Regulatory Decisions on Endocrine Disrupting Chemicals Should be Based on the Principles of Endocrinology.

Center for Regenerative & Developmental Biology, and Department of Biology, Tufts University, Medford, MA. Electronic address: .
Reproductive Toxicology (Impact Factor: 3.23). 02/2013; 38. DOI: 10.1016/j.reprotox.2013.02.002
Source: PubMed

ABSTRACT For years, scientists from various disciplines have studied the effects of endocrine disrupting chemicals (EDCs) on the health and wellbeing of humans and wildlife. Some studies have specifically focused on the effects of low doses, i.e. those in the range that are thought to be safe for humans and/or animals. Others have focused on the existence of non-monotonic dose-response curves. These concepts challenge the way that chemical risk assessment is performed for EDCs. Continued discussions have clarified exactly what controversies and challenges remain. We address several of these issues, including why the study and regulation of EDCs should incorporate endocrine principles; what level of consensus there is for low dose effects; challenges to our understanding of non-monotonicity; and whether EDCs have been demonstrated to produce adverse effects. This discussion should result in a better understanding of these issues, and allow for additional dialogue on their impact on risk assessment.

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Available from: Tom Zoeller, Aug 06, 2015
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    • "Calabrese (2010) asserted that hormesis is a generalized phenomenon rather than an exceptional case. Numerous studies have revealed that many chemicals such as bisphenol A, energetic trinitrotoluene, pesticide and antibiotic to cell, bacteria or plant display the non-monotonic concentration response (Bouskine et al., 2009; Belz et al., 2011; Pupo et al., 2012; Gressel and Dodds, 2013; Sheng et al., 2013; Stanley et al., 2013; Vandenberg et al., 2013). In our previous work, we also found the HCRs of some organic solvents, ionic liquids and inorganic salts to Vibrio qinghaiensis sp.-Q67 and firefly luciferase (Wang et al., 2011; Zhang et al., 2013a,b). "
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    ABSTRACT: The hormesis characterized by low-concentration stimulation and high-concentration inhibition has gained significant interest over the past decades. Some organic solvents and ionic liquids (ILs) have hormetic concentration responses (HCR) to bioluminescence such as firefly luciferase and Vibrio qinghaiensis sp.-Q67. In this study, we determine the effects of 1-alkyl-3-methylimidazolium chlorine ILs ([Cnmim]Cl, n=2, 4, 6, 8, 10 and 12) to firefly luciferase in order to verify the mechanism of hormesis. The luminescence inhibition toxicity tests show that the stimulation effects of [C8mim]Cl and [C10mim]Cl are obvious, [C6mim]Cl and [C12mim]Cl are minor, and [C2mim]Cl and [C4mim]Cl are rare. The enzyme kinetics show that [C8mim]Cl and [C10mim]Cl are the competitive inhibitors with ATP while [C2mim]Cl and [C4mim]Cl are the noncompetitive ones. Molecular dynamics simulation results reveal that imidazolium rings of [C8mim] and [C10mim] locate at the entrance of luciferin pocket which is adjacent to AMP pocket, while alkyl-chains insert into the bottom of the luciferin pocket. Combining the results from inhibition test, kinetics assay and molecular simulation, we can deduce that occupying AMP pocket by imidazolium ring is responsible for hormetic stimulation. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemosphere 03/2015; 132:108-113. DOI:10.1016/j.chemosphere.2015.03.030 · 3.34 Impact Factor
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    • "The presence (or absence) of NMDRCs from guideline studies is an important issue, as these are the studies that regulators rely on heavily when making decisions about chemical safety and in setting " safe " reference doses (Tyl, 2009). Yet analyses of guideline studies indicate that NMDRCs are present, but are often ignored or dismissed as paradoxical or irrelevant (Patisaul et al., 2012; Vandenberg et al., 2013a). "
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    ABSTRACT: Non-monotonic dose response curves (NMDRCs) have been demonstrated for natural hormones and endocrine disrupting chemicals (EDCs) in a variety of biological systems including cultured cells, whole organ cultures, laboratory animals and human populations. The mechanisms responsible for these NMDRCs are well known, typically related to the interactions between the ligand (hormone or EDC) and a hormone receptor. Although there are hundreds of examples of NMDRCs in the EDC literature, there are claims that they are not 'common enough' to influence the use of high-to-low dose extrapolations in risk assessments. Here, we chose bisphenol A (BPA), a well-studied EDC, to assess the frequency of non-monotonic responses. Our results indicate that NMDRCs are common in the BPA literature, occurring in greater than 20% of all experiments and in at least one endpoint in more than 30% of all studies we examined. We also analyzed the types of endpoints that produce NMDRCs in vitro and factors related to study design that influence the ability to detect these kinds of responses. Taken together, these results provide strong evidence for NMDRCs in the EDC literature, specifically for BPA, and question the current risk assessment practice where 'safe' low doses are predicted from high dose exposures.
    Dose-Response 05/2014; 12(2):259-76. DOI:10.2203/dose-response.13-020.Vandenberg · 1.22 Impact Factor
    • "These many and varied sources can make it difficult to estimate the contribution of any one endocrine disrupting compound to changes in reproduction and energy balance, but this difficulty does not diminish the importance of understanding the mechanisms. There is general agreement that increasing exposure of humans and wildlife to endocrine-disrupting compounds is a major societal problem that requires a concerted interdisciplinary focus that includes cooperation among behavioral neuroendocrinologists, reproductive biologists, conservation biologists, clinicians, epidemiologists, ecologists, evolutionary biologists, molecular biochemists as well as scientists and policy-makers in other disciplines (Balthazart and Levine, 2014; Crews and Gore, 2011; Gore et al., 2014; Vandenberg et al., 2013; Zoeller et al., 2012). We argue that this interdisciplinary focus must include scientists that specialize in neuroendocrinology of ingestive behavior, energy balance, and obesity. "
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    ABSTRACT: The prevalence of adult obesity has risen markedly in the last quarter of the 20th century and has not been reversed in this century. Less well known is the fact that obesity prevalence has risen in domestic, laboratory, and feral animals, suggesting that all of these species have been exposed to obesogenic factors present in the environment. This review emphasizes interactions among three biological processes known to influence energy balance: Sexual differentiation, endocrine disruption, and maternal programming. Sexual dimorphisms include differences between males and females in body weight, adiposity, adipose tissue distribution, ingestive behavior, and the underlying neural circuits. These sexual dimorphisms are controlled by sex chromosomes, hormones that masculinize or feminize adult body weight during perinatal development, and hormones that act during later periods of development, such as puberty. Endocrine disruptors are natural and synthetic molecules that attenuate or block normal hormonal action during these same developmental periods. A growing body of research documents effects of endocrine disruptors on the differentiation of adipocytes and the central nervous system circuits that control food intake, energy expenditure, and adipose tissue storage. In parallel, interest has grown in epigenetic influences, including maternal programming, the process by which the mother's experience has permanent effects on energy-balancing traits in the offspring. This review highlights the points at which maternal programming, sexual differentiation, and endocrine disruption might dovetail to influence global changes in energy balancing traits.
    Hormones and Behavior 03/2014; 66(1). DOI:10.1016/j.yhbeh.2014.03.011 · 4.63 Impact Factor
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