Bisphenol-A Overview
Originally produced for use as a synthetic hormone in
1936, today bisphenol A (BPA) is manufactured in excess of six billion pounds
per year. BPA is most commonly used as the building block of
polycarbonate plastic for products such as plastic kids cups, baby bottles,
water bottles, epoxy resins (coatings that line food containers), and white
dental sealants. It is also an additive in other types of plastic used
to make children’s toys.
BPA molecules are bound by "ester bonds” to form a
polymer used to make polycarbonate plastic. As the building
block of polycarbonate, BPA is the primary chemical in polycarbonate,
and it thus does not exist in only trace amounts. While plastics
are typically thought of as stable, scientists have known for many
years that the chemical bond between BPA molecules is unstable.
The bond is disrupted by heat and acidic or basic conditions that
release BPA into food or beverages in contact with the plastics. There
is extensive scientific literature reporting adverse effects of BPA at
doses lower than the current level considered safe by U.S. EPA, a high
rate of leaching of BPA from food and beverage containers, and
evidence that the median BPA level in humans is higher than the level
that causes adverse effects in lab studies.
Scientific Research on BPA:
Bisphenol A linked to diabetes and heart disease in adults
A research team from the Peninsula Medical Teaching, the University of
Exeter, the University of Plymouth and the University of Iowa, have set up
evidence linking Bisphenol A (BPA) to diabetes and heart infirmity in
adults.
Their research paper is to be published in the Journal of the American
Medical Association on Wednesday 17 September, 2009, and it is the first
time that evidence has emerged of the association between higher BPA
levels and disease in adults.
BPA is a controversial chemical commonly used in food and drink
containers. It has previously caused concerns over health risks to babies,
as it is present in some baby’s bottles.
BPA is used in polycarbonate plastic products such as refillable drinks
containers, compact disks, some plastic eating utensils and many other
products in everyday use. It is one of the world’s highest production
volume chemicals, with over 2.2 million tonnes (6.4 billion pounds)
produced in 2003, with an annual growth in demand of between six and 10
per cent each year.
Many previous studies in laboratory animals have suggested that BPA is
safe, but some laboratory studies have raised doubts. Experiments in which
mice and rats were exposed to BPA have shown that higher doses of the
chemical can lead to liver damage, insulin resistance, diabetes and
obesity. The laboratory animal evidence is complicated and controversial.
Some scientists believe that BPA can disrupt the work done by hormones,
especially oestrogen, but the full biological effects of BPA in humans is
far from clear.
The research team analysed information from the US government’s
National Health and Nutrition Examination Survey (NHANES) 2003-2004, the
only large-scale data available on BPA concentrations excreted in urine.
The research team analysed the results for the 1455 adults aged between 18
and 74 years old for whom measures were available. This study group is
representative of the general population of the USA.
The analysis found that the 25 per cent of the population with the
highest BPA levels were more than twice as likely to have heart disease
and/or diabetes, compared to the 25 per cent with the lowest BPA levels.
Higher BPA levels were also associated with clinically
abnormal liver
enzyme concentrations.
While this study has identified a statistical association between BPA
and adult diseases
for the first time, much more research is needed. Future work needs to
exclude the small possibility that the association is due to some other
unstudied factor, or that people with these diseases somehow become more
exposed to BPA. It is also unclear whether the liver enzyme changes are
linked to liver damage.
Professor David Melzer, Professor of Epidemiology and Public Health at
the Peninsula Medical School (Exeter, UK), who led the team commented:
“Our study has revealed, for the first time, an association between raised
BPA loads and two common diseases in adults. At the moment we can’t be
absolutely sure that BPA is the direct cause of the extra cases of heart
disease and diabetes: if it is, some cases of these serious conditions
could be prevented by reducing BPA exposure. This is therefore an exciting
finding, but it is also just the first step in understanding the role of
BPA.”
He emphasised that this new possible link does not detract from the
existing health advice to people on how to prevent heart disease and
diabetes. Professor Melzer also praised the NHANES study and the US
Division of Environmental Health Laboratory Sciences, National Center for
Environmental Health, Centers for Disease Control and Prevention, who
released these data for analysis by researchers.
Tamara Galloway, Professor of eco-toxicology from the School of
Biosciences, the University of Exeter, added: “Our results illustrate how
important human bio-monitoring programmes such as NHANES are in providing
high quality information on the extent of human exposure to common
chemicals such as BPA, allowing us to explore the relationship between
exposure and health outcomes more fully.”
http://www.pms.ac.uk/
Common Plastic Disrupts Endocrine System - Xeno Estrogen Effect.
Analytical and Bioanalytical Chemistry - 2006 Oct 21
Hormonal compounds are a
class of pharmaceutical product that disrupt the endocrine system of animals
and humans. Exposure to these molecules, even at low concentrations, can have
severely damaging effects on the environment, to organisms, and to humans. The
cumulative presence of these compounds is also characterized by synergistic
effects which are difficult to estimate. They are an underestimated danger to
the environment and to the human population. This paper presents an in-vivo
model enabling to assessment of the real impact of exposure to hormonal
compounds and the synergistic effect which can be involved. The anatomical
effects of in-ovo exposure to two natural estrogen compounds (estrone and
estriol, at 600 ng g(-1)) and a synthetic estrogen (ethynylestradiol, at 20 ng
g(-1)) have been investigated. Estrone and estriol lead to morphological
defects, mainly in the urogenital system of the developing chick embryo,
whereas ethynylestradiol has fewer effects. Estriol caused persistence of
Mullerian ducts in 50% of male embryos and hypertrophic oviducts in 71% of
females. Estrone had the same effects but at the percentages were lower.
Kidney dysfunction was also observed, but only with estrone, in both males and
females. We also tested estrogenic compounds in two types of cell line which
are estrogen sensitive (BG1 and MCF7) then completed and confirmed our
previous in-vivo results. Seven pharmaceutical-like compounds-estrone (E1),
estradiol (E2), estriol (E3), ethynylestradiol (EE(2)), carbamazepine (C),
genistein (G), and bisphenol-A (BPA)-were tested alone or in mixtures.
Different effects on the two cell lines were observed, indicating that
endocrine compounds can act differently on this organism. Experiments also
showed that these molecules have synergistic action and induce more severe
effects when they are in mixtures.
Endocrine disruptor bisphenol A strongly binds to human estrogen-related
receptor gamma (ERRgamma) with high constitutive activity.
Toxicol Lett. 2006 Sep 3. Laboratory of Structure-Function
Biochemistry, Department of Chemistry, Faculty and Graduate School of
Sciences, Kyushu University, Fukuoka, Japan.
Bisphenol A (BPA) has been
acknowledged as an estrogenic chemical able to interact with human estrogen
receptors (ER). Many lines of evidence reveal that BPA has an impact as an
endocrine disruptor even at low doses. However, its binding to ER and hormonal
activity is extremely weak, making the intrinsic significance of low dose
effects obscure. We thus supposed that BPA might interact with nuclear
receptor(s) other than ER. Here we show that BPA strongly binds to human
estrogen-related receptor gamma (ERRgamma), an orphan receptor and one of 48
human nuclear receptors. In a binding assay using [(3)H]4-hydroxytamoxifen
(4-OHT) as a tracer, BPA exhibited a definite dose-dependent receptor binding
curve with the IC(50) value of 13.1nM. 4-Nonylphenol and diethylstilbestrol
were considerably weaker (5-50-fold less than BPA). When examined in the
reporter gene assay for ERRgamma using HeLa cells, BPA completely preserved
ERRgamma's high constitutive activity. Notably, BPA exhibited a distinct
antagonist action to reverse the inverse agonist activity of 4-OHT, retaining
high basal activity. ERRgamma is expressed in a tissue-restricted manner, for
example very strongly in the
mammalian
brain during development, and in the adult in the brain, lung and other
tissues.
It will now be important to evaluate whether BPA's hitherto reported low dose
effects may be mediated through ERRgamma.
The food contaminants bisphenol A
and 4-nonylphenol act as agonists for estrogen receptor alpha in MCF7 breast
cancer cells.
Endocrine. 2003 Dec;22(3):275-84. Department of Pharmaco-Biology,
University of Calabria Rende, Italy.
Xenoestrogens are chemically
distinct industrial products potentially able to disrupt the endocrine system
by mimicking the action of endogenous steroid hormones. Among such compounds,
the ubiquitous environmental contaminants bisphenol A (BPA) and 4-nonylphenol
(NPH) may promote adverse effects in humans triggering estrogenic signals in
target tissues. Following a research program on human exposure to endocrine
disruptors, we found contamination of fresh food by BPA and NPH. More
important, these contaminants were found to display estrogen-like activity
using as a model system the estrogen-dependent MCF7 breast cancer cells
(MCF7wt); its variant named MCF7SH, which is hormone-independent but still
ERalpha-positive, and the steroid receptor-negative human cervical carcinoma
HeLa cells. In transfection experiments BPA and NPH activated in a direct
manner the endogenous ERalpha in MCF7wt and MCF7SH cells, as the antiestrogen
hydroxytamoxifen was able to reverse both responses. Moreover, only the
hormone-binding domains of ERalpha and ERbeta expressed by chimeric proteins
in HeLa cells were sufficient to elicit the transcriptional activity upon BPA
and NPH treatments. Transfecting the same cell line with ERalpha mutants, both
contaminants triggered an estrogen-like response. These transactivation
properties were interestingly supported in MCF7wt cells by the autoregulation
of ERalpha which was assessed by RT-PCR for the mRNA evaluation and by
immunoblotting and immunocytochemistry for the determination of protein
levels. The ability of BPA and NPH to modulate gene expression was further
confirmed by the upregulation of an estrogen target gene like pS2. As a
biological counterpart, concentrations of xenoestrogens eliciting
transcriptional activity were able to stimulate the proliferation of MCF7wt
and MCFSH cells. Only NPH at a dose likely too high to be of any physiological
relevance induced a severe cytotoxicity in an ERalpha-independent manner as
ascertained in HeLa cells. The estrogenic effects of such industrial agents
together with an increasing widespread human exposure should be taken into
account for the potential influence also on hormone-dependent
breast cancer disease.
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