Large Effects from Small Exposures. III. Endocrine Mechanisms Mediating Effects of Bisphenol A at Levels of Human Exposure

Abstract

Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, in dental sealants, and in blends with other types of plastic products. The ester bond linking BPA molecules in polycarbonate and resins undergoes hydrolysis, resulting in the release of free BPA into food, beverages, and the environment, and numerous monitoring studies now show almost ubiquitous human exposure to biologically active levels of this chemical. BPA exerts estrogenic effects through the classical nuclear estrogen receptors, and BPA acts as a selective estrogen receptor modulator. However, BPA also initiates rapid responses via estrogen receptors presumably associated with the plasma membrane. Similar to estradiol, BPA causes changes in some cell functions at concentrations between 1 pM and 1 nM, and the mean and median range of unconjugated BPA measured by multiple techniques in human pregnant maternal, fetal, and adult blood and other tissues exceeds these levels. In contrast to these published findings, BPA manufacturers persist in describing BPA as a weak estrogen and insist there is little concern with human exposure levels. Our concern with human exposure to BPA derives from 1) identification of molecular mechanisms mediating effects in human and animal tissues at very low doses, 2) in vivo effects in experimental animals caused by low doses within the range of human exposure, and 3) widespread human exposure to levels of BPA that cause adverse effects in animals.

Can endocrine disruptors influence neuroplasticity in the aging brain?

“…Furthermore, spine synapse proliferation seems not to require high concentrations of estradiol in normal females; endogenous stores are adequate. In fact, Tanapat et al (2005) found that low doses of estradiol enhanced proliferation while high doses did not; U-shaped or inverted U-shaped functions are a common finding in endocrinology (Welshons et al, 2006). Cooke and Wooley (2005), in their review of these relationships, also noted evidence that, during the period of elevated synaptogenesis, spatial navigation performance improved, followed by diminished performance when synaptogenesis waned.…”

“…Bisphenol A, by conventional assays, would be considered a weak estrogen. Through enzyme induction, rather than by binding to the estrogen receptor, it enhances cell proliferation to produce estrogen-like results (Welshons et al, 2006). It is not an estrogen, that is, in the conventional sense, and, in fact, as shown by MacLusky et al (2005b), it can also counteract the effects of estrogens.…”

“…EDCs are "weak;" that is, they produce relatively minor effects at environmental levels. Welshons et al (2006) effectively demolish this argument. They point out that the "weak" label is the result of insensitive and irrelevant assay procedures as well as the mistaken view that it is essentially an estrogen.…”

Bisphenol A exposure and associations with obesity among adults: a critical review

“…While excess energy intake and a sedentary lifestyle are known risk factors for gaining weight, there has been increasing interest in the effects that environmental chemicals may have on the development of obesity (4) . Food and water provide us with essential nutrients; however, food and water are also sources of exposure to environmental chemicals, including pesticides (5,6) , food packaging and processing-derived contaminants such as bisphenol A (BPA) and phthalates (7)(8)(9)(10)(11)(12)(13)(14)(15) , and naturally occurring contaminants such as arsenic (16,17) . Chemicals detected in the food and water supply include endocrine-disrupting chemicals, a class of chemicals that interfere in some way with the normal functioning of the endocrine system and includes chemicals that may alter hormonal regulation of body weight.…”

Bisphenol A may reduce the efficacy of androgen deprivation therapy in prostate cancer

“…A recent study by Calafat et al [38] found that up to 95% of their demographically diverse sample of the United States adult population had detectable BPA in their urine, with concentrations reported to range in the nanomolar range (mean concentration in urine of 1.33 lg/l). Additionally, several other studies have reported adult BPA levels in the nanomolar range (using both serum and urine analyses), with nearly 100% of sample populations having detectable BPA or BPA metabolites [reviewed in 39].…”