenic Effects of Developmental Bisphenol A Exposure Are Associated with Gene Expression Changes in the Juvenile Rat Amygdala and Mitigated by Soy. PLoS ONE 7(9): e43890. doi:10.1371/journal.pone.0043890

Official views on bisphenol A

SummaryBisphenol A has been used in the production of food contact materials since the 1960s. Some recent findings point to possible low dose effects at levels of current human exposure. As a precaution some official authorities have introduced limited bans on bisphenol A to protect babies and young children, while others take a wait and see approach pointing to the need for more research.

bisphenol A

Structure of bisphenol A (credit: Wikipedia)

The use of the industrial chemical bisphenol A (BPA) to make food contact plastics and resins, although questioned for some time as a potential risk to human health by some scientists, is still approved by official authorities in most countries. Polycarbonate baby bottles is a recent exception. Question is, with some new scientific findings, will official risk assessment authorities change their general view and will risk managers take further action?

The European Union situation

BPA is permitted for use in food contact materials in the European Union (EU), most recently as listed under Regulation 10/2011/EU. The European Food Safety Authority (EFSA) completed a full risk assessment of BPA in 2006 and set a Tolerable Daily Intake (TDI) of 0.05 mg/kg body weight per day for the substance – that is the amount that can be ingested daily over a lifetime without appreciable risk. Since the initial opinion, EFSA has been asked three times to review the initial assessment and as a result published updated scientific advice in 2008, 2010 and 2011. EFSA also evaluated intakes of BPA through food and drink, for adults, infants and children and found that they were all well below the TDI.

Due to the controversial debate on BPA and despite EFSA’s view on the safety of BPA, the EU member states Denmark and France banned BPA in baby bottles in 2010. The ban was imposed for reasons of precautionary consumer protection. In order to create a consistent legal framework within the EU and following a similar move in Canada, the European Commission adopted Directive 2011/8/EU in January 2011 prohibiting the use of BPA for the manufacture of polycarbonate infant feeding bottles and their placing on the market within the EU.

Contrary to the prevailing view of EFSA, on 27 September 2011 the French L’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (ANSES) published two reports on bisphenol A reaching a different conclusion. One report related to the health effects associated with exposure to BPA while the other concerned its uses. In the report on health effects – “Effets sanitaires du bisphénol A” – ANSES concluded that health effects have been proven in animals and suspected in humans, even at low levels of exposure below current regulatory thresholds. On the basis of these findings it recommended that exposure to bisphenol A should be limited in the most susceptible populations of infants, young children, pregnant and breastfeeding women. A previous Danish report produced by the DTU Fødevareinstituttet on behalf of the Danish government reached similar conclusions. It noted that neurodevelopment effects were seen in young male rats even at low doses of BPA raising some concern of possible human effects.

The CEF Panel did not consider that the information in the ANSES report would immediately change the views the Panel expressed in 2010, but wanted more time to review in depth the new studies. Consequently, in February 2012, the CEF Panel decided to undertake a full re-evaluation of the human risks associated with exposure to BPA through both dietary and non-dietary sources. The intention is to review all the available data and scientific studies on exposure published since 2006. The Panel will further evaluate uncertainties about the possible relevance to human health of some BPA-related effects observed in rodents at low dose levels. New findings from ongoing studies on low dose effects as well as on dietary and non-dietary exposure to BPA will be considered as they become available during 2012, with the intention to publish the new opinion by May 2013.

The Canadian situation

Health Canada’s Food Directorate has conducted periodic reviews of BPA as new information has become available relating to its toxicity and potential exposure from food packaging applications. The purpose of these reviews was to determine whether dietary exposure to BPA could pose a health risk to consumers. Based on the overall weight of evidence, the view is still that current dietary exposure to BPA through food packaging uses is not expected to pose a health risk to the general population, including newborns and infants.

However, due to the uncertainty raised in some animal studies relating to the potential effects of low levels of BPA, the Government of Canada banned the use of BPA in baby bottles in March 2010 to enhance the protection of infants and young children. It further added BPA to the list of substances deemed potentially harmful to health or the environment in October the same year to make it easier to take further action should this be deemed necessary.

The Bureau of Chemical Safety, in the Food Directorate of Health Canada, is investing further resources in exploring the potential impact of BPA on the health of the Canadian population. It will improve estimates of dietary exposure to BPA from all Canadian food sources. It is also a partner in assessing information gaps on the occurrence and significance of BPA in human milk from Canadian mothers in a project funded by Health Canada, the Canadian Institutes of Health Research and the Ontario Ministry of the Environment.

The situation in the USA

BPA was first approved by the Food and Drug Administration in the early 1960s. Due to some concerns raised, the FDA released a draft report in August 2008 finding that BPA remained safe in food contact materials. However, a few months later a subcommittee of FDA’s science board raised questions about whether the review had adequately considered the most recent scientific information available.

On January 15, 2010 and again on March 30, 2012, the FDA issued interim updates on BPA. They claimed that studies employing standardised toxicity tests had thus far supported the safety of current low levels of human exposure to BPA. However, on the basis of results from recent studies using novel approaches to test for subtle effects, FDA, supported by the view of the National Toxicology Program at the National Institutes of Health, expressed some concern about the potential effects of BPA on the brain, behaviour, and prostate gland in foetuses, infants, and young children. This concern was expressed because it was noted that developmental changes in some animal studies occurred at BPA exposure levels similar to those experienced by humans. A collaborative effort is underway to carry out further in-depth studies to clarify the outstanding uncertainties about the risks of BPA.

While awaiting the new results, FDA expressed support for actions to stop the production of BPA-containing baby bottles and infant feeding cups for the U.S. market and the recommendations issued by the Department of Health and Human Services for infant feeding and food preparation to reduce exposure to BPA.

The Australian situation

The Australian Government has limited its action on BPA to an introduction of a voluntary phase out of BPA use in polycarbonate baby bottles. Food Standards Australia New Zealand (FSANZ) is firm in its view that there are no health issues associated with BPA at the levels people are exposed to. They state that extremely large amounts of food and beverages would have to be consumed to even reach still acceptable intake level.

There is no suggestions of further activities as they claim that countries that banned the use of BPA in some products did so without any support of risk assessment conclusions on the safety of BPA. To further support this view the FSANZ website lists shortcomings in 17 scientific studies purporting to show the toxicity of BPA.

The international view

According to the World Health Organization website the scientific controversy around the safety of BPA is driven by the disparate results reported in the many studies exploring toxicity and endocrine activity of BPA in animals. This has led to different risk management decisions taken by national authorities. The issue has also received much attention in the media and among the general public. In light of possible adverse human health effects at low doses of BPA, especially on reproduction, the nervous system and on behavioural development, and considering the relatively higher exposure of very young children compared with adults, a meeting of ad hoc experts was jointly organised by FAO and WHO in late 2010 to assess the safety of BPA.

It was difficult for the meeting to reach definitive conclusions on the safety of BPA because of a lack of data from experimental animal studies suitable for risk assessment. Controversy persisted over the biological significance of many of the more sensitive end-points and it was uncertain if all relevant end-points had been covered by the studies used for past risk assessments.

It was clear that for many traditional end-points, human exposure was much too low to be of any health concern. However, for some emerging new end-points (sex-specific neurodevelopment, anxiety, pre-neoplastic changes in mammary glands and prostate in rats, and impaired sperm parameters) a few studies showed associations at levels close to the estimated human exposure, which was clearly of concern if their toxicological significance were to be confirmed. Further research would be needed before these results could provide a basis for a realistic estimate of the human health risk.

The maligned bisphenol A

Summary – Bisphenol A is an industrial chemical that has been present in many hard plastic bottles and metal-based food and beverage cans since the 1960s. Recent studies using novel approaches to test for subtle effects raised some concern about its potential influence on the brain, behaviour and prostate gland development in foetuses, infants and young children. It is currently under extensive review.

Bisphenol A (BPA) is an industrial chemical used since the 1960’s as an ingredient in making a clear plastic known as polycarbonate. Polycarbonate is used to make a variety of common products including baby and water bottles, sports equipment, medical and dental devices, dental fillings and sealants, CDs and DVDs, household electronics, and eyeglass lenses. BPA is also found in epoxy resins, which act as a protective lining on the inside of metal-based food and beverage cans. It can leach into food, and a study of over 2,000 people found that more than 90 percent of them had BPA in their urine. Traces have also been found in breast milk, the blood of pregnant women and umbilical cord blood.

BPA is permitted for use in food contact materials in the European Union (EU) and in most other countries.  In the past, the European’s Scientific Committee on Food, the European Chemicals Bureau, the European Food Safety Authority, and the US Food and Drug Administration all concluded that current levels of BPA present no risk to the general population. However, recently it was found to exert detectable hormone-like properties, raising concerns about its presence in consumer products and foods contained in such products. Starting in 2008, several governments questioned its safety, prompting some retailers to voluntarily withdraw polycarbonate products. Canada was the first country to ban the use of BPA in baby bottles from 2010 followed by the European Commission in January 2011. In 2012, also the United States banned the use of BPA in baby bottles including in infant feeding cups.

Bisphenol A toxicity

There is a great diversity of opinion about the health effects of BPA. Overall, empirical evidence in support of negative health effects of BPA varies significantly across studies.  Standardised toxicity tests used globally for regulatory decision-making long supported the safety of current low levels of human exposure to BPA. However, results of recent studies using novel approaches and different endpoints found detrimental effects in laboratory animals at very low doses similar to estimated human exposure.

Several new studies evaluated developmental or behavioural effects that are not typically assessed in standardised tests. For example, perinatal exposure to BPA in rodents modified sex differences in the brain. In mice, prenatal exposure to BPA was associated with increased anxiety, aggression and cognitive impairment. In the offspring of BPA-exposed monkeys, males displayed less social behaviours and were more exploratory. In humans, BPA exposure during gestation has been associated with hyperactivity and aggression in young children and with anxiety and depression in older children. Together, these reports and many others demonstrate that BPA exposure during gestation affects several types of behaviours in a number of species.

It is clear that bisphenol A is a weak endocrine disruptor, which can mimic oestrogen and may lead to negative health effects. Early developmental stages seem to be the period of greatest sensitivity to its effects. Regulatory bodies have determined safety levels for humans, but those safety levels are being questioned or are under review as a result of the new findings. Experts in the field of endocrine disruptors have stated that the entire population may suffer adverse health effects from current BPA levels. In 2009, the Endocrine Society released a statement citing the adverse effects of endocrine-disrupting chemicals, and the controversy surrounding BPA.

In 2010, the WHO organised an expert meeting to review toxicological and health aspects of BPA supported by Health Canada, the European Food Safety Authority, the U.S. National Institute of Environmental Health Sciences and the US Food and Drug Administration. Although the meeting concluded that doses much higher than estimated human exposure were necessary for most toxicological effects, it did agree that for some emerging effects, like sex-specific neurodevelopment, anxiety, preneoplastic changes in mammary glands and prostate in rats, and impaired sperm parameters, a few studies showed associations at levels close to estimated human exposure. Because of the considerable uncertainty of the validity and relevance of these observations it was recommended that further research should be undertaken to reduce the uncertainty.

Re-evaluation of human risks

EFSA completed a full risk assessment of BPA in 2006 and set a limit of 0.05 mg/kg body weight per day that could be ingested daily over a lifetime without appreciable risk (Tolerable Daily Intake – TDI). It evaluated intakes of BPA through food and drink, for adults, infants and children and found that they were all well below the TDI.

EFSA has updated its scientific advice on BPA several times since 2006, most recently updating its risk assessment in 2011, reaching similar conclusions.

In February 2012, following further consideration of new scientific studies, EFSA decided to undertake a full re-evaluation of the human risks associated with exposure to BPA through the diet, also taking into consideration the contribution of non-dietary sources to the overall exposure to BPA. The new opinion will review all the available data and scientific studies on dietary exposure published since EFSA’s 2006 Opinion. The Panel will further evaluate uncertainties about the possible relevance to human health of some BPA-related effects observed in rodents at low dose levels.

FDA is also continuing to consider the low dose toxicity studies of BPA as well as other recent peer-reviewed studies related to BPA. At this stage, FDA has stated its current perspective on BPA, its support for further studies, its establishment of a public docket for its assessment of BPA use in food contact applications. FDA has issued interim public health recommendations, including its view of the appropriate regulatory framework for BPA use in food contact applications. It is expressing the wish to pursue the issue in collaboration with international partners.