Review of U.S. EPA’s ORD Staff Handbook
for Developing IRIS Assessments
2020 Version
Committee to Review EPA’S IRIS Assessment Handbook
Board on Environmental Studies and Toxicology
Division on Earth and Life Studies
A Consensus Study Report of
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This activity was supported by Contract No. 68HERC19D0011 between the National Academy of Sciences and the U. S. Environmental Protection Agency. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. A Review of U.S. EPA’s ORD Staff Handbook for Developing IRIS Assessments: 2020 Version. Washington, DC: The National Academies Press. https://doi.org/10.17226/26289.
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COMMITTEE TO REVIEW EPA’S IRIS ASSESSMENT HANDBOOK
Members
Lisa A. Bero (Chair), Colorado School of Public Health, Aurora
Hugh A. Barton, Consultant, Mystic, CT
Weihsueh A. Chiu, Texas A&M University, College Station
Gary L. Ginsberg, New York State Department of Health, Albany
Julie B. Herbstman, Columbia University, New York, NY
Jessica L. Myers, Texas Commission on Environmental Quality, Austin
Heather B. Patisaul, North Carolina State University, Raleigh
David B. Richardson, University of California, Irvine
Paul Whaley, Lancaster University, Lancaster, United Kingdom
Kristine L. Willett, University of Mississippi, University
Corwin M. Zigler, University of Texas, Austin
Staff
Raymond Wassel, Scholar
Clifford S. Duke, Director, Board on Environmental Studies and Toxicology
Kathryn Guyton, Senior Program Officer
Leslie Beauchamp, Program Assistant
Melissa Franks, Senior Program Officer (until May 14, 2021)
Sponsor
U.S. Environmental Protection Agency
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Members
William H. Farland (Chair), Colorado State University, Fort Collins
Dana Boyd Barr, Emory University, Atlanta, GA
Ann M. Bartuska, U.S. Department of Agriculture (retired), Washington, DC
E. William Colglazier, American Association for the Advancement of Science, Washington, DC
Francesca Dominici, Harvard University, Boston, MA
George Gray, The George Washington University, Washington, DC
R. Jeffrey Lewis, ExxonMobil Biomedical Sciences, Inc., Annandale, NJ
Germaine M. Buck Louis, George Mason University, Fairfax, VA
Linsey C. Marr, Virginia Polytechnic Institute and State University, Blacksburg
R. Craig Postlewaite, U.S. Department of Defense, Burke, VA
Reza J. Rasoulpour, Corteva Agriscience, Indianapolis, IN
Ivan Rusyn, Texas A&M University, College Station
Joshua Tewksbury, Future Earth, Boulder, CO
Sacoby M. Wilson, University of Maryland, College Park
Staff
Clifford S. Duke, Director
Raymond Wassel, Scholar
Kathryn Guyton, Senior Program Officer
Marilee Shelton-Davenport, Senior Program Officer
Kaley Beins, Associate Program Officer
Laura Llanos, Finance Business Partner
Tamara Dawson, Program Coordinator
Leslie Beauchamp, Program Assistant
Thomasina Lyles, Program Assistant
Acknowledgments
This Consensus Study Report was reviewed in draft form by individuals 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 the institutional standards for 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 individuals for their review of this report:
HARVEY CLEWELL, Ramboll US Consulting, Inc.
PENNY FENNER-CRISP, private consultant
SUE JINKS-ROBERTSON (NAS), Duke University
JULEEN LAM, California State University East Bay
JENNIFER McPARTLAND, Environmental Defense Fund
MOSHE OREN (NAS/NAM), Weizmann Institute of Science
KAREN ROBINSON, Johns Hopkins University
ANDREW ROONEY, National Institute of Environmental Health Sciences
KAN SHAO, Indiana University
KIM TRUONG, California Environmental Protection Agency
LAURA VANDENBERG, University of Massachusetts – Amherst
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 this report was overseen by JOEL KAUFMAN, University of Washington and LYNN GOLDMAN (NAM), the George Washington University. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
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Abbreviations and Acronyms
ADME | Absorption, Distribution, Metabolism, Excretion |
BMR | Benchmark Response |
CRO | Contract Research Organization |
EPA | U.S. Environmental Protection Agency |
GRADE | Grading of Recommendations, Assessment, Development and Evaluation |
HAWC | Health Assessment Workspace Collaborative |
IAP | IRIS Assessment Plan |
IRIS | Integrated Risk Information System |
KC | Key Characteristics |
LOAEL | Lowest-observed-adverse-effect Level |
MOA | Mode of Action |
NAMs | New Approach Methods/Methodologies |
OHAT | Office of Health Assessment and Translation |
OPPT | U.S. Environmental Protection Agency Office of Pollution Prevention and Toxics |
ORD | U.S. Environmental Protection Agency Office of Research and Development |
PBPK | Physiologically Based Pharmacokinetic |
PECO | Population, Exposure, Comparator, Outcome |
PK | Pharmacokinetic |
PODs | Points of Departure |
RfC | Reference Concentration |
RfD | Reference Dose |
ROBINS-E | Risk of Bias in Non-randomized Studies of Exposures |
ROBINS-I | Risk of Bias in Non-randomized Studies of Interventions |
TACIT | Tool for Addressing Conflicts of Interest in Trials |
TK | Toxicokinetics |
TSCA | Toxic Substances Control Act |
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Contents
The Committee, Its Task, and Its Approach
2 OVERVIEW OF ORGANIZATION AND CONTENT OF THE HANDBOOK
Illustrations of the IRIS Assessment Process
Overall Content of the Handbook
Overview of the Handbook’s Material on Planning IRIS Assessments
Responsiveness to the 2014 National Academies Report
Critique of Methods for Planning
Overview of the Handbook’s Material on Study Evaluation
Responsiveness to Previous National Academies Reports
Critique of Methods for Study Evaluation
Overview of Evidence Synthesis As Covered in the Handbook
Critique on Evidence Synthesis
Overview of the Handbook’s Material on Evidence Integration
Responsiveness to Previous National Academies Reports
Critique of Methods for Evidence Integration
7 HAZARD CONSIDERATIONS AND STUDY SELECTION FOR DERIVING TOXICITY VALUES
Overview of the Handbook’s Chapters 12 and 13
Responsiveness to Previous National Academies Reports
Critique of Methods for Study Selection and Deriving Toxicity Values
A COMMITTEE MEMBER BIOSKETCHES
B 2020 IRIS HANDBOOK ORGANIZATION AND CONTENTS AND EPA QUESTIONS TO THE COMMITTEE
BOXES, FIGURES, AND TABLES
BOXES
S-1 Stages in the Development of IRIS Assessments Listed in the Handbook
1-2 Considerations for Critique of Handbook Chapters
FIGURES
3-1 Mapping of three stages of the IRIS planning process identified by the committee
6-1 Example of a terminology map illustrating units of analysis
TABLES
1-1 Mapping of Committee’s Report Chapters and EPA Questions
2-1 Common Uses of Mechanistic and Toxicokinetic Evidence in IRIS Assessments