Bisphenol A is thought to be an endocrine disruptor which can mimic estrogen and may lead to negative health effects. More specifically, 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. Early developmental stages appear to be the period of greatest sensitivity to its effects, and some studies have linked prenatal exposure to later physical and neurological difficulties. Regulatory bodies have determined safety levels for humans, but those safety levels are currently being questioned or are under review as a result of new scientific studies. A 2011 study that investigated the number of chemicals pregnant women are exposed to in the U.S. found BPA in 96% of women.
Overall, empirical evidence supporting the negative health effects of BPA varies significantly across studies. Opinions vary greatly about the health effects of BPA. Some studies conclude that BPA poses no health risks while others state that BPA causes a number of adverse health effects. 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. However, 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 2012 the FDA did ban the use of BPA in baby bottles, however the Environmental Working Group called the ban "purely cosmetic". In a statement they said,"If the agency truly wants to prevent people from being exposed to this toxic chemical associated with a variety of serious and chronic conditions it should ban its use in cans of infant formula, food and beverages." The Natural Resources Defense Council called the move inadequate, saying the FDA needs to ban BPA from all food packaging. In a statement a FDA spokesman said the agency's action was not based on safety concerns and that "the agency continues to support the safety of BPA for use in products that hold food."
The Environmental Protection Agency (EPA) also holds the position that BPA is not a health concern. In 2011, Andrew Wadge, the chief scientist of the United Kingdom's Food Standards Agency, commented on an EPA study on dietary exposure of adult humans to BPA, saying, "This corroborates other independent studies and adds to the evidence that BPA is rapidly absorbed, detoxified, and eliminated from humans – therefore is not a health concern." In the study 20 subjects were tested for BPA every hour for twenty-four hours while consuming three meals consisting of canned food. This study has been criticized, however, as lacking data and having flawed assumptions.
Expert panel conclusions
In 2006, the US Government sponsored an assessment of the scientific literature on BPA. 38 opponents of bisphenol A gathered in Chapel Hill, North Carolina to review several hundred studies on BPA, many conducted by members of the group. At the end of the meeting, the group issued the Chapel Hill Consensus Statement, which stated "BPA at concentrations found in the human body is associated with organizational changes in the prostate, breast, testis, mammary glands, body size, brain structure and chemistry, and behavior of laboratory animals."
The Chapel Hill Consensus Statement claimed that average levels in people are above those that cause harm to many animals in laboratory experiments. They noted that while BPA is not persistent in the environment or in humans, biomonitoring surveys indicate that exposure is continuous, however, which is problematic because acute animal exposure studies are used to estimate daily human exposure to BPA, and no studies that had examined BPA pharmacokinetics in animal models had followed continuous low-level exposures. They added that measurement of BPA levels in serum and other body fluids suggests the possibilities that BPA intake is much higher than accounted for, and/or that BPA can bioaccumulate in some conditions (such as pregnancy). A 2011 study, the first to examine BPA in a continuous low-level exposure throughout the day, did find an increased absorption and accumulation of BPA in the blood of mice.
In 2007, studies indicating harm reported a variety of deleterious effects in rodent offspring exposed in the uterus: abnormal weight gain, insulin resistance, prostate cancer, and excessive mammary gland development.
A panel convened by the U.S. National Institutes of Health in 2007 noted that many of the studies referenced by the Chapel Hill group had methodological problems. This panel could not rule out "some concern" about BPA's effects on fetal and infant brain development and behavior. The concern over the effect of BPA on infants was also heightened by the fact that infants and children are estimated to have the highest daily intake of BPA. A 2008 report by the U.S. National Toxicology Program (NTP) later agreed with the panel, expressing "some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A," and "minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A." The NTP had "negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring."
A 2008 review has concluded that obesity may be increased as a function of BPA exposure, which "...merits concern among scientists and public health officials." A 2009 review of available studies has concluded that "perinatal BPA exposure acts to exert persistent effects on body weight and adiposity". Another 2009 review has concluded that "Eliminating exposures to (BPA) and improving nutrition during development offer the potential for reducing obesity and associated diseases". Other reviews have come with similar conclusions. A later study on rats has suggested that perinatal exposure to drinking water containing 1 **/L of BPA increased adipogenesis in females at weaning. Another study suggested that larger size-for-age was due to a faster growth rate rather than obesity.
A panel convened by 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 report by the U.S. National Toxicology Program (NTP) later agreed with the panel, expressing "some concern for effects on the brain". In January 2010 the FDA expressed the same level of concern.
A 2007 review has concluded that BPA, like other xenoestrogens, should be considered as a player within the nervous system that can regulate or alter its functions through multiple pathways. A 2007 review has concluded that low doses of BPA during development have persistent effects on brain structure, function and behavior in rats and mice. A 2008 review concluded that low-dose BPA maternal exposure causes long-term consequences at the level of neurobehavioral development in mice. A 2008 review has concluded that neonatal exposure to Bisphenol-A (BPA) can affect sexually dimorphic brain morphology and neuronal adult phenotypes in mice. A 2008 review has concluded that BPA altered long-term potentiation in the hippocampus and even nanomolar dosage could induce significant effects on memory processes. A 2009 review raised concerns about BPA effect on anteroventral periventricular nucleus.
A 2008 study by the Yale School of Medicine demonstrated that adverse neurological effects occur in non-human primates regularly exposed to bisphenol A at levels equal to the United States Environmental Protection Agency's (EPA) maximum safe dose of 50 µg/kg/day. This research found a connection between BPA and interference with brain cell connections vital to memory, learning, and mood.
A 2010 study with rats prenatally exposed to 40 µg/kg bw BPA has concluded that corticosterone and its actions in the brain are sensitive to the programming effects of BPA.
Disruption of the dopaminergic system
A 2005 review concluded that prenatal and neonatal exposure to BPA in mice can potentiate the central dopaminergic systems, resulting in the supersensitivity to the drugs-of-abuse-induced reward effects and hyperlocomotion.
A 2008 review has concluded that BPA mimics estrogenic activity and affects various dopaminergic processes to enhance mesolimbic dopamine activity resulting in hyperactivity, attention deficits, and a heightened sensitivity to drugs of abuse.
A 2009 study on rats has concluded that prenatal and neonatal exposure to low-dose BPA causes deficits in development at dorsolateral striatum via altering the function of dopaminergic receptors. Another 2009 study has found associated changes in the dopaminergic system.
A 2007 review has concluded that bisphenol-A has been shown to bind to thyroid hormone receptor and perhaps have selective effects on its functions.
A 2009 review about environmental chemicals and thyroid function raised concerns about BPA effects on triiodothyronine and concluded that "available evidence suggests that governing agencies need to regulate the use of thyroid-disrupting chemicals, particularly as such uses relate exposures of pregnant women, neonates and small children to the agents".
A 2009 review summarized BPA adverse effects on thyroid hormone action.
According to the WHO's INFOSAN, carcinogenicity studies conducted under the US National Toxicology Program, have shown increases in leukaemia and testicular interstitial cell tumours in male rats. However, according to the note "these studies have not been considered as convincing evidence of a potential cancer risk because of the doubtful statistical significance of the small differences in incidences from controls."
A 2010 review at Tufts University Medical School concluded that Bisphenol A may increase cancer risk.
Further information: Risk factors of breast cancer#Bisphenol A
A 2008 review stated that "evidence from animal models is accumulating that perinatal exposure to (...) low doses of (..) BPA, alters breast development and increases breast cancer risk". Another 2008 review concluded that "animal experiments and epidemiological data strengthen the hypothesis that fetal exposure to xenoestrogens may be an underlying cause of the increased incidence of breast cancer observed over the last 50 years".
A 2009 in vitro study has concluded that BPA is able to induce neoplastic transformation in human breast epithelial cells. Another 2009 study concluded that maternal oral exposure to low concentrations of BPA during lactation increases mammary carcinogenesis in a rodent model.
A 2010 study with the mammary glands of the offspring of pregnant rats treated orally with 0, 25 or 250 µg BPA/kg body weight has found that key proteins involved in signaling pathways such as cellular proliferation were regulated at the protein level by BPA.
A 2010 study has found that BPA may reduce sensitivity to chemotherapy treatment of specific tumors.
In vitro studies have suggested that BPA can promote the growth of neuroblastoma cells. A 2010 in vitro study has concluded that BPA potently promotes invasion and metastasis of neuroblastoma cells through overexpression of MMP-2 and MMP-9 as well as downregulation of TIMP2.
Prostate development and cancer
A 1997 study in mice has found that neonatal BPA exposure of 2 μg/kg increased adult prostate weight. A 2005 study in mice has found that neonatal BPA exposure at 10 μg/kg disrupted the development of the fetal mouse prostate. A 2006 study in rats has shown that neonatal bisphenol A exposure at 10 μg/kg levels increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis. A 2007 in vitro study has found that BPA within the range of concentrations currently measured in human serum is associated with permanent increases in prostate size. A 2009 study has found that newborn rats exposed to a low-dose of BPA (10 µg/kg) showed increased prostate cancer susceptibility when adults.
At least one study has suggested that bisphenol A suppresses DNA methylation which is involved in epigenetic changes.
Reproductive system and sexual behavior research
A 2007 study using pregnant mice showed that BPA changes the expression of key developmental genes that form the uterus, which may impact female reproductive tract development and future fertility of female fetuses.
A series of studies made in 2009 found:
- Mouse ovary anomalies from exposure as low as 1 µg/kg, concluded that BPA exposure causes long-term adverse reproductive and carcinogenic effects if exposure occurs during prenatal critical periods of differentiation.
- Neonatal exposure of as low as 50 µg/kg disrupts ovarian development in mice.
- Neonatal BPA exposition of as low as 50 µg/kg permanently alters the hypothalamic estrogen-dependent mechanisms that govern sexual behavior in the adult female rat.
- Prenatal exposure to BPA at levels of (10 μg/kg/day) affects behavioral sexual differentiation in male monkeys.
- In placental JEG3 cells in vitro BPA may reduce estrogen synthesis.
- BPA exposure disrupted the blood-testis barrier when administered to immature, but not to adult, rats.
- Exposure to BPA in the workplace was associated with self-reported adult male sexual dysfunction.
A 2009 rodent study, funded by EPA and conducted by some of its scientists, concluded that, compared with ethinyl estradiol, low-dose exposures of bisphenol A (BPA) showed no effects on several reproductive functions and behavioral activities measured in female rats. That study was criticized as flawed for using polycarbonate cages in the experiment (since polycarbonate contains BPA) and the claimed resistance of the rats to estradiol, but that claim was contested by the authors and others. Another 2009 rodent study found that BPA exposure during pregnancy has a lasting effect on one of the genes that are responsible for uterine development and subsequent fertility in both mice and humans (HOXA10). The authors concluded, "We don't know what a safe level of BPA is, so pregnant women should avoid BPA exposure."
In a 2010 study, mice were given BPA at doses thought to be equivalent to levels currently being experienced by humans. The research showed that BPA exposure affects the earliest stages of egg production in the ovaries of the developing mouse fetuses, thus suggesting that the next generation may suffer genetic defects in such biological processes as mitosis and DNA replication. In addition, the research team noted that their study "revealed a striking down-regulation of mitotic/cell cycle genes, raising the possibility that BPA exposure immediately before meiotic entry might act to shorten the reproductive lifespan of the female" by reducing the total pool of fetal oocytes. Another 2010 study with mice concluded that BPA exposure in utero leads to permanent DNA alterations in sensitivity to estrogen. Also in 2010, a rodent study found that by exposing fetal mice to BPA during pregnancy and examining gene expression and DNA in the uteruses of female fetuses, BPA exposure permanently affected the uterus by decreasing regulation of gene expression. The changes caused the mice to over-respond to estrogen throughout adulthood, long after the BPA exposure, thus suggesting that early exposure to BPA genetically "programmed" the uterus to be hyper-responsive to estrogen. Extreme estrogen sensitivity can lead to fertility problems, advanced puberty, altered mammary development and reproductive function, as well as a variety of hormone-related cancers. One of the authors concluded that BPA may be similar to diethylstilbestrol that caused birth defects and cancers in young women whose mothers were given the drug during pregnancy.
A 2011 study using the rhesus monkey – a species that is very similar to humans in regard to pregnancy and fetal development – found that prenatal exposure to BPA causes changes in female primates' uterus development. A 2011 rodent study found that male rats exposed to BPA had lower sperm counts and testosterone levels than those of unexposed males. A 2011 mice study found that male mice exposed to BPA became demasculinized and behaved more like females in their spatial navigational abilities. They were also less desirable to female mice.