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COMMITTEE TO REVIEW EPA’S 2022 DRAFT FORMALDEHYDE ASSESSMENT

Members

JONATHAN M. SAMET, (Chair), Colorado School of Public Health

AISHA S. DICKERSON, Johns Hopkins Bloomberg School of Public Health

DANA C. DOLINOY, University of Michigan

DAVID C. DORMAN, North Carolina State University

RAKESH GHOSH, University of California, San Francisco

SABINE S. LANGE, Texas Commission on Environmental Quality

ANDREW F. OLSHAN, University of North Carolina at Chapel Hill

IVAN RUSYN, Texas A&M University

LIANNE SHEPPARD, University of Washington School of Public Health

KATYA TSAIOUN, Johns Hopkins Bloomberg School of Public Health

JOSEPH WIEMELS, University of Southern California

LAUREN ZEISE, California Environmental Protection Agency

YILIANG ZHU, University of New Mexico

Staff

KATHRYN GUYTON, Study Director

BRENNA ALBIN, Senior Program Assistant

NATALIE ARMSTRONG, Associate Program Officer

ELIZABETH BOYLE, Senior Program Officer

ANTHONY DEPINTO, Associate Program Officer

DARLENE GROS, Senior Program Assistant

KATHERINE KANE, Senior Program Assistant

Sponsor

U.S. ENVIRONMENTAL PROTECTION AGENCY

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Members

FRANK W. DAVIS (Chair), University of California, Santa Barbara

ANN M. BARTUSKA, U.S. Department of Agriculture

DANA BOYD BARR, Emory University

GERMAINE M. BUCK LOUIS, George Mason University

FRANCESCA DOMINICI, Harvard University

R. J. LEWIS, ExxonMobil Biomedical Sciences Inc

MARIE L. MIRANDA, Children’s Environmental Health Initiative

REZA J. RASOULPOUR, Dow AgroSciences

JOSHUA TEWKSBURY, Smithsonian Tropical Research

SACOBY M. WILSON, University of Maryland

TRACEY J. WOODRUFF, University of California, San Francisco

Staff

CLIFFORD DUKE, Director

NATALIE ARMSTRONG, Associate Program Officer

LESLIE BEAUCHAMP, Senior Program Assistant

ANTHONY DEPINTO, Associate Program Officer

KATHRYN GUYTON, Senior Program Officer

KATHERINE KANE, Senior Program Assistant

LAURA LLANOS, Finance Business Partner

THOMASINA LYLES, Senior Program Assistant

RAYMOND WASSEL, Scholar and Director of Environmental Studies

Reviewers

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:

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 DANNY REIBLE, Texas Tech University (Monitor), and DON MATTISON, University of South Carolina (Coordinator). 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.

Acknowledgments

Many people were critical in helping the committee accomplish its charge. The committee gratefully acknowledges the participants at its information-gathering sessions, who provided insights and viewpoints pertinent to the committee’s task (see Appendix B). We thank Lisa Bero, Professor of Medicine and Public Health, University of Colorado, for her presentation at the committee’s first information-gathering session. Importantly, the committee heard from more than 40 individuals who shared their perspectives during the public comment periods of the information-gathering sessions, as well as in written input provided for the committee’s consideration. The committee is very grateful for these valuable contributions to its work.

In addition, we are grateful to the U.S. Environmental Protection Agency (EPA) for sponsoring the study, and to the following EPA staff for their presentations to the committee: Andrew Kraft and Thomas Bateson, Office of Research and Development.

Gratitude is also extended to the staff of the National Academies of Sciences, Engineering, and Medicine who contributed to producing this report, especially the outstanding and tireless study staff: Brenna Albin, Natalie Armstrong, Elizabeth Boyle, Anthony DePinto, Darlene Gros, Kathryn Guyton, and Katherine Kane. Thanks also go to the staff of the Division on Earth and Life Studies Executive Office and other Academies staff who provided additional support.

Preface

This report documents the lengthy history of the Integrated Risk Information System (IRIS) Program’s assessment of the health risks of formaldehyde, which dates to 1989. The predecessor of the 2022 Draft Assessment is an IRIS assessment completed in 2010 and reviewed by the National Academies in 2011. The 2011 National Research Council (NRC) report on the 2010 Draft Assessment called for substantial revisions to the assessment and to the processes used to develop it. The 2011 NRC report included the recommendation that completion of the formaldehyde assessment not await the possible development of these revisions and their finalization. Over the ensuing twelve years and in response to additional recommendations of the National Academies, the methods used by the IRIS Program have evolved. These evolving methods increasingly reflect the state of practice for carrying out systematic reviews, evidence integration, and quantitative risk estimation for human health risk assessments of environmental contaminants. The 2022 Draft Assessment reviewed by this committee was prepared across this decade of rapid change. Consequently, there was no static benchmark for evaluating the methods used. The committee took a broad view of the state of practice as it evaluated the 2022 Draft Assessment, recognizing that the methods used for that assessment would not correspond in all respects to the state of practice in 2023. Overall, the committee found that the methods used for the assessment were appropriate and reflect EPA’s current practices in some components of the IRIS process.

Not surprisingly, given its length and complexity, there are opportunities to strengthen and clarify the 2022 Draft Assessment. The committee offers numerous recommendations to that end. The committee was asked to prioritize its recommendations in tiers. Tier 1 represents important recommendations that would address critical scientific concepts, issues, or narrative in the assessment. Currently the methods for the 2022 Draft Assessment are located in several places throughout its three documents, which together consist of more than 2000 pages. Perhaps the most critical area for structural and editorial revision is to bring greater clarity as to the methods used and to facilitate their consideration by readers. The committee’s single Tier 1 recommendation calls for the changes needed to make the assessment’s methods sufficiently accessible for its users, and to facilitate access to related sections across the different elements of the assessment for the different outcomes analyzed. In accordance with its statement of task, the committee did not conduct an independent hazard assessment or recommend alternative toxicity values.

Tier 2 recommendations are suggested revisions intended to strengthen or clarify the scientific concepts, issues, or narrative in the assessment, while Tier 3 recommendations are considerations that might inform future evaluations of key science issues. The committee has made many Tier 2 and Tier 3 recommendations regarding methods, the assessment narrative, and the dose-response assessment. We point to opportunities to harmonize the assessment narrative across health outcome domains and to bring greater consistency by structuring them more carefully around a common review framework. We also urge rigorous editing to enhance the overall quality of the assessment.

Quoting the website for the IRIS Program:

The 2022 Formaldehyde Draft Assessment, which addresses a widely used, high-volume production chemical, needs to be completed to support EPA in accomplishing this mission.

Finally, the committee urges closure on the Draft Assessment. The committee members have a long perspective on the Formaldehyde Draft Assessment and the changes in the IRIS Program’s methods over the last decade. The assessment has been revised and improved substantially, and its findings on hazard and quantitative risk are supported by the scientific evidence identified. A confined set of revisions will enhance clarity and transparency. The committee’s recommendations should be undertaken expeditiously to complete a revised assessment document that can be implemented without delay.

Jonathan M. Samet, M.D., M.S
Committee Chair
Committee to Review EPA’s 2022 Draft Formaldehyde Assessment

Contents

SUMMARY

1 INTRODUCTION

The Committee, Its Task, and Its Approach

Organization of the Report

References

2 METHODS AND ORGANIZATION

The State of Practice for Systematic Review

Response to the 2011 NRC Report

Response to the 2014 NRC Report

Alignment of the 2022 Draft Assessment Methods with the State of Practice

Documentation of Methods

Evidence Identification (Steps 1 and 2)

Study Evaluation (Steps 3 and 4)

Evidence Synthesis (Steps 5 and 6)

Evidence Integration (Step 7)

Dose-Response Assessment (Step 8)

References

3 TOXICOKINETICS

Overview of Inhaled Formaldehyde Toxicokinetics in the 2022 Draft Assessment

Distribution of Inhaled Formaldehyde

Metabolism, Binding, and Removal of Inhaled Formaldehyde

Dosimetry Models

EPA’s Use of Toxicokinetic Data and Dosimetry Models

References

4 NONCANCER HEALTH EFFECTS

Noncancer Portal-of-Entry Effects

Sensory Irritation

Pulmonary Function

Respiratory Pathology

Noncancer Systemic Effects

Allergy and Asthma

Reproductive and Developmental Toxicity

Nervous System

Derivation of the RfC

References

5 CANCER

Hazard Identification

Literature Identification and Evaluation of Study Methods

Study Evaluation

Syntheses of Results and Synthesis Judgments

Dose-Response Analysis of Cancer Effects of Formaldehyde

Inhalation Unit Risk for Nasopharyngeal Cancer from Epidemiological Data

References

APPENDIXES

A COMMITTEE MEMBER BIOGRAPHICAL SKETCHES

B PUBLIC SESSION AGENDAS

C CASE STUDY: HANRAHAN ET AL., 1984, HUMAN SENSORY IRRITATION

D POINT OF DEPARTURE ANALYSIS USING TWO STUDIES: A CASE STUDY

E EXAMPLES OF ISSUES IDENTIFIED BY THE COMMITTEE

Acronyms and Abbreviations