Designing endocrine disruption out of the next generation of chemicals

T. T. Schug; R. Abagyan; B. Blumberg; T. J. Collins; D. Crews; P. L. DeFur; S. M. Dickerson; T. M. Edwards; A. C. Gore; L. J. Guillette; T. Hayes; J. J. Heindel; A. Moores; H. B. Patisaul; T. L. Tal; K. A. Thayer; L. N. Vandenberg; J. C. Warner; C. S. Watson; F. S. vom Saal; R. T. Zoeller; K. P. O'Brien; J. P. Myers

doi:10.1039/C2GC35055F

Designing endocrine disruption out of the next generation of chemicals†

T. T. Schug,*^a R. Abagyan,^b B. Blumberg,^c T. J. Collins,^d D. Crews,^e P. L. DeFur,^f S. M. Dickerson,^g T. M. Edwards,^h A. C. Gore,ⁱ L. J. Guillette,^j T. Hayes,^k J. J. Heindel,^a A. Moores,^l H. B. Patisaul,^m T. L. Tal,ⁿ K. A. Thayer,^o L. N. Vandenberg,^p J. C. Warner,^q C. S. Watson,^r F. S. vom Saal,^s R. T. Zoeller,^t K. P. O'Brien*^g and J. P. Myers*^u

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* Corresponding authors

^a Division of Extramural Research and Training, Cellular, Organ and Systems Pathobiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
E-mail: schugt2@niehs.nih.gov, kpobrien@advancinggreenchemistry.org, jpmyers@ehsciences.org

^b Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA

^c Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA

^d Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA, USA

^e Section of Integrative Biology, University of Texas at Austin, Austin, TX, USA

^f Center for Environmental Studies, Virginia Commonwealth University, Richmond, VA, USA

^g Advancing Green Chemistry , Charlottesville, VA, USA

^h School of Biological Sciences, Louisiana Tech University, Ruston, LA, USA

ⁱ Institute for Neuroscience, University of Texas at Austin, Austin, TX, USA

^j Department of Obstetrics and Gynaecology, Medical University of South Carolina, Charleston, SC, USA

^k Laboratory for Integrative Studies in Amphibian Biology, Molecular Toxicology, Group in Endocrinology, Energy and Resources Group, Museum of Vertebrate Zoology, and Department of Integrative Biology, University of California, Berkeley, CA, USA

^l Centre for Green Chemistry and Catalysis, Department of Chemistry, McGill University, Montréal, QC, Canada

^m Department of Biology, North Carolina State University, Raleigh, NC, USA

ⁿ Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR. Current Address: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA

^o Office of Health Assessment and Translation, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

^p Center for Regenerative and Developmental Biology and Department of Biology, Tufts University, Medford, MA, USA

^q Warner Babcock Institute for Green Chemistry, Wilmington, MA, USA

^r Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, USA

^s Division of Biological Sciences and Department ,University of Missouri-Columbia, Columbia, MO, USA

^t Biology Department, University of Massachusetts-Amherst, Amherst, MA, USA

^u Environmental Health Sciences, Charlottesville, VA, USA

Abstract

A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at “the drawing board.” It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a ‘proof-of-principle’ test, we ran 6 endocrine disrupting chemicals (EDCs) that act via different endocrinological mechanisms through the protocol using published literature. Each was identified as endocrine active by one or more tiers. We believe that this voluntary testing protocol will be a dynamic tool to facilitate efficient and early identification of potentially problematic chemicals, while ultimately reducing the risks to public health.

Green Chemistry

Designing endocrine disruption out of the next generation of chemicals†

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Designing endocrine disruption out of the next generation of chemicals

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