BPA opinion is nigh

BPA can be found in cans and plastic bottles

BPA can be found in cans and plastic bottles contributing to oral exposure.

Bisphenol A (BPA) is a chemical used in plastic bottles and inner coating of beverage cans, and its exposure is almost ubiquitous. The European Food Safety Authority (EFSA) has previously reviewed the use of BPA in food contact materials four times. It has now reviewed BPA for the fifth time and has at last settled on a final version of the new BPA opinion. But we don’t yet know what the EFSA Panel has decided since the opinion is undergoing final editorial work and will not be published until sometime in January 2015.

From the initial draft we know that EFSA believes that exposure to BPA is likely to adversely affect the kidney, liver and mammary glands and possibly also the reproductive, nervous, immune, metabolic and cardiovascular systems. It might also pose a risk for development of cancer.

Quite a list of negative effects you would think. But only at very high exposure levels, EFSA said.

Reduced tolerable levels proposed

To be brave EFSA proposes that the tolerable daily intake of BPA should be reduced to 5 µg/kg bodyweight from previously 50 µg/kg bodyweight. This allows EFSA to claim that the health risk for any population group is low. It is because the highest estimates for combined oral and non-oral exposure to BPA now would be 3-5 times lower than the proposed limit, depending on the age group.

Not everyone agreed with the EFSA view as evidenced by stakeholders submitting almost 500 comments during online public consultations of the draft opinion. Comments were received from a broad range of interested parties including NGOs, members of the public, academia, national food safety agencies and the food industry ranging from positive to negative. Predictably, industry thought that the draft opinion went too far, while some NGOs wanted an outright ban.

So a good compromise you would think. Not so sure.

The Americans and the French at opposing ends

The Americans are relaxed as usual. Just days before the adoption of the EFSA opinion, the Food and Drug Administration issued a statement saying that BPA is safe at current levels. The FDA said its verdict was based on a four-year review of more than 300 scientific studies. However, it mentioned three ongoing safety assessments and said that the agency might revise its conclusions pending their findings. A bit of hedging there.

But what about the food-loving French? Well, the French are not so sure that EFSA is right and has actually banned BPA from all packaging, containers, and utensils intended to be used in direct contact with food from 1 January 2015. Health issues potentially caused by BPA are thus taken much more seriously by the French Government. However, reasonably, there seems to be an allowance exempting packages introduced onto the market before this date to remain until stock is exhausted.

So what is a simple soul to believe? Just following the literature introduces further doubts.

Thermal receipts can contain high levels of BPA.

Thermal receipts can contain high levels of BPA contributing to dermal exposure.

New research findings

It is well-known that BPA is applied to the outer layer of thermal receipt paper as a print developer and can be present in very high quantities of around 20 mg BPA/g paper. Although EFSA’s assessment indeed did include exposure from thermal receipts, a recently published study showed that using hand sanitisers or other skin care products often containing mixtures of dermal penetration enhancing chemicals, can increase by up to 100-fold the dermal absorption of BPA. Significant free BPA was also transferred from hands to French fries leading to a rapid and dramatic increase in BPA exposure from the two sources.

There are some previous indications that BPA might be associated with hypertension and decreased heart rate variability. Now, a just published new study confirm without doubt that BPA can acutely increase blood pressure at normal exposure levels. In a randomised crossover trial, 60 non-institutionalised adults aged 60 years and over visited a study site three times, and were provided with the same beverage in two glass bottles, two cans, or one can and one glass bottle at a time. The researchers found that after consuming two canned beverages the systolic blood pressure increased by a statistically significant 4.5 mm Hg compared to consuming two glass bottled beverages and the urinary BPA concentration increased  by more than 1,600 per cent.

Don’t expect revolution

Of course those two late studies are not included in the EFSA review, but if they were would they change the conclusions? Not so sure. It seems overwhelming evidence is needed for the scientific experts to change their view. Thus don’t hold your breath, it is unlikely that the final opinion, when published, will change much from the earlier draft.

The safety of bisphenol A

Canned food

Bisphenol A can be found in many canned food products (Credit: andrivete – Flickr)

Let’s face it, we are all exposed to bisphenol A (BPA), if not daily, at least several times a week. It as an unwelcome contamination of our food, with most of it coming from migration of BPA from the epoxy lining covering the inside of food cans, except for babies. Babies get their BPA either indirectly through breast milk or directly from liquid formula served out of baby bottles made of polycarbonate plastic. We are also “foolish” enough to effectively absorb it from the gut to allow the BPA to circulate in our bodies. But here is the good bit. Within minutes we start to attack the circulating BPA to neutralise its potentially dangerous effects and then we fairly quickly excrete the modified BPA through the urine. However, a small amount of free BPA might linger for a bit longer. The big question is what damage will that small amount cause, if any? And here there is big disagreement between scientists. So let’s look at how they see it by following their traditional way of assessing food safety risks. Bear with me, it is only four steps.

What is all the fuss about (hazard analysis)?

As mentioned upfront, it is very difficult to totally avoid consuming some BPA. It can actually be found in the urine of well over 90% of people examined worldwide. This is no surprise since BPA is a high volume industrial chemical used since the 1960s as a major ingredient in making clear polycarbonate plastic. This plastic 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. More importantly, BPA is also found in epoxy resins, which act as a protective lining on the inside of metal-based food and beverage cans and in the lid of glass bottles. There are many other applications of BPA outside of the food area. It is used as a colour developer in carbonless copy paper and thermal point-of-sale receipt paper. Close to 4 million tonnes of BPA are used by manufacturers yearly. In other words it is all around us and most of us carry some daily traces of BPA in our blood.

But does it matter? Well, yes it might. It is well-known that BPA acts as an endocrine disruptor, that is it is influencing hormone responses in our bodies. As a matter of fact, because of its oestrogen-like effects, it was briefly used as a growth promoter in cattle and poultry in the 1930s and even as a hormone-replacement therapy for women. However, the oestrogen effect was quite weak so it was quickly replaced by more powerful substances. The biggest worry is for the developing foetus. There are concerns that exposure in the womb to even small amounts of the chemical at this very sensitive stage of life could disturb normal development.

SO How much do we eat (exposure assessment)?

So now we have to find out if the levels of BPA we consume are high enough to cause damage. We do that by looking at contamination levels in different foods and checking how much of the respective food we eat. Sounds simple enough, but it isn’t and here is why. Since food is generally contaminated by BPA through migration from food packaging and food consumption information rarely indicates the exact source of the food, it makes accurate calculations of BPA exposure difficult.

Of course most foods would not be contaminated by BPA, but a quick review of “suspect” foods for infants up to adults indicates levels from 1 to 70 μg/kg. BPA levels in breast milk for the very young can vary from an average of about 2 μg/kg up to a maximum of just below 8 μg/kg. Liquid formula can contain slightly higher levels from an average of about 4 μg/kg to a maximum of around 11 μg/kg of BPA calculated as consumed. BPA in toddler food in glass jars can vary from an average of about 1 μg/kg to a high of around 7 μg/kg. For adult foods, average concentrations can range from 10 to 70 μg/kg in solid canned food and from 1 to 23 μg/L in liquid canned food.

As a next step we have to make qualified guesses about the amount of the respective food consumed to be able to estimate BPA exposure. The following theoretical calculations assume consumption of BPA-containing food on that day.

High exposure in children (Credit: paparutzi – Flickr

It is easiest for exclusively breastfed babies (0–6 months) where average daily exposure to BPA can be estimated to be 0.3 μg/kg bodyweight, up to a high of 1.3 μg/kg bodyweight. Bottle fed babies in the same age range go higher if the liquid formula is fed using polycarbonate bottles. Average exposure for such babies can be estimated to be 2.4 μg/kg bodyweight per day, up to a high of 4.5 μg/kg bodyweight per day. This is the reason why polycarbonate baby bottles are phased out in several countries. Once solid foods are introduced, exposure to BPA decreases. For children older than 3 years, average daily exposure would probably not exceed 0.7 μg/kg bodyweight with a possible high of up to 1.9 μg/kg bodyweight.

ŠFor adults, consumption of canned food might give an average daily exposure not exceeding 1.4 μg/kg bodyweight, with a possible high exposure of 4.2 μg/kg bodyweight when you really splash out. Handling of point-of-sale receipts and BPA circulating in the air might contribute to exposure, but the common view is that food is by far the major contributor of overall exposure to BPA for most population groups.

The theoretical calculations can be compared with biomonitoring data from analysing the total BPA excreted through urine on any day irrespective of the consumption of BPA-contaminated food or not. As was to be expected, children data compared the best with the average for infants with fairly consistent day-to-day food consumption patterns at 0.07–1.61 μg/kg bodyweight per day and children 3-5 years of age at 0.12-0.78 μg/kg bodyweight per day. Adult exposure estimates on the other hand were in the range of 0.05-0.27 μg/kg bodyweight per day, reflecting the irregular consumption of BPA-contaminated food.

But what about the unborn baby? Here we have to rely on reported normal blood levels of free BPA in pregnant women of 0.3-4.0 ng/ml as typical serum levels. Since BPA passes freely over the placenta, the same levels could be expected in the unborn baby.

The potential public health issue (HAZARD CHARACTERISATION)?

Public health concerns have been raised by findings that BPA exposure can influence brain development and modify normal behaviour. Exposure to BPA in the immediate period before and after birth has been shown to modify sex differentiation in the brain of rodents. In mice it was associated with increased anxiety, aggression, cognitive impairments, and decreased novelty seeking. In the offspring of BPA-exposed monkeys, males displayed less social activity.

Animal experiments point to the damage that can be caused by BPA (Credit: Brian_Kellett – Flickr)

But that’s in animals, right? And we all know that it is the dose that makes the poison. In most cases the animals were given quite high doses of BPA. So do we even come near the levels of BPA needed to cause damage? Many scientists don’t believe that is the case, but recent finding of suspected low-dose effects might change this around. And associations in human epidemiological studies between BPA exposure before birth and later behavioural changes would need a closer review.

In recent reports covering humans, BPA exposure has been associated with hyperactivity and aggression in 2-year-old female children when exposed before birth and with anxious, depressive, and hyperactive behaviours related to impaired behavioural regulation at 3 years of age. In contrast, childhood BPA exposure was not associated with changes in behaviour or executive function at 3 years of age.

Together, these reports and many others demonstrate that BPA exposure before birth affects several types of behaviour in a number of species and at blood levels that might be relevant for humans. What makes it even worse is that it can have immediate and long-lasting, transgenerational effects in brain development and social behaviour. That is the changes can move along to following generations by modifying gene response in something called epigenetic changes.

So what about the controversy surrounding the high BPA doses given to experimental animals compared to relatively low amounts consumed by humans? In most experiments animals have been given amounts of BPA higher than 50 μg/kg bodyweight and often at mg level while human daily consumption would be 5 μg/kg bodyweight at the most. Curiously enough the resulting blood levels in animals and humans have been very similar. Animals given 50 μg/kg bodyweight showed serum levels of free BPA of 2.0-4.6 ng/ml, well within the range of normally exposed humans. There is now speculation that other sources could contribute to human exposure or that metabolism after repeated exposure as is typical in humans could be different.

To be clear there is still remaining uncertainty about the exact doses of BPA needed for the described effects to occur. Additional large prospective cohort studies are needed to confirm and validate findings from animal studies. However, even in the absence of epidemiological studies, concern over adverse effects of BPA is warranted given the unique vulnerability of the developing foetus and child.

What does it all mean for us (risk characterisation)?

Based on previous scientific reports a Tolerable Daily Intake (TDI) of 50 μg/kg body weight per day has been set for the substance – that is the amount that can be ingested daily over a lifetime without appreciable risk. This is well above the calculated intake levels of BPA for most people.

However, although initially considered to be a weak environmental oestrogen, more recent studies have demonstrated that BPA may be similar in potency to the natural oestradiol hormone in stimulating some cellular responses. Emerging evidence also suggests that BPA may influence multiple endocrine-related pathways. Some scientists suggest that studies in rodents have identified adverse effects of BPA at exposure levels at or below the current acceptable daily intake level for this compound. However, when scrutinising the administered doses given to animals they seem to be much higher then the estimated intake in the exposure chapter above. Still they show that the circulating blood levels of free BPA in the age group with highest dietary exposures in humans (i.e. infants 0–6 months of age) is the same as measured in the animals. This is puzzling.

Pregnant women

The child during pregnancy is the most sensitive to BPA (Credit: molly_darling – Flickr)

Much more investigation is needed to understand the potential adverse health effects of BPA exposure in humans and to understand the multiple pathways through which it may act. Although many questions remain to be answered, it is becoming increasingly apparent that exposure to BPA is ubiquitous and that the effects of this endocrine disruptor are complex and wide-ranging.

At this stage it seems prudent to focus on the effects on the most vulnerable population group, the developing foetus and child. The most recent research seems to point to real life effects at this vulnerable life stage at current exposure levels. The only way to reduce this risk would be to limit BPA exposure in pregnant and lactating females. However, since this would be impractical, a general phasing out of the use of BPA in products in contact with food seems to be the only safe solution. New research underway and the current review of the scientific literature by food safety authorities will hopefully be able to resolve the issue once and for all.