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

By F. V. vom Saal, C. Hughes. Environmental Health Perspectives, 2005

1,183 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Health, Toxicology and Mutagenesis, Small Animals

View Paper: https://www.semanticscholar.org/paper/6d6aaaf24f1898d6ca00b88faadc81273fe7111d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. S. Swan
2. J. Rochester
3. W. Welshons
4. Susan C. Nagel
5. F. V. vom Saal

In Health, Toxicology and Mutagenesis

1. J. Rochester
2. S. Swan
3. F. V. vom Saal
4. B. Rubin
5. W. Welshons
6. A. Calafat
7. Susan C. Nagel
8. M. Wong

In Small Animals

1. J. Rochester
2. W. Welshons
3. Susan C. Nagel
4. S. Swan
5. F. V. vom Saal

Citations in the corpus

• Bisphenol A and human health: a review of the literature. (2013, background): “greater effects at lower doses [2], and because of the numerous laboratory studies indicating 19 lower doses cause adverse effects [2, 5], researchers have raised concerns that the current ‘safe’ 20 cutoff for BPA is much too high [200].”
• Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. (2006, methodology): “We will use BPA as our model hormone-mimicking chemical, because there are now over 40 published studies reporting significant effects in rats and mice at doses below the predicted safe dose of 50 g/kg d (22, 23).”
• Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. (2012, neutral): “In several fields, significant controversy has been produced based on the results obtained from independent scientists compared with results obtained from scientists affiliated with the chemical industry (75, 76).”
• Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts. (2012, background): “Many animal studies also showed that BPA exposure decreases sperm production (Zhang et al., 2004b), increases the stillbirth rate (Wang et al., 2005b), affects embryonic development (Pei et al., 2003), and decreases the viability of mesencephalic neuronal cell (Lin et al., 2006).”
• Genetically modified crops safety assessments: present limits and possible improvements (2011, result): “For instance in the latter case, it was observed that none of the industry-funded studies showed adverse effects of Bisphenol A, whereas 90% of government-funded studies showed hazards at various levels and various doses [8].”
• Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans (2008, background): “If dose responses are nonlinear, as has been demonstrated for other environmental chemicals, this testing strategy will not protect human health (vom Saal and Hughes, 2005).”
• Food packaging--roles, materials, and environmental issues. (2007, background): “An extensive literature analysis by vom Saal and Hughes (2005) suggests the need for a new risk assessment for the low-dose effects of this compound.”