Evidence mounts on BPA’s adverse effects on human health

Lindsay McCormick is a Research Analyst.

Bisphenol A (BPA) is a high production volume chemical that is used to make polycarbonate plastics and epoxy resins.  It is commonly found in food and beverage packaging, such as plastic bottles and the lining of food cans, as well as thermal paper receipts (see our previous blog).  BPA is widely-recognized as an endocrine-disrupting chemical, meaning that it can alter the normal functioning of the body’s hormonal system.  Hundreds of studies have been published associating BPA exposure with health effects, ranging from cancer to obesity to attention-deficit hyperactivity disorder.  Data from the Center for Disease and Control (CDC) show that nearly all people tested have BPA in their bodies.

Despite a plethora of data, numerous calls for action (for example, see here, here and here), and comprehensive regulation in France, it does not seem that national regulation of BPA in food packaging in the U.S. will be happening any time soon.  The official position of the U.S. Food and Drug Administration (FDA) is that, while BPA exhibits endocrine-disrupting properties at high doses, it is safe at the current levels occurring in food.  Although the FDA banned the use of BPA-based materials in baby bottles, sippy cups, and infant formula packaging in 2012, FDA said it based this action on changes in the market, rather than safety concerns.

In the fall of 2014, FDA completed a four-year review of the literature, including more than 300 scientific studies, and concluded that the information does not “prompt a revision of FDA’s safety assessment of BPA in food packaging at this time.”

The European Food Safety Authority (EFSA) recently followed suit with their announcement that BPA does not pose a health risk to consumers, including children, at current exposure levels.  (This is in contrast to the action of several EU member states, which have banned BPA in food contact materials for children under 3 years of age over the past few years.)

Meanwhile, scientists continue to churn out studies linking low-level BPA exposure to a variety of health effects.  In this post, we discuss several new studies.  

Metabolic health

Last week, researchers from the University of Michigan, New York State Department of Health, and North Carolina State University published a study investigating the following hypothesis: Prenatal exposure to BPA, at levels representative of actual human exposure, affect metabolic risk factors for the development of diseases such as type 2 diabetes and cardiovascular disease later in life.

In order to test this hypothesis, the researchers used a unique study design, where human research was conducted alongside animal studies in sheep, rats, and mice.  For the human portion of the study, the researchers collected blood samples from 24 mothers during the first trimester of pregnancy as well as from the umbilical cord at delivery.  They analyzed the samples for BPA levels and known risk factors for type 2 diabetes and cardiovascular disease, specifically markers of oxidative stress and imbalances in the levels of free fatty acids (FFAs).  Mothers with higher levels of BPA showed greater evidence of oxidative stress and increased palmitic acid, a common fatty acid.

These results were supported by the experimental animal studies, where adult sheep, rats, and mice that had been prenatally exposed to BPA at levels similar to those to which humans are currently exposed showed evidence of increased oxidative stress (in sheep and rats) and altered FFA levels (in mice).  These experimental studies indicate the potential for prenatal BPA exposure to have long-lasting effects on metabolic health, into adulthood.

Cardiovascular effects

Earlier this month, researchers from the University of Cincinnati College of Medicine published a study linking cardiovascular effects in mice to low levels of BPA exposure.  The researchers administered BPA to mice in their food in a manner and at doses that mimic human exposure patterns and levels.  Female mice were dosed so as to expose their offspring from conception.  Researchers then continued to dose these offspring after birth through adulthood.  The low end of the dose range used was comparable to estimated current levels of human oral exposure, while the high end of the dose range was near FDA’s current No Observed Adverse Effect Level (i.e., the highest dose that FDA maintains yields no health effects).

The study identified several effects on markers of heart health, including decreased systolic blood pressure, structural changes in the heart, and changes in the expression of genes related to metabolic function in heart tissue.  The response was dose-dependent for many (although not all) outcomes, and the dose-response often differed between males and females.  In female mice only, co-exposure to BPA and isoproterenol, a drug that mimics the effects of a heart attack, increased heart muscle damage and collagen formation – an indicator of scarring – over that seen with the drug alone.  Overall, female mice exposed to BPA demonstrated more pronounced stress-induced effects than male mice.  The authors conclude that this study adds to a body of evidence suggesting that BPA exposure may adversely affect heart health, particularly in females.

A study published last month by researchers from Seoul National University in Korea found that acute increases in systolic blood pressure in humans were associated with BPA exposure from an everyday scenario: drinking beverages from cans.  60 participants (>60 years old) consumed the same beverage either out of glass bottles or cans; researchers then measured urinary BPA concentration, blood pressure, and heart rate variability two hours later.

The researchers used a crossover study design, in which each participant came to the study site three times and consumed the same beverage in three different combinations: two bottles, two cans, or one bottle and one can.  Urinary BPA levels were 1,600% higher and systolic blood pressure significantly increased after beverage consumption out of two cans, compared to consumption out of two bottles.  A smaller, but still statistically significant, increase in urinary BPA levels was seen in the one-can/one-bottle scenario, although there was no significant change in blood pressure.  No change in heart rate variability was observed among the three scenarios.

Developmental neurotoxicity

The University of Cincinnati study comes on the heels of research published by the University of Calgary in Canada, which found associations between BPA exposure at low doses (comparable to or lower than current human exposure levels) and altered neurodevelopment and hyperactive behavior in zebrafish.  The authors note that the BPA concentration used was 2-3 orders of magnitude lower than typical BPA levels found in the human placenta, levels measured in human fetal serum, and levels determined to be safe by U.S., Canadian, and EU international regulatory agencies.  Bisphenol S (BPS), a BPA analogue that is frequently used as a theoretically “safer” BPA replacement in products, was also studied.

The study found that exposure to BPA and BPS was associated with 180% and 240% increases in the growth of new neurons (brain cells), respectively, in the hypothalamus — a region of the brain involved in hyperactivity in humans.  In addition, exposing zebrafish to BPA or BPS during a developmental period analogous to human gestation was associated with hyperactive behavior at a later lifestage.

Zebrafish are frequently used as an animal model for human development.  Not only do they share approximately 70% of their genes with humans, but their organ development and function is remarkably similar to that in humans.  Nonetheless, extrapolating findings from animal models to humans should always be done with caution.  Although the relevance of these effects observed in zebrafish to humans remains to be seen, the study provides evidence that biologically relevant levels of BPA – and BPS – may alter neurodevelopment.

Money talks

Dr. Leonardo Trasande, an associate professor in pediatrics, environmental medicine and health policy at NYU, published an intriguing economic argument in early 2014 for substituting BPA in food packaging with a safer alternative.  He calculates that BPA-associated childhood obesity and adult cardiovascular disease costs the U.S. an estimated $2.98 billion annually, and that removing BPA from food packaging uses would result in a potential annual economic benefit of $1.74 billion.  He argues that these numbers underestimate the true cost of exposure to BPA, as they do not include the potential costs from the numerous other health effects associated with BPA (such as asthma, cancer, and fertility problems).

Unfortunately, finding both a safe and an effective BPA alternative has proven difficult.  Dr. Trasande discusses the potential, and limitations, of several proposed substitutes such as oleoresin, a plant-based mixture of oil and resin, which he suggests may not be associated with adverse health effects.


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