REVIEW OF THE ENVIRONMENTAL PROTECTION AGENCY’S DRAFT IRIS ASSESSMENT OF FORMALDEHYDE
NATIONAL RESEARCH COUNCIL
OF THE NATIONAL ACADEMIES
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COMMITTEE TO REVIEW EPA’S DRAFT IRIS ASSESSMENT OF FORMALDEHYDE
Members
JONATHAN M. SAMET (Chair),
University of Southern California, Los Angeles
ANDREW F. OLSHAN (Vice-Chair),
University of North Carolina at Chapel Hill
JOHN BAILER,
Miami University, Oxford, OH
SANDRA J.S. BAIRD,
Massachusetts Department of Environmental Protection, Boston
HARVEY CHECKOWAY,
University of Washington School of Public Health and Community Medicine, Seattle
RICHARD A. CORLEY,
Pacific Northwest National Laboratory, Richland, WA
DAVID C. DORMAN,
North Carolina State University, Raleigh
CHARLES H. HOBBS,
Lovelace Respiratory Research Institute, Albuquerque, NM
MICHAEL D. LAIOSA,
University of Wisconsin, Milwaukee
IVAN RUSYN,
University of North Carolina at Chapel Hill
MARY ALICE SMITH,
University of Georgia, Athens
LESLIE T. STAYNER,
University of Illinois, Chicago
HELEN H. SUH,
National Opinion Research Center, University of Chicago, IL
YILIANG ZHU,
University of South Florida, Tampa
PATRICK A. ZWEIDLER-MCKAY,
The University of Texas M. D. Anderson Cancer Center, Houston
Staff
ELLEN K. MANTUS, Project Director
HEIDI MURRAY-SMITH, Program Officer
KERI SCHAFFER, Research Associate
NORMAN GROSSBLATT, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Manager,
Technical Information Center
RADIAH ROSE, Manager,
Editorial Projects
PANOLA GOLSON, Program Associate
Sponsor
U.S. ENVIRONMENTAL PROTECTION AGENCY
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1
Members
ROGENE F. HENDERSON (Chair),
Lovelace Respiratory Research Institute, Albuquerque, NM
PRAVEEN AMAR,
Northeast States for Coordinated Air Use Management, Boston, MA
TINA BAHADORI,
American Chemistry Council, Washington, DC
MICHAEL J. BRADLEY,
M.J. Bradley & Associates, Concord, MA
DALLAS BURTRAW,
Resources for the Future, Washington, DC
JAMES S. BUS,
Dow Chemical Company, Midland, MI
JONATHAN Z. CANNON,
University of Virginia, Charlottesville
GAIL CHARNLEY,
HealthRisk Strategies, Washington, DC
FRANK W. DAVIS,
University of California, Santa Barbara
RICHARD A. DENISON,
Environmental Defense Fund, Washington, DC
H. CHRISTOPHER FREY,
North Carolina State University, Raleigh
J. PAUL GILMAN,
Covanta Energy Corporation, Fairfield, NJ
RICHARD M. GOLD,
Holland & Knight, LLP, Washington, DC
LYNN R. GOLDMAN,
George Washington University, Washington, DC
LINDA E. GREER,
Natural Resources Defense Council, Washington, DC
WILLIAM E. HALPERIN,
University of Medicine and Dentistry of New Jersey, Newark
PHILIP K. HOPKE,
Clarkson University, Potsdam, NY
HOWARD HU,
University of Michigan, Ann Arbor
ROGER E. KASPERSON,
Clark University, Worcester, MA
THOMAS E. MCKONE,
University of California, Berkeley
TERRY L. MEDLEY,
E.I. du Pont de Nemours & Company, Wilmington, DE
JANA MILFORD,
University of Colorado at Boulder, Boulder
FRANK O’DONNELL,
Clean Air Watch, Washington, DC
RICHARD L. POIROT,
Vermont Department of Environmental Conservation, Waterbury
DANNY D. REIBLE,
University of Texas, Austin
ROBERT F. SAWYER,
University of California, Berkeley
KATHRYN G. SESSIONS,
Health and Environmental Funders Network, Bethesda, MD
JOYCE S. TSUJI,
Exponent Environmental Group, Bellevue, WA
MARK J. UTELL,
University of Rochester Medical Center, Rochester, NY
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Scholar
RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
ELLEN K. MANTUS, Senior Program Officer for Risk Analysis
EILEEN N. ABT, Senior Program Officer
RUTH E. CROSSGROVE, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Manager,
Technical Information Center
RADIAH ROSE, Manager,
Editorial Projects
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Review of the Environmental Protection Agency’s Draft IRIS Assessment of Formaldehyde (2011)
The Use of Title 42 Authority at the U.S. Environmental Protection Agency (2010)
Review of the Environmental Protection Agency’s Draft IRIS Assessment of Tetrachloroethylene (2010)
Hidden Costs of Energy: Unpriced Consequences of Energy Production and Use (2009)
Contaminated Water Supplies at Camp Lejeune—Assessing Potential Health Effects (2009)
Review of the Federal Strategy for Nanotechnology-Related Environmental, Health, and Safety Research (2009)
Science and Decisions: Advancing Risk Assessment (2009)
Phthalates and Cumulative Risk Assessment: The Tasks Ahead (2008)
Estimating Mortality Risk Reduction and Economic Benefits from Controlling Ozone Air Pollution (2008)
Respiratory Diseases Research at NIOSH (2008)
Evaluating Research Efficiency in the U.S. Environmental Protection Agency (2008)
Hydrology, Ecology, and Fishes of the Klamath River Basin (2008)
Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007)
Models in Environmental Regulatory Decision Making (2007)
Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007)
Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007)
Environmental Impacts of Wind-Energy Projects (2007)
Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget (2007)
Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)
New Source Review for Stationary Sources of Air Pollution (2006)
Human Biomonitoring for Environmental Chemicals (2006)
Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment (2006)
Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (2006)
State and Federal Standards for Mobile-Source Emissions (2006)
Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005)
Health Implications of Perchlorate Ingestion (2005)
Air Quality Management in the United States (2004)
Endangered and Threatened Species of the Platte River (2004)
Atlantic Salmon in Maine (2004)
Endangered and Threatened Fishes in the Klamath River Basin (2004)
Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003)
Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002)
Biosolids Applied to Land: Advancing Standards and Practices (2002)
The Airliner Cabin Environment and Health of Passengers and Crew (2002)
Arsenic in Drinking Water: 2001 Update (2001)
Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001)
Compensating for Wetland Losses Under the Clean Water Act (2001)
A Risk-Management Strategy for PCB-Contaminated Sediments (2001)
Acute Exposure Guideline Levels for Selected Airborne Chemicals (nine volumes, 2000-2010)
Toxicological Effects of Methylmercury (2000)
Strengthening Science at the U.S. Environmental Protection Agency (2000)
Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)
Ecological Indicators for the Nation (2000)
Waste Incineration and Public Health (2000)
Hormonally Active Agents in the Environment (1999)
Research Priorities for Airborne Particulate Matter (four volumes, 1998-2004)
The National Research Council’s Committee on Toxicology: The First 50 Years (1997)
Carcinogens and Anticarcinogens in the Human Diet (1996)
Upstream: Salmon and Society in the Pacific Northwest (1996)
Science and the Endangered Species Act (1995)
Wetlands: Characteristics and Boundaries (1995)
Biologic Markers (five volumes, 1989-1995)
Science and Judgment in Risk Assessment (1994)
Pesticides in the Diets of Infants and Children (1993)
Dolphins and the Tuna Industry (1992)
Science and the National Parks (1992)
Human Exposure Assessment for Airborne Pollutants (1991)
Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)
Decline of the Sea Turtles (1990)
Copies of these reports may be ordered from the National Academies Press
(800) 624-6242 or (202) 334-3313
Preface
The U.S. Environmental Protection Agency (EPA) released noncancer and cancer assessments of formaldehyde for its Integrated Risk Information System (IRIS) in 1990 and 1991, respectively. The agency began reassessing formaldehyde in 1998 and released a draft IRIS assessment in June 2010. Much research has been conducted since the original assessments, and scientists are currently debating the carcinogenic properties of formaldehyde and the ways that it might cause cancer. Given the complexity of the issues and the knowledge that the assessment will be used as the basis of regulatory decisions, EPA asked the National Research Council (NRC) to conduct an independent scientific review of the draft IRIS assessment.
In this report, the Committee to Review EPA’s Draft IRIS Assessment of Formaldehyde first addresses some general issues associated with the draft IRIS assessment. The committee next focuses on questions concerning specific aspects of the draft assessment, including derivation of the reference concentrations and the cancer unit risk estimates for formaldehyde. The committee closes with recommendations for improving the IRIS assessment of formaldehyde and provides some general comments on the IRIS development process.
The present report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the NRC Report Review Committee. The purpose of the independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards of 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: Margit L. Bleecker, Center for Occupational and Environmental Neurology; Claude Emond, Université de Montréal; George L. Delclos, The University of Texas Health Science Center at Houston School of Public Health; Lynn R. Goldman, George Washington University; Ulrike Luderer, University of California, Irvine; Roger O. McClellan, Toxicology and Human Health Risk Analysis; Martha S. Sandy, California Environmental Protec-
tion Agency; Jeffrey D. Schroeter, The Hamner Institutes for Health Sciences; Susan J. Simmons, University of North Carolina, Wilmington; Joyce S. Tsuji, Exponent; Elizabeth W. Triche, Brown University; Clifford P. Weisel, University of Medicine and Dentistry of New Jersey; Joseph L. Wiemels, University of California, San Francisco.
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of the report was overseen by the review coordinator, Kenneth S. Ramos, University of Louisville Health Science Center, and the review monitor, Frank E. Speizer, Harvard Medical School and Harvard School of Public Health. Appointed by NRC, they 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 of the report rests entirely with the committee and the institution.
The committee gratefully acknowledges Danielle DeVoney, Sue Makris, Peter Preuss, and Kathleen Raffaele, of the U.S. Environmental Protection Agency, and Bruce Fowler, of the Agency for Toxic Substances and Disease Registry, for making presentations to the committee.
The committee is also grateful for the assistance of NRC staff in preparing this report. Staff members who contributed to the effort are Ellen Mantus, project director; Heidi Murray-Smith, program officer; Keri Schaffer, research associate; James Reisa, director of the Board on Environmental Studies and Toxicology; Norman Grossblatt, senior editor; Mirsada Karalic-Loncarevic, manager, Technical Information Center; Radiah Rose, manager, editorial projects; and Panola Golson, program associate.
We thank especially the members of the committee for their efforts throughout the development of this report.
Jonathan M. Samet, Chair
Andrew F. Olshan, Vice-Chair
Committee to Review EPA’s Draft IRIS Assessment of Formaldehyde
BOXES, FIGURES, AND TABLES
BOXES
1-1 |
Statement of Task, |
FIGURES
S-1 |
Illustration of potential process for identifying an RfC, |
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1-1 |
Formaldehyde chemical structure, |
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1-2 |
Formaldehyde concentration in various environments, |
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1-3 |
Timeline of the development of the draft IRIS assessment, |
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2-1 |
Elements of the IRIS process, |
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3-1 |
Schematic representation of the mammalian nasal epithelium, |
4-1 |
Odds ratios for physician-diagnosed asthma in children associated with in-home formaldehyde concentrations in air, |
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5-1 |
Origins of lymphohematopoietic cancers, |
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5-2 |
Relative incidence and estimated annual new diagnoses of common lymphohematopoietic cancer subtypes in the United States, |
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6-1 |
Illustration of EPA’s process for deriving a reference concentration for formaldehyde, |
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6-2 |
Illustration of a potential process for identifying an RfC from a full database, |
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7-1 |
New IRIS assessment process, |
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7-2 |
Elements of the key steps in the development of a draft IRIS assessment, |
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7-3 |
Example of an article-selection process, |
TABLES
3-1 |
Analysis of 3D CFD Models by Kimbell et al. (2001a,b) and Overton et al. (2001) for Rat, Monkey, and Human Airways, |
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3-2 |
Overview of the Conolly et al. BBDR Models, |
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3-3 |
Effects of Different Parameters on Predicted Results of the Conolly et al. BBDR Models, |
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6-1 |
Derivation of Candidate RfCs by EPA, |
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6-2 |
Cancer Unit Risk Estimates for Formaldehyde, |
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7-1 |
Criteria for Determining Causality, |
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7-2 |
Hierarchy for Classifying Strength of Causal Inferences on the Basis of Available Evidence, |