Identifying and Controlling Pulmonary Toxicants June 1992 OTA-BP-BA-91 NTIS order #PB92-193457 For sale by the U.S. Government Printing Office Superintendent of Document\, Mail Stop: SSOP, Washington, DC 20402-9328” ISBN 0-16 -037923-7 Foreword History reveals an enduring respect for lung function. In the biblical account of creation, man becomes a living soul when he receives the breath of life. Edward I of England banned the use of coal in 1273 because he found inhaling its smoke detrimental to human health. When asked how to ensure a long life, Sophie Tucker replied, “Keep breathing.” This Background Paper examines whether the agencies responsible for administering Federal environmental and health and safety laws have taken this concern for respiratory health to heart. Prepared at the request of the Senate Committee on Environment and Public Works and its Subcom- mittee on Toxic Substances, Environmental Oversight, Research and Development, the study describes technologies available to identify substances toxic to the lung and Federal efforts to control human exposure to such substances through regulatory and research programs. The analysis shows that new technologies hold great promise for revealing the potential adverse effects on the lung of new and existing substances, but that much remains to be learned. This Background Paper provides a partial response to the committees’ request for an assessment of noncancer health risks in the environment and follows OTA’s previous work on carcinogenic, neurotoxic, and immunotoxic substances. OTA acknowledges the generous help of the workshop participants, reviewers, and contributors who gave their time to ensure the accuracy and completeness of this study. OTA, however, remains solely responsible for the contents of this Background Paper. @’&# ‘ > ~f~ John H. Gibbons Director . 111 Workshop on Identifying and Controlling Pulmonary Toxicants, September 1991 Dr. Robert M. Friedman, Workshop Chair Senior Associate Oceans and Environment Program Office of Technology Assessment Dr. Margaret Becklake Dr. Robert R. Mercer Director, Respiratory Epidemiology Unit Assistant Medical Research Professor McGill University Department of Medicine Duke University Dr. Arnold Brody Head, Pulmonary Pathology Dr. Richard B. Schlesinger National Institute of Environmental Professor, Department of Health Sciences Environmental Medicine New York University School of Medicine Dr. Daniel L. Costa Chief, Pulmonary Toxicology Branch Dr. Mark J. Utell Inhalation Toxicology Division Director, Pulmonary and Critical Health Effects Research Laboratory Care Unit U.S. Environmental Protection Agency University of Rochester Medical Center Dr. Joe L. Mauderly Dr. Gregory Wagner Director Director, Division of Respiratory Inhalation Toxicology Research Institute Disease Studies Lovelace Biomedical and Environmental National Institute for Occupational Research Institute, Inc. Safety and Health Dr. Roger O. McClellan Dr. Ronald K. Wolff President Research Scientist Chemical Industry Institute of Toxicology Lilly Research Laboratories Note: OTA appreciates the valuable assistance and thoughtful critiques provided by the workshop participants. The participants do not, however, necessarily approve, disapprove, or endorse this background paper. OTA assumes full responsibility for the background paper and the accuracy of its contents. iv Reviewers and Contributors In addition to the workshop participants, OTA acknowledges the following individuals who reviewed drafts or otherwise contributed to this study. Lois Adams Fran Du Melle Office of Technology Assessment Liaison Deputy Managing Director Office of Legislative Affairs American Lung Association U.S. Food and Drug Administration June Friedlander Heinz W. Ahlers, J.D. Staff Specialist Division of Standards Development National Institute for Occupational Safety and Technology Transfer and Health National Institute for Occupational Safety and Health Suzie Hazen Director, 33/50 Program John R. Balmes, M.D. Office of Air and Radiation Assistant Professor of Medicine U.S. Environmental Protection Agency Center for Occupational and Environmental Health University of California, San Francisco Hillel S. Koren, Ph.D. Acting Director Rebecca Bascom, M.D. Human Studies Division Director, Environmental Research Facility Health Effects Research Laboratory School of Medicine U.S. Environmental Protection Agency University of Maryland Martin Landry Robert P. Baughman, M.D. Budget Analyst Associate Professor of Medicine Financial Management Office Pulmonary/Critical Care Division National Institute for Occupational Safety University of Cincinnati and Health Paul D. Blanc, M.D., M. S.P.H. John L. Mason, Ph.D. Assistant Professor of Medicine Vice President Division of Occupational and Engineering and Technology Environmental Medicine Allied Signal Aerospace Co. (Ret.) University of California-San Francisco Barbara Packard, M. D., Ph.D. James C. Bonner, Ph.D. Associate Director for Scientific Staff Fellow Program Operations Laboratory of Pulmonary Pathobiology National Heart, Lung, and Blood Institute National Institute of Environmental Health Sciences Jerry Phelps Carroll E. Cross, M.D. Program Analyst Division of Pulmonary-Critical Care Medicine Office of Program Planning and Evaluation Department of Internal Medicine Office of Director University of California-Davis Medical Center National Institute of Environmental Health Sciences Roger Detels, M. D., M.S. William A. Pryor, Ph.D. Professor of Epidemiology Director School of Public Health Biodynamics Institute University of California-Los Angeles Louisiana State University Victor L. Roggli, M.D. Joel Schwartz, Ph.D. Associate Professor of Pathology U.S. Environmental Protection Agency Department of Pathology Duke University Medical Center Andrew Sivak, Ph.D. President Robert Roth, Ph.D. Health Effects Institute Professor Department of Pharmacology and Toxicology Frank E. Speizer, M.D. Michigan State University Professor of Medicine and Environmental Science School of Public Health Jonathan M. Samet, M.D. Harvard University Professor of Medicine Medical Center Jaro J. Vestal, M. D., Ph.D. University of New Mexico Environmental Activities Staff General Motors Corp. Anne P. Sassaman, Ph.D. Director David B. Warheit, Ph.D. Division of Extramural Research and Training Haskell Laboratory for Toxicology National Institute of Environmental Health Sciences and Industrial Medicine I.E. Du Pont De Nemours and Co. David A. Schwartz, M. D., M.P.H. Director, Occupational Medicine Jane Warren, Ph.D. Pulmonary Disease Division Research Committee Director Department of Internal Medicine Health Effects Institute University of Iowa vi OTA Project Staff-Identifying and Controlling Pulmonary Toxicants Roger C. Herdman, Assistant Director, OTA Health and Life Sciences Division Michael Gough, Biological Applications Program Manager Holly L. Gwin, Project Director Margaret McLaughlin, Analyst Ellen Goode, Research Assistant Katherine Kelly, Contractor Desktop Publishing Specialists Jene Lewis Linda Rayford-Journiette Carolyn Swarm support staff Cecile Parker, Office Administrator vii Contents Chapter l: Introduction and Summary . 3 Chapter 2: The Respiratory System and Its Response to Harmful Substances . 15 Chapter 3: Pulmonary Toxicology and Epidemiology . 29 Chapter 4: Federal Attention to Pulmonary Toxicants . 49 Boxes Boxes 3-A—General Principles of Toxicology . 30 3-B—The UCLA Population Studies of Chronic Obstructive Respiratory Disease . 42 Figures Figures l-l—The Human Respiratory Tract . 5 2-l—The Human Respiratory Tract . 15 2-2—Branching of the Tracheobronchial Region (Human Lung Cast) . 16 2-3—Alveoli . 16 2-4—Gas Exchange in the Pulmonary Region . 17 2-5—Ciliated Cells and Alveolar Macrophages . 18 2-6—Effects of Emphysema on Alveolar Walls . 20 3-l—Framework for Exposure Assessment . 32 3-2—Integrated Approach to Identifying Pulmonary Toxicants . 35 3-3--Spectrum of Biological Response to Pollutant Exposure . 36 Tables Tables l-l—The Seventeen Chemicals of the 33/50 Program, 1989 . 7 2-l—Respiratory Tract Clearance Mechanisms . 19 2-2—Causes of Occupational Asthma . 21 2-3—Industrial Toxicants Producing Lung Disease . 23 3-l—Defining Gases and Aerosols . 33 3-2-Summary of Characteristics of Physiologic Assays . 40 4-l—National Primary Ambient Air Quality Standards . 50 4-2—Hazardous Air Pollutants Regulated Under the CAA Due to NonCancer Health Effects on the Pulmonary System . 52 4-3—Pulmonary Toxicants Controlled Under EPA’s Early Reduction and 33/50 Programs . 54 4-4—Regulated Levels of Pulmonary Toxicants Under RCRA . 55 4-5—Pulmonary Toxicants Regulated Under FIFRA . 55 4-6—Air Contaminants Regulated by OSHA Because of Pulmonary Effects . 56 . Vlll Chapter 1 Introduction and Summary Chapter 1 Introduction and Summary INTRODUCTION bined with limited agency resources, has led to neglect of noncancer health risks-risks that may be as wide- Breathing sustains life. Each day an individual in- spread and severe as carcinogenicity. hales between 10,000 and 20,000 liters of air. In the lungs, air releases oxygen to the bloodstream and picks The Senate Committee on Environment and Public up carbon dioxide and other waste products, which are Works, and its Subcommittee on Toxic Substances, then exhaled. Inhaled air contains many substances— Environmental Oversight, Research and Develop- naturally occurring and anthropogenic--other than ment, asked for assistance from the Office of Technol- oxygen. Some of these substances can injure the lungs