Bisphenol A: The Chemical Used in Plastics

Overview

Bisphenol A, commonly abbreviated as BPA, is an organic compound with two phenol functional groups. It is a difunctional building block of several important plastics and plastic additives, 2–3 million metric ton are produced every year.

Suspected of being hazardous to humans since the 1930s, concerns about the use of bisphenol A in consumer products were regularly reported in the news media in 2008 after several governments issued reports questioning its safety, and some retailers have removed products made of it from their shelves.

Bisphenol A is used primarily to make plastics, and products containing bisphenol A-based plastics have been in commerce for more than 50 years. 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.

Epoxy resins containing bisphenol A are used as coatings on the inside of almost all food and beverage cans. BPA is used to produce paper such as thermal paper and carbonless copy paper. Bisphenol A is also a precursor to the flame retardant, tetrabromobisphenol A, and was formerly used as a fungicide.

Global production of bisphenol A in 2003 was estimated to be over 2 million metric tonnes (t). In the U.S., it is manufactured by Bayer MaterialScience, Dow Chemical Company, SABIC Innovative Plastics (formerly GE Plastics), Hexion Specialty Chemicals, and Sunoco Chemicals. In 2004, these companies produced just over 1 million t of bisphenol A, up from just 7,260 t in 1991. In 2003, annual U.S. consumption was 856,000 t, 72% of which was used to make polycarbonate plastic and 21% going into epoxy resins. The amount of BPA used in the US is equivalent to six pounds per habitant per year.

Health effects

Bisphenol A is an endocrine disruptor, which can mimic the body's own hormones and may lead to negative health effects. Early development appears to be the period of greatest sensitivity to its effects. Regulatory bodies have determined safety levels for humans, but those safety levels are currently being questioned as a result of new scientific studies. In 2009 the The Endocrine Society released a scientific statement expressing concern over current human exposure to BPA. In 2007, a consensus statement by 38 experts on bisphenol A concluded that average levels in people are above those that cause harm to animals in laboratory experiments. A panel convened by the U.S. National Institutes of Health determined that there was "some concern" about BPA's effects on fetal and infant brain development and behavior. A 2008 report by the U.S. National Toxicology Program (NTP) later agreed with the panel, expressing "some concern for effects on the brain, 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."

Obesity

A 2008 review has concluded that obesity may be increased as a function of BPA exposure, which "merits concern among scientists and public health officials". A 2009 review of available studies has concluded that "perinatal BPA exposure acts to exert persistent effects on body weight and adiposity". Another 2009 review has concluded that "Eliminating exposures to (BPA) and improving nutrition during development offer the potential for reducing obesity and associated diseases". Other reviews have come with similar conclusions. A later study on mice has shown that perinatal exposure to drinking water containing 1 mg/L of BPA increased adipogenesis in females at weaning.

Breast cancer

A 2008 review has concluded that "perinatal exposure to low doses of BPA, alters breast development and increases breast cancer risk". Another 2008 review concluded that " animal experiments and epidemiological data strengthen the hypothesis that foetal exposure to xenoestrogens may be an underlying cause of the increased incidence of breast cancer observed over the last 50 years". A 2009 review, funded by the "Breast Cancer Fund", has recommended "a federal ban on the manufacture, distribution and sale of consumer products containing bisphenol A". Neither the U.S. Environmental Protection Agency nor the International Agency for Research on Cancer have evaluated bisphenol A for possible carcinogenic activity.

Neurological issues

A panel convened by the U.S. National Institutes of Health determined that there was "some concern" about BPA's effects on fetal and infant brain development and behavior.  A 2008 report by the U.S. National Toxicology Program (NTP) later agreed with the panel, expressing "some concern for effects on the brain". A 2007 review has concluded that BPA, like other xenoestrogens, should be considered as a player within the nervous system that can regulate or alter its functions through multiple pathways. A 2007 review has concluded that low doses of BPA during development have persistent effects on brain structure, function and behavior in rats and mice. A 2008 review concluded that low-dose BPA maternal exposure causes long-term consequences at the level of neurobehavioral development in mice. A 2008 review has concluded that neonatal exposure to Bisphenol-A (BPA) can affect sexually dimorphic brain morphology and neuronal phenotypes in adulthood. A 2008 review has concluded that BPA altered long-term potentiation in the hippocampus and even nanomolar dosage could induce significant effects on memory processes. A 2009 review raised concerns about BPA effect on anteroventral periventricular nucleus. A 2008 study by the Yale School of Medicine demonstrated that adverse neurological effects occur in non-human primates regularly exposed to bisphenol A at levels equal to the United States Environmental Protection Agency's (EPA) maximum safe dose of 50 µg/kg/day.  This research found a connection between BPA and interference with brain cell connections vital to memory, learning and mood.

Disruption of the dopaminergic system

A 2005 review concluded that prenatal and neonatal exposure to BPA can potentiate the central dopaminergic systems, resulting in the supersensitivity of the drugs of abuse-induced rewarding effects and hyperlocomotion in the mouse. A 2009 study on rats has concluded that prenatal and neonatal exposure to low-dose BPA causes deficits in development at dorsolateral striatum via altering the function of dopaminergic receptors.

Thyroid function

A 2007 review has concluded that bisphenol-A have been shown to bind to thyroid hormone receptor and perhaps have selective effects on its functions. A 2009 review about environmental chemicals and thyroid function, raised concerns about BPA effects on triiodothyronine and concluded that "available evidence suggests that governing agencies need to regulate the use of thyroid-disrupting chemicals, particularly as such uses relate exposures of pregnant women, neonates and small children to the agents". A 2009 review summarized BPA adverse effects on thyroid hormone action.

Research

Reproductive system and sexual behavior

A study in mice in 2009, which found ovary anomalies from exposition 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. Another study in 2009 suggested that neonatal exposure of as low as 50 µg/kg disrupts ovarian development in mice. Yet another study on mice in 2009 has concluded that 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. A 2009 study has found that prenatal exposure to BPA at levels of (10 μg/kg/day) affects behavioral sexual differentiation in male monkeys. A 2009 in vitro study on placental JEG3 cells concluded that BPA potentially reduced estrogen synthesis. A 2009 study has found that BPA exposure disrupted the blood-testis barrier when administered to immature, but not to adult, rats.

Prostate development and cancer

A 1997 study in mice has found that neonatal BPA exposure of 2 μg/kg increased adult prostate weight. A 2005 study in mice has found that neonatal BPA exposure at 10 μg/kg disrupted the development of the fetal mouse prostate. A 2006 study in rats has shown that neonatal bisphenol A exposure at 10 μg/kg levels increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis.  A 2007 in vitro study has found that BPA within the range of concentrations currently measured in human serum is associated with permanently increase in prostate size. A 2009 study has found that newborns rats exposed to a low-dose of BPA (10 µg/kg) increased prostate cancer susceptibility when adults.

General research

In 2009, at an Endocrine Society meeting new research reported data from animals experimentally treated with BPA. 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.

Studies on humans

Lang study

The first major 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. 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 notes that while this preliminary study needs to be confirmed and cannot prove causality, there is precedent for analogous effects in animal studies, which "add[s] biological plausibility to the results reported by Lang et al."

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.  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.

Other studies

Studies have associated recurrent miscarriage with BPA serum concentrations, oxidative stress and inflammation in postmenopausal women with urinary concentrations, and externalizing behaviors in two-year old children, especially among female children, with urinary concentrations.

Historical studies

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.

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) Study Year
0.025 "Permanent changes to genital tract" 2005
0.025 "Changes in breast tissue that predispose cells to hormones and carcinogens" 2005
1 long-term adverse reproductive and carcinogenic effects 2009
2 "increased prostate weight 30%" 1997
2 "lower bodyweight, increase of anogenital distance in both genders, signs of early puberty and longer estrus." 2002
2.4 "Decline in testicular testosterone" 2004
2.5 "Breast cells predisposed to cancer" 2007
10 "Prostate cells more sensitive to hormones and cancer" 2006
10 "Decreased maternal behaviors" 2002
30 "Reversed the normal sex differences in brain structure and behavior" 2003
50 Adverse neurological effects occur in non-human primates 2008
50 Disrupts ovarian development 2009
50 Current U.S. human exposure limit (a guideline set by EPA) 1998

Manuel Martinez

Project GreenBag, 2200 Market St, San Francisco, CA, 94114, United States