Bisphenol A (BPA) is a chemical that is mainly used in combination with other chemicals to manufacture plastics and resins. For example, BPA is used in polycarbonate, a high performance transparent, rigid plastic. Polycarbonate is used to make food containers, such as returnable beverage bottles, infant feeding (baby) bottles, tableware (plates and mugs) and storage containers. Residues of BPA are also present in epoxy resins used to make protective coatings and linings for food and beverage cans and vats. BPA can migrate in small amounts into food and beverages stored in materials containing the substance.
Dec 2017 – EFSA’s expert Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) discussed and endorsed a scientific protocol for the upcoming re-evaluation of bisphenol A (BPA) hazards, scheduled to start in 2018. The protocol is a detailed plan that defines upfront the scope, methodology and information needs before the assessment starts in 2018.
Referring to the extensive consultation and workshop on the protocol, Chair of the CEF Panel, Prof Vittorio Silano said: “EFSA’s new approach has helped to facilitate a consensus among the interested parties.” He also stated: “Now and at the meeting in September it [the protocol] has been accepted with a lot of support, so now we are ready to start analysing the new data to make an updated assessment.”
An EFSA international working group developed the protocol under the CEF Panel. Experts from Denmark, France, Germany, the Netherlands, Norway, Sweden and Switzerland were appointed by their governments to take part in the protocol working group as well as four independent scientists appointed by EFSA.
EFSA published its comprehensive re-evaluation of BPA exposure and toxicity, in January 2015 when it reduced the TDI for BPA from 50 to 4 µg/kg bw/day. The TDI was made temporary and EFSA committed to re-evaluate BPA toxicity again when a two-year study by the U.S. National Toxicology Program is expected to become available in 2017.
EFSA completed its first full risk assessment of BPA in 2006. Since then, the Authority and its scientific panels have considered hundreds of scientific publications in peer-reviewed scientific journals as well as reports from studies submitted by industry. EFSA reviewed new scientific information on BPA in 2008, 2009, 2010, 2011 and 2016. Its comprehensive re-evaluation was published in January 2015.
2017 – EFSA consults publicly on the approach for its next re-evaluation of BPA toxicity, laid down in a “scientific protocol” that defines upfront the scope, methodology and information needs before the assessment starts.
2016 – New data confirm EFSA’s previous conclusion that BPA might affect the immune system in animals, but the evidence is too limited to draw any conclusions for human health.
2015 – EFSA’s comprehensive review of 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.
2014 - EFSA presents the second part of its draft opinion relating to the human health risks posed by exposure to BPA, accompanied by an eight-week public consultation.
2013 - EFSA consults publicly on the first part of its draft scientific opinion, its assessment of consumer exposure to BPA. EFSA provisionally concludes that for all population groups diet is the major source of exposure to BPA and exposure is lower than previously estimated by EFSA.
2012 - EFSA’s experts decide to do a full re-evaluation of the human risks from exposure to BPA in the diet, also taking into consideration of non-dietary sources in overall exposure to BPA.
2012 - EFSA tackles the issue of low dose effects in toxicology and risk assessment at its dedicated Scientific Colloquium, with the participation of international experts, taking place in Parma in June.
2011 - EFSA addresses reports on BPA published by the French Health and Safety Agency (ANSES) in September 2011. The experts consider overall that the report on health effects of BPA does not change the views expressed by the Panel in its earlier opinions on the safety of BPA. Following an exchange of information, EFSA and ANSES conclude that ANSES’ work was limited to hazard identification while EFSA had carried out a full risk assessment of BPA in 2006.
2010 - EFSA updates its advice on BPA in September 2010 following a comprehensive review of then recent scientific literature and studies on BPA toxicity at low doses. The CEF Panel conclude they cannot identify any new evidence which would lead them to revise the TDI for BPA of 0.05 mg/kg body weight set by EFSA in its 2006 opinion.
2010 - EFSA receives a request from the Commission to take into account any new scientific evidence available that might affect the conclusions of the previously adopted opinions on BPA and to liaise closely with EU Member State risk assessment bodies on this issue.
2009 - EFSA assesses a new study by Stump on possible neurodevelopmental effects of BPA. The study had been commissioned by the American Chemistry Council to address safety concerns raised by the Canadian government, which had introduced legislation to ban the use of polycarbonate in baby feeding bottles.
2008 - EFSA addresses the differences in the ability of infants and adults to clear BPA from the body. EFSA confirms that exposure to BPA is well below the then TDI of 0.05 mg/kg bw for both adults and newborns. After exposure to BPA the human body rapidly metabolises and eliminates the substance. This is also true for newborns who can clear BPA at levels far in excess of the TDI.
2008 - EFSA assesses a study by Lang et al. that suggested a link between levels of urinary BPA and increased occurrence of heart disease and diabetes. EFSA notes that the study does not include information on long-term exposure to BPA which would be needed to establish a correlation between BPA and the development of the chronic medical conditions in question.
2006 - EFSA completes its first full risk assessment of BPA in 2006 and sets a TDI of 0.05 milligrams/kilogram of body weight (mg/kg bw/day) for this substance. At the same time, EFSA also evaluates intakes of BPA through food and drink, for adults, infants and children and finds that they are all below the TDI.
EFSA adopts scientific opinions and provides scientific advice for risk managers on the safety of BPA when used in materials which come into contact with food. This work is carried out by EFSA’s Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF).
As part of its safety evaluations of food contact materials EFSA establishes, when possible (i.e. when sufficient information is available), a Tolerable Daily Intake (TDI) for each substance. The TDI is an estimate of the amount of a substance that people can consume on a daily basis during their whole life without any appreciable risk to health. TDIs are usually expressed in mg or µg per kg of body weight per day (mg/kg bw/day).
EFSA liaises closely with European and national bodies engaged in BPA evaluations as well as with other scientific experts on studies currently in progress.
BPA is permitted for use in food contact materials in the European Union (EU) under Regulation 10/2011/EU, relating to plastic materials and articles intending to come into contact with foodstuffs. In January 2011, the European Commission adopted Directive 2011/8/EU, prohibiting the use of BPA for the manufacture of polycarbonate infant feeding bottles.
- Regulation EU 10/2011 on plastic materials and food contact materials – EUR-Lex
- Directive 2011/8/EU restricting the use of bisphenol A in plastic infant feeding bottles – EUR-Lex
BPA is also permitted for food contact use in other countries such as the USA and Japan.
1. What is bisphenol A (BPA) and how is it used?
BPA is also used in a number of non food-related applications, including epoxy-resin based paints, medical devices, dental sealants, surface coatings, printing inks and flame retardants. A widespread application of BPA is in thermal paper commonly used for till/cash register receipts. As a result of abrasive contact with epoxy-based floorings, adhesives, paints, electronic equipment and printed circuit boards BPA may also be present in household dust.
2. How can BPA get into our diet?
3. Is BPA from food and other sources a health concern?
EFSA’s latest comprehensive re-evaluation of BPA exposure and toxicity was published in January 2015. EFSA’s scientific experts concluded that BPA poses no health risk to consumers of any age group (including unborn children, infants and adolescents). Exposure from the diet or from a combination of sources (diet, dust, cosmetics and thermal paper) is considerably under the safe level (“tolerable daily intake” or TDI) of BPA in food: four micrograms per kilogram of body weight per day (µg/kg of bw/day). The highest estimates for dietary exposure and for exposure from a combination of sources (called “aggregated exposure”) are three to five times lower than the TDI.
The TDI is an estimate of the amount of a substance (expressed on a body weight basis) that can be ingested daily over a lifetime without appreciable risk.
4. Has EFSA carried out previous safety reviews of BPA?
EFSA’s 2015 risk assessment of BPA in foodstuffs
5. Why did EFSA carry out a new risk assessment of BPA?
6. How did EFSA assess the potential human health risks of BPA?
- Hazard assessment – using data from animal and human studies to identify any health hazards associated with exposure to BPA.
- Exposure assessment – using data on the levels of BPA present in food and in food contact material and comparing them to data on food consumption in Europe to estimate average and high level exposure to BPA from food. Data on BPA levels in and from non-food sources were combined with data on behaviour patterns to estimate non-dietary exposure to BPA.
- Risk characterisation – analysing the extent of the risk posed by the identified hazards to consumers at current levels of exposure to BPA – via oral ingestion, breathing in dust and exposure through the skin.
7. Are ‘hazards’ and ‘risks’ the same?
- how much of the substance humans are exposed to
- the length of time of the exposure
- when exposure occurs i.e. as a fetus, child or adult.
8. What potential health effects of BPA has EFSA identified?
Based on animal studies, high doses of BPA (hundreds of times above the TDI) are likely to cause adverse effects in the kidney and liver. BPA is also likely to have effects on the mammary glands of rodents. How these effects are caused (the ‘mechanism of action’) is not clear.
Possible effects of BPA 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. They add to the overall uncertainty about BPA-related hazards and therefore have been considered in the assessment.
9. Does this mean that BPA poses a health risk to humans?
BPA poses no health risk to consumers because current exposure to the chemical is too low to cause harm. EFSA’s scientific opinion shows the level of BPA that consumers of all ages are exposed to is well below the estimated level of safe exposure – known as the tolerable daily intake (TDI). EFSA finds there is no health concern as the highest estimates for dietary and aggregate exposure to BPA are 3-5 times lower than the TDI, depending on the age group. For all population groups, dietary exposure on its own is more than 5-fold below the TDI.
10. Why has EFSA reduced the Tolerable Daily Intake (TDI)?
More accurate data is available now so the calculations used in the risk assessment are based on substance-specific information and less on commonly used standard default values. In addition, an extensive analysis based on new techniques shows uncertainty in the data regarding mammary gland and reproductive, metabolic, neurobehavioural and immune systems, which had to be taken into account.
11. How did EFSA’s scientists calculate the new safe level (TDI)?
In its 2015 re-evaluation of BPA, EFSA used a more refined methodology than before supported by new data. Also, EFSA’s experts quantified uncertainty about some potential effects to be able to factor them in to the risk assessment and the derivation of the tolerable daily intake (TDI).
- Experts analysed toxicological studies and used a method known as benchmark dosing to calculate the lowest dose (called the “benchmark dose”) at which BPA causes a small adverse effect in the kidneys of mice – in this case a 10% change in the mean relative weight of the organ. This effect would occur at a dose of 8960 µg/kg bw/day.
- Using new information on the differences in the ways in which various animal species and humans metabolise and eliminate BPA, EFSA’s experts could convert the dose that causes the adverse effect on the kidneys in mice into a human equivalent dose for humans of 609 µg/kg bw/day.
- Normally scientists would apply an uncertainty factor of 100 to take into account the differences between species and the differences between individual persons. Derivation of the human equivalent dose meant the differences between species in metabolism and elimination were already considered, leaving an uncertainty factor of 25.
- An extra factor of six was included to take into account the uncertainty in the database related to effects on mammary gland and reproductive, neurobehavioural, immune and metabolic systems. Experts derived this factor of six by performing a detailed uncertainty analysis based on expert judgement.
- Thus, an overall uncertainty factor of 150 (25 × 6) was applied to the equivalent human dose of 609 µg/kg bw per day to derive the new TDI of 4 µg/kg bw/day.
12. What is a benchmark dose approach?
The BMD is recognised to be a more accurate and sophisticated method for calculating a health-based guidance value because it uses all the data generated by a study rather than a single reference point.
13. Why is EFSA setting a temporary TDI (t-TDI) for BPA?
The TDI is temporary (t-TDI) pending the outcome of an on-going long-term study in rats involving prenatal as well as postnatal exposure to BPA. Research by the US National Toxicology Program (NTP) will address many of the remaining uncertainties about the potential health effects of BPA.
14. What is a weight of evidence approach?
A weight of evidence (WOE) approach assesses the strengths and weaknesses of experimental data or a study in being able to provide a scientifically rigorous answer to a specific question.
In EFSA’s 2015 opinion on BPA, this approach estimated the degree to which the newly considered evidence strengthened or weakened the likelihood of an association between BPA exposure and a certain health hazard. The conclusions of earlier assessments of BPA by EFSA in 2006 and/or 2010 were taken as the starting point for the new evaluation. EFSA assessed the strength of the evidence linking BPA to each hazard and graded them on a six-point sliding scale. This ranged from ‘very likely’ and ‘likely’, to signify the strongest links, to ‘unlikely’ and ‘very unlikely’ where the link was considered weakest. EFSA said that only those health hazards evaluated as having a likely or very likely link to BPA exposure would be considered directly in characterising the risk posed by the chemical.
15. Is BPA an “endocrine disruptor”?
- firstly, the presence of an adverse effect;
- second, the presence of endocrine activity; and
- thirdly, a causal relationship between the two.
In their 2015 opinion on BPA, EFSA’s experts reviewed all literature published up to the end of 2012 on potential endocrine-related effects of BPA. They concluded that scientific knowledge of how BPA behaves in humans was still unclear and there was no single explanation for how BPA potentially affects humans. Therefore, based on the WHO criteria, it was not considered possible to conclude that BPA is an endocrine disruptor.
BPA is one of a number of chemicals that may have the potential to interact with hormone systems in the body. It has been known since the 1930s that BPA can mimic the female sex hormone, oestrogen. The effects of BPA on fertility and reproduction and the endocrine system have been subject to much scientific debate.
In 2017, the Member State Committee (MSC) of the European Chemicals Agency (ECHA) supported a proposal from France to identify BPA as a substance of very high concern (SVHC) based on its endocrine disrupting effects on humans. The MSC agreement took account of all identified relevant studies published to date including those published since the cut-off point for EFSA’s previous work on BPA. The MSC carried out hazard identification, meaning it takes account of the intrinsic properties of the substance but it does not take into consideration the different uses, the dose required to cause effects or the potential for exposure.
Once identified as a SVHC, the substance is placed on the Candidate List for authorisation. ECHA regularly assesses the substances from the Candidate List to decide which ones should be recommended for inclusion in the Authorisation List as a priority. This priority assessment is based on criteria defined in REACH - intrinsic properties, volume, uses - and follows an agreed approach. The priority assessment is published on ECHA’s website and is the basis for ECHA’s draft recommendation. After a three-month public consultation ECHA finalises its recommendation and sends it to the European Commission (EC). The EC takes the final decision about the inclusion of substances in the Authorisation List.
16. Does BPA cause “low-dose effects”?
BPA’s potential for endocrine activity is often linked to reports of "low-dose effects" or non-monotonic dose-response relationships (NMDR) of BPA. In toxicity testing on animals, a conventional "monotonic dose-response" shows a consistent increase in (adverse) effects along the dose range. The slope of a NMDR curve, however, changes direction along the dose interval studied resulting, for example, in U-shaped or inverted U-shaped curves. Low dose effects are non-monotonic responses occurring at lower doses than those used in regulatory toxicity studies.
Based on scientific criteria, EFSA’s experts concluded that the available data do not provide evidence that BPA results in non-monotonic dose-response relationships for the health effects considered
17. What is important about EFSA’s latest assessment of BPA exposure?
This is EFSA’s first review of consumer exposure to BPA since 2006 and the first to cover both dietary and non-dietary sources (for example, thermal paper and environmental sources such as air and dust). EFSA’s exposure assessment also considers more specific groups of the population than in its previous exposure assessment. For example, these groups include breastfed infants, bottle-fed infants, infants up to 5 days, 3 months, 6 months and 12 months old, teenagers (10-18 years) and women of child-bearing age (18-45 years).
Data on BPA levels in food were combined with figures for food consumption (including human milk) to estimate dietary exposure. Since this exposure assessment also considers non-dietary sources of exposure, data on levels of BPA in and from non-food sources (including dust, thermal paper and cosmetics) were combined with data on behaviour patterns. In addition, the results of biomonitoring (that is, analysis of BPA levels in human urine) were used to corroborate the estimates derived from data modelling, which were found to be consistent.
18. How high is consumer exposure to BPA?
- The highest estimates for dietary exposure and for exposure from a combination of sources (called “aggregated exposure”) are three to five times lower than the t-TDI of four micrograms per kilogram of body weight per day (4 µg/kg of bw/day).
- Dietary exposure is from four to 15 times lower than previously estimated by EFSA in 2006, depending on the age group considered. This is due to better data and less conservative assumptions for the exposure calculations.
- Dietary exposure to BPA is highest among infants and toddlers. The highest estimates are 4 and a half times below the t-TDI. This is explained by their higher food consumption on a body weight basis.
- Dietary exposure for bottle-fed infants aged 0-6 months is 50-fold below the t-TDI for the highest estimates.
- Aggregated exposure, which reflects the summated exposure to the toxicologically relevant form of BPA – known as ‘unconjugated BPA’ – through all routes (diet, dust, cosmetics and thermal paper), is highest for adolescents at over 1 µg/kg bw/day.
19. What are the main sources of consumer exposure to BPA?
- Canned food and non-canned meat and meat products are major contributors to dietary BPA exposure for all age groups. Canned food is known to be a dietary source of BPA because of the substance’s use in the lining of cans.
- BPA might be present in meat and meat products through contact with packaging, processing equipment or through other forms of contamination (e.g. environment, feed). However, EFSA’s experts have not seen any firm scientific evidence to support this.
- Exposure to BPA in thermal paper through the skin is the second largest source of external exposure in all age groups above three years of age, ranging from 4-fold to 8-fold below the t-TDI.
20. Were there any uncertainties in EFSA’s assessment of exposure to BPA?
There is a lack of supporting data on dermal (skin) exposure – for example, how much BPA the body absorbs through skin by touching thermal paper. This increases the uncertainty of the exposure estimates from thermal paper and cosmetics.
The uncertainty around dietary exposure is relatively low.
21. Why are the estimates of dietary exposure from 2006 and 2015 so different?
In 2006, estimates of dietary exposure to BPA were far higher due to the lack of data at that time, which led to very conservative assumptions about possible BPA levels in food and drinks. Following a call for data in 2012, EFSA reviewed over 2,500 samples to assess BPA levels in a range of food categories. In addition, EFSA can now call on its Comprehensive European Food Consumption Database, first made available in 2010, for a more detailed picture of food consumption patterns in Europe than that which existed at the time of EFSA’s previous exposure assessment of BPA. These new data have led to a considerable refinement of exposure estimates compared to 2006.
22. Is exposure to BPA from till/cash register receipts a concern?
For population groups above three years of age thermal paper (commonly used for till/cash register receipts) was the second most important source of BPA exposure after the diet, potentially accounting for up to 75% of total exposure for adolescents. Due to uncertainties around the estimates of exposure, EFSA’s experts consider more data are needed (especially related to BPA skin absorption and cash receipt handling habits) to perform a more refined estimate of exposure through this source.
23. How did EFSA quantify remaining uncertainties about BPA toxicity and exposure?
EFSA’s experts used new methodologies to take account of the uncertainties regarding potential health effects, exposure estimates and evaluation of risks for humans. By analysing each uncertainty one by one and combining the Panel’s expert judgement, EFSA’s experts were able to quantify these uncertainties and to factor them in to its risk assessment and derivation of the TDI.
24. How open and transparent was EFSA during its latest review of BPA?
Given the high level of public interest in this work and to be as open and transparent as possible, EFSA thoroughly consulted and engaged with national authorities and stakeholders during this risk assessment to ensure the widest possible range of scientific views and information were considered.
EFSA held a two-stage public consultation: in July 2013 on EFSA’s draft assessment of exposure to BPA, and in January 2014 on its draft assessment of the human health risks posed by exposure to BPA.
The results of both consultation phases as well as EFSA’s responses to the comments received are available in a report published together with EFSA’s 2015 opinion.
25. Did EFSA work together with risk assessors in Member States while developing its scientific opinion?
Whenever EFSA carries out a risk assessment it informs and engages with the competent EU Member State authorities and other partners. For example, while developing its 2015 on BPA in foodstuffs, EFSA and the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) discussed their respective assessments of BPA. The two agencies agreed that most differences concern the relevance of certain studies and the interpretation of uncertainties regarding potential human health effects of BPA. Both agencies are committed to working closely together on future risk assessments of BPA when new information is available.
26. What are the main differences between the draft and final versions of EFSA’s opinion?
The most important changes to EFSA’s opinion following the public consultations are:
- The refinement of the reference point used for derivation of the temporary TDI by (1) recalculating the critical dose for kidney effects in mice based on the availability of individual data from the key study, and (2) use of a more refined factor to convert this dose into an oral human equivalent dose
- Quantification and factoring in of uncertainty regarding other potential health effects, exposure estimates and evaluation of risks for humans
- A reduction from 30% to 10% of estimated skin absorption of BPA to compare with biomonitoring data (BPA levels in human urine)
- Assessment of risk is from dietary sources instead of all "oral" sources (i.e. dietary plus dust ingestion), as well as from all sources combined (diet, dust, cosmetics and thermal paper).
27. What is EFSA’s role? Who regulates the safe use of BPA in the food chain?
EFSA’s role in the EU food safety system is to carry out scientific risk assessment. This risk assessment will inform the decision-making of EU risk managers in the European Commission, European Parliament and Member States who regulate the safe use of BPA as a food contact material. Risk managers take account of scientific risk assessment and other factors when making risk management decisions. These other considerations are outside EFSA’s remit as defined by European law.