The Otium Post

The Otium Post


What they did´nt tell you about Bisphenol (BPA)

Bisphenol A (BPA)

CATEGORY*: Endocrine disruptor

FOUND IN: Plastics, epoxy resins used in food cans

THE GIST: It’s one of the most common chemicals we’re exposed to each day, and it’s in everything from food and drink containers to dental fillings. BPA is a synthetic estrogen that can disrupt the hormone system, particularly when exposures occur while babies are still in the womb or in early life. Even miniscule exposures increase risks for breast cancer, prostate cancer, infertility, early puberty, metabolic disorders and type-2 diabetes. Some BPA alternatives, such as BPS, have come on the market, but have yet to be proven safe. The FDA has banned BPA from baby bottles and infant formula packaging.

The State of the Evidence on Bisphenol A (BPA)

Bisphenol A (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 resinsfound in many common consumer products (Beronius, 2010). It is also prevalent in thermal receipts and other paper products, including in recycled paper products as a result of the recycling of thermal receipts (Liao, 2011).

Avoid canned foods; clear, shatterproof plastic food and drink containers; and thermal receipts. And even if a plastic is labeled as BPA-free, do not assume that it's safe!

An estimated 5 million US tons of this endocrine-disrupting chemical were produced globally in 2008, and more than 2.4 million tons were produced in the United States in 2007 (CEPA, 2009). According to Global Industry Analysts, the global market is expected to reach 6 million tons by 2015 (GIA, 2010). Over 500 tons of BPA are released into the U.S. environment annually, according to an estimate by the U.S. Environmental Protection Agency (EPA, 2012). Significant levels of BPA have been measured in ambient air (Matsumoto, 2005), house dust (Rudel, 2003), and river and drinking water(Rodriguez-Mozaz, 2005). 

Present in many common household products such as eyeglasses and compact discs, BPA is also commonly found in the epoxy lining of metal food cans; polycarbonate plastic food containers, including some baby bottles; microwave ovenware; and eating utensils. Because BPA is an unstable compound and is also lipophilic (fat-seeking), it can leach into food products, 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 studies have explored the effects of increased ingestion of food and drink packaged in materials containing endocrine-disrupting compounds. Both found rapid increases (within a few days to a week) 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). Another study took the opposite approach and demonstrated that just a three-day period of limiting intake of packaged foods decreased the concentrations of BPA found in urine by an average 65 percent (Rudel, 2011).

Clearance of BPA from the body is quite rapid, with its urinary half-life on the order of hours to days. A recent study of samples taken from fasting people indicates 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), a finding supported by growing evidence of BPA’s presence in thermal receipts and other paper goods. 

Centers for Disease Control and Prevention researchers have measured BPA in 93 percent of about 2,500 urine samples from a broad national sample of adults through the NHANES study (Calafat, 2008). BPA has been found in the blood (Padmanabhan, 2008) and urine (Ye, 2009a) of pregnant women, and in breast milk soon after women gave birth (Kuruto-Niwa, 2006). BPA has also been found in blood samples from developing fetuses and the surrounding amniotic fluid (Ikezuki, 2002); it has also 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. Nevertheless, one of the big controversies in the field is related to the form of BPA that is measured in these human biomonitoring studies. The parent chemical, bisphenol A, is known to be weakly estrogenic (Markey, 2001; Wetherill, 2007). However BPA is rapidly metabolized (converted) by the gastrointestinal tract and the liver to a form of BPA (called conjugated BPA) that does not display known estrogenic activity (Matthews, 2001; Volkel, 2002). 

Analysis of human urine and blood samples has led some investigators to conclude that levels of the parent, estrogenic form of BPA are insignificant in both blood and urine samples of people, and that the conjugated metabolites being reported by most scientists have no known physiological activity (Teeguarden, 2011; Volkel 2008). Others recognize the importance of BPA conversion by metabolism, but conclude that the cumulative evidence from human biomonitoring studies indicates sufficient continued exposure of people to unconjugated (parent) BPA to explain its observed effects on physiological systems (Vandenberg, 2010b).

A further complication in understanding the data from human and animal studies is that, while adult rodents and mammals appear to have similar rates of metabolizing BPA, there may be important differences in metabolism of BPA between rodent and primate (including human) metabolism of the compound in very young animals, a factor that would influence the usefulness of using rodent models for understanding development effects of early BPA exposures in humans (Doerge, 2011; Taylor, 2010).

Despite these important controversies over the form and amount of BPA to which developing and adult humans are exposed, considerable data indicate that exposure of humans to BPA is associated with increased risk for cardiovascular disease, miscarriages, decreased birth weight at term, breast and prostate cancer, reproductive and sexual dysfunctions, altered immune system activity, metabolic problems and diabetes in adults, and cognitive and behavioral development in young children (Braun, 2009, 2011; Rees-Clayton, 2011; Lang, 2008; Li, 2009; Miao, 2011; Sugiura-Ogasawara, 2005). These findings are entirely consistent with parallel research in rodent models demonstrating reproductive, metabolic and neurodevelopmental problems in animals exposed to environmentally relevant levels of BPA (e.g., Salian, 2011; Wei, 2011; Wolstenholme, 2011).

With regard to mammary development and increased risk for development of breast cancer, 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). Early exposure to BPA led to abnormalities in mammary tissue development that were observable even during gestation and were maintained into adulthood (Vandenberg, 2007; 2008). Prenatal exposure of rats to BPA resulted in increases in the number of pre-cancerous lesions and in situ tumors (carcinomas) (Murray, 2007a), as well as an 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).

Another mechanism by which perinatal exposures to low levels of BPA may affect mammary tissue development at puberty and into adulthood is through increased synthesis of the progesterone receptor and activation of progesterone-regulated mammary-cell proliferation (Ayyanan, 2011).

Changes in mammary development comparable to those observed in rodent models were also observed when female rhesus monkeys were exposed to environmentally relevant doses of BPA during gestation (Tharp, 2012).

Some of the long-term effects of neonatal exposures to BPA may be dose dependent, with low- and high-dose exposures resulting in different timing and profiles of changes in gene expression in cells of the mammary gland. In one study, low-dose exposures had the most profound effect on rat mammary glands during the period just prior to the animals’ reaching reproductive maturity, while higher doses had more delayed effects, altering gene expression in mammary tissues from mature adults (Moral, 2008). In a study of chronic exposure of adult mice to different concentrations of BPA, only low doses decreased the latency of tumor appearance and increased the number of mammary tumors as well as their rate of metastasis. All doses enhanced the rate of mammary cellproliferation, but only relatively higher doses counteracted this increased proliferation with parallel increases in programmed cell death (apoptosis) (Jenkins, 2011).

In addition to physical abnormalities in the developing mammary tissue of rodents treated around the time of birth with low levels of BPA (0.7 ug/kg body weight/day or 64 ug/kg body weight/day), there are also functional deficits. Female rats exposed to BPA during gestation and suckling had physical abnormalities in their adult mammary tissue as well as decreases in yield and different protein content of their own milk when as new mothers, they were feeding their pups. Observed differences following BPA exposure were similar to those found in rats that had been similarly exposed to diethylstilbestrol, a known breast tumor inducer (Kass, 2012).

Studies using cultures of human breast cancer cells demonstrate that BPA acts through the same cellular response pathways as the natural estrogen estradiol (Rivas, 2002; Welshons, 2006). BPA can interact weakly with the intracellular estrogen receptor, and it can also induce mammary 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).

Exposure of normal and cancerous human breast cells to low levels of BPA leads to altered expression of hundreds of genes including many involved in hormone-receptor-mediated processes, cell proliferation and programmed cell death, and carcinogenesis (Goodson, 2011; Tilghman, 2012; Weng, 2010).

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). Studies indicate that BPA reduces the efficacy of common chemotherapy agents (cisplatin, doxirubicin and vinblastin) in their blocking the proliferation of 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.




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