Markers of Exposure to Diesel Exhaust in Railroad Workers

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Markers of Exposure to Diesel Exhaust in Railroad Workers Markers of Exposure to Diesel Exhaust in Railroad Workers Marc B. Schenker, Steven J. Samuels, Norman Y. Kado, S. Katharine Hammond, Thomas J. Smith, Susan R. Woskie Division of Occupational and Environmental Medicine, Department of Internal Medicine, Center for Occupational and Environmental Health, and Department of Environmental Toxicology; University of California, Davis, CA; California Air Resources Board, Sacramento, CA; and Department of Family and Community Medicine, Environmental Health Sciences Program, University of Massachusetts Medical School, Worcester, MA Includes the Conunentary by the Institute~s Health Review Committee Research Report Number 33 ---------rr..tHEALTH EFFECTS INSTITUTE I.J:T The Health Effects Institute (HEI) is a nonprofit corporation founded in 1980 to assure that objective, credible, high-quality scientific studies are conducted on the potential human health effects of motor vehicle emissions. Funded equally by the U.S. Environmental Protection Agency (EPA) and 28 automotive manufacturers or marketers in the United States, HEI is independently governed. Its research projects are selected, conducted, and evaluated according to a careful public process, including a rigorous peer review process, to assure both credibility and high scientific standards. HEI makes no recommen­ dations on regulatory and social policy. Its goal, as stated by former EPA Administrator William D. Ruckelshaus, is "simply to gain acceptance by all parties of the data that may be necessary for future regulations:' The Board of Directors Archibald Cox Chairman Donald Kennedy Carl M. Loeb University Professor (Emeritus), Harvard Law School President, Stanford University William 0. Baker Walter A. Rosenblith Chairman (Emeritus), Bell Laboratories Institute Professor (Emeritus), Massachusetts Institute of Technology Health Research Committee Richard Remington Chairman Robert F. Sawyer University of Iowa Foundation Distinguished Professor of Preventive Class of 1935 Professor of Energy, University of California at Berkeley Medicine and Environmental Health, University of Iowa John W. Tukey Joseph D. Brain Senior Research Statistician and Donner Professor of Science Emeritus, Cecil K. and Philip Drinker Professor of Environmental Physiology, Princeton University Harvard University School of Public Health Mark J. Utell Leon Gordis Professor of Medicine and Toxicology, University of Rochester School of Professor and Chairman, Department of Epidemiology, Johns Hopkins Medicine University, School of Hygiene and Public Health Gerald N. Wogan Curtis C. Harris Professor of Toxicology, Massachusetts Institute of Technology Chief, Laboratory of Human Carcinogenesis, National Cancer Institute Roger 0. McClellan President, Chemical Industry Institute of Toxicology Health Review Committee Arthur Upton Chairman Robert M. Senior Professor and Chairman, Institute of Environmental Medicine, New York Professor of Medicine and Director, Respiratory and Critical Care University Division, The Jewish Hospital at Washington University Medical Center Bemard Goldstein James H. Ware Professor and Chairman, Department of Environmental and Community Dean of Academic Affairs and Professor of Biostatistics, Harvard Medicine, University of Medicine and Dentistry of New Jersey, Robert University School of Public Health Wood Johnson Medical Center Mary C. Williams Gareth M. Green Professor of Medicine (Cell Biology), Boston University School Associate Dean for Education, Harvard School of Public Health of Medicine Millicent W. P. Higgins W. Kent Anger Special Consultant to the Committee Associate Director for Epidemiology and Biometry, National Heart, Lung Associate Director for Occupational and Environmental Toxicology, and Blood Institute The Oregon Health Sciences University Herbert Rosenkranz Chairman, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh Officers and Staff Andrew Sivak President and Treasurer Martha E. Richmond Consulting Staff Scientist Richard M. Cooper Corporate Secretary Ann Y. Watson Consulting Staff Scientist Debra N. Johnson Controller Judith Zalon Lynch Director of Administration and Finance L. Virgi Hepner Publications Manager Kathleen M. Nauss Director for Scientific Review and Evaluation Gail V. Allosso Assistant to the Director of Administration and Finance Jane Warren Director of Research Robin A. Cuozzo Accounting Assistant William F. Busby, Jr. Senior Staff Scientist Jean C. Murphy Research Assistant Brenda E. Barry Staff Scientist Mary-Ellen Patten Administrative Assistant Aaron F. Cohen Staff Scientist Kate Rose Publications Assistant Maria G. Costantini Staff Scientist Hannah J. Protzman Secretary Bemard Jacobson Staff Scientist Joyce L. Speers Secretary Debra A. Kaden Staff Scientist Carolyn N. White Secretary Alison M. Dorries Consulting Staff Scientist Patricia White Receptionist Copyright © 1990 by Health Effects Institute. § The paper in this publication meets the minimum requirements of the Printed at Capital City Press, Montpelier, VT. ANSI Standard Z39.4B-19B4 (Permanence of Paper) effective with Report Library of Congress Catalogue No. for the HE! Research Report Series: Number 21, December 19BB, and with Report Numbers 25 and 26 excepted. WA 754 R432. Reports 1 through 20, 25, and 26 are printed on acid-free coated paper. TABLE OF CONTENTS Research Report Number 33 Markers of Exposure to Diesel Exhaust in Railroad Workers INVESTIGATORS' REPORT Marc B. Schenker, Steven J. Samuels, Norman Y. Kado, S. Katharine Hammond, Thomas J. Smith, Susan R. Woskie Abstract . 1 Results . 18 Introduction . 1 Specific Aim 1 . 18 Exposure Assessment. 2 Phenanthrene as a Marker for Diesel Exhaust . 18 Variability of Exposure . 2 Nicotine as a Marker for Environmental Complex Composition of Diesel Exhaust . 3 Tobacco Smoke . 19 Use of Markers for Air Contaminants . 3 Specific Aim 2 . 21 Mutagenicity Assay . 4 Microsuspension Assay Sensitivity for Diesel Exposure and the Kinetics of Mutagen Excretion . 5 Extracts . 21 Dose-Response Relationships of Diesel Extracts 21 Specific Aims .......... 0 • • • • • • • • • • • • • • • • • • • • • • 5 Mutagenicity of Respirable Particles from Methods...................................... 6 Personal Samplers. 23 Epidemiology ........................... 0 • • • 6 Specific Aim 3 . 23 Industrial Hygiene . 7 Study Population . 23 General Approach . 7 Cigarette Smoking . 24 Quality Control . 7 Respirable Particles Exposure . 24 Respirable Particles . 8 Phenanthrene Exposure . 26 Nicotine . 9 Specific Aim 4 . 27 Phenanthrene . 9 Markers of Active Cigarette Smoking . 27 Sampling Strategy . 10 Markers of Passive Cigarette Smoking . 28 Mutagenicity . 11 Other Non-Diesel Exhaust Predictors of Chemicals . 11 Urinary Mutagenicity . 29 Microsuspension Assay Method . 11 Diesel Exhaust Exposure . 29 Diesel Extracts . 11 Other Analyses . 33 Urine Collection and Extraction Methods . 11 Discussion . 33 Mutagenicity Testing of Urine . 12 Diesel Exhaust Exposure . 33 Clinical Chemistry . 13 Respirable Particle and Environmental Tobacco Data Management . 14 Smoke Exposure . 33 Statistical Methods . 14 Phenanthrene Exposure . 34 General Strategy . 14 Urinary Mutagenicity. 34 Preliminary Smoking Analyses . 14 Diesel Exhaust . 34 Indices of Diesel Exhaust Exposure . 14 Dietary Factors . 35 Index Construction . 15 Antimutagenic Activity of Naturally Occurring Interaction Model for Exposure Effects . 16 Compounds . 35 Phenanthrene Models . 16 Study .Power . .. 36 Other Predictive Factors for Regression Models 16 Implications of the Findings . 36 Transformations and Model Diagnostics . 17 Acknowledgments . 37 Model Form: Accounting for Differential References ........ 0 • • • • • • • • • • • • • • • • • • • • • • • • • • 37 Sensitivity of Bacterial Strains . 17 Appendices . 42 Generalized Least Squares . 18 A. Health Survey . 42 B. Effects of Storage on Urinary Mutagenicity and E. Statistical Descriptions of Mutagenic Activity Thiocyanate Concentration . 43 Controls . 48 C. Comparison of Point-Deletion and Tangent-Slope F. Phenanthrene as a Marker for Diesel Exhaust . 49 Methods for Computing the Number of Revertants About the Authors . 51 per Milliliter Equivalent of Urine . 45 Abbreviations . 51 D. Urinary Mutagenicity Correlation with Multivariate Regression Variables. 46 HEALTH REVIEW COMMITTEE'S COMMENTARY Health Effects Institute Introduction ................................... 53 Cigarette Smoke . 58 Regulatory Background . 53 Mutagenicity of Respirable Particles from Scientific Background ........................... 53 Personal Samples ....................... 58 Justification for the Study ....................... 56 Urine Monitoring ............................ 59 Goals and Objectives ............................ 56 Cigarette Smoke Exposure . 59 Study Design .................................. 57 Diesel Exhaust Exposure .................... 59 Technical Evaluation . 57 Other Factors . 60 Environmental Monitoring . 57 Implications for Future Research .................. 60 Total Respirable Particle Concentration ........ 57 Conclusions ................................... 61 Phenanthrene . 58 References . 61 ii INVESTIGATORS' REPORT Markers of Exposure to Diesel Exhaust in Railroad Workers 1 Marc B. Schenker , Steven J. Samuels, Norman Y. Kado, S. Katharine Hammond, Thomas J. Smith, Susan R. Woskie ABSTRACT grouping. A constant ratio of phenanthrene to respirable particles in area samples from diesel exhaust-exposed work locations suggested that phenanthrene
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