LITERATURE REVIEW http://suite101.com/article/xeno-estrogens-in-water-bottles-disrupting-male-and-female-hormon-a232123 A new study from Harvard School of Public Health (HSPH) researchers found that participants who drank for a week from polycarbonate bottles -- the popular, hard-plastic drinking bottles and baby bottles -- showed a two-thirds increase in their urine of the chemical bisphenol A (BPA). Exposure to BPA, used in the manufacture of polycarbonate and other plastics, has been shown to interfere with reproductive development in animals and has been linked with cardiovascular disease and diabetes in humans. The study is the first to show that drinking from polycarbonate bottles increased the level of urinary BPA, and thus suggests that drinking containers made with BPA release the chemical into the liquid that people drink in sufficient amounts to increase the level of BPA excreted in human urine.
In addition to polycarbonate bottles, which are refillable and a popular container among students, campers and others and are also used as baby bottles, BPA is also found in dentistry composites and sealants and in the lining of aluminum food and beverage cans. (In bottles, polycarbonate can be identified by the recycling number 7.) Numerous studies have shown that it acts as an endocrine-disruptor in animals, including early onset of sexual maturation, altered development and tissue organization of the mammary gland and decreased sperm production in offspring. It may be most harmful in the stages of early development.
"We found that drinking cold liquids from polycarbonate bottles for just one week increased urinary BPA levels by more than two-thirds. If you heat those bottles, as is the case with baby bottles, we would expect the levels to be considerably higher. This would be of concern since infants may be particularly susceptible to BPA's endocrine-disrupting potential," said Karin B. Michels, associate professor of epidemiology at HSPH and Harvard Medical School and senior author of the study.
The researchers, led by first author Jenny Carwile, a doctoral student in the department of epidemiology at HSPH, and Michels, recruited Harvard College students for the study in April 2008. The 77 participants began the study with a seven-day "washout" phase in which they drank all cold beverages from stainless steel bottles in order to minimize BPA exposure. Participants provided urine samples during the washout period. They were then given two polycarbonate bottles and asked to drink all cold beverages from the bottles during the next week; urine samples were also provided during that time.
The results showed that the participants' urinary BPA concentrations increased 69% after drinking from the polycarbonate bottles. (The study authors noted that BPA concentrations in the college population were similar to those reported for the U.S. general population.) Previous studies had found that BPA could leach from polycarbonate bottles into their contents; this study is the first to show a corresponding increase in urinary BPA concentrations in humans.
One of the study's strengths, the authors note, is that the students drank from the bottles in a normal use setting. Additionally, the students did not wash their bottles in dishwashers nor put hot liquids in them; heating has been shown to increase the leaching of BPA from polycarbonate, so BPA levels might have been higher had students drunk hot liquids from the bottles.
Canada banned the use of BPA in polycarbonate baby bottles in 2008 and some polycarbonate bottle manufacturers have voluntarily eliminated BPA from their products. With increasing evidence of the potential harmful effects of BPA in humans, the authors believe further research is needed on the effect of BPA on infants and on reproductive disorders and on breast cancer in adults.
"This study is coming at an important time because many states are deciding whether to ban the use of BPA in baby bottles and sippy cups. While previous studies have demonstrated that BPA is linked to adverse health effects, this study fills in a missing piece of the puzzle—whether or not polycarbonate plastic bottles are an important contributor to the amount of BPA in the body," said Carwile.
The study was supported by the Harvard University Center for the Environment and the National Institute of Environmental Health Sciences Biological Analysis Core, Department of Environmental Health, HSPH. Carwile was also supported by the Training Program in Environmental Epidemiology
A study by Dr. De-Kun Li, an epidemiologist with Kaiser Permanente, released in 2009, followed hundreds of male workers in several Chinese factories for a period of 5 years. In a startling report, Dr. Li demonstrated that men exposed to excessive concentrations of BPA had significantly higher chances of developing sexual dysfunction.
Following the release of these findings, many governments, including the United States and the European Union announced that they are reevaluating the risk associated with this chemical in consumer products, especially products intended for food contact or for children.
The use of BPA in consumer products was completely legal just about everywhere in the world until Canada restricted the substance in baby bottles in 2008. Canada’s action on BPA was followed by several state and local governments in the United States, including Minnesota, Connecticut, San Francisco and a handful of counties in New York State. Many products contain toxic chemicals that may have detrimental health impact for children exposed during critical stages of development. In this report, we analyze the extent to which five popular brands of baby bottles leach bisphenol A, a developmental, neural, and reproductive toxicant, into liquids coming into contact with them.
Bisphenol A is a Developmental, Neural, and Reproductive Toxicant - Scientists have linked very low doses of bisphenol A exposure to cancers, impaired immune function, early puberty, obesity, diabetes, and hyperactivity, among other problems. In addition, ABC New just reported on 4/15/08 that Bisphenol A was found in the urine of adults and children, umbilical cord, placentia, and is suspected to cause breast cancer and prostate cancer later in life.
Exposure to Bisphenol A is Widespread - Bisphenol A is most commonly used to make clear polycarbonate plastic for consumer products, such as baby bottles and water bottles. Through use, this plastic breaks down and leaches bisphenol A into liquids and foods with which they come into contact.
The U.S. Centers for Disease Control and Prevention (USCDCP) found bisphenol A in the urine of over 95% of people they tested. Alarmingly, the median level of bisphenol A in humans is higher than the level that causes adverse effects in animal studies.

WWF is particularly concerned because the reproduction and development of many wildlife species have already been affected by EDCs released into the environment. WWF is therefore working to ensure that these substances are adequately controlled, which in many circumstances will include phasing them out of use. Even at very low levels, recent studies have shown that BPA can affect the sex ratio of frogs ( Kloas, W. et al 1999) and can cause the sterilisation of water snails. Given the intricate nature of ecosystems, and the lack of knowledge of the effects on many other species, this is a major concern.
With regard to possible effects in humans, alarm bells really started to ring in 1997, when one research team, fronted by Fred vom Saal and Wade Welshons, found that even very low levels of BPA could cause harmful effects. Male mice exposed in the womb to low levels of BPA were shown to have increased prostate weights, (Nagel, S.C. vom Saal, et al 1997) and decreased daily sperm production. ( Vom Saal, F.S. et al 1998).
Furthermore, these scientists found that BPA could cause greater effects at low dose levels than at higher doses. This launched the debate on the “low dose theory” or the inverted U-shaped dose response curve. As rodents are used to predict effects in humans these findings were critical.
Industry rushed to examine these low level effects of BPA, and several industry studies were published which could find no effects. (Ashby, J. et al 1999). Subsequently, however, independent scientists working in the USA and Germany have confirmed that relatively low levels of BPA can indeed cause effects on male animals exposed in the womb. Industry scientists have argued that the divergence of results with regard to prostate weights, is due to the natural variability of the pups within a litter. Whilst this may be so for some of these experiments, it is unable to explain the effects that have now been noted in female offspring and in young animals. For example, vom Saal’s team have reported effects on female offspring, indicating that animals exposed to low doses may come to puberty earlier, and in this study the natural variability due to their position in the womb was fully taken into account. (Howdeshell, K.L. Hotchkiss, et al 1999). Furthermore, other studies have reported changes in vaginal cells and the oestrous cycle in female mice exposed in the womb to relatively low levels of BPA. (Markey, C. Michaelson, et al 1999). Reported effects on young animals also underline the need to be concerned about exposure to low levels. For example, a Japanese study has suggested a direct effect on sperm production in rats given a low dose for just 6 days.( Ohsako, S. Sakaue, et al 1999). Also, behavioural effects from early life exposures have now been identified.14 Therefore, there are now several studies that strongly support the suggestion that BPA can cause effects at low doses, including effects on the female reproductive tract, and on breast tissue, (Colerangle, J.B. & Roy, D. 1997) as well as effects on the testes and sperm production, and on the behaviour of both males and females.
The experience gained with BPA, and similarly with tobacco, underlines the need to ensure that research scientists with no industry connections are properly resourced. It is notable that it is independent researchers who have highlighted possible concerns with regard to the effects of BPA exposure on human health and the environment.
This briefing provides background information on the production and use of BPA, and summarises the known exposure routes and research detailing the effects of BPA. Given the concerns about the effects of BPA and related substances, it is of paramount importance to identify and quantify all likely exposure routes. This briefing also highlights some hitherto unpublished work, which suggests that in Europe, some polycarbonate babies feeding bottles may leach bisphenol A. This is clearly undesirable, particularly in view of the dose level which vom Saal considers may bring on earlier puberty in females. Male babies may also be at risk, as it would be a mistake to assume that hormonally speaking, babies are inactive. For example, during the first three months of life, male babies have high levels of male hormones (around 50% of adult levels). (Forest M.G., 1974). It is not known exactly why this is, but it is believed that the subsequent behaviour of the individual is imprinted at this time. (Sachs, B.D. and Meisel, R.L. 1988). Therefore, interference in hormonal processes at this age could have significant consequences to development.

Healthy eating may no longer be a matter of just what you eat and drink. It may also depend on what you buy, store, prepare, and heat those food and beverages in.
A growing body of scientific research has linked the weak estrogenic compound bisphenol-A (BPA) to a variety of health problems, such as infertility, prostate cancer, and breast cancer.
BPA is the main building block of polycarbonate plastic, a hard plastic widely used to make kitchen utensils, food storage containers, travel mugs, and water bottles. BPA is also a main component of the epoxy linings found in metal food and beverage cans.
The problem: Polycarbonate plastics can leach BPA into our food and beverages.
Heat, acid, alcohol, harsh detergents, age, and microwaving can also exacerbate the release of BPA, says Frederick vom Saal, a biology professor and BPA researcher at the University of Missouri.
Because their reproductive organs are still developing, fetuses, infants, and children are especially vulnerable to synthetic estrogens BPA. This means pregnant women and kids can benefit from reduced exposure to BPA. Reproductive-aged women may also want to be careful.
“From animal models, it appears that the period right after fertilization and before a woman even knows she’s pregnant, is the most sensitive time in development,” says Randy Jirtle, a Professor of Radiation Oncology at Duke University. “So if women are even thinking of becoming pregnant, they should consider limiting their exposure to BPA.”
While BPA may be impossible to completely eliminate it from your life, there are a few key steps you can take to reduce exposure.
Limit canned foods & beverages. The epoxy liners of metal food and beverage cans most likely contain BPA. Vom Saal especially recommends avoiding canned foods that are acid (tomatoes, tomato-based soups, citrus products, and acidic beverages like cokes) and canned alcoholic beverages, since acids and alcohols can exacerbate the leaching of BPA.
The good news: Many foods and beverages can be purchased in glass containers (think beer, olive oil, and tomato paste) or frozen (like vegetables).
Don’t store foods in plastic. Glass food storage containers are inert and there are plenty of wonderful Pyrex containers on the market. Just be sure to wash the lids, which are made of plastic, by hand.
Filter your drinking and cooking water. Since detectable levels of BPA have been found in the water, vom Saal recommends removing it using a reverse osmosis and carbon filter, which generally can be found for less than $200. “In the long run, it’s cheaper than buying bottled water, which isn’t tested for BPA,” he says.
Filter your shower and tub water. According to vom Saal, the relatively small BPA molecules can easily be absorbed through the skin. BPA can be removed from the water by adding ceramic filters to showerheads and tubs. Just be sure to change them regularly.
Don’t transport beverages in plastic mugs. Instead, opt for an unlined stainless steel travel mug. This is especially important when transporting hot beverages, like coffee or tea.
Limit use of hard plastic water bottles. Those colorful light-weight plastic bottles may be great for hiking, but unfortunately, they are made of polycarbonate plastic. For everyday use when a little extra weight isn’t an issue, choose a stainless steel water bottle, and make sure it’s unlined—some metal water bottles contain a plastic liner that may contain BPA.
Klean Kanteen makes an excellent series of unlined stainless steel water bottles
Minimize hard plastics in the kitchen. Hard plastic stirring spoons, pancake flippers, blenders, measuring cups, and colanders regularly come into contact with both food and heat. Fortunately, all of these can easily be replaced with wooden, metal, or glass alternatives.
Skip the water cooler. Those hard plastic five-gallon jugs that many companies use to provide their employees and customers with “pure” water are usually made of BPA-containing polycarbonate. Opt for tap water instead.

Bisphenol A May Trigger Human Breast Cancer
Study in rats provides strongest case yet against common environmental chemical
Bette Hileman
A new study finds the strongest evidence yet for the hypothesis that widespread environmental exposure to bisphenol A during fetal life causes breast cancer in adult women. The research, led by Ana M. Soto, professor of anatomy and cellular biology at Tufts University School of Medicine, in Boston, was published Dec. 6 in the online edition of Reproductive Toxicology (DOI: 10.1016/j.reprotox.2006.10.002).

Soto and her colleagues exposed pregnant rats to bisphenol A at doses ranging from 2.5 to 1,000 µg per kg of body weight per day. By the time the pups exposed at the lowest dose reached the equivalent of puberty (50 days old), about 25% of their mammary ducts had precancerous lesions, a proportion three to four times higher than among the nonexposed controls. Mammary ducts from all other exposure groups showed elevated levels of lesions. Cancerous lesions were found in the mammary glands of one-third of the rats exposed to 250 µg/kg/day.
Bisphenol A, a known estrogenic compound, is ubiquitous in the environment. Many people receive exposures of about 2.5 µg/kg/day, and mammary gland development in rats and humans is very similar. Therefore, Soto says, "bisphenol A could be one factor causing the increase in breast cancer incidence over the past 50 years."
Bisphenol A is used in the manufacture of polycarbonate plastics and epoxy resins. It is found in many food and beverage containers, including baby bottles. It is also found in canned food linings and dental composites, and it leaches from all of these products. In one study, Soto notes, urine samples from 95% of the human subjects contained the chemical.
According to Soto, a large body of previous research suggests bisphenol A might cause breast cancer. One study shows that the daughters of women who took the potent synthetic nonsteroidal estrogen diethylstilbestrol (DES) during their pregnancies between 1948 and 1971 have 2.5 times the normal incidence of breast cancer. Bisphenol A, which is structurally similar to DES, may act by a similar mechanism, she explains.
"What is important to note is that Soto's research is not a one-shot finding," says Frederick vom Saal, professor of biology at the University of Missouri. "It follows five years of research demonstrating precancerous changes in the mammary glands of mice with prenatal bisphenol A exposure. Now, Soto has switched to the rat, which is considered a much better animal model for studying human carcinogenesis."
The Environmental Protection Agency has set a safe human intake dose of 50 µg/kg/day for bisphenol A. "On the basis of the effects observed in recent studies, this seems to be an unsafe level," Soto says.

Bisphenol A (BPA) has been associated with increased risk for cardiovascular disease, miscarriages, breast and prostate cancer, reproductive dysfunction, metabolic dysfunction and diabetes, and neurological and behavioral disorders (Braun, 2009; Lang, 2008; Li, 2009; Sugiura-Ogasawara, 2005).
BPA is one of the most common chemicals to which we are exposed in everyday life. It is the building block of polycarbonate plastic and is also used in the manufacture of epoxy resins. According to Environment Canada (the Canadian equivalent of the EPA), more than 4 billion kilograms (4.4 million tons) of the chemical were produced globally in 2006, and more than 1 billion kilograms (1.1 million tons) were produced in the United States in 2007 (CEPA, 2009).
Present in many household products, BPA is also commonly found in the epoxy lining of metal food cans and in polycarbonate plastic food containers, including some baby bottles, microwave ovenware and eating utensils. Because BPA is an unstable polymer and is also lipophilic (fat-seeking), it can leach into canned foods (Noonan, 2011), infant formula and other food products (Schecter, 2010), especially when heated (Brotons, 1995). Once in food, BPA can move quickly into people—a particular concern for women of childbearing age and young children. Two recent studies have explored the effects of increased ingestion of food and drink packaged in EDC-containing sources. Both found rapid (within a few days to a week) increases in BPA levels in urine and/or blood samples taken from subjects who intentionally increased their intake of common foods and drinks packaged in BPA-containing products (Carwile, 2009; Smith, 2009).
Clearance rates for BPA are quite rapid, with a urinary half-life in the order of hours to days. A recent study of samples taken from fasting people indicate that sources other than foods may also be responsible for the pervasive exposure to BPA, as levels of the chemical did not decrease as rapidly as would have been predicted were food the only source of contamination (Stahlhut, 2009). However, a recent dietary study demonstrated that eating a diet free of packaging containing BPA contaminants led to an average 66 percent decrease in urinary BPA levels after only three days on the package-free diet (Rudel, 2011). Significant levels of BPA have also been measured in ambient air (Matsumoto, 2005), house dust (Rudel, 2003), and river and drinking water (Rodriguez-Mozaz, 2005) samples.
CDC researchers have measured BPA in 93 percent of about 400 urine samples from a broad national sample of adults (Calafat, 2005). BPA has been found in blood (Padmanabhan, 2008) and urine (Ye, 2009a) of pregnant women, and in breast milk soon after women gave birth (Kuroto-Niwa, 2006). BPA has also been found in blood samples from developing fetuses as well as the surrounding amniotic fluid (Ikezuki, 2002), and it has been measured in placental tissue and umbilical cord blood at birth (EWG, 2009; Schonfelder, 2002) as well as in the urine of premature infants housed in neonatal ICUs (Calafat, 2009).
That BPA is found so extensively in people, from prenatal to adult ages, is particularly impressive given the relatively short half-life of the chemical.
Several studies using both rat and mouse models have demonstrated that even brief exposures to environmentally relevant doses of BPA during gestation or around the time of birth lead to changes in mammary tissue structure predictive of later development of tumors (Maffini, 2006; Markey, 2001; Muñoz-de-Toro, 2005). Exposure also increased sensitivity to estrogen at puberty (Wadia, 2007). Recent data demonstrate that early exposure to BPA leads to abnormalities in mammary tissue development that are observable even during gestation and are maintained into adulthood (Vandenberg, 2007; 2008).
Interestingly, some of the long-term effects of neonatal exposure to BPA may be dose dependent, with low- and high-dose exposures resulting in different timing and profiles of changes in mammary gland gene expression. In one study, low-dose exposures had the most profound effect on rat mammary glands during the period just prior to animals reaching reproductive maturity, while higher doses had more delayed effects, altering gene expression in mammary tissues from mature adults (Moral, 2008).
Prenatal exposure of rats to BPA results in increases in the number of pre-cancerous lesions and in situ tumors (carcinomas) (Murray, 2007a), as well as increased number of mammary tumors following adulthood exposures to subthreshold doses (lower than that needed to induce tumors) of known carcinogens (Durando, 2007; Jenkins, 2009; Lozada, 2011). Exposures to BPA in adulthood also enhance the rate of growth and proliferation of existing hormone-sensitive mammary tumors, suggesting multiple mechanisms by which BPA may affect breast cancer development (Lozada, 2011).
Studies using cultures of human breast cancer cells demonstrate that BPA acts through the same response pathways as the natural estrogen estradiol (Rivas, 2002; Welshons, 2006). BPA can interact weakly with the intracellular estrogen receptor (ER), and it can also alter breast cell responsiveness and induce cell proliferation in vitro and in vivo. It affects cellular functions through interactions with the membrane estrogen receptor (Watson, 2005; Wozniak, 2005). Along with its many other effects on cell growth and proliferation, BPA has been shown to mimic estradiol in causing direct damage to the DNA of cultured human breast cancer cells (Iso, 2006).
Cell culture studies support animal evidence that BPA has dose-dependent effects. One recent study showed estrogen-like effects at extremely low concentrations; when somewhat higher concentrations were used, there were no effects on the cellular kinase pathway being studied. And at an even higher dose, the BPA inhibited the effects of estradiol. Despite the wide ranges of doses used in the study, even the very highest was in the nanomolar region; for all conditions, they were low and in the environmentally relevant range of concentrations (Jeng, 2011).
In the presence of BPA, cells from the non-cancerous breast of women diagnosed with breast cancer had a gene-response profile associated with the development of highly aggressive tumors (Dairkee, 2008). Two new studies indicate that BPA reduces the efficacy of common chemotherapy agents (cisplatin, doxirubicin and vinblastin) in their actions against proliferating breast cancer cells when tested in cell systems (LaPensee, 2009; 2010). Thus, not only does early exposure to BPA lead to an increased risk for development of breast tumors, but exposure to BPA during chemotherapy treatment for breast cancer may make the treatment less effective. Recent data further suggests that BPA leads normal human breast cells to behave like cancer cells, and indicates that BPA may also make cells less responsive to the cancer-inhibiting effects of the anti-estrogen tamoxifen (Goodson, 2011).