Bisphenol-A Overview - Environment California: 130 studies suggest that BPA exposure at very low doses is linked to a staggering number of health problems

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In April 2008, the National Toxicology Program of the U.S. National Institutes

of Health finally acknowledged health concerns about children’s exposure

to BPA. Unfortunately, it is unclear whether this determination will lead to

any federal policy changes to protect children from BPA"

Bisphenol-A Overview - Environment California More than 130 studies suggest that BPA exposure at very low doses is linked to

.... In studies with mice, BPA causes aneuploidy even at extremely low

doses. ...

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- 54k - similar pages 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 baby bottles and 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. In brief, this

summary reveals that 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.

·

Children are Most at Risk

Growing children are particularly at risk to chemicals in their environment

because they face greater exposure per pound of body weight and are

physiologically more susceptible to them.Children’s exposures begin at conception, as chemicals, including BPA,

cross the placenta in a pregnant woman’s body

and can affect the embryo or fetus during critical periods of

development. Even after birth, children’s bodies remain immature,

with underdeveloped detoxification mechanisms to protect them from BPA as well

as drugs. Their brains and other organ systems are constantly developing,

undergoing periods of particular sensitivity to damage or disruption.

Especially because growing children are particularly at risk from BPA exposure

and adverse effects on intellectual ability, social behaviors, fertility, and

potential for disease may take decades to detect, precautionary measures must

be taken to protect children from exposure to products containing BPA that they

use everyday. ·

BPA Levels in Humans are Above Harmful Levels Found in Studies

According to the U.S. Centers for Disease Control, 95% of Americans have

detectable levels of bisphenol-A in their bodies.

In a recent CDC study, the observed BPA levels detected—0.1 to 9 parts

per billion (ppb)—were at and above the concentrations known to reliably

cause adverse effects in laboratory experiments. Despite the fact that

BPA is metabolized by the body, the findings provide strong evidence that

exposure to BPA is very frequent or nearly continuous

In fact, one recent study found significant increases in calcium inflow even at

the lowest levels of BPA exposure in the parts per trillion (ppt) level.

Increases in calcium within the cell initiate a wide array of processes within

the cell such as regulating hormone secretion and controlling gene

activity. The CDC data show that people contain BPA in the parts per

billion (ppb) level—1,000 times higher than the lowest exposure at which

an effect was seen on calcium influx. These CDC findings are confirmed by

numerous studies conducted in other countries showing virtually identical

levels of BPA in blood and tissues collected from human fetuses and adults.Dangers of BPA are Confirmed by Weight of the

Science

Bisphenol-A can alter the expression of several hundred genes with effects

varying among specific tissues and also depending upon the timing of

exposure. More than 130 studies suggest that BPA exposure at very low

doses is linked to a staggering number of health problems, including prostate

and breast cancer, obesity, attention deficit and hyperactivity disorder, brain

damage, altered immune system, lowered sperm counts, and early puberty. Although the safe

level of BPA exposure set by U.S. EPA based on experiments conducted prior to

1988 is 50 ppb, some examples of effects at significantly lower doses of BPA

include: Behavioral

changes: Many laboratory studies show that low-dose exposure to BPA

causes behavioral effects, including hyperactivity (at 30 ppb);

increase in aggression (at 2 to 40 ppb);

changes in response to painful or fear-provoking stimuli (at 40 ppb);

impaired learning (at 100 ppb);

reversal of normal sex differences in the brain structure and elimination of

sex differences in behavior (at 30 ppb);

decreased maternal behavior such as reductions in time spent nursing, increases

in time resting away from offspring, and increases in time spent out of the

nest (at 10 ppb);

altered play and other socio-sexual behaviors (at 40 ppb);

and increased susceptibility to drug addiction (at 40-300 ppb). Diabetes and

obesity: Low-level, chronic exposure to BPA causes insulin resistance in

adult mice.

Such insulin resistance leads to Type II diabetes in people as well as

hypertension and cardiovascular disease. A recent study shows that even a

single dose of BPA at levels currently found in humans can result in altered

levels of blood glucose and insulin, and twice-daily exposure for just four

days results in insulin resistance. Several studies show an increased rate of

postnatal growth in both males and females as a result of maternal doses

between 2.4 and 500 ppb per day, and accelerated postnatal growth is associated

with obesity, insulin-resistant diabetes, hypertension, and heart disease. Early

puberty: Low-dose exposure to BPA can affect the timing of

the onset of puberty. Several studies reveal the early onset of sexual

maturation in females occurring at maternal doses between 2.4 and 50 ppb per

day. Down

Syndrome: BPA exposure is linked to an error in cell division

called aneuploidy, which causes 10-20% of all birth defects in people,

including Down Syndrome. In studies with mice, BPA causes aneuploidy even

at extremely low doses.

Reduced sperm count: Several

studies show that low-dose developmental or adult exposure at levels between

0.2 and 20 ppb reduces daily sperm production and fertility in males.

In one such study, low-dose exposure to male rats caused decreased sperm count

and affected testicular weight and structure. The authors concluded that “BPA alter spermatogenesis in a linear

manner in a dose range which is perhaps relevant to the daily level of exposure

in man." An important aspect of this finding is that BPA decreases

the levels of testosterone in males. Breast

cancer: Studies show that low-dose BPA exposure stimulates

mammary gland development. In one study, scientists exposed mouse fetuses to a daily dose of 250 nanograms

per kilogram of their body weight—less than 1% the amount deemed safe for

humans in the U.S—causing increased breast tissue development.

Higher density breast tissue is a risk factor for cancer. One study

author, Dr. Ana Soto, indicated the results lead her to believe that BPA likely

increases the risk of breast cancer in humans.

Prostate disease and cancer:

Low-dose exposure to BPA can significantly increase prostate size.

Several studies show an increase in prostate size due to hyperplasia in male

mouse offspring at very low maternal doses.

Another study shows extremely low doses of BPA initiate the proliferation

of human prostate cancer cells.

In addition, exposure to a very low dose of BPA for just a few days after

birth predisposes male rats to develop prostate cancer in adulthood.

Impaired immune function: Studies show

altered immune function occurring at BPA doses between 2.5 and 30 ppb.

Decreased anti-oxidant enzyme levels:

A decrease in antioxidant enzymes (required to protect against cell damage)

occurred at the very low dose of 200 parts per trillion (ppt) in adult male

rats. Brain

damage: Low doses of BPA can disrupt important effects

of estrogen in the developing brain, causing brain damage. In most

studies, BPA has been found to mimic the actions of estrogen in developing

neurons, but in specific areas of the brain, BPA can have the paradoxical

effect of inhibiting the activity of estrogen, which normally increases the

growth and regulates the viability of connections between neurons. The

concern relating to this finding is that this type of disruption is associated

with impaired learning and memory. Changes

in brain chemistry: Low-dose exposure to BPA causes changes

in the brain, including an increase in progesterone receptor mRNA levels at 400

ppb of BPA,

increase in estrogen receptor alpha mRNA levels at 40 ppb of BPA,

increase in estrogen receptor beta mRNA levels at 25 ppb of BPA,

and a change in brain somatostatin receptors at 400 ppb of BPA.

These receptors are involved in regulating the brain control systems that

coordinate the functioning of the reproductive system as well as reproductive

and other social behaviors.

The U.S. government has concluded that animal studies are a vital guide to identifying

health risks for humans.

Furthermore, there is extensive evidence that the sensitivity of tissues to BPA

in the animals used in the experiments cited above is virtually identical to

the sensitivity of human tissues to BPA. There are some strains of rat that are

particularly insensitive to BPA as well as any other estrogenic chemical or

drug, but these highly insensitive animals are considered by regulatory

agencies to be inappropriate for use in toxicological studies aimed at

predicting the potential risks to human health posed by exposure to low,

environmentally relevant doses of BPA.

Miscarriage and polycystic ovarian disease in women: Low-dose BPA exposure

is also associated with miscarriages in women.

In one recent study, scientists found levels of BPA in women with a history of

recurrent miscarriage three times higher than in women who had normal

pregnancies.

Specifically, the scientists examined patients who had suffered three or more

consecutive miscarriages and compared the BPA levels of women who had

subsequent successful pregnancies with women who miscarried again. In

another study, women who had polycystic ovary syndrome (PCOS) had higher levels

of BPA, were more obese, and had higher levels of male sex hormones, suggesting

a range of physiological abnormalities, relative to normal, non-obese women

without PCOS. · Polycarbonate Plastic Breaks Down and Leaches BPA

Numerous studies show that polycarbonate plastics break down and leach BPA into

food or beverages in contact with the plastic.

In one study, BPA leaching was detected in 12 polycarbonate baby bottles after

dishwashing, brushing, and boiling. Levels of BPA detected in liquid held

in these bottles exceeded 8 ppb. ·

Independent Science Shows Harmful Effects from BPA, while Industry Science

Shows None

A recently-published review of scientific studies shows that, in the last 7

years (through November 2005), 151 studies on the low-dose effects of BPA have

been published.

None of the 12 studies funded by the chemical industry reported adverse effects

at low levels, whereas 128 of 139 government-funded studies found

effects. These many studies were conducted in academic laboratories in

the U.S. and abroad. Even the 12 industry-funded studies have flaws, however. Of the

industry studies, two had its positive control fail—an indication that

the entire experiment had failed, not that BPA had not caused an effect.

Adverse effect

No effect

Industry funded

0

12

Government funded

128

11

Another industry study

concluded BPA caused no effect, but an independent analysis of the experiment's

data by scientists convened by the National Toxicology Program of the U.S.

Department of Health & Human Services concluded that in fact there was an

effect. Industry scientists had misreported their own results.

The chemical industry relies on an incomplete review of scientific studies by

an effort funded by the American Plastics Council at the

Harvard Center for Risk Analysis. The panel funded by the American Plastics Council only

considered 19 studies in concluding in 2004 that the weight of the evidence for

low-dose effects of BPA was weak.

As of November 2005, there were 151 published studies on the low-dose effects

of BPA. ·

California Must Lead the Way Due to Outdated Federal Government Action on BPA The last U.S. EPA

risk assessment for BPA was based on research conducted in the 1980s and did

not consider that BPA was a chemical estrogen. The most recent risk

assessment of BPA was based on a comprehensive review of the scientific

literature conducted in 1998 by the European Union, with some selected articles

added through 2001, at which time few of the current 151 low-dose BPA studies

had been published. The most recent review of scientific studies shows

effects from exposure to BPA at levels significantly below the current

“safe exposure” level established by the

U.S. based on experiments conducted

prior to 1988.

In April 2008, the National Toxicology Program of the U.S. National Institutes

of Health finally acknowledged health concerns about children’s exposure

to BPA. Unfortunately, it is unclear whether this determination will lead to

any federal policy changes to protect children from BPA.

<!--[endif]--> <!--[if !supportFootnotes]-->[1]<!--[endif]-->

Environment California Research & Policy Center would like to thank the

authors of Our Stolen Future, Dr. Theo Colborn, Dianne Dumanoski, and Dr. Pete

Myers, for their updates on the science of endocrine disruption found at www.ourstolenfuture.org from which

we obtained much of the valuable information contained herein. <!--[if !supportFootnotes]-->[2]<!--[endif]-->

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U.S. National Research Council of the National Academy of Sciences, Committee

on Hormonally Active Agents in the Environment (1999) (In August 1999, the

National Research Council released its long awaited report on endocrine

disruption, commissioned in 1995 by the U.S. EPA, the U.S. Department of the

Interior, and Congress. The National Academy confirmed that

human exposure to contaminants such as BPA and phthalates is widespread and

that animal studies are a vital guide to identifying health risks for people.

“Laboratory studies using male and female rats, mice, and guinea pigs and

female rhesus monkeys have shown that exposure of these animals during

development to a variety of concentrations of certain HAAs (e.g., DDT,

methoxychlor, PCBs, dioxin, bisphenol A, octylphenol, butyl benzyl phthalate

(BBP), dibutyl phthalate (DBP), chlordecone, and vinclozolin) can produce

structural and functional abnormalities of the reproductive tract.”). <!--[if !supportFootnotes]-->[32]<!--[endif]-->

Hunt, PA, KE Koehler, M Susiarjo, CA Hodges, A Ilagan, RC Voigt, S , BF

and TJ Hassold. 2003. Bisphenol A exposure causes meiotic aneuploidy in

the female mouse. Current Biology 13: 546-553 (2003); Sugiura-Ogasawara, M, Y Ozaki, S

Sonta , T Makino and Kaoru Suzumori 2005. Exposure to bisphenol A

is associated with recurrent miscarriage. Human Reproduction 20:2325-2329

(2005). <!--[if !supportFootnotes]-->[33]<!--[endif]-->

Sugiura-Ogasawara, M, Y Ozaki, S Sonta , T

Makino and Kaoru Suzumori 2005. Exposure to bisphenol A is associated with

recurrent miscarriage. Human Reproduction 20:2325-2329 (2005). <!--[if !supportFootnotes]-->[34]<!--[endif]-->

Takeuchi T, Tsutsumi O, Ikezuki Y, Takai Y, Taketani Y. 2004. Positive

relationship between androgen and the endocrine disruptor, bisphenol A, in

normal women and women with ovarian dysfunction. Endocrin. J. 51:165-169

(2004). <!--[if !supportFootnotes]-->[35]<!--[endif]-->

Brede, C., P. Fjeldal, I. Skjevrak and H. Herikstad (2003). Increased migration

levels of bisphenol A from polycarbonate baby bottles after dishwashing,

boiling and brushing. Food Addit. Contam. 20(7): 684-9 (2003); Factor, A. (1996). Mechanisms of thermal and

photodegradations of bisphenol A polycarbonate. Polymer Durability: Degradation,

Stabilization, and Lifetime Prediction. R. L. Clough, N. C. Billingham and K.

T. Gillen. Washington ,

D.C. , American Chemistry Society: 59-76

(1996); Howdeshell, K. L., P. H. man, B. M. Judy, J. A.

, C. E. Orazio, R. L. Ruhlen, F. S. vom Saal and W. V. Welshons (2003).

Bisphenol A is released from used polycarbonate animal cages into water at room

temperature. Environ. Health Perspect. 111:1180-1187 (2003); Hunt, P. A., K. E. Koehler, M. Susiarjo, C. A. Hodges,

A. Hagan, R. C. Voigt, S. , B. F. and T. J. Hassold (2003).

Bisphenol A causes meiotic aneuploidy in the female mouse. Current Biol.

13:546-553 (2003). Sajiki, J. and J. Yonekubo (2004). Leaching of

bisphenol A (BPA) from polycarbonate plastic to water containing amino acids

and its degradation by radical oxygen species. Chemosphere 55:861-7 (2004). <!--[if !supportFootnotes]-->[36]<!--[endif]-->

Brede, C., P. Fjeldal, I. Skjevrak and H. Herikstad (2003). Increased migration

levels of bisphenol A from polycarbonate baby bottles after dishwashing,

boiling and brushing. Food Addit. Contam. 20(7): 684-9 (2003). <!--[if !supportFootnotes]-->[37]<!--[endif]-->

vom Saal, F and C , An Extensive New Literature Concerning Low-Dose

Effects of Bisphenol A Shows the Need for a New Risk Assessment. Environmental

Health Perspectives 113:926-933 (2005). <!--[if !supportFootnotes]-->[38]<!--[endif]-->

vom Saal, F and C , An Extensive New Literature Concerning Low-Dose

Effects of Bisphenol A Shows the Need for a New Risk Assessment. Environmental

Health Perspectives 113:926-933 (2005) (“The charge to the HCRA panel,

which was to perform a weight-of-the evidence evaluation of available data on

the developmental and reproductive effects of exposure to BPA in laboratory

animals, led to an analysis of only 19 of 47 available published studies on

low-dose effects of BPA. The deliberations of the HCRA were in 2001–2002,

and accordingly, a cut-off date of April 2002 was selected for consideration of

the published literature. It is regrettable that the relevance of the

analysis was further undermined by a delay of 2.5 years in publication of the

report. During the intervening time, between April 2002 and the end of

2004, a large number of additional articles reporting low-dose effects of BPA

in experimental animals have been published. The result is that by the

end of 2004, a PubMed (National Library of Medicine,

Bethesda , MD )

search identified 115 published studies concerning effects of low doses of BPA

in experimental animals.”).

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