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Science And Policy On Endocrine Disrupters Must Not Be Mixed: A Reply To A "Common Sense" Intervention By Toxicology Journal Editors, Åke Bergman, Anna-Maria Andersson, Georg Becher, Martin Van Den Berg, Bruce Blumberg, Poul Bjerregaard, Carl-Gustaf Bornehag, Riana Bornman, Ingvar Brandt, Jayne V. Brian, Stephanie C. Casey, Paul A. Fowler, Heloise Frouin, Linda C. Giudice, Taisen Iguchi, Ulla Hass, Susan Jobling, Anders Juul, Karen A. Kidd, Andreas Kortenkamp, Monica Lind, Olwenn V. Martin, Derek Muir, Roseline Ochieng, Nicolas Olea, Leif Norrgren, Erik Ropstad, Peter S. Ross, Christina Rudén, Martin Scheringer, Niels Erik Skakkebaek, Olle Söder, Carlos Sonnenschein, Ana Soto, Shanna Swan, Jorma Toppari, Charles R. Tyler, Laura N. Vandenberg, Anne Marie Vinggaard, Karin Wiberg, R. Thomas Zoeller
Science And Policy On Endocrine Disrupters Must Not Be Mixed: A Reply To A "Common Sense" Intervention By Toxicology Journal Editors, Åke Bergman, Anna-Maria Andersson, Georg Becher, Martin Van Den Berg, Bruce Blumberg, Poul Bjerregaard, Carl-Gustaf Bornehag, Riana Bornman, Ingvar Brandt, Jayne V. Brian, Stephanie C. Casey, Paul A. Fowler, Heloise Frouin, Linda C. Giudice, Taisen Iguchi, Ulla Hass, Susan Jobling, Anders Juul, Karen A. Kidd, Andreas Kortenkamp, Monica Lind, Olwenn V. Martin, Derek Muir, Roseline Ochieng, Nicolas Olea, Leif Norrgren, Erik Ropstad, Peter S. Ross, Christina Rudén, Martin Scheringer, Niels Erik Skakkebaek, Olle Söder, Carlos Sonnenschein, Ana Soto, Shanna Swan, Jorma Toppari, Charles R. Tyler, Laura N. Vandenberg, Anne Marie Vinggaard, Karin Wiberg, R. Thomas Zoeller
R. Thomas Zoeller
The “common sense” intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
Flawed Experimental Design Reveals The Need For Guidelines Requiring Appropriate Positive Controls In Endocrine Disruption Research, F. S. Vom Saal, B. T. Akingbemi, S. M. Belcher, D. A. Crain, D. Crews, L. C. Guidice, P. A. Hunt, J. P. Myers, C. Leranth, A. Nadal, N. Olea, V. Padmanabhan, C. S. Rosenfield, A. Schneyer, G. Schoenfelder, C. Sonnenenschein, A. M. Soto, R. W. Stahlhut, S. H. Swan, L. N. Vandenberg, H. S. Wang, C. S. Watson, W. V. Welshons, R. Thomas Zoeller
Flawed Experimental Design Reveals The Need For Guidelines Requiring Appropriate Positive Controls In Endocrine Disruption Research, F. S. Vom Saal, B. T. Akingbemi, S. M. Belcher, D. A. Crain, D. Crews, L. C. Guidice, P. A. Hunt, J. P. Myers, C. Leranth, A. Nadal, N. Olea, V. Padmanabhan, C. S. Rosenfield, A. Schneyer, G. Schoenfelder, C. Sonnenenschein, A. M. Soto, R. W. Stahlhut, S. H. Swan, L. N. Vandenberg, H. S. Wang, C. S. Watson, W. V. Welshons, R. Thomas Zoeller
R. Thomas Zoeller
A study published in Toxicological Sciences (Ryan et al., 2009) illustrates the importance of examining appropriate doses of both the positive control and the test chemical in research on endocrine-disrupting chemicals. For the three low doses of bisphenol A (BPA) that were fed to rats during pregnancy and lactation, there were no effects on female offspring (there were also no effects on male offspring from the same experiment; Howdeshell et al., 2008). A review of the results of the positive control doses makes it clear that the experiment cannot adequately assess the consequences of low-dose exposure to BPA because the …
Identification Of Thyroid Hormone Receptor Binding Sites And Target Genes Using Chip-On-Chip In Developing Mouse Cerebellum, H. Dong, C. L. Yauk, A. Rowan-Carroll, S. H. You, R. Thomas Zoeller, I Lambert, M. G. Wade
Identification Of Thyroid Hormone Receptor Binding Sites And Target Genes Using Chip-On-Chip In Developing Mouse Cerebellum, H. Dong, C. L. Yauk, A. Rowan-Carroll, S. H. You, R. Thomas Zoeller, I Lambert, M. G. Wade
R. Thomas Zoeller
Thyroid hormone (TH) is critical to normal brain development, but the mechanisms operating in this process are poorly understood. We used chromatin immunoprecipitation to enrich regions of DNA bound to thyroid receptor beta (TRβ) of mouse cerebellum sampled on post natal day 15. Enriched target was hybridized to promoter microarrays (ChIP-on-chip) spanning −8 kb to +2 kb of the transcription start site (TSS) of 5000 genes. We identified 91 genes with TR binding sites. Roughly half of the sites were located in introns, while 30% were located within 1 kb upstream (5′) of the TSS. Of these genes, 83 with …
Why Public Health Agencies Cannot Depend On Good Laboratory Practices As A Criterion For Selecting Data: The Case Of Bisphenol A, I Chahoud, F. S. Vom Saal, B. T. Akingbemi, S. M. Belcher, D. A. Crain, D. Crews, L. C. Guidice, P. A. Hunt, F. Farabollini, L. J. Guillette Jr., T. Hassold, S. M. Ho, K. Arizono, T. Colborn, T. Iguchi, S. Jobling, J. Kanno, H. Laufer, M. Marcus, A. Nadal, J. A. Mclachlan, J Oehlmann, N. Olea, P. Palanza, S. Parmigiani, B. S. Rubin, G. Schoenfelder, C. Sonnenschein, A. M. Soto, C. E. Talsness, J. A. Taylor, L. N. Vandenberg, J. G. Vandenbergh, S. Vogel, C. S. Watson, W. V. Welshons, R. Thomas Zoeller
Why Public Health Agencies Cannot Depend On Good Laboratory Practices As A Criterion For Selecting Data: The Case Of Bisphenol A, I Chahoud, F. S. Vom Saal, B. T. Akingbemi, S. M. Belcher, D. A. Crain, D. Crews, L. C. Guidice, P. A. Hunt, F. Farabollini, L. J. Guillette Jr., T. Hassold, S. M. Ho, K. Arizono, T. Colborn, T. Iguchi, S. Jobling, J. Kanno, H. Laufer, M. Marcus, A. Nadal, J. A. Mclachlan, J Oehlmann, N. Olea, P. Palanza, S. Parmigiani, B. S. Rubin, G. Schoenfelder, C. Sonnenschein, A. M. Soto, C. E. Talsness, J. A. Taylor, L. N. Vandenberg, J. G. Vandenbergh, S. Vogel, C. S. Watson, W. V. Welshons, R. Thomas Zoeller
R. Thomas Zoeller
Background In their safety evaluations of bisphenol A (BPA), the U.S. Food and Drug Administration (FDA) and a counterpart in Europe, the European Food Safety Authority (EFSA), have given special prominence to two industry-funded studies that adhered to standards defined by Good Laboratory Practices (GLP). These same agencies have given much less weight in risk assessments to a large number of independently replicated non-GLP studies conducted with government funding by the leading experts in various fields of science from around the world. Objectives We reviewed differences between industry-funded GLP studies of BPA conducted by commercial laboratories for regulatory purposes and …
Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers Of Adverse Outcomes, M. D. Miller, K. M. Crofton, D. C. Rice, R. Thomas Zoeller
Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers Of Adverse Outcomes, M. D. Miller, K. M. Crofton, D. C. Rice, R. Thomas Zoeller
R. Thomas Zoeller
Background There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health. Objectives We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals. Data sources We drew on an …
A Clash Of Old And New Scientific Concepts In Toxicity, With Important Implications For Public Health, J. P. Myers, R. Thomas Zoeller, F. S. Vom Saal
A Clash Of Old And New Scientific Concepts In Toxicity, With Important Implications For Public Health, J. P. Myers, R. Thomas Zoeller, F. S. Vom Saal
R. Thomas Zoeller
Background A core assumption of current toxicologic procedures used to establish health standards for chemical exposures is that testing the safety of chemicals at high doses can be used to predict the effects of low-dose exposures, such as those common in the general population. This assumption is based on the precept that “the dose makes the poison”: higher doses will cause greater effects. Objectives We challenge the validity of assuming that high-dose testing can be used to predict low-dose effects for contaminants that behave like hormones. We review data from endocrinology and toxicology that falsify this assumption and summarize current …
Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points For Improved Risk Assessment And Decision-Making, R. Thomas Zoeller, T. J. Woodruff, L. Zeise, D. A. Axelrad, K. Z. Guyton, S. Janssen, M. Miller, G. G. Miller, J. M. Schwartz, G. Alexeeff, H. Anderson, L. Birnbaum, F. Bois, V. J. Cogliano, K. Crofton, S. Y. Euling, P. M. Foster, D. R. Germolec, E. Gray, D. B. Hattis, A. D. Kyle, R. W. Luebke, M. I. Luster, C. Portier, D. C. Rice, G Solomon, J. Vandenberg, R. Thomas Zoeller
Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points For Improved Risk Assessment And Decision-Making, R. Thomas Zoeller, T. J. Woodruff, L. Zeise, D. A. Axelrad, K. Z. Guyton, S. Janssen, M. Miller, G. G. Miller, J. M. Schwartz, G. Alexeeff, H. Anderson, L. Birnbaum, F. Bois, V. J. Cogliano, K. Crofton, S. Y. Euling, P. M. Foster, D. R. Germolec, E. Gray, D. B. Hattis, A. D. Kyle, R. W. Luebke, M. I. Luster, C. Portier, D. C. Rice, G Solomon, J. Vandenberg, R. Thomas Zoeller
R. Thomas Zoeller
Background Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an “adverse effect” in the context of hazard identification and risk assessment. Objectives Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, …