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      Molecular Mechanisms of Action of BPA

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          Abstract

          Bisphenol A (BPA) exposure has been associated with serious endocrine-disrupting effects in humans and wildlife. Toxicological and epidemiological studies evidenced that BPA increases body mass index and disrupts normal cardiovascular physiology by interfering with endogenous hormones in rodents, nonhuman primates, and cell culture test systems. The BPA concentration derived from these experiments were used by government regulatory agencies to determine the safe exposure levels of BPA in humans. However, accumulating literature in vivo and in vitro indicate that at concentrations lower than that reported in toxicological studies, BPA could elicit a different endocrine-disrupting capacity. To further complicate this picture, BPA effects rely on several and diverse mechanisms that converge upon endocrine and reproductive systems. If all or just few of these mechanisms concur to the endocrine-disrupting potential of low doses of BPA is at present still unclear. Thus, taking into account that the incidence and/or prevalence of health problems associated with endocrine disruption have increased worldwide, the goal of the present review is to give an overview of the many mechanisms of BPA action in order to decipher whether different mechanisms are at the root of the effect of low dose of BPA on endocrine system.

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          Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004

          Background Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States. Objectives We aimed to assess exposure to BPA and tOP in the U.S. general population. Methods We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003–2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry. Results BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p $45,000/year). Conclusions Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.
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            Bisphenol A and human health: a review of the literature.

            There is growing evidence that bisphenol A (BPA) may adversely affect humans. BPA is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between BPA and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking BPA to human health; 53 published within the last year. This review outlines this body of literature, showing associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental BPA exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental BPA exposure can be harmful to humans, especially in regards to behavioral and other effects in children. Copyright © 2013 Elsevier Inc. All rights reserved.
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              A review of dietary and non-dietary exposure to bisphenol-A.

              Due to the large number of applications of bisphenol-A (BPA), the human exposure routes are multiple. We aimed to review shortly the food and non-food sources of BPA, and to evaluate their contribution to the human exposure. Food sources discussed here include epoxy resins, polycarbonate and other applications, such as paperboard and polyvinylchloride materials. Among the non-food sources, exposures through dust, thermal paper, dental materials, and medical devices were summarized. Based on the available data for these exposure sources, it was concluded that the exposure to BPA from non-food sources is generally lower than that from exposure from food by at least one order of magnitude for most studied subgroups. The use of urinary concentrations from biomonitoring studies was evaluated and the back-calculation of BPA intake seems reliable for the overall exposure assessment. In general, the total exposure to BPA is several orders of magnitude lower than the current tolerable daily intake of 50 μg/kg bw/day. Finally, the paper concludes with some critical remarks and recommendations on future human exposure studies to BPA. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Dose Response
                Dose Response
                DOS
                spdos
                Dose-Response
                SAGE Publications (Sage CA: Los Angeles, CA )
                1559-3258
                7 October 2015
                Oct-Dec 2015
                : 13
                : 4
                : 1559325815610582
                Affiliations
                [1 ]Department of Science, Roma Tre University, Roma, Italy
                [2 ]INBB-National Laboratory of Gender and Endocrine Disruptors, Roma, Italy
                Author notes
                [*]Maria Marino, Department of Science, Roma Tre University, Viale G. Marconi 446, I-00146 Roma, Italy. Email: maria.marino@ 123456uniroma3.it
                Article
                10.1177_1559325815610582
                10.1177/1559325815610582
                4679188
                26740804
                da461a76-2a44-4e4a-aa9e-b5b8bff82f6e
                © The Author(s) 2015

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License ( http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

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                October-December 2015

                bisphenol a,endocrine disruptors,low doses,nuclear receptors,signal transduction pathways

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