A Class Approach to Hazard
Assessment of Organohalogen
Flame Retardants
Committee to Develop a Scoping Plan to Assess the Hazards of
Organohalogen Flame Retardants
Board on Environmental Studies and Toxicology
Division on Earth and Life Studies
A Consensus Study Report of
THE NATIONAL ACADEMIES PRESS
Washington, DC
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International Standard Book Number-13: 978-0-309-49118-1
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Digital Object Identifier: https://doi.org/10.17226/25412
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Suggested Citation: National Academies of Sciences, Engineering, and Medicine. 2019. A Class Approach to Hazard Assessment of Organohalogen Flame Retardants. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25412.
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COMMITTEE TO DEVELOP A SCOPING PLAN TO ASSESS THE HAZARDS OF ORGANOHALOGEN FLAME RETARDANTS
Members
DAVID C. DORMAN (Chair), North Carolina State University, Raleigh, NC
HUGH A. BARTON (retired), Pfizer, Groton, CT
KAREN BLACKBURN, Procter & Gamble Company, Cincinnati, OH
JOHN BUCHER, National Institute of Environmental Health Sciences, Durham, NC
JULIE L. DANIELS, University of North Carolina at Chapel Hill, Chapel Hill, NC
JENNIFER L. FREEMAN, Purdue University, West Lafayette, IN
KAMEL MANSOURI, Integrated Laboratory Systems, Raleigh, NC
CARMEN MESSERLIAN, Harvard T.H. Chan School of Public Health, Boston, MA
DAVID M. REIF, North Carolina State University, Raleigh, NC
GINA M. SOLOMON, Public Health Institute, Oakland, CA
CHIHAE YANG, Molecular Networks GMbH, Columbus, OH
Staff
ELLEN K. MANTUS, Project Director
SUSAN N.J. MARTEL, Senior Program Officer
RADIAH ROSE-CRAWFORD, Manager, Editorial Projects
JESSICA WOLFMAN, Senior Program Assistant
Sponsor
US CONSUMER PRODUCT SAFETY COMMISSION
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Members
WILLIAM H. FARLAND (Chair), Colorado State University, Fort Collins, CO
LESA AYLWARD, Summit Toxicology, LLP, Falls Church, VA
ANN M. BARTUSKA, Resources for the Future, Washington, DC
RICHARD A. BECKER, American Chemistry Council, Washington, DC
E. WILLIAM COLGLAZIER, American Association for the Advancement of Science, Washington, DC
DOMINIC M. DITORO, University of Delaware, Newark, DE
DAVID C. DORMAN, North Carolina State University, Raleigh, NC
GEORGE GRAY, George Washington University, Washington, DC
R. JEFFREY LEWIS, ExxonMobil Biomedical Sciences, Inc., Annandale, NJ
GERMAINE M. BUCK LOUIS, George Mason University, Fairfax, VA
ROBERT PERCIASEPE, Center for Climate and Energy Solutions, Arlington, VA
REZA J. RASOULPOUR, Dow AgroSciences, Indianapolis, IN
JOAN B. ROSE, Michigan State University, East Lansing, MI
GINA M. SOLOMON, Public Health Institute, Oakland, CA
DEBORAH L. SWACKHAMER, University of Minnesota, St. Paul, MN
JOSHUA TEWKSBURY, Future Earth, Boulder, CO
PETER S. THORNE, University of Iowa, Iowa City, IA
Senior Staff
CLIFFORD DUKE, Director
ELLEN K. MANTUS, Scholar and Director of Risk Assessment
RAYMOND A. WASSEL, Scholar and Director of Environmental Studies
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
LAURA LLANOS, Financial Associate
TAMARA DAWSON, Program Associate
Acknowledgments
This Consensus Study Report was reviewed in draft form by persons chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets institutional standards of quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following for their review of this report:
Vinicius Alves, University of North Carolina, Chapel Hill
Joseph Braun, Brown University
Weisueh Chiu, Texas A&M University
Nigel Greene, AstraZeneca
Richard Judson, US Environmental Protection Agency
Andres Kortenkamp, Brunel University, London
Eugene Muratov, University of North Carolina, Chapel Hill
Reza Rasoulpour, Dow AgroSciences
Heather Stapleton, Duke University
David Volz, University of California, Riverside
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report, nor did they see the final draft before its release. The review of the report was overseen by David Allison, Indiana University, and Joseph Rodricks, Ram-boll Environ, who were responsible for making certain that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
The committee gratefully acknowledges the staff of the US Consumer Product Safety Commission for their presentations to the committee during open sessions. The committee is also grateful for the assistance of Norman Grossblatt who served as the report editor.
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Contents
Conceptual Advantages of a Class Approach
Petition to Ban Organohalogen Flame Retardants in Selected Consumer Products
Committee’s Approach to Its Task
2 HAZARD ASSESSMENT SCOPING PLAN
Determine the Viability of a Class Approach
Search the Literature and Extract Data
Integrating a Hazard Assessment That Uses a Class Approach into Risk Assessment
Improved Efficiency and Cost-Effectiveness
3 A CLASS APPROACH TO EVALUATING ORGANOHALOGEN FLAME RETARDANTS: CASE STUDIES
Can Organohalogen Flame Retardants Be Defined as a Single Class?
Definition of Subclasses of Organohalogen Flame Retardants
Case Study 1: Polyhalogenated Organophosphates
Case Study 2: Polyhalogenated Bisphenol Aliphatics
BOXES, FIGURES, AND TABLES
BOXES
1-2 Definitions of Terms Used in This Report
2-1 OECD Guidance on Development of Categories under REACH
2-2 An Example of a Potentially Hazardous Subclass
2-3 A Tiered Approach for Assessing a Subclass on Which There Are No Relevant Toxicity Data
3-2 Identification of Analogues to the OFR Seed Chemicals
3-3 Use of NAM Data in Regulatory Decision-Making
FIGURES
3-1 Substructures identified in OFR seed chemicals
3-2 Histogram of data availability for the seed chemicals
3-3 Histogram of data availability for the expanded set of chemicals
3-4 Representative members of the polyhalogenated organophosphate subclass
3-5 Representative members of polyhalogenated bisphenol aliphatics
B-3 Principal component analysis of the seed OFRs and analogues
B-4 Enrichment sites of OFRs from seed list and expanded set of analogues
B-6 Major chemotypes found in OFR seed set
B-7 Screenshot of OFR categories and matching structures in ChemoTyper
C-1 Explicit mapping of data availability for inventory chemicals
C-2 Histogram of data availability for inventory chemicals
C-3 Histogram of data availability for the expanded set of chemicals
C-4 Heatmap that represents availability of Tox21data on the chemicals in the OFR inventory
C-5 Heatmap that represents availability of ToxCast data on the chemicals in the OFR inventory
TABLES
3-2 OFR Subclasses Formulated by Using Chemotypes and Predicted Biologic Activity
3-3 Members of the Polyhalogenated Organophosphate Subclass
3-4 Genotoxicity Data on the Polyhalogenated Organophosphate Subclass
3-5 Polyhalogenated Organophosphate Chronic Toxicity Studies
3-6 Available Human Epidemiologic Data on Organophosphate Flame Retardants
3-7 Developmental Toxicity of Polyhalogenated Organophosphates
3-8 Zebrafish Teratology and Developmental Neurotoxicity Studies of Polyhalogenated Organophosphates
3-10 Polyhalogenated Bisphenol Aliphatics
3-11 Genotoxicity Data on Polyhalogenated Bisphenol Aliphatics
3-12 Subchronic and Chronic Toxicity Studies of Polyhalogenated Bisphenol Aliphatics
3-13 Summary of Human Epidemiologic Studies of Polyhalogenated Bisphenol Aliphatics
3-14 Mammalian Developmental Toxicity Studies of Polyhalogenated Bisphenol Aliphatics
3-15 Summary of Evidence on TBBPA and Changes in Thyroid Homeostasis
3-17 Options and Approaches for Handling Discordant Data
B-1 Sources Used to Identify Chemicals in the OFR Inventory
B-2 Fourteen OFR Subclasses Formulated on the Basis of Chemotypes and Predicted Biologic Activity
C-1 Number of Results of the PubChem Database Search
C-2 Number of Results of the PubMed Database Search
D-3 Effects of Tetrabromobisphenol A on Thyroid Homeostasis in Zebrafish
D-4 Effects of Polyhalogenated Bisphenols on Zebrafish Development or Behavior
D-5 Additional Zebrafish Studies of Polyhalogenated Bisphenol