bpa is a thyroid-disrupting chemical, that may especially affect pregnant women, neonates and small children. a 2007 review concluded that bisphenol-a has been shown to bind to thyroid hormone receptor and perhaps has 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. a 2016 case control study found that there was a significant association between urinary bpa levels and increased tsh levels (thyroid- stimulating hormone) in a group of adult women. neurological effects limited epidemiological evidence suggests that exposure to bpa in the uterus and during childhood is associated with poor behavioral outcomes in humans. exposure may be associated with higher levels of anxiety, depression, hyperactivity, and aggression in children. a panel convened by the national toxicology program (ntp) of 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. in january 2010, based on the ntp report, the fda expressed the same level of concern. a 2007 literature review concluded that bpa, like other chemicals that mimic estrogen (xenoestrogens), should be considered as a player within the nervous system that can regulate or alter its functions through multiple pathways. a 2008 review of animal research found that low-dose bpa maternal exposure can cause long-term consequences for the neurobehavioral development in mice. a 2008 review of studies concluded that bpa altered long-term potentiation in the hippocampus and even nanomolar (10−9 mol) dosage could induce significant effects on memory processes. a 2009 review raised concerns about a bpa effect on the anteroventral periventricular nucleus. disruption of the dopaminergic system main article: dopaminergic system a 2008 review 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 2008 review of human participants 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. cancer according to the who's infosan, carcinogenicity studies conducted under the u.s. national toxicology program have shown increases in leukemia and testicular interstitial cell tumors 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 concluded that bisphenol a may increase cancer risk. several studies show evidence that the formation of prostate cancer in men is directly proportional to bpa exposure. male subject diagnosed with prostate cancer were found to have higher urine concentration of bpa as opposed to the concentrations found in the control group's. this correlation may be due to bpa's ability to induce cell proliferation of the prostate cancer cells. breast cancer further information: risk factors of breast cancer § bisphenol a evidence from animal models is accumulating that perinatal exposure to bpa alters breast development and increases breast cancer risk. higher susceptibility to breast cancer has been found in many studies of rodents and primates exposed to bpa. however, it is the impact bpa has on breast cancer development in humans is unclear, as it is difficult to quantify an individual's bpa exposure over their lifetime. bpa, which includes a phenolic structure, has shown an association with agonist and antagonistic endocrine receptors that facilitate endocrine disorders such as breast and prostate cancer. other endocrine disorders include infertility, polycystic ovary syndrome, and precocious puberty. more oxidative stress in breast cancer cells were found to be directly proportional to bpa exposure as per the findings in several in vitro studies. additionally, work related exposure to bpa, and women who are postmenopausal have suggested an increase in breast cancer incidence. mechanism of action bpa is an endocrine disruptor, meaning bpa has a similar structure to oestrogen (ligand) and can bind to the oestrogen receptor erα and erβ and activate it. oestrogen is hydrophobic and is able to diffuse through the plasma membrane and into the target cell. oestradiol binding to the oestrogen receptor releases the heat shock protein from the ligand binding domain of the receptor causing dimerization. the nuclear localisation signal targets the ligand-receptor complex to the nucleus where it can bind oestrogen response elements within the promoter of target genes on dna. subsequently, various cofactors are recruited allowing transcription of genes including those involved in cell proliferation. when bpa is exposed to high temperatures or changes in ph, the ester bond linking bpa monomers is hydrolysed. free bpa then competes with oestrogen for erα and erβ binding sites. when bpa successfully binds the receptor, it interacts with ere and increases expression of target genes like wnt-4 and rankl; two key players in stem cell proliferation and carcinogenesis. bpa was also shown to inactivate p53 which prevents tumour formation as it triggers apoptosis. fertility as of 2022, current evidence shows a possible positive correlation between bpa levels, lower sperm quality, decreased motility and an increase in sperm immaturity. there is tentative evidence to support the idea that bpa exposure has negative effects on human fertility. few studies have investigated whether recurrent miscarriage is associated with bpa levels. exposure to bpa does not appear to be linked with higher rates of endometrial hyperplasia. exposure to bpa does not appear to be linked with higher rates of endometrial hyperplasia. a 2009 cohort study linked urinary bpa concentration of women undergoing ivf egg retrieval, with an inverse correlation to oocyte release. the study found that for each unit increase in day 3 fsh (iu/l), there was an average decrease of 9 in the number of oocytes retrieved. the positive correlations found in animal studies warrants the continued research of bpa for couple fecundity. ubiquitous in environment through consumer products such as reusable plastics, food and beverage container liners, baby bottles, water resistant clothing. it has been identified as an edc and found in urine, blood, amniotic fluid, breast milk and cord blood. comparing blood bpa and phthalate levels between fertile and infertile women between the ages of 20–40, using gas chromatographic-mass spectrometry to analyze the amount of bpa, phthalate and their metabolites in peripheral venous blood, showed significantly elevated serum bpa level in infertile women, as well as women with pcos (polycystic ovarian syndrome) and women with endometriosis bpa is shown to have transgenerational effect by targeting ovarian function by changes in the structural integrity of microtubules that constitute meiotic spindles. bpa contaminants pass through amniotic fluid can alter steroidogenesis in fetal development. this will result if oocyte maturation failure as well as fertility this in turn will result in transgenerational effect and affect the third generation of offspring sexual function higher bpa exposure has been associated with increased self-reporting of decreased male sexual function but few studies examining this relationship have been conducted. asthma studies in mice have found a link between bpa exposure and asthma; a 2010 study on mice has concluded that perinatal exposure to 10 µg/ml of bpa in drinking water enhances allergic sensitization and bronchial inflammation and responsiveness in an animal model of asthma. a study published in jama pediatrics has found that prenatal exposure to bpa is also linked to lower lung capacity in some young children. this study had 398 mother-infant pairs and looked at their urine samples to detect concentrations of bpa. they study found that every 10-fold increase in bpa was tied to a 55% increase in the odds of wheezing. the higher the concentration of bpa during pregnancy were linked to decrease lung capacity in children under four years old but the link disappeared at age 5. associate professor of pediatrics at the university of maryland school of medicine said, "exposure during pregnancy, not after, appears to be the critical time for bpa, possibly because it's affecting important pathways that help the lung develop." in 2013, research from scientists at the columbia center for children's environmental health also found a link between the compound and an increased risk for asthma. the research team reported that children with higher levels of bpa at ages 3, 5 and 7 had increased odds of developing asthma when they were between the ages of 5 and 12. the children in this study had about the same concentration of bpa exposure as the average u.s child. dr. kathleen donohue, an instructor at columbia university medical center said, "they saw an increased risk of asthma at fairly routine, low doses of bpa." kim harley, who studies environmental chemicals and children's health, commented in the scientific american journal saying while the study does not show that bpa causes asthma or wheezing, "it's an important study because we don't know a lot right now about how bpa affects immune response and asthma...they measured bpa at different ages, measured asthma and wheeze at multiple points, and still found consistent associations." animal research the first evidence of the estrogenicity of bisphenol a came from experiments on rats conducted in the 1930s, but it was not until 1997 that adverse effects of low-dose exposure on laboratory animals were first reported. bisphenol a is an endocrine disruptor that can mimic estrogen and has been shown to cause negative health effects in animal studies. bisphenol a closely mimics the structure and function of the hormone estradiol by binding to and activating the same estrogen receptor as the natural hormone. early developmental stages appear to be the period of greatest sensitivity to its effects, a study from 2008 concluded that blood levels of bisphenol a in neonatal mice are the same whether it is injected or ingested. the current u.s. human exposure limit set by the epa is 50 µg/kg/day. in a 2010 commentary a group of scientists criticized a study designed to test low dose bpa exposure published in "toxicological sciences" and a later editorial by the same journal, which claimed the rats used in the study were insensitive to estrogen and that had other problems like the use of bpa-containing polycabonate cages while the authors disagreed. 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. environmental effects in 2010, the u.s. environmental protection agency reported that over one million pounds of bpa are released into the environment annually. bpa can be released into the environment by both pre-consumer and post-consumer leaching. common routes of introduction from the pre-consumer perspective into the environment are directly from chemical plastics, coat and staining manufacturers, foundries who use bpa in casting sand, or transport of bpa and bpa-containing products . post-consumer bpa waste comes from effluent discharge from municipal wastewater treatment plants, irrigation pipes used in agriculture, ocean-borne plastic trash, indirect leaching from plastic, paper, and metal waste in landfills, and paper or material recycling companies. despite a rapid soil and water half-life of 4.5 days, and an air half-life of less than one day, bpa's ubiquity makes it an important pollutant. bpa has a low rate of evaporation from water and soil, which presents issues, despite its biodegradability and low concern for bio-accumulation. bpa has low volatility in the atmosphere and a low vapor pressure between 5.00 and 5.32 pascals. bpa has a high water solubility of about 120 mg/l and most of its reactions in the environment are aqueous. an interesting fact is that bpa dust is flammable if ignited, but it has a minimal explosive concentration in air. also, in aqueous solutions, bpa has shown absorption of wavelengths greater than 250 nm. the ubiquitous nature of bpa makes the compound an important pollutant to study as it has been shown to interfere with nitrogen fixation at the roots of leguminous plants associated with the bacterial symbiont sinorhizobium meliloti. a 2013 study also observed changes in plant health due to bpa exposure. the study exposed soybean seedlings to various concentrations of bpa and saw changes