An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment

Abstract

Bisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, the resin lining of cans, and other products, with global capacity in excess of 6.4 billion lb/year. Because the ester bonds in these BPA-based polymers are subject to hydrolysis, leaching of BPA has led to widespread human exposure. A recent report prepared by the Harvard Center for Risk Analysis and funded by the American Plastics Council concluded that evidence for low-dose effects of BPA is weak on the basis of a review of only 19 studies; the report was issued after a delay of 2.5 years. A current comprehensive review of the literature reveals that the opposite is true. As of December 2004, there were 115 published in vivo studies concerning low-dose effects of BPA, and 94 of these report significant effects. In 31 publications with vertebrate and invertebrate animals, significant effects occurred below the predicted "safe" or reference dose of 50 µg/kg/day BPA. An estrogenic mode of action of BPA is confirmed by in vitro experiments, which describe disruption of cell function at 10 -12 M or 0.23 ppt. Nonetheless, chemical manufacturers continue to discount these published findings because no industry-funded studies have reported significant effects of low doses of BPA, although > 90% of government-funded studies have reported significant effects. Some industry-funded studies have ignored the results of positive controls, and many studies reporting no significant effects used a strain of rat that is inappropriate for the study of estrogenic responses. We propose that a new risk assessment for BPA is needed based on a) the extensive new literature reporting adverse effects in animals at doses below the current reference dose; b) the high rate of leaching of BPA from food and beverage containers, leading to widespread human exposure; c) reports that the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice; and d) recent epidemiologic evidence that BPA is related to disease in women.

The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

“…Examples of low dose effects of BPA have been reported in a wide variety of tissues and cell types (vom Saal & Hughes, 2005;Wetherill et al, 2007), although the mechanism of action to explain them are still unclear. One explanation could be that BPA may act via ER through mechanisms other than binding to ERE.…”

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

“…However, no histopathologic abnormalities were observed in young adulthood. Furthermore, the low-dose estrogenic response in the prostate gland has not been consistently reported (71), due in part to species/strain differences, background estrogen levels and other experimental variables, and is a matter of considerable debate (72,73). To examine this issue in the neonatal rat model, we administered estradiol over a 7-log range of doses on neonatal days 1, 3 and 5 in both Sprague-Dawley rats and the more estrogen-sensitive Fischer 344 rats (74).…”

Impact of Environmental Contaminants on Breast Cancer / Wpływ Zanieczyszczenia Środowiska Na Raka Piersi

“…However, research on very low dose exposure to BPA suggested an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities [122]. For example, a dose of BPA that is 2,000 times lower (0.025 µg kg −1 d −1 ) than the reference dose for human populations (50 µg kg −1 d −1 ) can stimulate mammary gland development in animal offspring whose mothers were exposed to this low dose [123,124]. There is a concern that exposure to low doses of BPA, defined as less than or equal to 5 mg kg −1 body weight per day, may have developmental effects on various hormone-responsive organs including the mammary gland.…”