Definition
Bisphenol A (BPA) is a carbon-based synthetic compound with the chemical formula (CH3)2C(C6H4OH)2 belonging to the group of diphenylmethane derivatives and bisphenols.
BPA is used to make certain plastics and epoxy resins; it has been in commercial use since 1957. BPA-based plastic is clear and tough, and is used to make a variety of common consumer goods (such as baby and water bottles, sports equipment, CDs, and DVDs) and for industrial purposes, like lining water pipes. Epoxy resins containing BPA are used as coatings on the inside of many food and beverage cans. It is also used in making thermal paper such as that used in sales receipts.
This compound is synthesized by the condensation of acetone (hence the suffix A in the name) with two equivalents of phenol. The reaction is catalyzed by a strong acid, such as hydrochloric acid (HCl) or a sulfonatedpolystyrene resin.
Regulatory mechanism
Bisphenol A is an endocrine disruptor that can mimic estrogen and has been shown to cause negative health effects in animal studies. To be specific, bisphenol A closely mimics the structure and function of the hormone estradiol with the ability to bind to and activate the same estrogen receptor as the natural hormone.
Estrogen-related receptors (ERRs) are orphan nuclear receptors that were initially investigated in breast cancer because of their structural relationship to estrogen receptors. Recent data have shown that the ERRs control vast gene networks that are involved in glycolysis, glutaminolysis, oxidative phosphorylation, nutrient sensing and biosynthesis pathways. The ERRs also modulate breast cancer cell metabolism, growth and proliferation through the regulation of key oncoproteins. (Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond, 2012)
A 2007 study investigated the interaction between bisphenol A's and estrogen-related receptor y (ERR-γ). This orphan receptor (endogenous ligand unknown) behaves as a constitutive activator of transcription. BPA seems to bind strongly to ERR-γ (dissociation constant = 5.5 nM), but not to the estrogen receptor (ER). BPA binding to ERR-γ preserves its basal constitutive activity. It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxythamoxifen. This may be the mechanism by BpA acts as a xenoestrogen. Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects. For instance, ERR-γ has been found in high concentration in the placenta, explaining reports of high bisphenol accumulation in this tissue.
Is BPA Harmful?
Modern studies began finding possible connections to health issues caused by exposure to BPA during pregnancy and during development.
Although public authorities set BPA safety levels, many experts believe these levels should be reviewed after a number of recent studies were published. The Endocrine Society, USA, in 2009 expressed concern in a public statement over current human exposure to BPA.
BPA exhibits hormone-like properties at high dosage levels that raise concern about its suitability in consumer products and food containers where exposure is orders of magnitude lower.
Since 2008, several governments have investigated its safety, which prompted some retailers to withdrawpolycarbonate products. A 2010 report from the United States Food and Drug Administration (FDA) identified possible hazards to fetuses, infants, and young children.
In 2012 the FDA banned the use of BPA in baby bottles.
The major human exposure route to BPA is diet, Dermal absorption, inhalation, including ingestion of contaminated food and water.
Bisphenol A is leached from the lining of food and beverage cans where it is used as an ingredient in the plastic used to protect the food from direct contact with the can. It is especially likely to leach from plastics when they are cleaned with harsh detergents or when they contain acidic or high-temperature liquids.
A 2009 Health Canada study found that the majority of canned soft drinks it tested had low, but measurable levels of bisphenol A.
A 2009 study found that drinking from polycarbonate bottles increased urinary bisphenol A levels by two thirds, from 1.2 μg/g creatinine to 2 μg/g creatinine.
A 2011 study published in Environmental Health Perspectives found that BPA exposure is widespread, with detectable levels in urine samples in more than an estimated 90% of the U.S. population
A 2011 experiment by researchers at the Harvard School of Public Health indicated that BPA used in the lining of food cans is absorbed by the food and then ingested by consumers.
In adults, BPA is eliminated from the body through a detoxification process in the liver. In infants and children, this pathway is not fully developed so they have a decreased ability to clear BPA from their systems.
Babies and young children are said to be especially sensitive to the effects of BPA.
One often overlooked source of exposure occurs when a pregnant woman is exposed, thereby exposing the fetus. Animal studies have shown that BPA can be found in both the placenta and the amniotic fluid of pregnant mice. After the baby is born, maternal exposure can continue to affect the infant through transfer of BPA to the infant via breast milk. (What Is BPA (Bisphenol A)? Is BPA Harmful?, 2013).
What are the possible health effects of BPA on humans?
As an endocrine disruptor that mimics estrogen and thyroid hormone, BPA also acts as a metabolic and immune disruptor.
Thus, the adverse health effects of BPA are extensive and higher levels of BPA exposure correlate with increased risk of cardiovascular disease, obesity, diabetes, immune disorders, and a host of reproductive dysfunctions.
Moreover, in vitro and animal studies have shown that BPA exposure can increase the risk of mammary gland, brain, and prostate cancers. However, human studies linking BPA exposure to heightened cancer risk are scarce. (Exposure to bisphenol a correlates with early-onset prostate cancer and promotes centrosome amplification and anchorage-independent growth in vitro, 2014).
- Reproductive disorders - BPA exposure can affect egg maturation in humans.
- Male impotence – journal Human Reproduction reported that BPA exposure may raise the risk of erectile dysfunction. Sexual desire and problems with ejaculation were also linked to BPA exposure among men.
- Heart disease (females) - BPA can cause heart disease in women, Patients with the highest levels of BPA in their urine carried a 33% increased risk of coronary heart disease.
- Heart disease in adults - another US study linked BPA exposure to diabetes and heart disease in adults.
- Sex hormones in men - an August 2010 study linked BPA exposure to changes in sex hormones in men.
- Type 2 diabetes - A UK study linked higher levels of urinary BPA to type 2 diabetes, cardiovascular disease and liver-enzyme abnormalities.
Recent studies have been shown to be associated with a higher risk for self-reported adverse health outcomes that may lead to insulin resistance and the development of type-2 diabetes mellitus.
Urinary Bisphenol A levels are found to be associated with diabetes independent of traditional diabetes risk factors. Higher Bisphenol A exposure, reflected in higher urinary concentrations of Bisphenol A, is consistently associated with diabetes in the general adult population. (Association of urinary bisphenol a concentration with type-2 diabetes mellitus, 2014).
- Brain function, memory, learning - US researchers linked BPA exposure to loss of connections between brain cells in primates, potential problems with memory and learning, as well as depression.
The U.S. National Institutes of Health determined that there was "some concern" about BPA's effects on fetal and infant brain development and behavior. A 2008 study concluded that BPA altered long-term potentiation in the hippocampus and even nanomolar (10−9 mol) dosage could induce significant effects on memory processes.
- Women's eggs - Californian researchers found that exposure to bisphenol A may affect the quality of a woman's eggs retrieved for in vitro fertilization (IVF).
- Chemotherapy scientists found that BPA exposure may reduce chemotherapy treatment efficacy.
- Breast cancer - A Yale School of Medicine study found a possible increase in breast cancer risk among females exposed to BPA and DES (Diethylstilbestrol) in the womb.
The up-regulation caused by BPA could disrupt the cell cycle and, in consequence, cell survival and differentiation. Ovarian pieces exposed to BPA also showed an up-regulation of ERs, Erα, Erβ and Errγ, which was also observed in ovarian fibroblasts, suggesting that these receptors could be related to the effects of BPA on the ovary
- Asthma - A US study suggested a link between increasing asthma rates and a particular threshold of BPA. Studies in mice have found a link between BPA exposure and asthma; a 2010 study on mice has concluded that perinatalexposure to 10 µg/ml of BPA in drinking water enhances allergic sensitization and bronchial inflammation and responsiveness in an animal model of asthma.
- Obesity: Endocrine disruptors, like bisphenol A (a monomer of polycarbonate plastic), can influence transcriptional regulation of genes involved in obesity. BPA works by imitating the natural hormone 17B-oestradiol. When it binds to estrogen receptors it triggers alternative estrogenic effects that alter glucose and lipid metabolism in animal studies, causing weight gain in some cases.
A 2013 study found an association between urinary concentrations of BPA and body mass indexes of children and adults aged 6–19 years.
There are different effects of BPA exposure during different stages of development: During adulthood, BPA exposure modifies insulin sensitivity and insulin release without affecting weight. Exposure during pregnancy has effects on both mother and offspring later in life. During pregnancy and lactation (perinatally) BPA exposure induces metabolic alterations, including weight gain. (Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4, 2006).
Cancer research
A 2010 review concluded that bisphenol A may increase cancer risk. At least one study suggested that bisphenol A suppresses DNA methylation, which is involved in epigenetic changes.
In animal models, estrogens can drive carcinogenesis of the prostate and have long been suspected of playing a role in human prostate cancer. Scientists have hypothesized that prenatal exposure to estrogen-like compounds, including monomeric bisphenol A (BPA), may account for recent increases in rates of prostate cancer, but human data are scarce. (Chemical Exposures: Prostate Cancer and Early BPA Exposure, 2006).
The evidence shows that in an animal model, some genes are altered by the addition or removal of methyl groups on the DNA, which changes the ability of those genes to be transcribed and translated to proteins.
How to avoid A Bisphenol exposure
According to various consumer groups, those wishing to reduce BPA exposure should not eat/drink canned foods and drinks unless the labeling says it is BPA free.
Scientist from the Silent Spring Institute, USA and Breast Cancer Fund, USA report that after just three days on a fresh food diet, BPA and DEHP levels in children and adults fell considerably.
You should not microwave foods in plastic containers. Plastic containers should not be washed in the dishwasher. You should avoid cleaning plastic containers with harsh detergents.
In November 2009, the WHO announced to organize an expert consultation in 2010 to assess low-dose BPA exposure health effects, focusing on the nervous and behavioral system and exposure to young children. The 2010 WHO expert panel recommended no new regulations limiting or banning the use of Bisphenol-A, stating that "initiation of public health measures would be premature.
Because of concerns expressed in the last few years about the safety of BPA, FDA initiated additional studies to help determine whether or not BPA is safe as it is currently used in food packaging and containers. Some of these studies have been completed and others are on-going.
Consumers can be assured that the FDA supports the strongest regulatory approaches to protect them from risks in the food supply, and will act swiftly to eliminate any individual product, ingredient or chemical that is determined to present a risk to the public health. (Bisphenol A (BPA): Use in Food Contact Application, 2013).
In general, the European Commission's Scientific Committee on Food, the EU's European Chemicals Bureau, the European Food Safety Authority, and the US Food and Drug Administration have concluded that current levels of BPA present no risk to the general population.
Consumer groups recommend that people wishing to lower their exposure to bisphenol A avoid canned food and polycarbonate plastic containers (which shares resin identification code 7 with many other plastics) unless the packaging indicates the plastic is bisphenol A-free. To avoid the possibility of BPA leaching into food or drink, the National Toxicology Panel recommends avoiding microwaving food in plastic containers, putting plastics in the dishwasher, or using harsh detergents.
Substitute chemicals
The industry over time responded to criticism of BPA by promoting "BPA-free" products, which are made from plastic containing a compound called bisphenol S (BPS). BPS, which shares a similar structure and versatility to BPA, is now being used in numerous products from currency to thermal receipt paper, and widespread human exposure to BPS was confirmed in a 2012 analysis of urine samples.
According to a 2013 study, BPS shares similar problems to BPA in that it has been found to be an estrogen hormone disruptor even at extremely low levels of exposure.
The study concluded: Almost all commercially available plastic products we sampled, independent of the type of resin, product, or retail source, leached chemicals having reliably-detectable EA [endocrine activity], including those advertised as BPA-free.
In some cases, BPA-free products released chemicals having more EA than BPA-containing products.
