the body through the urine. this allows exposure to be easily determined by urine testing, facilitating convenient biomonitoring of populations. health effects and regulation main article: health effects of bisphenol a the health effects of bpa have been the subject of prolonged public and scientific debate, with pubmed listing more than 17,000 scientific papers as of 2023. concern is mostly related to its estrogen-like activity, although it can interact with other receptor systems as an endocrine-disrupting chemical. these interactions are all very weak, but exposure to bpa is effectively lifelong, leading to concern over possible cumulative effects. studying this sort of long‑term, low‑dose interaction is difficult, and although there have been numerous studies, there are considerable discrepancies in their conclusions regarding the nature of the effects observed as well as the levels at which they occur. a common criticism is that industry-sponsored trials tend to show bpa as being safer than studies performed by academic or government laboratories, although this has also been explained in terms of industry studies being better designed. public health agencies in the eu, us, canada, australia and japan as well as the who have all reviewed the health risks of bpa, and found normal exposure to be below the level currently associated with risk. regardless, due to the scientific uncertainty, many jurisdictions have taken steps to reduce exposure on a precautionary basis. in particular, infants are considered to be at greater risk, leading to bans on the use of bpa in baby bottles and related products by the us, canada, and eu amongst others. bottle producers have largely switched from polycarbonate to polypropylene and there is some evidence that bpa exposure in infants has decreased as a result of this. the european chemicals agency has added bpa to the candidate list of substances of very high concern (svhc), which would make it easier to restrict or ban its use in future. bpa exhibits very low acute toxicity as indicated by its ld50 of 4 g/kg (mouse). reports indicate that it is a minor skin irritant as well, although less so than phenol. pharmacology overlay of estradiol, the major female sex hormone in humans (green) and bpa (purple). this displays the structure–activity relationship which allows bpa to mimic the effects of estradiol and other estrogens. bpa has been found to interact with a diverse range of hormone receptors, in both humans and animals. it binds to both of the nuclear estrogen receptors (ers), erα and erβ. bpa can both mimic the action of estrogen and antagonise estrogen, indicating that it is a selective estrogen receptor modulator (serm) or partial agonist of the er. although it is 1000- to 2000-fold less potent than estradiol, the major female sex hormone in humans. at high concentrations, bpa also binds to and acts as an antagonist of the androgen receptor (ar). in addition to receptor binding, the compound has been found to affect leydig cell steroidogenesis, including affecting 17α-hydroxylase/17,20 lyase and aromatase expression and interfering with lh receptor-ligand binding. bisphenol a's interacts with the estrogen-related receptor γ (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 only weakly to the er. bpa binding to err-γ preserves its basal constitutive activity. it can also protect it from deactivation from the serm 4-hydroxytamoxifen (afimoxifene). this may be the mechanism by which bpa acts as a xenoestrogen. different expression of err-γ in different parts of the body may account for variations in bisphenol a effects. bpa has also been found to act as an agonist of the gper (gpr30). environmental safety distribution and degradation bpa has been detectable in the natural environment since the 1990s and is now widely distributed. it is primarily a river pollutant, but has also been observed in the marine environment, in soils, and lower levels can also be detected in air. the solubility of bpa in water is low (~300 g/ton of water) but this is still sufficient to make it a significant means of distribution into the environment. many of the largest sources of bpa pollution are water-based, particularly wastewater from industrial facilities using bpa. paper recycling can be a major source of release when this includes thermal paper, leaching from pvc items may also be a significant source, as can landfill leachate. in all cases, wastewater treatment can be highly effective at removing bpa, giving reductions of 91–98%. regardless, the remaining 2–9% of bpa will continue through to the environment, with low levels of bpa commonly observed in surface water and sediment in the u.s. and europe. once in the environment bpa is aerobically biodegraded by a wide a variety of organisms. its half life in water has been estimated at between 4.5 and 15 days, degradation in the air is faster than this, while soil samples degrade more slowly. bpa in sediment degrades most slowly of all, particularly where this is anaerobic. abiotic degradation has been reported, but is generally slower than biodegradation. pathways include photo-oxidation, or reactions with minerals such as goethite which may be present in soils and sediments. environmental effects bpa is an environmental contaminant of emerging concern. despite its short half-life and non-bioaccumulating character, the continuous release of bpa into the environment causes continuous exposure to both plant and animal life. although many studies have been performed, these often focus on a limited range of model organisms and can use bpa concentrations well beyond environmental levels. as such, the precise effects of bpa on the growth, reproduction, and development of aquatic organism is not fully understood. regardless, the existing data shows the effects of bpa on wildlife to be generally negative. bpa appears able to affect development and reproduction in a wide range of wildlife, with certain species being particularly sensitive, such as invertebrates and amphibians.