Bisphenol A

From Wikipedia, the free encyclopedia
Jump to: navigation, search
The English used in this article or section may not be easy for everybody to understand.
 You can help Wikipedia by reading Wikipedia:How to write Simple English pages, then simplifying the article. (January 2012)
Bisphenol A
Bisphenol A.svg
Bisphenol A.png
IUPAC name 4,4'-(propane-2,2-diyl)diphenol
Other names BPA, p,p'-isopropylidenebisphenol,
2,2-bis(4-hydroxyphenyl)propane.
Identifiers
CAS number 80-05-7
PubChem 6623
EC number 201-245-8
DrugBank DB06973
KEGG C13624
ChEBI CHEBI:33216
RTECS number SL6300000
SMILES Oc1ccc(cc1)C(c2ccc(O)cc2)(C)C
Properties
Molecular formula C15H16O2
Molar mass 228.28 g mol-1
Appearance White to light brown flakes or powder
Density 1.20 g/cm³, solid
Melting point

158 to 159 °C (430 K)
Boiling point

220 °C (493 K) / 4 mmHg
Solubility in water 120–300 ppm (at 21.5 °C)
Hazards
NFPA 704

NFPA 704.svg

0
3
0
 
R-phrases R36, R37, R38, R43
S-phrases S24, S26, S37
Flash point 227 °C
Related compounds
Related compounds phenols
Bisphenol S
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

Bisphenol A (BPA) is an organic compound with two phenol functional groups. It is used to make polycarbonate plastic, epoxy resins, and other things.

Scientist found out in the mid 1930s that people and animals react to BPA as if it were a hormone (estrogenic effects.) Government reports say BPA is not safe for humans. So, in 2008, some retail stores removed products made with BPA. Many news stories wrote about BPA safety.

A 2010 report from the United States Food and Drug Administration (FDA) warned about harm when fetuses, infants and young children contact BPA.[1] In September 2010, Canada became the first country to declare BPA as a toxic substance.[2][3] In the European Union and Canada, BPA can not be used to make baby bottles.[4]

Contents

[change] Production

The world could make 1 million tonnes of BPA per year in the 1980s,[5] and more than 2.2 million tonnes in 2009.[6] In 2003, U.S. consumption was 856,000 tonnes, 72% of which was used to make polycarbonate plastic and 21% going into epoxy resins.[7] In the US, less than 5% of the BPA made each year is used in ways that would touch food.[8]

Bisphenol A was first made in a laboratory by the Russian chemist A.P. Dianin in 1891.[9][10] This compound is synthesized by the condensation of two equivalents of phenol with acetone. (That is why its name ends with a capital letter A.)[11] The reaction is catalyzed by a strong acid, such as hydrochloric acid (HCl) or a sulfonated polystyrene resin. When large batches are made in factories, a large excess of phenol is used to ensure full condensation. The product mixture of the cumene process (acetone and phenol) may also be used as starting material:[5]

Synthesis of bisphenol A from phenol and acetone

Many types of ketones (other than phenol) can make a condensation reaction under these conditions. When factories make BPA, the BPA must be separated from the resin impurities that are made from these other ketones. So, after the BPA is made, the factories separate the BPA from many resinous byproducts under high vacuum, or solvent-based extraction using additional phenol followed by distillation.[5]

[change] Use

Further information: Polycarbonate

Most bisphenol A is used to make plastics. Commercial products containing bisphenol A-based plastics have been used since 1957.[12] Manufacturers use at least 8 billion pounds of BPA each year.[13] It is a key monomer in production of epoxy resins[14][15] and in the most common form of polycarbonate plastic.[5][16][17] The chemical equation to make polycarbonate is:

Polycarbonatsynthese.svg

Polycarbonate plastic, which is clear and nearly shatter-proof, is used to make a variety of common products including baby and water bottles, sports equipment, medical and dental devices, dental fillings and sealants, eyeglass lenses, CDs and DVDs, and household electronics.[7] BPA is also used in the synthesis of polysulfones and polyether ketones, as an antioxidant in some plasticizers, and as a polymerization inhibitor in PVC. Epoxy resins containing bisphenol A are used as coatings on the inside of almost all food and beverage cans,[18] however, due to BPA health concerns, in Japan epoxy coating was mostly replaced by PET film.[19] Bisphenol A is also a precursor to the flame retardant tetrabromobisphenol A, and was formerly used as a fungicide.[20] Bisphenol A is a preferred color developer in carbonless copy paper and thermal paper,[21] with the most common public exposure coming from some[22] thermal point of sale receipt paper.[23][24] BPA-based products are also used in foundry castings and for lining water pipes.[8]

[change] Identification in plastics

Main page: Resin identification code
Some type 7 plastics may leak bisphenol A
Flexible type 3 plastics may leak bisphenol A

The chemical industry puts a symbol on plastic items to identify the type of plastic. "In general, plastics that are marked with recycle codes 1, 2, 4, 5, and 6 are very unlikely to contain BPA. Some, but not all, plastics that are marked with recycle codes 3 or 7 may be made with BPA."[25]

There are seven classes of plastics used in packaging applications. Type 7 is the catch-all "other" class, and some type 7 plastics, such as polycarbonate (sometimes identified with the letters "PC" near the recycling symbol) and epoxy resins, are made from bisphenol A monomer.[5] When such plastics are exposed to hot liquids, bisphenol A leaks out 55 times faster than it does under normal conditions.[26]

Type 3 (PVC) can also contain bisphenol A as an antioxidant in plasticizers.[5] This is particularly true for "flexible PVC". It is generally not true for rigid PVC pipes.

[change] Health effects

Bisphenol A hurts the way hormones regulate the human body (endocrine disruptor). BPA can pretend to be the body's own hormones. BPA may lead to negative health effects.[27][28][29][30] Very young children are most sensitive to BPA.[31] Some studies have linked BPA exposure before birth (prenatal) to later neurological difficulties. Regulatory bodies have determined safety levels for humans, but those safety levels are currently being questioned or under review as a result of new scientific studies.[32][33] A 2011 study that investigated the number of chemicals to which pregnant women in the U.S. are exposed found BPA in 96% of women.[34]

In 2009, The Endocrine Society said it was concerned over current human exposure to BPA.[35]

In 2011, the United Kingdom Food Standards Agency's chief scientist said "the evidence [is] that BPA is rapidly absorbed, detoxified, and eliminated from humans – therefore is not a health concern."[36]

[change] Expert panel conclusions

In 2007, 38 experts on bisphenol A wrote a consensus statement which said average levels in people are above those that cause harm to many animals in laboratory experiments. However, the experts noted that 1) BPA is not persistent in the environment or in humans, 2) biomonitoring surveys indicate that exposure is continuous, 3) it is hard to use acute animal exposure studies to estimate daily human exposure to BPA, and 4) no studies that had examined BPA pharmacokinetics in animal models had followed continuous low level exposures. The measurement of BPA levels in human serum and other body fluids suggests that either BPA intake is much higher than previously thought or that BPA can bioaccumulate in some conditions such as pregnancy, or both.[37] 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.[38]

In 2007, 153 government-funded BPA experiments on lab animals and tissues found adverse effects and 14 did not. In contrast, all 13 studies funded by chemical corporations reported no harm. The studies indicating harm reported a variety of deleterious effects in rodent offspring exposed in the womb: abnormal weight gain, insulin resistance, prostate cancer, and too much mammary gland development.[39]

A panel convened by the U.S. National Institutes of Health in 2007 determined that there was "some concern" about BPA's effects on fetal and infant brain development and behavior.[7] 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.[40] 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."[41]

[change] Obesity

A 2008 review has concluded that BPA exposure increases obesity, which "merits concern among scientists and public health officials".[42] A 2009 review of available studies has concluded that "perinatal BPA exposure acts to exert persistent effects on body weight and adiposity".[43] Another 2009 review has concluded that "Eliminating exposures to (BPA) and improving nutrition during development offer the potential for reducing obesity and associated diseases".[44] Other reviews have come with similar conclusions.[45][46] A later study on rats has suggested that perinatal exposure to drinking water containing 1 mg/L of BPA increased adipogenesis in females at weaning.[47] Another study suggested that larger size-for-age was due to a faster growth rate rather than obesity.[48]

[change] Neurological issues

A U.S. National Institutes of Health panel determined that there was "some concern" about BPA's effects on fetal and infant brain development and behavior.[7] A 2008 report by the U.S. National Toxicology Program (NTP) later agreed with the panel, expressing "some concern for effects on the brain".[41] In January 2010 the FDA expressed the same level of concern.

A 2007 review has concluded that BPA, like other xenoestrogens, can affect the human nervous system. BPA can regulate or alter nervous system functions several possible ways.[49] A 2007 review article said that low doses of BPA during development have long-term effects on brain structure, function and behavior in rats and mice.[50] A 2008 review concluded that low-dose BPA maternal exposure causes long-term consequences at the level of neurobehavioral development in mice.[51] A 2008 review concluded that exposure to BPA before birth (neonatal) can affect sexually dimorphic brain morphology and neuronal adult phenotypes in mice.[52] A 2008 review has concluded that BPA altered long-term potentiation in the hippocampus. Even a nanomolar BPA dosage could cause significant effects on memory.[53] A 2009 review raised concerns about BPA effect on anteroventral periventricular nucleus.[54]

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.[55][56] 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 microg/kg bw BPA has concluded that corticosterone and its actions in the brain are sensitive to the programming effects of BPA.[57]

[change] Disruption of the dopaminergic system

A 2005 review concluded that prenatal and neonatal exposure to BPA in mice can make the central dopaminergic systems more active. This can result in the supersensitivity to the drugs-of-abuse-induced reward effects and hyperlocomotion.[58]

A 2008 review has concluded that BPA mimics estrogenic activity and impacts various dopaminergic processes to enhance mesolimbic dopamine activity. This can result in hyperactivity, attention deficits, and higher sensitivity to drugs of abuse.[59]

A 2009 study on rats has concluded that prenatal and neonatal exposure to low-dose BPA causes deficits in development at dorsolateral striatum by altering the function of dopaminergic receptors.[60] Another 2009 study has found associated changes in the dopaminergic system.[61]

[change] Thyroid function

A 2007 review has concluded that bisphenol A has been shown to bind to thyroid hormone receptor. BPA may have selective effects on thyroid functions.[62]

A 2009 review about environmental chemicals and thyroid function raised concerns about BPA effects on triiodothyronine. It 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".[63]

A 2009 review summarized BPA adverse effects on thyroid hormone action.[64]

[change] Cancer research

According to the WHO's INFOSAN, "animal studies have not provided convincing evidence of risk of cancer from BPA exposure."[65]

Neither the U.S. Environmental Protection Agency[66] nor the International Agency for Research on Cancer[67] has evaluated bisphenol A for possible carcinogenic activity.

A 2010 review at Tufts University Medical School concluded that Bisphenol A may increase the chances that a person will get cancer.[68]

[change] Breast cancer

Further information: Risk factors of breast cancer#Bisphenol A

A 2008 review concluded that "perinatal exposure to (...) low doses of (..) BPA, alters breast development and increases breast cancer risk".[69] 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".[70]

A 2009 laboratory (in vitro) study concluded that BPA is able to induce neoplastic transformation in human breast epithelial cells.[71] Another 2009 study concluded that maternal oral exposure to low concentrations of BPA during lactation increases mammary carcinogenesis in a rodent model.[72]

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 BPA regulated (at the protein level) key proteins involved in signaling pathways such as cellular proliferation.[73]

A 2010 study has found that BPA may reduce sensitivity to chemotherapy treatment of specific tumors.[74]

[change] Neuroblastoma

In vitro studies have suggested that BPA can promote the growth of neuroblastoma cells.[75][76] A 2010 in vitro study has concluded that BPA potently promote invasion and metastasis of neuroblastoma cells through overexpression of MMP-2 and MMP-9 as well as downregulation of TIMP2.[77]

[change] Prostate development and cancer

A 1997 study in mice has found that neonatal BPA exposure of 2 μg/kg increased adult prostate weight.[78] A 2005 study in mice has found that neonatal BPA exposure at 10 μg/kg disrupted the development of the fetal mouse prostate.[79] 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.[80] A 2007 in vitro study has found that BPA within the range of concentrations currently measured in human serum is associated with permanently increase in prostate size.[81] A 2009 study has found that newborn rats exposed to a low-dose of BPA (10 µg/kg) increased the prostate cancer rates when those rats become adults.[82]

[change] DNA methylation

Bisphenol A suppresses deoxyribonucleic acid (DNA) methylation[83] which is linked to epigenetic changes.[84]

[change] Reproductive system and sexual behavior research

In 2007, biologists found that BPA changes the expression of key developmental genes that form the uterus in female mice embryos. For example, it affects the HOXA10 gene. This may impact female reproductive tract development and the future fertility of female fetuses the mother is carrying.[85]

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.[86]
  • Neonatal exposure of as low as 50 µg/kg disrupts development of ovaries in mice.[87][88][89]
  • 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.[90]
  • Prenatal exposure to BPA at levels of (10 μg/kg/day) affects behavioral sexual differentiation in male monkeys.[91]
  • In placental JEG3 cells in vitro BPA may reduce estrogen synthesis.[92]
  • BPA exposure disrupted the blood-testis barrier when administered to young rats. But, it did not disrupt the barrier in adult rats.[93]
  • When adult men are exposed to BPA at work, the men are more likely to self-report sexual dysfunction.[94]

In 2009, the scientists at the United States Environmental Protection Agency (EPA) studied rodents exposed to either ethinyl estradiol or to low-dose exposures of bisphenol A. There was no difference between the two groups regarding several reproductive functions and behavioral activities measured in female rats.[95] 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,[96] but that claim was contested by the authors and others.[97] Another 2009 rodent study found that BPA exposure during pregnancy has a lasting effect on one of the genes that is 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."[98]

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. This suggests 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.[99] Another 2010 study with mice concluded that BPA exposure in utero leads to permanent DNA alterations in sensitivity to estrogen.[100] 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. This suggests 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 caused birth defects and cancers in young women whose mothers were given the drug during pregnancy.[101]

A 2011 study found that prenatal exposure to BPA causes changes in female rhesus monkey's uterus development. (The rhesus monkey is a species that is very similar to humans in regard to pregnancy and fetal development.)[102] A 2011 rodent study found that male rats exposed to BPA had lower sperm counts and testosterone levels than those of unexposed males.[103] A 2011 mice study found that male mice exposed to BPA became demasculinized and behaved more like females in their spatial navigational abilities. The BPA-exposed male mice were also less desirable to female mice.[104]

[change] General research

At an Endocrine Society meeting in 2009, new research reported data from animals experimentally treated with BPA.[105] Studies presented at the group's annual meeting show BPA can affect the hearts of women, can permanently damage the DNA of mice, and appear to be entering the human body from a variety of unknown sources.[106]

A 2009 in vitro study on cytotrophoblasts cells has found cytoxic effects in exposure of BPA doses from 0.0002 to 0.2 micrograms per millilitre and concluded this finding "suggests that exposure of placental cells to low doses of BPA may cause detrimental effects, leading in vivo to adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction, prematurity and pregnancy loss"[107]

A 2009 study in rats concluded that BPA, at the reference safe limit for human exposure, was found to impact intestinal permeability and may represent a risk factor in female offspring for developing severe colonic inflammation in adulthood.[108]

A 2010 study on mice has concluded that perinatal exposure to 10 micrograms/mL of BPA in drinking water enhances allergic sensitization and bronchial inflammation and responsiveness in an animal model of asthma,[109]and a 2011 study found that higher BPA concentrations in the urine of the pregnant women at 16 weeks were associated with wheezing, a symptom of asthma, in their babies.[110]

[change] Studies on humans

[change] Lang study and heart disease

The first large study of health effects on humans associated with bisphenol A exposure was published in September 2008 by Iain Lang and colleagues in the Journal of the American Medical Association.[111][112] The cross-sectional study of almost 1,500 people assessed exposure to bisphenol A by looking at levels of the chemical in urine. The authors found that higher bisphenol A levels were significantly associated with heart disease, diabetes, and abnormally high levels of certain liver enzymes. An editorial in the same issue concludes:

"Based on this background information, the study by Lang et al.,1​ while preliminary with regard to these diseases in humans, should spur US regulatory agencies to follow the recent action taken by Canadian regulatory agencies, which have declared BPA a “toxic chemical” requiring aggressive action to limit human and environmental exposures.4 Alternatively, Congressional action could follow the precedent set with the recent passage of federal legislation designed to limit exposures to another family of compounds, phthalates, also used in plastic. Like BPA,5​ phthalates are detectable in virtually everyone in the United States.6 This bill moves US policy closer to the European model, in which industry must provide data on the safety of a chemical before it can be used in products."[30][113]

A later similar study performed by the same group of scientists, published in January 2010, confirmed, despite of lower concentrations of BPA in the second study sample, an associated increased risk for heart disease but not for diabetes or liver enzymes. Patients with the highest levels of BPA in their urine carried a 33% increased risk of coronary heart disease.[114]

[change] Other studies

Studies have associated recurrent miscarriage with BPA serum concentrations,[115] oxidative stress and inflammation in postmenopausal women with urinary concentrations,[116] externalizing behaviors in two-year old children, especially among female children, with mother's urinary concentrations,[117] altered hormone levels in men[118][119] and declining male sexual function[120] with urinary concentrations. The Canadian Health Measures Survey, 2007 to 2009 published in 2010 found that teenagers carry 30 percent more l bisphenol A (BPA) in their bodies than older adults. The reason for this is not known.[121] A 2010 study that analyzed BPA urinary concentrations has concluded that for people under 18 years of age BPA may negatively impact human immune function.[122] A study done in 2010 reported the daily excretion levels of BPA among European adults in a large-scale and high-quality population-based sample, and it was shown that higher BPA daily excretion was associated with an increase in serum total testosterone concentration in men.[123] A 2011 study found higher BPA levels in women with polycystic ovary syndrome compared to controls. Furthermore, researchers found a statistically significant positive association between male sex hormones and BPA in these women suggesting a potential role of BPA in ovarian dysfunction.[124] A 2010 study found that people over age 18 with higher levels of BPA exposure had higher CMV antibody levels, which suggests their cell-mediated immune system may not be functioning properly.[125]

[change] Sexual difficulties

A 2009 study on Chinese workers in BPA factories found that workers were four times more likely to report erectile dysfunction, reduced sexual desire and overall dissatisfaction with their sex life than workers with no heightened BPA exposure.[126] BPA workers were also seven times more likely to have ejaculation difficulties. They were also more likely to report reduced sexual function within one year of beginning employment at the factory, and the higher the exposure, the more likely they were to have sexual difficulties.[127]

[change] Historical studies

The first evidence of the estrogenicity of bisphenol A came from experiments on rats conducted in the 1930s,[128][129] but it was not until 1997 that adverse effects of low-dose exposure on laboratory animals were first reported.[18]

[change] Low-dose exposure in animals

Dose (µg/kg/day) Effects (measured in studies of mice or rats,
descriptions (in quotes) are from Environmental Working Group)[130][131]		 Study Year
0.025 "Permanent changes to genital tract" 2005[132]
0.025 "Changes in breast tissue that predispose cells to hormones and carcinogens" 2005[133]
1 long-term adverse reproductive and carcinogenic effects 2009[86]
2 "increased prostate weight 30%" 1997[134]
2 "lower bodyweight, increase of anogenital distance in both genders, signs of early puberty and longer estrus." 2002[135]
2.4 "Decline in testicular testosterone" 2004[136]
2.5 "Breast cells predisposed to cancer" 2007[137]
10 "Prostate cells more sensitive to hormones and cancer" 2006[138]
10 "Decreased maternal behaviors" 2002[139]
30 "Reversed the normal sex differences in brain structure and behavior" 2003[140]
50 Adverse neurological effects occur in non-human primates 2008[55]
50 Disrupts ovarian development 2009[87]

The current U.S. human exposure limit set by the EPA is 50 µg/kg/day.[141]


[change] Xenoestrogen

There is evidence that bisphenol A functions as a xenoestrogen by binding strongly to estrogen-related receptor γ (ERR-γ).[142] This orphan receptor (endogenous ligand unknown) acts as a constitutive activator of transcription. BPA seems to bind strongly to ERR-γ. (Its dissociation constant is 5.5 nM.) But BPA does not bind to the estrogen receptor (ER).[142] BPA binding to ERR-γ preserves its basal constitutive activity.[142] It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxytamoxifen.[142]

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.[143]

[change] Human exposure sources

“ The problem is, BPA is also a synthetic estrogen, and plastics with BPA can break down, especially when they're washed, heated or stressed, allowing the chemical to leach into food and water and then enter the human body. That happens to nearly all of us; the CDC has found BPA in the urine of 93% of surveyed Americans over the age of 6. If you don't have BPA in your body, you're not living in the modern world. ”

—The Perils of Plastic, TIME Magazine[144]

Bisphenol A can leached from the plastic lining of canned foods[145] and polycarbonate plastics, especially those that are cleaned with harsh detergents or those which contain acidic or high-temperature liquids. BPA is an ingredient in the internal coating of metal food and beverage cans used to protect the food from direct contact with the can. A recent Health Canada study found that the majority of canned soft drinks it tested had low, but measurable levels of bisphenol A.[146] Also, in 2010, the University of Texas School of Public Health found BPA in 63 of 105 samples of fresh and canned foods, foods sold in plastic packaging, and in cat and dog foods in cans and plastic packaging. This included fresh turkey, canned green beans, and canned infant formula. [147] While most human exposure is through diet, exposure can also occur through air and through skin absorption.[148]

A 2011 study published in Environmental Health Perspectives, “Food Packaging and Bisphenol A and Bis(2-Ethyhexyl) Phthalate Exposure: Findings from a Dietary Intervention," selected 20 participants based on their self-reported use of canned and packaged foods to study BPA. Participants ate their usual diets, followed by three days of consuming foods that were not canned or packaged. The study's findings include: 1) evidence of BPA in participants’ urine decreased by 50% to 70% during the period of eating fresh foods; and 2), participants’ reports of their food practices suggested that consumption of canned foods and beverages and restaurant meals were the most likely sources of exposure to BPA in their usual diets. The researchers note that, even beyond these 20 participants, BPA exposure is widespread, with detectable levels in urine samples in more than an estimated 90% of the U.S. population.[149]

BPA is used both by itself (Free BPA) and also bound into resins or plastics. Thermal paper and carbonless copy paper have a high concentration of free BPA.[24][150][151] Popular uses of thermal paper include receipts, event and cinema tickets, labels, and airline tickets. A Swiss study found that 11 of 13 thermal printing papers contained 8 - 17 g/kg Bisphenol A (BPA). Upon dry finger contact with a thermal paper receipt, roughly 1 μg BPA (0.2 – 6 μg) was transferred to the forefinger and the middle finger. For wet or greasy fingers approximately 10 times more was transferred. Scientists could find BPA on people's fingers up to 2 hours after they touched the paper receipts.[152] While there is little concern for dermal absorption of BPA, free BPA can readily be transferred to skin and residues on hands can be ingested.[8]

Studies conducted by the CDC found bisphenol A in the urine of 95% of adults sampled in 1988–1994[153] and in 93% of children and adults tested in 2003–04.[154] While the EPA considers exposures up to 50 µg/kg/day to be safe, the most sensitive animal studies show effects at much lower doses.[130][155]

In 2009, a study found that drinking from polycarbonate bottles increased bisphenol A levels in urine by two thirds, from 1.2 micrograms/gram creatinine to 2 micrograms/gram creatinine.[156] 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.[157] In order 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.[158] In the U.S., consumption of soda, school lunches, and meals prepared outside the home was statistically significantly associated with higher BPA in urine.[159]

BPA is also used to form epoxy resin coating of water pipes. In older buildings, such resin coatings are used to avoid replacement of deteriorating hot and cold water pipes.[160]

[change] Fetal and Early Childhood Exposures

Children may be more sensitive to BPA exposure than adults. A recent study found higher BPA concentrations in the urine of young children than in adults under typical exposure conditions.[161] This increased susceptibility is most likely based on chidren's reduced capacity to eliminate xenobiotics[162] and also their estimated higher daily exposure to BPA, adjusted for weight, compared to adults.[163]

Infants fed with liquid formula are among the most exposed, and those fed formula from polycarbonate bottles can consume up to 13 micrograms of bisphenol A per kg of body weight per day (μg/kg/day; see table below).[164] In the US and Canada, BPA has been found in infant liquid formula in concentrations varying from 0.48 to 11 ng/g.[165][166] BPA has been rarely found in infant powder formula (only 1 of 14).[165] While breast milk is the optimal source of nutrition for infants, it is not always an option. The U.S. Department of Health & Human Services (HHS) states that "the benefit of a stable source of good nutrition from infant formula and food outweighs the potential risk of BPA exposure.".[167]

A 2010 study of people in Austria, Switzerland, and Germany has suggested polycarbonate (PC) baby bottles as the most prominent role of exposure for infants, and canned food for adults and teenagers.[168] In the United States, the growing concern over BPA exposure in infants in recent years has lead the manufacturers of plastic baby bottles to stop using BPA in their bottles. However, babies may still be exposed if they are fed with old or hand-me-down bottles bought before the companies stopped using 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.[169] A small US study in 2009, funded by the EWG, detected an average of 2.8 ng/mL BPA in the blood of 9 out of the 10 umbilical cords tested.[170] After the baby is born, maternal exposure can continue to effect the infant through transfer of BPA to the infant via breast milk.[171][172] Because of these exposures that can occur both during and after pregnancy, mothers wishing to limit their child’s exposure to BPA should attempt to limit their own exposures during that time period.

While the majority of exposures have been shown to come through the diet, accidental ingestion can also be considered a source of exposure. One study conducted in Japan tested plastic baby books to look for possible leaching into saliva when babies chew on them.[173] While the results of this study have yet to be replicated, it gives reason to question whether exposure can also occur in infants through ingestion by chewing on certain books or toys.


Population Estimated daily bisphenol A intake, μg/kg/day.
Table adapted from the National Toxicology Program Expert Panel Report.
Infant (0–6 months)
formula-fed
1–24
Infant (0–6 months)
breast-fed
0.2–1
Infant (6–12 months)
1.65–13
Child (1.5–6 years)
0.043–14.7
Adult
0.008–1.5

[change] Pharmacokinetics

Physiologically-based pharmacokinetic (PBPK) modeling is a mathematical representation of the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animals. Scientists do not agree on a PBPK BPA model for humans. The effects of BPA on an organism depend on how much free BPA is available and how long cells are exposed to it. Glucuronidation in the liver, by conjugation with glucuronic acid to form the metabolite BPA-glucuronide (BPAG),[8] reduces the amount of free BPA, however BPAG can be deconjugated by the enzyme beta-glucuronidase. (A high concentration of beta-glucuronidase is in the placenta and other tissues.[174][175]) Free BPA can also be inactivated by sulfation, a process that can also be reverted by arylsulfatase C.[174] A 2010 vitro study has shown that placenta P-glycoprotein may cause BPA to flow out of placenta cells.[176]

Scientists disagree on the best test methods for studying BPA effects.[177]

A 2010 review of 80+ biomonitoring studies concluded that the general population is internally exposed to significant amounts of unconjugated BPA (in the ng/ml blood range).[178] Using GC/MS on 20 samples, BPA was detected in 100% of urine samples with a median of 1.25 ng/ml, and 10% of blood samples (LOD 0.5 ng/ml).[179]

A 2009 research has found that some drugs, like naproxen, salicylic acid, carbamazepine and mefenamic acid can, in vitro, significantly inhibit BPA glucuronidation.[180]

A 2010 study on rats embryos has found that genistein may enhance the developmental toxicity of BPA.[181]

[change] Environmental risk

In general, studies have shown that BPA can affect growth, reproduction and development in organisms that live in water. Among freshwater organisms, fish appear to be the most sensitive species. Evidence of endocrine-related effects in fish, aquatic invertebrates, amphibians and reptiles has been reported at environmentally relevant exposure levels lower than those required for acute toxicity. There is a widespread variation in reported values for endocrine-related effects, but many fall in the range of 1μg/L to 1 mg/L.[8]

BPA can contaminate the environment either directly or through degradation of products containing BPA, such as ocean-borne plastic trash.[182]

As an environmental contaminant this compound interferes with nitrogen fixation at the roots of leguminous plants associated with the bacterial symbiont Sinorhizobium meliloti. BPA concentration in the soil drops in half (half-life) in only 1–10 days. It decays quickly, but its widespread use still makes it an important pollutant.[183] According to Environment Canada, "initial assessment shows that at low levels, bisphenol A can harm fish and organisms over time. Studies also indicate that it can currently be found in municipal wastewater."[184]

A 2009 review of the biological impacts of plasticizers on wildlife published by the Royal Society with a focus on annelids (both aquatic and terrestrial), molluscs, crustaceans, insects, fish and amphibians concluded that BPA have been shown to affect reproduction in all studied animal groups, to impair development in crustaceans and amphibians and to induce genetic aberrations.[185]

A large 2010 study of two rivers in Canada found that areas contaminated with hormone-like chemicals including bisphenol A showed females made up 85 per cent of the population of a certain fish. At the same time, in uncontaminated areas, females made up only 55 per cent.[186]

[change] Other pages

[change] References

  1. ↑ "Update on Bisphenol A for Use in Food Contact Applications: January 2010". U.S. Food and Drug Administration. 15 January 2010. http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm197739.htm. Retrieved 15 January 2010. 
  2. ↑ Canada Gazette Part II 144 (21): 1806–18. 13 October 2010. http://www.gazette.gc.ca/rp-pr/p2/2010/2010-10-13/pdf/g2-14421.pdf. 
  3. ↑ Martin Mittelstaedt (13 October 2010). "Canada first to declare bisphenol A toxic". The Globe and Mail (Canada). http://www.theglobeandmail.com/news/national/canada-first-to-declare-bisphenol-a-toxic/article1755272/. 
  4. ↑ EU to ban Bisphenol A in baby bottles in 2011 101125
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Fiege, Helmut; Heinz-Werner Voges, Toshikazu Hamamoto, Sumio Umemura, Tadao Iwata, Hisaya Miki, Yasuhiro Fujita, Hans-Josef Buysch, Dorothea Garbe, Wilfried Paulus (2002). Phenol Derivatives. Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a19_313. 
  6. ↑ "Experts demand European action on plastics chemical". Reuters. 22 June 2010. http://www.reuters.com/article/idUSTRE65L6JN20100622?loomia_ow=t0:s0:a49:g43:r3:c0.084942:b35124310:z0. 
  7. ↑ 7.0 7.1 7.2 7.3 National Toxicology Program, U.S. Department of Health and Human Services (26 November 2007). "CERHR Expert Panel Report for Bisphenol A" (PDF). Archived from the original on 18 February 2008. http://web.archive.org/web/20080218195117/http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPAFinalEPVF112607.pdf. Retrieved 18 April 2008. 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 "Bisphenol A Action Plan". U.S. Environmental Protection Agency. 29 March 2010. http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/bpa_action_plan.pdf. Retrieved 12 April 2010. 
  9. ↑ Dianin (1891). Zhurnal russkogo fiziko-khimicheskogo obshchestva. 23. pp.  492–. 
  10. ↑ Zincke, Theodor (1905). "Ueber die Einwirkung von Brom und von Chlor auf Phenole: Substitutionsprodukte, Pseudobromide und Pseudochloride". Justus Liebigs Annalen der Chemie 343: 75–99. doi:10.1002/jlac.19053430106. 
  11. ↑ Uglea, Constantin V.; Ioan I. Negulescu (1991). Synthesis and Characterization of Oligomers. CRC Press. p. 103. ISBN 0849349540. 
  12. ↑ "Bisphenol A Information Sheet". Bisphenol A Global Industry Group. October 2002. http://www.bisphenol-a.org/pdf/DiscoveryandUseOctober2002.pdf. Retrieved 7 December 2010. 
  13. ↑ "Studies Report More Harmful Effects From BPA". U.S. News & World Report. 10 June 2009. http://health.usnews.com/health-news/family-health/heart/articles/2009/06/10/studies-report-more-harmful-effects-from-bpa.html. Retrieved 28 October 2010. 
  14. ↑ Replogle, Jill (17 July 2009). "Lawmakers to press for BPA regulation". California Progress Report. http://www.californiaprogressreport.com/site/lawmakers-press-bpa-regulation. Retrieved 2 August 2009. 
  15. ↑ Ubelacker, Sheryl (16 April 2008). "Ridding life of bisphenol A a challenge". Toronto Star. http://www.thestar.com/article/415296. Retrieved 2 August 2009. 
  16. ↑ Kroschwitz, Jacqueline I.. Kirk-Othmer encyclopedia of chemical technology. 5 (5 ed.). pp. 8. ISBN 0471526959. 
  17. ↑ "Polycarbonate (PC) Polymer Resin". Alliance Polymers, Inc. http://www.alliancepoly.com/polycarbonate.asp. Retrieved 2 August 2009. 
  18. ↑ 18.0 18.1 Erickson, Britt E. (2 June 2008). "Bisphenol A under scrutiny". Chemical and Engineering News (American Chemical Society) 86 (22): 36–39. http://pubs.acs.org/isubscribe/journals/cen/86/i22/html/8622gov1.html. 
  19. ↑ Byrne, Jane (22 September 2008). "Consumers fear the packaging - a BPA alternative is needed now". http://www.foodnavigator.com/Financial-Industry/Consumers-fear-the-packaging-a-BPA-alternative-is-needed-now. Retrieved 5 January 2010. 
  20. ↑ Pesticideinfo.org: Bisphenol A
  21. ↑ , US 6562755
  22. ↑ Raloff, Janet (27 July 2001). "More evidence that BPA laces store receipts". Science News. http://www.sciencenews.org/view/generic/id/61490/title/Science_%2B_the_Public__More_evidence_that_BPA_laces_store_receipts. Retrieved 3 August 2010. "Bill Van Den Brandt of Appleton Papers says that the receipts paper made by his company (which bills itself as the nation's leading producer of carbonless and thermal papers) is BPA-free." 
  23. ↑ Raloff, Janet (7 October 2009). "Concerned about BPA: Check your receipts". Science News. http://www.sciencenews.org/view/generic/id/48084/title/Science_%2B_the_Public__Concerned_about_BPA_Check_your_receipts. Retrieved 3 August 2010. 
  24. ↑ 24.0 24.1 Fukazawa, H.; Hoshino, K.; Shiozawa, T.; Matsushita, H.; Terao, Y. (2001). "Identification and quantification of chlorinated bisphenol a in wastewater from wastepaper recycling plants". Chemosphere 44 (5): 973–979. doi:10.1016/S0045-6535(00)00507-5. PMID 11513431. 
  25. ↑ http://www.hhs.gov/safety/bpa/
  26. ↑ Biello D (19 February 2008). "Plastic (not) fantastic: Food containers leach a potentially harmful chemical". Scientific American 2. http://www.sciam.com/article.cfm?id=plastic-not-fantastic-with-bisphenol-a. Retrieved 9 April 2008. 
  27. ↑ Gore, Andrea C. (8 June 2007). Endocrine-Disrupting Chemicals: From Basic Research to Clinical Practice. Contemporary Endocrinology. Humana Press. ISBN 978-1588298300. 
  28. ↑ O’Connor, JC; Chapin, RE (2003). "Critical evaluation of observed adverse effects of endocrine active substances on reproduction and development, the immune system, and the nervous system" (Full Article). Pure Appl. Chem 75 (11–12): 2099–2123. doi:10.1351/pac200375112099. http://www.iupac.org/publications/pac/2003/pdf/7511x2099.pdf. Retrieved 28 February 2007. 
  29. ↑ Okada H, Tokunaga T, Liu X, Takayanagi S, Matsushima A, Shimohigashi Y (January 2008). "Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma". Environ. Health Perspect. 116 (1): 32–8. doi:10.1289/ehp.10587. PMC 2199305. PMID 18197296. 
  30. ↑ 30.0 30.1 vom Saal FS, Myers JP (2008). "Bisphenol A and Risk of Metabolic Disorders". JAMA 300 (11): 1353–5. doi:10.1001/jama.300.11.1353. PMID 18799451. http://jama.ama-assn.org/cgi/content/full/300.11.1353. 
  31. ↑ Draft Screening Assessment for The Challenge Phenol, 4,4' -(1-methylethylidene)bis- (Bisphenol A)Chemical Abstracts Service Registry Number 80-05-7. Health Canada, 2008.
  32. ↑ Ginsberg G, Rice DC (2009). "Does Rapid Metabolism Ensure Negligible Risk from Bisphenol A?". EPH 117 (11): 1639–1643. doi:10.1289/ehp.0901010. PMC 2801165. PMID 20049111. http://www.ehponline.org/members/2009/0901010/0901010.html. 
  33. ↑ Beronius, A.; Rudén, C.; Håkansson, H.; Hanberg, A. (2009). "Risk to all or none?-A comparative analysis of controversies in the health risk assessment of Bisphenol A". Reproductive toxicology (Elmsford, N.Y.) 29 (2): 132–146. doi:10.1016/j.reprotox.2009.11.007. PMID 19931376. 
  34. ↑ http://www.sciencedaily.com/releases/2011/01/110114081653.htm
  35. ↑ Endocrine Society released scientific statement on endocrine-disrupting chemicals
  36. ↑ Wage, Andrew (27 July 2011). "Small pond, same big issues". FSA. http://blogs.food.gov.uk/science/entry/small_pond_same_big_issues. Retrieved 3 August 2011. 
  37. ↑ vom Saal FS, Akingbemi BT, Belcher SM et al (2007). "Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure". Reprod. Toxicol. 24 (2): 131–8. doi:10.1016/j.reprotox.2007.07.005. PMC 2967230. PMID 17768031. 
  38. ↑ http://www.sciencedaily.com/releases/2011/06/110606075708.htm
  39. ↑ http://pubs.acs.org/cen/government/85/8516gov2.html
  40. ↑ Are BPA Products Safe for Infants and Children?, National Research Center for Women and Families Website.
  41. ↑ 41.0 41.1 Since you asked - Bisphenol A: Questions and Answers about the Draft National Toxicology Program Brief on Bisphenol A, National Institute of Environmental Health Sciences website.
  42. ↑ Elobeid, M.; Allison, D. (Oct 2008). "Putative environmental-endocrine disruptors and obesity: a review". Current opinion in endocrinology, diabetes, and obesity 15 (5): 403–408. doi:10.1097/MED.0b013e32830ce95c. ISSN 1752-296X. PMC 2566897. PMID 18769210. 
  43. ↑ Rubin, B.; Soto, A. (May 2009). "Bisphenol A: Perinatal exposure and body weight". Molecular and cellular endocrinology 304 (1–2): 55–62. doi:10.1016/j.mce.2009.02.023. ISSN 0303-7207. PMC 2817931. PMID 19433248. 
  44. ↑ Heindel, J.; Vom Saal, F. (May 2009). "Role of nutrition and environmental endocrine disrupting chemicals during the perinatal period on the aetiology of obesity". Molecular and cellular endocrinology 304 (1–2): 90–96. doi:10.1016/j.mce.2009.02.025. ISSN 0303-7207. PMID 19433253. 
  45. ↑ Newbold, R.; Padilla-Banks, E.; Jefferson, W. (May 2009). "Environmental estrogens and obesity". Molecular and cellular endocrinology 304 (1–2): 84–89. doi:10.1016/j.mce.2009.02.024. ISSN 0303-7207. PMC 2682588. PMID 19433252. 
  46. ↑ Grün, F.; Blumberg, B. (May 2009). "Endocrine disrupters as obesogens". Molecular and cellular endocrinology 304 (1–2): 19–29. doi:10.1016/j.mce.2009.02.018. ISSN 0303-7207. PMC 2713042. PMID 19433244. 
  47. ↑ Somm, E.; Schwitzgebel, V. R.; Toulotte, A.; Cederroth, C.; Combescure, C.; Nef, S.; Aubert, M.; Hüppi, P. (2009). "Perinatal Exposure to Bisphenol a Alters Early Adipogenesis in the Rat". Environmental Health Perspectives 117 (10): 1549–1555. doi:10.1289/ehp.11342. PMC 2790509. PMID 20019905. http://www.ehponline.org/members/2009/11342/11342.pdf. 
  48. ↑ Ryan, K.; Haller, A.; Sorrell, J.; Woods, S.; Jandacek, R.; Seeley, R. (2010). "Perinatal Exposure to Bisphenol-A and the Development of Metabolic Syndrome in CD-1 Mice". Endocrinology 151 (6): 2603–2612. doi:10.1210/en.2009-1218. PMC 2875828. PMID 20351315. 
  49. ↑ Panzica, G.; Viglietti-Panzica, C.; Mura, E.; Quinn Mj, J.; Lavoie, E.; Palanza, P.; Ottinger, M. (2007). "Effects of xenoestrogens on the differentiation of behaviorally-relevant neural circuits". Frontiers in neuroendocrinology 28 (4): 179–200. doi:10.1016/j.yfrne.2007.07.001. PMID 17868795. 
  50. ↑ Richter, C.; Birnbaum, L.; Farabollini, F.; Newbold, R.; Rubin, B.; Talsness, C.; Vandenbergh, J.; Walser-Kuntz, D. et al (2007). "In vivo effects of bisphenol a in laboratory rodent studies". Reproductive toxicology (Elmsford, N.Y.) 24 (2): 199–224. doi:10.1016/j.reprotox.2007.06.004. PMC 2151845. PMID 17683900. 
  51. ↑ Palanza, P.; Gioiosa, L.; Vom Saal, F. S.; Parmigiani, S. (2008). "Effects of developmental exposure to bisphenol a on brain and behavior in mice". Environmental research 108 (2): 150–157. doi:10.1016/j.envres.2008.07.023. PMID 18949834. 
  52. ↑ Patisaul, H.; Polston, E. (2008). "Influence of endocrine active compounds on the developing rodent brain". Brain research reviews 57 (2): 352–362. doi:10.1016/j.brainresrev.2007.06.008. PMID 17822772. 
  53. ↑ Ogiue-Ikeda, M.; Tanabe, N.; Mukai, H.; Hojo, Y.; Murakami, G.; Tsurugizawa, T.; Takata, N.; Kimoto, T. et al (2008). "Rapid modulation of synaptic plasticity by estrogens as well as endocrine disrupters in hippocampal neurons". Brain research reviews 57 (2): 363–375. doi:10.1016/j.brainresrev.2007.06.010. PMID 17822775. 
  54. ↑ 10.1016/j.yfrne.2008.02.002
  55. ↑ 55.0 55.1 Leranth C, Hajszan T, Szigeti-Buck K, Bober J, Maclusky NJ (September 2008). "Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates". Proc. Natl. Acad. Sci. U.S.A. 105 (37): 14187–91. doi:10.1073/pnas.0806139105. PMC 2544599. PMID 18768812. 
  56. ↑ Layton, Lindsey (4 September 2008). "Chemical in Plastic Is Connected to Health Problems in Monkeys". Washington Post: pp. A02. http://www.washingtonpost.com/wp-dyn/content/article/2008/09/03/AR2008090303397.html?hpid=topnews. Retrieved 6 September 2008. 
  57. ↑ Poimenova, A.; Markaki, E.; Rahiotis, C.; Kitraki, E. (2010). "Corticosterone - regulated actions in the rat brain are affected by perinatal exposure to low dose of bisphenol A.". Neuroscience 167 (3): 741–749. doi:10.1016/j.neuroscience.2010.02.051. PMID 20219646. 
  58. ↑ Suzuki; Mizuo, K.; Miyagawa, K.; Narita, M. (2005). "Exposure to bisphenol-A affects the rewarding system in mice". Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 25 (3): 125–128. PMID 16045194. 
  59. ↑ Jones, D.; Miller, G. (2008). "The effects of environmental neurotoxicants on the dopaminergic system: A possible role in drug addiction". Biochemical pharmacology 76 (5): 569–581. doi:10.1016/j.bcp.2008.05.010. PMID 18555207. 
  60. ↑ Zhou, R.; Zhang, Z.; Zhu, Y.; Chen, L.; Sokabe, M.; Chen, L. (2009). "Deficits in development of synaptic plasticity in rat dorsal striatum following prenatal and neonatal exposure to low-dose bisphenol A". Neuroscience 159 (1): 161–171. doi:10.1016/j.neuroscience.2008.12.028. PMID 19162132. 
  61. ↑ Tanida, T.; Warita, K.; Ishihara, K.; Fukui, S.; Mitsuhashi, T.; Sugawara, T.; Tabuchi, Y.; Nanmori, T. et al (2009). "Fetal and neonatal exposure to three typical environmental chemicals with different mechanisms of action: mixed exposure to phenol, phthalate, and dioxin cancels the effects of sole exposure on mouse midbrain dopaminergic nuclei.". Toxicology letters 189 (1): 40–47. doi:10.1016/j.toxlet.2009.04.005. PMID 19481886. 
  62. ↑ Zoeller, R. (2007). "Environmental chemicals impacting the thyroid: targets and consequences". Thyroid : official journal of the American Thyroid Association 17 (9): 811–817. doi:10.1089/thy.2007.0107. PMID 17956155. 
  63. ↑ Boas, M.; Main, K.; Feldt-Rasmussen, U. (Oct 2009). "Environmental chemicals and thyroid function: an update". Current opinion in endocrinology, diabetes, and obesity 16 (5): 385–391. doi:10.1097/MED.0b013e3283305af7. ISSN 1752-296X. PMID 19625957. 
  64. ↑ Kashiwagi, K.; Furuno, N.; Kitamura, S.; Ohta, S.; Sugihara, K.; Utsumi, K.; Hanada, H.; Taniguchi, K. et al (2009). "Disruption of Thyroid Hormone Function by Environmental Pollutants". Journal of Health Science 55 (2): 147. doi:10.1248/jhs.55.147. http://jhs.pharm.or.jp/data/55(2)/55_147.pdf. 
  65. ↑ "BISPHENOL A (BPA) - Current state of knowledge and future actions by WHO and FAO". 27 November 2009. http://www.who.int/entity/foodsafety/publications/fs_management/No_05_Bisphenol_A_Nov09_en.pdf. Retrieved 2 December 2009. 
  66. ↑ U.S.EPA, IRIS: Bisphenol A
  67. ↑ Agents Reviewed by the Monographs Volumes 1–99
  68. ↑ Soto, A. M.; Sonnenschein, C. (2010). "Environmental causes of cancer: endocrine disruptors as carcinogens". Nature Reviews Endocrinology 6 (7): 363–370. doi:10.1038/nrendo.2010.87. PMID 20498677. Lay summary. 
  69. ↑ Brisken, C. (2008). "Endocrine Disruptors and Breast Cancer". CHIMIA International Journal for Chemistry 62 (5): 406–409. doi:10.2533/chimia.2008.406. 
  70. ↑ Soto, A.; Vandenberg, L.; Maffini, M.; Sonnenschein, C. (2008). "Does breast cancer start in the womb?". Basic & Clinical Pharmacology & Toxicology 102 (2): 125–133. doi:10.1111/j.1742-7843.2007.00165.x. PMC 2817934. PMID 18226065. 
  71. ↑ Fernandez, S. V.; Russo, J. (2009). "Estrogen and Xenoestrogens in Breast Cancer". Toxicologic Pathology 38 (1): 110–122. doi:10.1177/0192623309354108. PMC 2907875. PMID 19933552. 
  72. ↑ Jenkins, S.; Raghuraman, N.; Eltoum, I.; Carpenter, M.; Russo, J.; Lamartiniere, C. A. (2009). "Oral Exposure to Bisphenol A Increases Dimethylbenzanthracene-Induced Mammary Cancer in Rats" (Free full text). Environmental Health Perspectives 117 (6): 910–915. doi:10.1289/ehp.11751. PMC 2702405. PMID 19590682. http://ehp.niehs.nih.gov/members/2009/11751/11751.html. 
  73. ↑ Betancourt, A.; Mobley, J.; Russo, J.; Lamartiniere, C. (2010). "Proteomic Analysis in Mammary Glands of Rat Offspring Exposed In Utero to Bisphenol A.". Journal of proteomics 73 (6): 1241–1253. doi:10.1016/j.jprot.2010.02.020. PMID 20219716. 
  74. ↑ Lapensee, E. W.; Lapensee, C. R.; Fox, S.; Schwemberger, S.; Afton, S.; Ben-Jonathan, N. (2010). "Bisphenol a and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells". Cancer Letters 290 (2): 167–173. doi:10.1016/j.canlet.2009.09.005. PMC 2853868. PMID 19796866. Lay summary. 
  75. ↑ Zhu, H.; Xiao, X.; Zheng, J.; Zheng, S.; Dong, K.; Yu, Y. (2009). "Growth-promoting effect of bisphenol a on neuroblastoma in vitro and in vivo☆". Journal of Pediatric Surgery 44 (4): 672–680. doi:10.1016/j.jpedsurg.2008.10.067. PMID 19361625. 
  76. ↑ Zheng, J.; Xiao, X.; Liu, J.; Zheng, S.; Yin, Q.; Y, Y. (2007). "Growth-promoting effect of environmental endocrine disruptors on human neuroblastoma SK-N-SH cells☆". Environmental Toxicology and Pharmacology 24 (2): 189–193. doi:10.1016/j.etap.2007.05.003. PMID 21783809. 
  77. ↑ Zhu, H.; Zheng, J.; Xiao, X.; Zheng, S.; Dong, K.; Liu, J.; Wang, Y. (2010). "Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells". Oncology reports 23 (1): 129–139. PMID 19956873. 
  78. ↑ Nagel, S. C.; Vom Saal, F. S.; Thayer, K. A.; Dhar, M. G.; Boechler, M.; Welshons, W. V. (1997). "Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol". Environmental health perspectives (Brogan & Partners) 105 (1): 70–76. doi:10.2307/3433065. PMC 1469837. PMID 9074884. 
  79. ↑ Timms, B.; Howdeshell, K.; Barton, L.; Bradley, S.; Richter, C.; Vom Saal, F. (2005). "Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra". Proceedings of the National Academy of Sciences of the United States of America 102 (19): 7014–7019. doi:10.1073/pnas.0502544102. PMC 1088066. PMID 15867144. 
  80. ↑ Ho, S.; Tang, W.; Belmonte De Frausto, J.; Prins, G. (2006). "Developmental exposure to estradiol and bisphenol a increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4". Cancer research 66 (11): 5624–5632. doi:10.1158/0008-5472.CAN-06-0516. PMC 2276876. PMID 16740699. 
  81. ↑ Richter, C.; Taylor, J.; Ruhlen, R.; Welshons, W.; Vom Saal, F. (2007). "Estradiol and Bisphenol a stimulate androgen receptor and estrogen receptor gene expression in fetal mouse prostate mesenchyme cells". Environmental health perspectives 115 (6): 902–908. doi:10.1289/ehp.9804. PMC 1892114. PMID 17589598. 
  82. ↑ Prins, G.; Tang, W.; Belmonte, J.; Ho, S. (2008). "Developmental exposure to bisphenol a increases prostate cancer susceptibility in adult rats: epigenetic mode of action is implicated". Fertility and Sterility 89 (2 Suppl): e41–e41. doi:10.1016/j.fertnstert.2007.12.023. PMC 2531072. PMID 18308059. 
  83. ↑ Bagchi, Debasis (2010). Genomics, Proteomics and Metabolomics in Nutraceuticals and Functional Foods. Wiley. p. 319. ISBN 0813814022. 
  84. ↑ Dolinoy, D. C.; Huang, D.; Jirtle, R. L. (2007). "Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development". Proceedings of the National Academy of Sciences 104 (32): 13056–13061. doi:10.1073/pnas.0703739104. PMC 1941790. PMID 17670942. 
  85. ↑ "Plastics In Common Household Items May Cause Fertility Defects". Science Daily. Feb. 15, 2007. http://www.sciencedaily.com/releases/2007/02/070215145120.htm. Retrieved 2011-08031. 
  86. ↑ 86.0 86.1 Newbold, R.; Jefferson, N.; Padilla-Banks, E. (Jun 2009). "Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life". Environmental health perspectives 117 (6): 879–885. doi:10.1289/ehp.0800045. ISSN 0091-6765. PMC 2702400. PMID 19590677. 
  87. ↑ 87.0 87.1 Adewale, B.; Jefferson, N.; Newbold, R.; Patisaul, B. (Jun 2009). "Neonatal Bisphenol-A Exposure Alters Rat Reproductive Development and Ovarian Morphology Without Impairing Activation of Gonadotropin Releasing Hormone Neurons" (Free full text). Biology of reproduction 81 (4): 690–699. doi:10.1095/biolreprod.109.078261. ISSN 0006-3363. PMC 2754884. PMID 19535786. http://www.biolreprod.org/cgi/pmidlookup?view=long&pmid=19535786. 
  88. ↑ Study Finds Reproductive Health Effects From Low Doses of Bisphenol-A
  89. ↑ Bosquiazzo, L.; Varayoud, J.; Muñoz-De-Toro, M.; Luque, H.; Ramos, G. (Aug 2009). "Effects of Neonatal Exposure to Bisphenol a on Steroid Regulation of Vascular Endothelial Growth Factor Expression and Endothelial Cell Proliferation in the Adult Rat Uterus" (Free full text). Biology of reproduction 82 (1): 86–95. doi:10.1095/biolreprod.109.078543. ISSN 0006-3363. PMID 19696011. http://www.biolreprod.org/cgi/pmidlookup?view=long&pmid=19696011. 
  90. ↑ Monje, L.; Varayoud, J.; Muñoz-De-Toro, M.; Luque, H.; Ramos, G. (Jul 2009). "Neonatal exposure to bisphenol a alters estrogen-dependent mechanisms governing sexual behavior in the adult female rat". Reproductive toxicology (Elmsford, N.Y.) 28 (4): 435–442. doi:10.1016/j.reprotox.2009.06.012. ISSN 0890-6238. PMID 19577632. 
  91. ↑ Nakagami, A.; Negishi, T.; Kawasaki, K.; Imai, N.; Nishida, Y.; Ihara, T.; Kuroda, Y.; Yoshikawa, Y. et al (Sep 2009). "Alterations in male infant behaviors towards its mother by prenatal exposure to bisphenol a in cynomolgus monkeys (Macaca fascicularis) during early suckling period". Psychoneuroendocrinology 34 (8): 1189–1197. doi:10.1016/j.psyneuen.2009.03.005. ISSN 0306-4530. PMID 19345509. 
  92. ↑ Huang, H.; Leung, K. (Sep 2009). "Bisphenol a downregulates CYP19 transcription in JEG-3 cells". Toxicology letters 189 (3): 248–252. doi:10.1016/j.toxlet.2009.06.853. ISSN 0378-4274. PMID 19539015. 
  93. ↑ Li; Mruk, D.; Lee, W.; Cheng, C. (2009). "Disruption of the blood-testis barrier integrity by bisphenol a in vitro: is this a suitable model for studying blood-testis barrier dynamics?". The international journal of biochemistry & cell biology 41 (11): 2302–2314. doi:10.1016/j.biocel.2009.05.016. PMID 19497385. 
  94. ↑ Li, D.; Zhou, Z.; Qing, D.; He, Y.; Wu, T.; Miao, M.; Wang, J.; Weng, X. et al (2009). "Occupational exposure to bisphenol-A (BPA) and the risk of Self-Reported Male Sexual Dysfunction". Human Reproduction 25 (2): 519–527. doi:10.1093/humrep/dep381. PMID 19906654. 
  95. ↑ Ryan, B.; Hotchkiss, A.; Crofton, K.; Gray Jr, L. (2010). "In utero and lactational exposure to bisphenol A, in contrast to ethinyl estradiol, does not alter sexually dimorphic behavior, puberty, fertility, and anatomy of female LE rats". Toxicological sciences : an official journal of the Society of Toxicology 114 (1): 133–148. doi:10.1093/toxsci/kfp266. PMID 19864446. 
  96. ↑ vom Saal, F. S.; Akingbemi, B.; Belcher, S.; Crain, D.; Crews, D.; Guidice, L.; Hunt, P.; Leranth, C. et al (2010). "Flawed Experimental Design Reveals the Need for Guidelines Requiring Appropriate Positive Controls in Endocrine Disruption Research.". Toxicological sciences : an official journal of the Society of Toxicology 115 (2): 612–613; author 613 614–613. doi:10.1093/toxsci/kfq048. PMID 20164146. 
  97. ↑ Gray LE, Ryan B, Hotchkiss AK, Crofton KM (March 2010). "Rebuttal of "Flawed Experimental Design Reveals the Need for Guidelines Requiring Appropriate Positive Controls in Endocrine Disruption Research" by (Vom Saal 2010)". Toxicol Sci 115 (2): 614. doi:10.1093/toxsci/kfq073. PMID 20207694. 
  98. ↑ http://www.sciencedaily.com/releases/2009/06/090610124428.htm
  99. ↑ http://www.sciencedaily.com/releases/2010/08/100825093249.htm
  100. ↑ Bromer, J. G.; Zhou, Y.; Taylor, M. B.; Doherty, L.; Taylor, H. S. (2010). "Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response". The FASEB Journal 24 (7): 2273–2280. doi:10.1096/fj.09-140533. PMC 3230522. PMID 20181937. Lay summary. 
  101. ↑ http://www.sciencedaily.com/releases/2010/02/100225101220.htm
  102. ↑ http://www.sciencedaily.com/releases/2011/06/110607121127.htm
  103. ↑ http://www.sciencedaily.com/releases/2011/06/110606092740.htm
  104. ↑ http://www.sciencedaily.com/releases/2011/06/110627151712.htm
  105. ↑ "More Troubling News About BPA / Science News". www.sciencenews.org. http://www.sciencenews.org/view/generic/id/44577/title/More_troubling_news_about_BPA. Retrieved 11 June 2009. 
  106. ↑ "Hormone experts worried about plastics, chemicals - Yahoo! News". Reuters. http://www.reuters.com/article/2009/06/11/us-bisphenol-idUSTRE55A0JK20090611. Retrieved 15 February 2012. 
  107. ↑ Benachour, N.; Aris, A. (2009). "Toxic effects of low doses of Bisphenol-A on human placental cells.". Toxicology and applied pharmacology 241 (3): 322–328. doi:10.1016/j.taap.2009.09.005. PMID 19769995. Lay summary. 
  108. ↑ Braniste, V.; Jouault, A.; Gaultier, E.; Polizzi, A.; Buisson-Brenac, C.; Leveque, M.; Martin, P.; Theodorou, V. et al (2009). "Impact of oral bisphenol a at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats" (PDF). Proceedings of the National Academy of Sciences of the United States of America 107 (1): 448–453. doi:10.1073/pnas.0907697107. PMC 2806743. PMID 20018722. http://www.pnas.org/content/early/2009/12/10/0907697107.full.pdf. 
  109. ↑ Midoro-Horiuti, T.; Tiwari, R.; Watson, C.; Goldblum, R. (2010). "Maternal bisphenol a exposure promotes the development of experimental asthma in mouse pups". Environmental health perspectives 118 (2): 273–277. doi:10.1289/ehp.0901259. PMC 2831929. PMID 20123615. 
  110. ↑ http://www.sciencedaily.com/releases/2011/05/110501183817.htm
  111. ↑ Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D (2008). "Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults". JAMA 300 (11): 1303–10. doi:10.1001/jama.300.11.1303. PMID 18799442. http://jama.ama-assn.org/cgi/content/full/300.11.1303. 
  112. ↑ Newscientist.com Plastic bottle chemical linked to heart disease
  113. ↑ Vom Saal, F. S.; Myers, J. P. (2008). "Bisphenol a and Risk of Metabolic Disorders". JAMA: the Journal of the American Medical Association 300 (11): 1353–1355. doi:10.1001/jama.300.11.1353. PMID 18799451. 
  114. ↑ Melzer, D.; Rice, N. E.; Lewis, C.; Henley, W. E.; Galloway, T. S.; Zhang, B. (2010). Zhang, Baohong. ed. "Association of Urinary Bisphenol A Concentration with Heart Disease: Evidence from NHANES 2003/06" (pdf). PLoS ONE 5 (1): e8673. doi:10.1371/journal.pone.0008673. PMC 2800195. PMID 20084273. http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0008673&representation=PDF. Lay summary. 
  115. ↑ Sugiura-ogasawara, M.; Ozaki, Y.; Sonta, S. -I.; Makino, T.; Suzumori, K. (2005). "Exposure to bisphenol a is associated with recurrent miscarriage". Human reproduction (Oxford, England) 20 (8): 2325–2329. doi:10.1093/humrep/deh888. PMID 15947000. 
  116. ↑ Yang, J.; Hong, C.; Oh, Y.; Park, S.; Kim, H.; Leem, H.; Ha, H. (Aug 2009). "Bisphenol a exposure is associated with oxidative stress and inflammation in postmenopausal women". Environmental research 109 (6): 797–801. doi:10.1016/j.envres.2009.04.014. ISSN 0013-9351. PMID 19464675. 
  117. ↑ Braun, J.; Yolton, K.; Dietrich, K.; Hornung, R.; Ye, X.; Calafat, A.; Lanphear, B. (2009). "Prenatal Bisphenol a Exposure and Early Childhood Behavior". Environmental Health Perspectives 117 (12): 1945–1952. doi:10.1289/ehp.0900979. PMC 2799471. PMID 20049216. 
  118. ↑ Meeker, J. D.; Calafat, A. M.; Hauser, R. (2009). "Urinary Bisphenol a Concentrations in Relation to Serum Thyroid and Reproductive Hormone Levels in Men from an Infertility Clinic". Environmental Science & Technology 44 (4): 1458–1463. doi:10.1021/es9028292. PMC 2823133. PMID 20030380. 
  119. ↑ Mendiola, J.; Jørgensen, N.; Andersson, A. M.; Calafat, A. M.; Ye, X.; Redmon, J. B.; Drobnis, E. Z.; Wang, C. et al (2010). "Are Environmental Levels of Bisphenol A Associated with Reproductive Function in Fertile Men?". Environmental Health Perspectives 118 (9): 1286–1291. doi:10.1289/ehp.1002037. PMC 2944091. PMID 20494855. 
  120. ↑ Li DK, Zhou Z, Miao M et al (May 2010). "Relationship between Urine Bisphenol-A (BPA) Level and Declining Male Sexual Function". J Androl 31 (5): 500–6. doi:10.2164/jandrol.110.010413. PMID 20467048. 
  121. ↑ "Bisphenol A concentrations in the Canadian population, 2007 to 2009". Statistics Canada: pp. 82–625–XWE. 16 August 2010. http://www.statcan.gc.ca/pub/82-625-x/2010002/article/11327-eng.htm. Retrieved 19 November 2010. 
  122. ↑ Clayton EMR, T. M.; Todd, M.; Dowd, J. B.; Aiello, A. E. (2010). "The Impact of Bisphenol A and Triclosan on Immune Parameters in the U.S. Population, NHANES 2003–2006". Environ Health Perspectives 119 (3): 390–396. doi:10.1289/ehp.1002883. PMC 3060004. PMID 21062687. 
  123. ↑ http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1289%2Fehp.1002367d
  124. ↑ http://www.sciencedaily.com/releases/2011/01/110113082720.htm
  125. ↑ Antibacterial Soaps: Being Too Clean Can Make People Sick, Study Suggests: http://www.sciencedaily.com/releases/2010/11/101129101920.htm
  126. ↑ D. Li, Z. Zhou, D. Qing, Y. He, T. Wu, M. Miao, J. Wang, X. Weng, J.R. Ferber, L.J. Herrinton, Q. Zhu, E. Gao, H. Checkoway, and W. Yuan (2009). "Occupational exposure to bisphenol-A (BPA) and the risk of Self-Reported Male Sexual Dysfunction". Human Reproduction 25 (2): 519–27. doi:10.1093/humrep/dep381. PMID 19906654. 
  127. ↑ BPA Tied to Impotence in Men
  128. ↑ Dodds E. C., Lawson Wilfrid (1936). "Synthetic Œstrogenic Agents without the Phenanthrene Nucleus". Nature 137 (3476): 996. doi:10.1038/137996a0. 
  129. ↑ E. C. Dodds and W. Lawson, Proceedings of the Royal Society of London, Series B, Biological Sciences, 125, #839 (27-IV-1938), pp. 222–232.
  130. ↑ 130.0 130.1 Mittelstaedt, Martin (7 April 2007). "'Inherently toxic' chemical faces its future". Toronto: Globe & Mail. http://www.theglobeandmail.com/servlet/story/RTGAM.20070406.wbisphenolA0407/BNStory/National/. Retrieved 7 April 2007. 
  131. ↑ This table is adapted from: EWG, 2007. "Many studies confirm BPA's low-dose toxicity across a diverse range of toxic effects," Environmental Working Group Report: A Survey of Bisphenol A in U.S. Canned Foods. Accessed 4 November 2007 at http://www.ewg.org/node/20941. All studies included in this table where judged by the CEHRH panel to be at least of moderate usefulness for assessing the risk of BPA to human reproduction.
  132. ↑ Markey CM, Wadia PR, Rubin BS, Sonnenschein C, Soto AM (2005). "Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract". Biol. Reprod. 72 (6): 1344–51. doi:10.1095/biolreprod.104.036301. PMID 15689538. http://www.biolreprod.org/cgi/pmidlookup?view=long&pmid=15689538. 
  133. ↑ Muñoz-de-Toro M, Markey CM, Wadia PR et al (2005). "Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice". Endocrinology 146 (9): 4138–47. doi:10.1210/en.2005-0340. PMC 2834307. PMID 15919749. http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=15919749. 
  134. ↑ Nagel SC, vom Saal FS, Thayer KA, Dhar MG, Boechler M, Welshons WV (1997). "Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol". Environ. Health Perspect. 105 (1): 70–6. doi:10.2307/3433065. PMC 1469837. PMID 9074884. 
  135. ↑ Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe H, Iguchi T (2002). "Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction". Reprod. Toxicol. 16 (2): 117–22. doi:10.1016/S0890-6238(02)00006-0. PMID 11955942. http://linkinghub.elsevier.com/retrieve/pii/S0890623802000060. 
  136. ↑ Akingbemi BT, Sottas CM, Koulova AI, Klinefelter GR, Hardy MP (2004). "Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells". Endocrinology 145 (2): 592–603. doi:10.1210/en.2003-1174. PMID 14605012. http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=14605012. 
  137. ↑ Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM (2007). "Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure". Reprod. Toxicol. 23 (3): 383–90. doi:10.1016/j.reprotox.2006.10.002. PMC 1987322. PMID 17123778. http://linkinghub.elsevier.com/retrieve/pii/S0890-6238(06)00263-2. 
  138. ↑ Ho SM, Tang WY, Belmonte de Frausto J, Prins GS (2006). "Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4". Cancer Res. 66 (11): 5624–32. doi:10.1158/0008-5472.CAN-06-0516. PMC 2276876. PMID 16740699. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16740699. 
  139. ↑ Palanza PL, Howdeshell KL, Parmigiani S, vom Saal FS (2002). "Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice". Environ. Health Perspect. 110 Suppl 3: 415–22. PMC 1241192. PMID 12060838. http://ehpnet1.niehs.nih.gov/docs/2002/suppl-3/415-422palanza/abstract.html. 
  140. ↑ Kubo K, Arai O, Omura M, Watanabe R, Ogata R, Aou S (2003). "Low dose effects of bisphenol A on sexual differentiation of the brain and behavior in rats". Neurosci. Res. 45 (3): 345–56. doi:10.1016/S0168-0102(02)00251-1. PMID 12631470. http://linkinghub.elsevier.com/retrieve/pii/S0168010202002511. 
  141. ↑ EPA (Environmental Protection Agency). 1988. Oral RfD Assessment: Bisphenol A. Integrated Risk Information System.
  142. ↑ 142.0 142.1 142.2 142.3 Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y (October 2007). "Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma". J. Biochem. 142 (4): 517–24. doi:10.1093/jb/mvm158. PMID 17761695. 
  143. ↑ Takeda Y, Liu X, Sumiyoshi M, Matsushima A, Shimohigashi M, Shimohigashi Y (July 2009). "Placenta expressing the greatest quantity of bisphenol A receptor ERR{gamma} among the human reproductive tissues: Predominant expression of type-1 ERRgamma isoform". J. Biochem. 146 (1): 113–22. doi:10.1093/jb/mvp049. PMID 19304792. 
  144. ↑ Walsh, Bryan (Thursday, 1 Apr. 2010). "The Perils of Plastic - Environmental Toxins - TIME". TIME. http://www.time.com/time/specials/packages/article/0,28804,1976909_1976908_1976938-2,00.html. Retrieved 2 July 2010. 
  145. ↑ "Environmental Working Group". http://www.ewg.org/reports/bisphenola. Retrieved 7 March 2007. 
  146. ↑ Health Canada. "Survey of Bisphenol A in Canned Drink Products". http://www.hc-sc.gc.ca/fn-an/securit/packag-emball/bpa/bpa_survey-enquete-can-eng.php. Retrieved 13 March 2009. 
  147. ↑ Schecter, A.; Malik, N.; Haffner, D.; Smith, S.; Harris, T. R.; Paepke, O.; Birnbaum, L. (2010). "Bisphenol A (BPA) in U.S. Food". Environmental Science & Technology 44 (24): 9425–9430. doi:10.1021/es102785d. PMID 21038926. 
  148. ↑ Lang IA Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace, Robert B, Melzer, D (2008). "Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults". JAMA 300 (11): 1303–10. doi:10.1001/jama.300.11.1303. PMID 18799442. http://jama.ama-assn.org/cgi/content/full/300.11.1303. 
  149. ↑ ""Food Packaging and Bisphenol A and Bis(2-Ethyhexyl) Phthalate Exposure: Findings from a Dietary Intervention"". Journalist's Resource.org. http://journalistsresource.org/studies/society/health/food-packaging-diet-bpa-chemical/. 
  150. ↑ Raloff, Janet (7 October 2009). "Concerned About BPA: Check Your Receipts". Society for Science and the Public. http://www.sciencenews.org/view/generic/id/48084/title/Concerned_about_BPA_Check_your_receipts. Retrieved 7 October 2009. 
  151. ↑ Gehring, Martin; Tennhardt, L., Vogel, D., Weltin, D., Bilitewski, B. (2004) (PDF). Bisphenol A Contamination of Wastepaper, Cellulose and Recycled Paper Products. Waste Management and the Environment II. WIT Transactions on Ecology and the Environment, vol. 78. WIT Press. http://rcswww.urz.tu-dresden.de/~gehring/deutsch/dt/vortr/040929ge.pdf. Retrieved 15 October 2009. Lay summary. 
  152. ↑ "CiteULike: Transfer of bisphenol A from thermal printer paper to the skin". http://www.citeulike.org/article/7497437.  100821 citeulike.org
  153. ↑ Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL (2005). "Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population". Environ. Health Perspect. 113 (4): 391–5. doi:10.1289/ehp.7534. PMC 1278476. PMID 15811827. http://ehpnet1.niehs.nih.gov/members/2004/7534/7534.html. 
  154. ↑ Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL (2008). "Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004". Environ. Health Perspect. 116 (1): 39–44. doi:10.1289/ehp.10753. PMC 2199288. PMID 18197297. 
  155. ↑ Bisphenol A - United States Environmental Protection Agency
  156. ↑ Carwile JL, Luu HT, Bassett LS, Driscoll DA, Yuan C, Chang JY, Ye X, Calafat AM, Michels KB (2009). "Use of Polycarbonate Bottles and Urinary Bisphenol A Concentrations". Environ. Health Perspect. 117 (9): 1368–72. doi:10.1289/ehp.0900604. PMC 2737011. PMID 19750099. http://www.ehponline.org/members/2009/0900604/0900604.pdf. 
  157. ↑ War of the Sciences Air Date: Week of 19 September 2008 - Ashley Ahearn, Living on Earth
  158. ↑ FDA Weighs Safety Of Bisphenol A
  159. ↑ Lakind, J. S.; Naiman, D. Q. (2010). "Daily intake of bisphenol a and potential sources of exposure: 2005–2006 National Health and Nutrition Examination Survey". Journal of Exposure Science and Environmental Epidemiology 21 (3): 272–279. doi:10.1038/jes.2010.9. PMC 3079892. PMID 20237498. 
  160. ↑ "Pipeline relining". http://www.aceduraflo.com/fixmypipes.html. Retrieved 18 October 2010. 
  161. ↑ Edginton, A. N.; Ritter, L. (2008). "Predicting Plasma Concentrations of Bisphenol a in Children Younger Than 2 Years of Age after Typical Feeding Schedules, using a Physiologically Based Toxicokinetic Model". Environmental Health Perspectives 117 (4): 645–652. doi:10.1289/ehp.0800073. PMC 2679611. PMID 19440506. 
  162. ↑ Hines, R. N. (2008). "The ontogeny of drug metabolism enzymes and implications for adverse drug events". Pharmacology & Therapeutics 118 (2): 250–267. doi:10.1016/j.pharmthera.2008.02.005. 
  163. ↑ "European Food Safety Authority Opinion" (Abstract). http://www.efsa.europa.eu/en/science/afc/afc_opinions/bisphenol_a.html. Retrieved 25 March 2011. 
  164. ↑ "European Food Safety Authority Opinion" (Abstract). http://www.efsa.europa.eu/en/science/afc/afc_opinions/bisphenol_a.html. Retrieved 28 February 2007. 
  165. ↑ 165.0 165.1 Ackerman, L.; Noonan, G.; Heiserman, W.; Roach, J.; Limm, W.; Begley, T. (2010). "Determination of Bisphenol a in U.S. Infant Formulas: Updated Methods and Concentrations". Journal of agricultural and food chemistry 58 (4): 2307–2313. doi:10.1021/jf903959u. PMID 20102208. 
  166. ↑ Cao, X.; Dufresne, G.; Belisle, S.; Clement, G.; Falicki, M.; Beraldin, F.; Rulibikiye, A. (2008). "Levels of bisphenol a in canned liquid infant formula products in Canada and dietary intake estimates". Journal of agricultural and food chemistry 56 (17): 7919–7924. doi:10.1021/jf8008712. PMID 18702469. 
  167. ↑ "Bisphenol A (BPA) Information for Parents". U.S. Department of Health and Human Services. http://www.hhs.gov/safety/bpa/. Retrieved 25 March 2011. 
  168. ↑ Von Goetz, N.; Wormuth, M.; Scheringer, M.; Hungerbühler, K. (2010). "Bisphenol A: How the Most Relevant Exposure Sources Contribute to Total Consumer Exposure". Risk analysis : an official publication of the Society for Risk Analysis 30 (3): 473–487. doi:10.1111/j.1539-6924.2009.01345.x. PMID 20136739. 
  169. ↑ Zalko, D.; Soto, A.; Dolo, L.; Dorio, C.; Rathahao, E.; Debrauwer, L.; Faure, R.; Cravedi, J. (2003). "Biotransformations of bisphenol a in a mammalian model: Answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice". Environmental health perspectives 111 (3): 309–319. doi:10.1289/ehp.5603. PMC 1241388. PMID 12611660. 
  170. ↑ "Cord Blood Contaminants in Minority Newborns". Environmental Working Group. 2009. http://www.ewg.org/files/2009-Minority-Cord-Blood-Report.pdf. Retrieved 2 December 2009. 
  171. ↑ Sun, Y.; Irie, M.; Kishikawa, N.; Wada, M.; Kuroda, N.; Nakashima, K. (2004). "Determination of bisphenol a in human breast milk by HPLC with column-switching andfluorescence detection". Biomedical Chromatography 18 (8): 501–507. doi:10.1002/bmc.345. PMID 15386523. 
  172. ↑ Ye, X.; Kuklenyik, Z.; Needham, L.; Calafat, A. (2006). "Measuring environmental phenols and chlorinated organic chemicals in breast milk using automated on-line column-switching–high performance liquid chromatography–isotope dilution tandem mass spectrometry". Journal of Chromatography B 831 (1–2): 110–115. doi:10.1016/j.jchromb.2005.11.050. PMID 16377264. 
  173. ↑ Sajiki, J.; Yanagibori, R.; Kobayashi, Y. (2010). "Study of experiment on leaching of bisphenol a from infant books to artificial saliva". Nippon eiseigaku zasshi. Japanese journal of hygiene 65 (3): 467–470. doi:10.1265/jjh.65.467. PMID 20508389. 
  174. ↑ 174.0 174.1 Gary Ginsberg and Deborah C. Rice, G; Rice, DC (November 2009). "Does Rapid Metabolism Ensure Negligible Risk from Bisphenol A?". Environmental Health Perspectives 117 (11): 1639–1643. doi:10.1289/ehp.0901010. PMC 2801165. PMID 20049111. http://www.ehponline.org/members/2009/0901010/0901010.pdf. Retrieved 16 November 2009. 
  175. ↑ Nishikawa, M.; Iwano, H.; Yanagisawa, R.; Koike, N.; Inoue, H.; Yokota, H. (2010). "Placental Transfer of Conjugated Bisphenol a and Subsequent Reactivation in the Rat Fetus". Environmental health perspectives 118 (9): 1196–1203. doi:10.1289/ehp.0901575. PMC 2944077. PMID 20382578. 
  176. ↑ Mørck, T. J.; Sorda, G.; Bechi, N.; Rasmussen, B. S.; Nielsen, J. B.; Ietta, F.; Rytting, E.; Mathiesen, L. et al (2010). "Placental transport and in vitro effects of Bisphenol A". Reproductive Toxicology 30 (1): 131–137. doi:10.1016/j.reprotox.2010.02.007. PMID 20214975. 
  177. ↑ Borrell, Brendan (21 April). "Toxicology: The big test for bisphenol A". Nature 464 (7292): 1122–1124. doi:10.1038/4641122a. PMID 20414285. http://www.nature.com/news/2010/100421/full/4641122a.html. Retrieved 21 April 2010. 
  178. ↑ Vandenberg, L. N.; Chauhoud, I.; Heindel, J. J.; Padmanabhan, V.; Paumgartten, F. J. R.; Schoenfelder, G. (2010). "Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A". Environmental Health Perspectives 118 (8): 1055–1070. doi:10.1289/ehp.0901716. PMC 2920080. PMID 20338858. 
  179. ↑ Geens T, Neels H, Covaci A (December 2009). "Sensitive and selective method for the determination of bisphenol-A and triclosan in serum and urine as pentafluorobenzoate-derivatives using GC-ECNI/MS". J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877 (31): 4042–6. doi:10.1016/j.jchromb.2009.10.017. PMID 19884050. 
  180. ↑ Verner, M.; Magher, T.; Haddad, S. (2009). "High concentrations of commonly used drugs can inhibit the in vitro glucuronidation of bisphenol a and nonylphenol in rats". Xenobiotica 40 (2): 83–92. doi:10.3109/00498250903383334. PMID 19916736. 
  181. ↑ Xing, L.; Xu, Y.; Xiao, Y.; Shang, L.; Liu, R.; Wei, X.; Jiang, J.; Hao, W. (2010). "Embryotoxic and teratogenic effects of the combination of bisphenol a and genistein on in vitro cultured postimplantation rat embryos". Toxicological Sciences 115 (2): 577–588. doi:10.1093/toxsci/kfq081. PMID 20299547. 
  182. ↑ Barry, Carolyn (20 August 2009). "Plastic Breaks Down in Ocean, After All -- And Fast". National Geographic News. http://news.nationalgeographic.com/news/2009/08/090820-plastic-decomposes-oceans-seas.html. Retrieved 30 August 2009. 
  183. ↑ Fox, J.E., J. Gulledge, E. Engelhaupt, M.E. Burrow & J.A. McLachlan (2007). "Pesticides reduce symbiotic efficiency of nitrogen-fixing rhizobia and host plants". Proc. Nat. Acad. Sci. 104 (24): 10282–7. doi:10.1073/pnas.0611710104. PMC 1885820. PMID 17548832. 
  184. ↑ Bisphenol A Fact Sheet, Government of Canada. Assessed 19 April 2008.
  185. ↑ Oehlmann, J.; Schulte-Oehlmann, U.; Kloas, W.; Jagnytsch, O.; Lutz, I.; Kusk, O.; Wollenberger, L.; Santos, M. et al (Jul 2009). "A critical analysis of the biological impacts of plasticizers on wildlife". Philosophical transactions of the Royal Society of London. Series B, Biological sciences 364 (1526): 2047–2062. doi:10.1098/rstb.2008.0242. ISSN 0962-8436. PMC 2873012. PMID 19528055. 
  186. ↑ http://www.sciencedaily.com/releases/2010/07/100729122332.htm

[change] Other websites

Health issues of plastics and Polyhalogenated compounds (PHCs)
Plasticizers: Phthalates
DIBP • DBP • BBP (BBzP) • DIHP • DEHP (DOP) • DIDP • DINP
Miscellaneous plasticizers
Monomers
Bisphenol A (BPA, in Polycarbonates) • Vinyl chloride (in PVC)
Miscellaneous additives incl. PHCs
PBDEs · PCBs · Organotins  · PFCs
Health issues
Miscellanea
Retrieved from "http://simple.wikipedia.org/w/index.php?title=Bisphenol_A&oldid=3531661"
Personal tools
Namespaces

Variants
Actions
Getting around
Print/export
Toolbox
In other languages