Table Of ContentAdvances in Controlled Clinical Inhalation Studies
ILSI Monographs
Carcinogenicity:
The Design, Analysis, and Interpretation of Long-Term Animal Studies
H.C. Grice and J.L. Ciminera, Editors
1988.279 pp. ISBN 0-387-18301-9
Inhalation Toxicology: The Design and Interpretation of Inhalation
Studies and Their Use in Risk Assessment
U. Mohr, Editor-in-Chief
D.L. Dungworth, G. Kimmerle, J. Lewkowski, R.O. McClellan, W. StOber
1988.318 pp. ISBN 0-387-17822-8
Radionuclides in the Food Chain
M.D. Carter, Editor-in-Chief
J.H. Harley, G.D. Schmidt, G. Silini, Editors
1988.518 pp. ISBN 0-387-19511-4
Assessment of Inhalation Hazards:
Integration and Extrapolation Using Diverse Data
U. Mohr, Editor-in-Chief
D.Y. Bates, D.L. Dungworth, P.N. Lee, R.O. McClellan, EJ.C. Roe, Editors
1989. 382 pp. ISBN 3-540-50952-6
Advances in Controlled Clinical Inhalation Studies
U. Mohr, Editor-in-Chief
D.Y. Bates, H. Fabel, M.J. Utell, Editors
1993.442 pp. ISBN 3-540-54958-7
ILSI Sponsored by
the International
MONOGRAPHS Life Sciences Institute
U. Mohr
Editor-in-Chief
Advances in
Controlled Clinical
Inhalation Studies
D.V. Bates H. Fabel M.J. Utell
Editors
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
Ulrich Mohr, Prof. Dr. med.
Medizinische Hochschule Hannover, Institut fiir Experimentelle Pathologie,
Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, FRG
David V. Bates, M.D., ER.C.P., ER.C.P.C., EA.C.P., ER.S.C.
University of British Columbia, Dept. Health and Epidemiology, 5804 Fairview
Crescent, Mather Building, Vancouver, BC, Canada V6T lW5
H. Fabel, Prof. Dr. med.
Medizinische Hochschule Hannover, Abteilung Pneumologie, Konstanty-Gutschow
StraBe 8, 3000 Hannover 61, FRG
Mark J. Utell, M.D.
Professor of Medicine and Environmental Medicine, Pulmonary and Critical Care
Unit, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester,
NY 14642, USA
With 101 Figures
ISBN-13:978-3-642-77178-1 e-ISBN-13:978-3-642-77176-7
DOl: 10.1007/978-3-642-77176-7
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Series Foreword
The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was
established in 1978 to advance the sciences of nutrition, toxicology, and food safety.
ILSI promotes the resolution of health and safety issues in these areas by sponsoring
research, conferences, publications, and educational programs. Through ILSI's
programs, scientists from government, academia, and industry unite their efforts to
resolve issues of critical importance to the public.
As part of its commitment to understanding and resolving health and safety issues,
ILSI is pleased to sponsor this series of monographs that consolidates new scientific
knowledge, defines research needs, and provides a background for the effective
application of scientific advances in toxicology and food safety.
Alex Malaspina
President
International Life Sciences Institute
Contents
Part I. Symposium Presentation .......................................................................... .
The Emergence of Controlled Human Exposure Studies
(D.V. BATES) .................................................................................................................. 3
Section 1. The Outdoor Environment in Europe .............................................. 9
Trend of Air Quality in North Rhine-Westphalia (Rhine-Ruhr Area)
During the Past 20 Years
(M. BUCK) ..................................................................................................................... 9
Air Pollution in the Former German Democratic Republic:
Consequences for Health Control
(B. THRIENE) .................................................................................................................. 21
The Outdoor Environment in North America ................................................... 31
Exposure to Oxidant Gases and Acidic Particles in the United States
(P.I. LIOy) ..................................................................................................................... 31
Section 2. Indoor Air: Home and Workplace .................................................... .43
Investigation of Indoor Air Pollution Sources in Climate Chambers:
Emissions from Textile Floor Coverings
(S. SOLLINGER and K. LEVSEN) ...................................................................................... 43
Dust Measurements at Workplaces: State of the Art and Future Demands
(W. KOCH) ..................................................................................................................... 57
Health Effects of Indoor Air Exposures
(M. LIPPMANN) ............................................................................................................... 69
Inhalation Studies in Investigation of the Sick Building Syndrome
(L. M0LHAVE) ................................................................................................................ 85
VIII Contents
Section 3. Assessing Personal Exposure ........................................................... 95
Personal Exposure Assessment: Implications for Clinical Studies
of Inhaled Pollutants
(J.M. SAMET and W.E. LAMBERT) ............................................................................... 95
Regional Deposition of Inhaled Particles
in the Human Respiratory Tract
(J. HEYDER) .................................................................................................................. 103
Calculation of Acid Aerosol Dose
(T.Y. LARSON, Q.S. HANLEY, J.Q. KOENIG, and O. BERNSTEIN) ................................... 109
Section 4. Clinical Inhalation Methodology ................................................... 123
Generation of Complex Aerosols
(W. HOLLANDER) .......................................................................................................... 123
Assessment of Ambient Exposures and Their Effects on Health in Chambers
(J.D. HACKNEY and W.S. LINN) .................................................................................. 135
Susceptible Populations: Lessons from Controlled Exposure Studies
of Inhaled Pollutants
(M.J. UTELL) ............................................................................................................... 143
Inhalation of Pollutants and Pollutant Mixtures in Subjects
with Bronchial Hyperresponsiveness
(H. MAGNUSSEN and R. JORRES) .................................................................................. 151
Section 5. New Methodologies ............................................................................. 159
Controlled Clinical Inhalation Studies with Environmental Air Pollutants
at Concentrations Commonly Found in the Ambient Air
(T.O.F. WAGNER, WH.T. SCHiiRMANN, and H. FABEL) ............................................... 159
Time- and Dose-Dependent Cellular and Biochemical Changes
in Response to Ozone Exposure
(H.S. KOREN, S. BECKER, P.A. BROMBERG, and R.B. DEVLIN) .................................... 169
Regeneration, Differentiation, and Neoplastic Transformation
of Type II Alveolar Epithelial Cells
(K.-U. THIEDEMANN, I. PAULINI, N. LUTHE, A. KREFr, U. ABEL, U. HEINRICH,
U. GLASER, and U. MOHR) .......................................................................................... 185
Infectivity Models in Clinical Inhalation Studies
(M.W. FRAMPfON) ....................................................................................................... 199
Does the Pulmonary Surfactant System Yield Meaningful Parameters
in Inhalation Toxicity Studies? A Review
(R. KLINGEBIEL AND U. HEINRICH) ............................................................................... 209
Contents IX
New Approaches to Evaluating the Pulmonary Effects
of Controlled Inhalation Exposures in Human Volunteers
(P.A. BROMBERG) ......................................................................................................... 235
Section 6. Clinical Data and Regulatory Decisions ....................................... 247
Meta-analysis and "Effective Dose" Revisited
(M.J. HAZUCHA.) ........................................................................................................... 247
Regulating Indoor Air
(B. SEIFERT) ................................................................................................................. 257
Perspective on the Regulator's Need for Future Clinical Studies
(D.J. MCKEE) .............................................................................................................. 269
Part II. Poster Presentations ................................................................................ 283
Use of Questionnaires for Assessment of Exposure to Airborne Pollutants
(N.C.G. FREEMAN and P.I. LIOY) ................................................................................ 285
Disorders in the Olfactory Function and Injury of the Upper Airways
of Exposed Workers in Copper-Producing Works
(N. GINCHEVA andA. SAVOV) ....................................................................................... 297
Elevated Bioaerosols in Manufactured/Conventional Homes
(C.T. HOWLETT, JR., L.R. NEWTON, T.N. VIRE, and J.J. TICE IV) ............................... 303
Single-Breath Bolus Exposure for Noninvasive Determination
of Ozone Dose Distribution
(S.c. Hu, J.S. ULTMAN, and A. BEN-JEBRIA) ............................................................... 309
Problems of Regulating Outdoor Ozone Levels
(A.D. KApPOs, G. Koss, I. TESSERAUX, and P. BRUCKMANN) ....................................... 317
Inhalation Studies with Airborne Particulates in Rodents:
Cytotoxic and Genotoxic Effects on Alveolar Macrophages
and Bone Marrow Cells
(A. KrELL, W. HADNAGY, N.H. SEEMAYER, H. BEHRENDT, and R. TOMINGAs) ............. 323
Assessment of Pollutant-Induced Impairment of the Pulmonary Surfactant
System by High-Performance Liquid Chromatography
(R. KLINGEBIEL, H.D. WINKELER, F. DRENK, and U. HEINRICH) ................................... 337
Assessment of 2,4-Dichlorophenoxyacetic Acid Exposure
in the Chemical Industry by Biological Monitoring
(D. KNopp, G. RICHTER, M. SKERSWETAT, H. HERMENAU, and E. STOTTMEISTER) ........ 345
Assessment by Aerosol Recovery Technique of Site of Airway Constriction
During Intravenous Histamine Challenge
(M. MEYER and A. RAHMEL) ....................................................................................... 347
X Contents
Attempted Selective Deposition of Aerosols Using Differently Sized Particles
in Man
(S.P. MOHAMMED, RW. BARBER, and T.W. HIGENBOTTAM) ......................................... 357
Acute Effects of Ambient Ozone in Physically Active Adults
(H.-G. MOcKE, U. RANFT, and M.S. ISLAM) ............................................................... 365
Respiratory Injuries in Workers from the Coke Chemical Industry
(E. PETRoVA and V. HRISTEVA) ..................................................................................... 373
Aerosol-Derived Airway Dimensions of Dog Lungs:
Comparison of Bolus and Single-Breath Techniques
(A. RAHMEL, A. SCHWALEN, E. CALZIA, A. HUBER, H. SCHULZ, and M. MEYER) ......... 377
Nonoccupational Exposure to Benzene
(G. SCHERER, C. CONZE, J. ANGERER, and F. ADLKOFER) ............................................. 387
Comparative Investigation of Genotoxic and Nongenotoxic Mechanisms
and Their Relevance in Carcinogenesis Induced by Airborne Particulates
and Automobile Exhaust Particulates
(N.H. SEEMAYER, W. HADNAGY, and R TOMINGAS) ..................................................... 393
Gestational Inhalation of Indoor Air Pollution Alters Neonatal Reflex
Development and Fetal Hematology
(J. SINGH) ..................................................................................................................... 405
Aerosol Deposition Pattern of Technetium-99m-Labeled Fenoterol
After Inhalation from Three Devices in Healthy Volunteers
(1. WAITZINGER, T. ZIMMERMANN, A. HAMMERMAIER, W. FLEISCHER, G. PABST,
AND H. JAEGER) ............................................................................................................ 411
Comparison of Bronchospasmolytic Effects of 200 /-Lg Fenoterol
After Inhalation with Respimat and Metered Dose Inhaler
(T. ZIMMERMANN, R STECHERT, H. SCHWEISFURTH, and R WETTENGEL) .................... .415
Subject Index ........................................................................................................... 423
Contributors*
ABEL, U. 185 HEYDER, J. 103
ADLKOFER, F. 387 HIGENBOTIAM, T.W. 357
ANGERER, J. 387 HOLLANDER, W. 123
HOWLETI, c.T., JR. 303
BARBER, R.W 357 HRISTEVA, V. 373
BATES, D.V. 3 Hu, S.C. 309
BECKER, S. 169 HUBER, A. 377
BEHRENDT,H. 323
BEN-JEBRIA, A. 309 ISLAM, M.S. 365
BERNSTEIN, O. 109
BROMBERG, P.A. 169,235 JAEGER, H. 411
BRUCKMANN, P. 317 JORRES, R. 151
BUCK, M. 9
KAPPaS, A.D. 317
CALZIA, E. 377 KiELL, A. 323
CONZE, C. 387 KLINGEBIEL, R. 209,337
KNopp, D. 345
DEVLIN, R.B. 169 KOCH, W 57
DRENK, F. 327 KOENIG, J.Q. 109
KOREN, H.S. 169
FABEL, H. 159 Koss,G. 317
FLEISCHER, W. 411 KREFT, A. 185
FRAMPTON, M.W. 199
FREEMAN, N.C.G. 285 LAMBERT, W.E. 95
LARSON, T.V. 109
GINCHEVA, N. 297 LEVSEN, K. 43
GLASER, U. 185 LINN, WS. 135
LIOY, P.J. 31, 285
HACKNEY, J.D. 135 LIPPMANN, M. 69
HADNAGY, W 323,393 LUTHE, N. 185
HAMMERMAIER, A. 411
HANLEY, Q.S. 109 MAGNUSSEN, H. 151
HAZUCHA, MJ. 247 MCKEE, DJ. 269
HEINRICH, U. 185, 209, 327 MEYER, M. 347,377
HERMENAU, H. 345 MOHAMMED, S.P. 357
* The numbers after the names refer to the contribution title page, where the author's complete address
can be found. Numbers in bold indicate senior authors.
