EPA-600/8-88-005F
April 1989
An Acid Aerosols Issue Paper:
Health Effects and Aerometrics
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
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DISCLAIMER
This document has been reviewed in accordance with U.S. Environmental
Protection Agency policy and approved for publication. Mention of trade names
or commercial products does not constitute endorsement or recommendation for
use.
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CONTENTS
TABLES vi i
FIGURES x
ABSTRACT xi i i
AUTHORS, CONTRIBUTORS, AND REVIEWERS xiv
1. INTRODUCTION 1-1
2. STRONG ACID AEROSOLS: CHARACTERIZATION AND EXPOSURE 2-1
2.1 INTRODUCTION 2-1
2.2 CHEMICAL AND PHYSICAL PROPERTIES OF ACID AEROSOLS 2-3
2.2.1 Particle Size of S0|~ and H 2-3
2.2.2 Atmospheric Acid Fogs 2-4
2.2.3 Formation of Acid Sulfates 2-12
2.2.3.1 Phase Equilibrium 2-15
2.2.4 Formation of Nitric Acid 2-17
2.2.5 Neutral ization 2-18
2.3 EMISSION DENSITIES AND DISTRIBUTION 2-23
2.3.1 Sulfur and Nitrogen Oxide Emission Densities 2-23
2.3.2 Sulfate Distribution 2-24
2.4 METHODOLOGY FOR STRONG ACID MEASUREMENT 2-30
2.4.1 Methodologies for Strong Acids and Sulfuric Acids .. 2-30
2.4.1.1 Sulfuric Acid 2-30
2.4.1.1.1 Filter collection 2-30
2.4.1.1.2 Extraction with pH measurement
or H titration 2-31
2.4.1.1.3 Specific extraction of
atmospheric acids 2-32
2.4.1.1.4 Specific extraction with
derivatization 2-32
2.4.1.1.5 Continuous and/or real-time
analysis 2-33
2.4.1.2 Nitric Acid 2-34
2.4.1.2.1 Nitric acid sampling
techniques 2-34
2.4.2 Sampling Anomalies 2-34
2.4.2.1 Sorption Losses 2-34
2.4.2.2 Equilibria-Driven Losses 2-36
2.4.3 Suggested Protocols 2-37
2.4.3.1 Strong Acid Aerosols 2-37
2.4.3.2 Specific Determination of H2S04 2-37
2.4.4 Applications 2-38
2.5 HISTORIC ACID LEVELS 2-38
2.5.1 London Sulfuric Acid Data 2-38
2.5.2 Los Angeles Data 2-41
2.6 ATMOSPHERIC CONCENTRATION 2-41
2.6.1 Atmospheric Acidic Sulfate Studies from
1974 to 1986 2-41
2.6.2 Acid Sulfate Exposure and Events 2-53
2.6.3 Atmospheric Nitric Acid Concentration 2-58
iii
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CONTENTS (continued)
2.7 METEOROLOGY 2-59
2.8 INDOOR AIR 2-65
2.9 SUMMARY 2-66
2.9.1 Implications for Atmospheric Pollution Studies 2-67
2.10 REFERENCES 2-68
3. DEPOSITION AND FATE OF INHALED ACID AEROSOLS IN THE
RESPIRATORY TRACT 3-1
3.1 INTRODUCTION 3-1
3.2 PARTICLE DEPOSITION MECHANISMS AND PATTERNS 3-2
3.3 HYGROSCOPIC AEROSOLS 3-10
3.4 NEUTRALIZATION BY AIRWAY SECRETIONS AND ABSORBED AMMONIA .. 3-11
3.4.1 Airway Surface Liquid Buffering 3-11
3.4.2 Reactions of Inhaled Acid with Airway Ammonia 3-16
3.5 CONCLUSIONS 3-21
3.6 REFERENCES 3-22
4. TOXICOLOGICAL STUDIES OF ACID AEROSOLS 4-1
4.1 INTRODUCTION 4-1
4.2 MORTALITY 4-3
4.3 PULMONARY FUNCTION 4-5
4.4 RESPIRATORY TRACT MORPHOLOGY AND BIOCHEMISTRY 4-14
4.5 RESPIRATORY TRACT DEFENSES 4-22
4.5.1 Clearance Function 4-22
4.5.1.1 Conducting Airways - Mucociliary
Clearance ' 4-23
4.5.1.2 Respiratory Region 4-30
4.5.2 Immunologic Defense 4-34
4.6 EFFECTS OF MIXTURES CONTAINING ACID AEROSOLS 4-35
4.7 SUMMARY AND CONCLUSIONS 4-44
4.8 REFERENCES 4-48
5. CONTROLLED HUMAN EXPOSURE STUDIES OF ACID AEROSOLS 5-1
5.1 INTRODUCTION 5-1
5.2 PULMONARY FUNCTION EFFECTS OF H2S04 IN NORMAL SUBJECTS 5-3
5.3 EFFECTS OF ACID AEROSOLS ON BLOOD BIOCHEMISTRY 5-13
5.4 EXPOSURE TO MIXTURES OF ACID AEROSOLS WITH OTHER
POLLUTANT GASES 5-13
5.5 EXPOSURE TO OTHER ACID AEROSOLS OR MIXTURES OF AEROSOLS ... 5-16
5.5.1 Nitrates 5-16
5.5.2 Other Sul fates 5-17
5.6 EFFECTS OF ACID AEROSOLS ON RESPIRATORY FUNCTION OF
ASTHMATICS 5-19
5.6.1 Effects of Nitric Acid Vapor in Asthmatics 5-30
5.7 EFFECT OF ACID AEROSOL INHALATION ON PULMONARY CLEARANCE
MECHANISMS 5-33
5.8 EFFECTS OF SULFURIC ACID AEROSOL ON AIRWAY REACTIVITY 5-40
IV
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CONTENTS (continued)
5.9 SUMMARY AND CONCLUSIONS
5.10 REFERENCES
EPIDEMIOLOGY STUDIES OF HEALTH EFFECTS ASSOCIATED WITH EXPOSURE'
TO ACID AEROSOLS
6.
6.
6.2.1
6.3
2.2
2.3
2.4
6.4
6.5
INTRODUCTION
ACUTE EFFECTS STUDIES -..'.'.'.'.'.'.'.'.'.'.'.'.'.
Acute Episode Studies
6.2.1.1 Meuse Valley '
6.2.1.2 Donora
6.2.1.3 London Acid Aerosol Fogs
European Pol 1utant Event of 1985
Acute Exposure Studies of Children
Acute Studies Relating Health Effects to Sulfates
CHRONIC EXPOSURE EFFECTS STUDIES
6.3.1 Acid Mists Exposure in Japan
Chronic Studies Relating Health Effects to
Sulfates
Chronic Studies Relating Health Effects to Oxides
of Nitrogen
Chronic Exposure Effects in Occupational Studies .
SUMMARY AND CONCLUSIONS
REFERENCES " " '
6.3.2
6.3.3
6.3.4
7. CONSIDERATIONS FOR LISTING ACID AEROSOLS AS A CRITERIA
POLLUTANT ,.
7.1
7.2
INTRODUCTION
7.1.1 Purpose ]
7.1.2 Background
7.1.3 Approach
CONSIDERATIONS FOR LISTING ACID AEROSOLS UNDER SECTION 108'
OF THE CLEAN AIR ACT
7.2.1 Characterization of Acid Aerosols
7.2.2 Available Health Effects Data on Acid Aerosols
2.3
2.4
7.3
7.4
7.2.2.1 Respiratory Mechanics and Symptoms
7.2.2.2 Host Defense Mechanisms
7.2.2.3 Morphological and Biochemical
Alterati ons
7.2.2.4 Aggravation of Existing Disease or
Illness
7.2.2.5 Mortality
7.2.2.6 Summary of Health Effects
Sources of Acid Aerosols
Implications of Listing Acid Aerosols
ALTERNATIVE APPROACHES FOR A LISTING DECISION
REFERENCES
Page
5-43
5-45
6-1
6-1
6-2
6-2
6-2
6-2
6-3
6-7
6-9
6-13
6-14
6-15
6-15
6-24
6-25
6-27
6-33
7-1
7-1
7-1
7-1
7-2
7-2
7-2
7-8
7-10
7-16
7-18
7-21
7-23
7-26
7-29
7-30
7-30
7-33
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CONTENTS (continued)
A.
B.
8. RESEARCH NEEDS
8.1 CHARACTERIZATION AND EXPOSURE
8.2 EXTROPOLATION AND DOSIMETRY
8.3 ANIMAL TOXICOLOGICAL STUDIES
8.4 CONTROLLED HUMAN EXPOSURE STUDIES
8.5 EPIDEMIOLOGY STUDIES
GLOSSARY OF TERMS AND SYMBOLS
REPORT OF THE CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE (CASAC):
ACID AEROSOL HEALTH EFFECTS WITH TRANSMITTAL LETTER FROM
ROGER 0. MCCLELLAN, CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
CHAIRMAN, TO LEE M. THOMAS, EPA ADMINISTRATOR
CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE SUBCOMMITTEE ON ACID
AEROSOLS REPORT ON ACID AEROSOL RESEARCH NEEDS WITH TRANSMITTAL
LETTER FROM ROGER 0. MCCLELLAN, CASAC CHAIRMAN, AND MARK J.
UTELL, CASAC SUBCOMMITTEE CHAIRMAN, TO LEE M. THOMAS, EPA
ADMINISTRATOR
8-1
8-1
8-5
8-5
8-8
8-10
A-l
B-l
C-l
VI
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TABLES
Number
2-1 Physical characteristics of compounds associated with
major acid aerosol precursors and products
2-2 Classification of major chemical species associated with
atmospheric particles
2-3 Summary of fogwater composition measurements ........
2-4 Important reaction rates for oxidation of sulfur dioxide ..
2-5 Aqueous S02 oxidation rates in the atmosphere
2-6 Estimated H2S04 (NH4)HS04 and (NH4)2S04 concentrations
based on TA-FPD and quartz filter measurements at
Sterl i ng Forest :.
2-7 Description of sampling systems and instruments that
measure chemical species that contribute to acidic dry
deposition
2-8 A summary of representative North America atmospheric
studies during which acid sulfate or total acidity was
measured by one or more techniques
2-9 Concentration ranges of SOf", H+ (as H2S04) and H2S04 (in
ug/m3) measured in various locations in North American
2-10 Acid concentrations measured above H9S04
£1 ng/m3 for ^2 h f
2-11 Episodic acidic aerosol data and estimates of personal
exposure from selected acid sulfate classified by sampling
time. Only intervals of time where concentrations
exceeded 5 pg/rn3 during the minimum sampling period of
apparent H2S04 are called as events 24 hour samples
2-12 Twelve hour acid aerosol samples and estimates of
exposure
2-13 Six hour acid aerosol samples and estimates of
exposure
2-14 One hour H2S04 data and estimates of exposure
2-15 Four-, eight- and sixteen-hour acid aerosol data and
estimates of exposure
Page
2-2
2-4
2-10
2-13
2-14
2-24
2-35
2-42
2-44
2-49
2-55
2-56
2-56
2-57
2-57
vii
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TABLES (continued)
Number
2-16
3-1
4-1
4-2
4-3
4-4
4-5
4-6
4-7
5-1
5-2
5-3
5-4
5-5
6-1
6-2
6-3
6-4
•
Results of Columbus ambient air sampling
Model estimates of neutralization of 0.5, 1.0, and 5.0 jjm
particles by "oral" and "nasal" levels of ammonia (Adapted
from Cocks and McEl roy , 1984)
Effect of 1^564 particle size on mortality
Effects of acid aerosols on pulmonary function
Effects of acid aerosols on respiratory tract morphology
Effects of acid aerosols on trachea! clearance
Effects of acid aerosols on bronchial clearance
Effects of acid aerosols on bacterial infectivity in mice ...
Toxicologic interactions to mixtures containing acid
aerosol s
Summary of controlled human exposure studies of acid
aerosol s
Summary of characteristics of asthmatic subjects partici-
pating in acid aerosol studies (1979-1988)
Analysis of covariance of ten adolescent asthmatics exposed
via mouth piece to 110 ug/m3 sulfuric acid aerosol
A summary of the percentage change in pulmonary functional
values after 10 minutes of moderate exercise
Estimated acid exposure controlled human studies
asthmatic subjects
Adjusted city-specific bronchitis prevalence rates and PM15
and H concentrations for Harvard six city studies
Acute exposure health effects seen under conditions of
measured or presumed acid aerosol exposure
Chronic exposure health effects seen under conditions of
measured or presumed acid aerosol exposure
Power of various camp studies to detect specified
di f f erences
Page
2-60
3-20
4-3
4-6
4-15
4-24
4-25
4-31
4-37
5-7
5-20
5-24
5-26
5-32
6-19
6-28
6-29
6-32
viii
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TABLES (continued)
Number
7-1
7-2
7-3
7-4
7-5
7-6
Alternative indicators for characterizing exposure to acid
aerosols
Effects of acid aerosols (<1,000 ug/m3) on respiratory
mechanics and symptoms
Effects of acid aerosols (<1,000 ug/m3) on host defense
mechani sms ,
Effects of acid aerosols (<1,000 ug/m3) on morphological
and bi ochemi cal i ndi ces
Effects of acid aerosols on individuals with existing
disease or illness
Mortality effects of acid aerosols
Page
7-4
7-12
7-17
7-19
7-22
7-24
IX
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FIGURES
Number
2-1 Particle size distributions of H+ and SO^ at the tower on
Allegheny Mountain, 2000 EOT 24 July to 0800 EOT 11
August, 1977 2-5
2-2 Log probability plot of H+, NH^, and SOf" size distribution
at the tower on Allegheny Mountain, August 12-17, 19-22,
and 28 2-6
2-3a Aerosol sulfur mass distribution, Pasadena, CA Dec. 26,
1978 2-7
2-3b Aerosol sulfur mass distribution, Trona, CA, May 13,
1978, from 0946-1145 PDT 2-7
2-4 Solubility diagram for the H+-NHt-SO|~H20 system at
equilibrium (30°C) 2-16
2-5 Annual average N-NH^ emissions from cattle and hogs 2-19
2-6 Annual average N-NH4 emissions from humans 2-20
2-7 Annual average N-NH^ emissions from cattle, hogs, humans,
and ferti 1 i zer 2-21
2-8 Scatter diagram of sulfate to ammonium mass concentration
ratios as a function of sulfate concentration for high
volume filter samples 2-22
2-9 Distribution of S02 emissions in the SURE area for summer
(metric tons/day). Emissions are based on data repre-
sentative of 1977 2-25
2-10 Distribution of NO emissions in the SURE area for summer
(metric tons/day). Emissions are based on data represen-
tative of 1977 2-26
2-11 Monthly average distribution of 24-hour HIVOL particulate
sulfate concentrations in the eastern United States 2-27
2-12 Geographical distribution of the ratio of sulfate sulfur
to total airborne sulfur for different seasonal periods
(in percent) 2-29
2-13 Historical London daily aerosol acidity data. (Total H+
as sulfuric acid) 2-40
2-14 6-hour 504 and H , and 6-hour maximum 03 samples
collected during August, 1977 at High Point, NJ 2-48
x
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FIGURES (continued)
Number
Page
2-15 Diurnal variation. The molar ratio of ammonium to sulfate
ion shows an acidity peak between noon and 6 p.m 2-52
2-16 Nitric acid measurements taken at Claremont, CA, 1979 2-60
2-17 Diurnal variation in nitrate concentration, Raleigh, NC,
1985 2-62
2-18 Maximum 24-hour average acid aerosol concentrations in the
Los Angeles CA basin in 1986 2-63
3-1 Deposition efficiency (percentage deposition of amount
inhaled) in humans and experimental animals for total
respi ratory tract 3-4
3-2 Deposition efficiency (percentage deposition of amount
inhaled) in humans and experimental animals for upper
respi ratory tract 3-5
3-3 Deposition efficiency (percentage deposition of amount
inhaled) in humans and experimental animals for tracheo-
bronchial region 3-6
3-4 Deposition efficiency (percentage deposition of amount
inhaled) in humans and experimental animals for pulmonary
regi on 3-7
5-1 Mean percent change in specific airway conductance (SGaw)
produced by a 16-minute inhalation of sulfate aerosols by
asthmatics 5-22
5-2 Change in FEN/i in asthmatics exposed to various concen-
trations and particle sizes of acid aerosol 5-31
5-3 Effect of H2S04 aerosol during and after a 60-min expo-
sure on group mean tracheobronchial mucociliary retention
of "Tc-labeled Fe203 particles. A. The response of ten
healthy subjects who inhaled a 7.6 urn Fe203 aerosol before
a 1 h H2S04 aerosol exposure. B. The response of eight
healthy subjects who inhaled a 4.2 pm Fe203 aerosol before
a 1 h H2S04 aerosol exposure 5-36
5-4 Clearance half-time (i.e., time required to clean half the
deposited tracer aerosol) as a function of the exposure con-
centration of acid aerosol x exposure duration in hours) .. 5-41
6-1 Bronchitis in the last year, children 10-12 years of age
in six U.S. cities, by PM15 6-20
xi
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FIGURES (continued)
Number
6-2
Bronchitis in the last year, children 10-12 years of age
in five U.S. cities, by hydrogen ion concentrations
6-20
xii
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ABSTRACT
This report evaluates scientific information on direct health effects
associated with exposure to acid aerosols. Although the literature up to 1988
has been reviewed thoroughly for information relevant to acid aerosols, the
present report is not intended as a complete and detailed review of all
literature pertaining to acid aerosols. Rather, an attempt has been made to
focus on the evaluation of those studies providing key information on health
effects and aerometrics. This report includes discussion of: the physical and
chemical properties of acid aerosols; ambient monitoring techniques and ambient
concentrations; the toxicology of acid aerosols in experimental animals;
respiratory tract deposition and neutralization of acid aerosols; assessment of
epidemiological studies of health effects of acid aerosols; assessment of
controlled human exposure studies evaluating the effects of acid aerosols; and
a summarization of the above information with interpretations and conclusions.
Important research needs are identified which are critical to be addressed in
order to improve the data base for acid aerosols and associated health effects
as a basis for decisions on whether to list acid aerosols as a criteria pollut-
ant for development of criteria and national ambient air quality standards.
Lastly, the Report of the Clean Air Scientific Advisory Committee (CASAC) that
reviews this document and makes recommendations to EPA and the CASAC Report on
Acid Aerosol Research Needs are included as Appendices.
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AUTHORS AND CONTRIBUTORS
Dr. Timothy Buckley
UMDNJ-Robert Wood Johnston Medical School
Piscataway, NJ 08854
Dr. Larry Folinsbee
Environmental Monitoring and Services, Inc.
Chapel Hill, NC 27519
Dr. Lester D. Grant
Environmental Criteria and Assessment Office
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Mr. John H. Haines
Office of Air Quality Planning and Standards (MD-12)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. Victor Hasselblad
Center for Health Policy Research and Education
Duke University
Durham, NC 27706
Dr. Kazuhiko Ito
Institute of Environmental Medicine
NYU Medical Center
Tuxedo, NY 10987
Dr. Dennis J. Kotchmar
Environmental Criteria and Assessment Office
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. Paul J. Lioy
UMDNJ-Robert Wood Johnston Medical School
Piscataway, NJ 08854
Mr. Scott W. Lounsbury
Office of Air Quality Planning and Standards (MD-12)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. Richard Schlesinger
New York University Medical Center
Tuxedo, NY 10987
Dr. Robert L. Tanner
Brookhaven National Laboratory
Upton, L.I., NY
xiv
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U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
Acid Aerosol Review Committee
Chai rman
Dr. Roger 0. McClellan
President, Chemical Industry
Institute if Toxicology
6 Davis Drive
P.O. box 12137
Research Triangle Park, NC 27709
Subcommittee Chairman
Dr. Mark Utell
Co-Director
Pulmonary Disease Unit
Professor of Medicine and Toxicology
University of Rochester Medical Center
box 692
Rochester, NY 14642
Director, Science Advisory Board
Dr. Donald Barnes
Science Advisory Board
United States Environmental Protection Agency
Washington, DC 20460
Members
Dr. Mary Amdur
Senior Research Scientist
Energy Laboratory
MIT
Room 16-339
Cambridge, MA 02139
Dr. Doug Dockery
Harvard University
School of Public Health
Department of Environmental Science and Physiology
665 Huntington Avenue
Boston, MA 02115
Dr. Robert Frank
Professor of Environmental Health Sciences
Johns Hopkins School of Hygiene and Public Health
615 N. Wolfe Street
Baltimore, MD 21205
xv
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Dr. Timothy Larson
Environmental Engineering and Sciences Program
Department of Civil Engineering FX-10
University of Washington
Seattle, WA 98195
Dr. Morton Lippmann
Professor
Institute of Environmental Medicine
NYU Medical Center
Tuxedo, NY 10987
Dr. Gilbert Omenn
Professor and Dean
School of Public Health and Community Medicine SC-30
University of Washington
Seattle, WA 98195
Dr. Robert F. Phalen
Community and Environmental Medicine
College of Medicine
University of California-Irvine
Irvine, CA 92717
Dr. Marc Schenker
Director-
Occupational and Environmental Health Unit
University of California
Davis, CA 95616
Dr. Jerry Wesolowski
Air and Industrial Hygiene Laboratory
California Department of Health
2151 Berkeley Way
Berkeley, CA 94704
Dr. George Wolff
Senior Staff Research Scientist
General Motors Research Labs
Environmental Science Department
Warren, MI 48090
Executive Secretary
Mr. A. Robert Flaak
Environmental Scientist
Science Advisory Board (A-101F)
U.S. Environmental Protection Agency
Washington, DC 20460
xvi
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REVIEWERS
A preliminary draft version of the present addendum was circulated for
review. Written or oral review comments were received from the following
individuals, most of whom participated (along with the above authors and
contributors) in a peer-review workshop held at the Radisson Plaza Hotel,
Raleigh, NC on June 10-12, 1987.
Dr. Karim Ahmed
Natural Resources Defense Council
122 E. 42nd Street
New York, NY 10168
Mr. John Bachmann
Office of Air Quality Planning and Standards (MD-12)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. David V. Bates
Department of Health Care and Epidemiology
Mather Building
University of British Columbia
Vancouver, BC V6T 1W5
Dr. Ronald L. Bradow
ASRL (MD-59)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. Steve Colome
Program in Social Ecology
University of California at Irvine
Irvine, CA 92717
Dr. Douglas Dockery
Harvard School of Public Health
Department of Environmental Science and Physiology
665 Huntington Avenue
Boston, MA 02115
Dr. Jonathan M. Fine
Chest Service (5K1)
San Francisco General Hospital
1001 Potrero Avenue
San Francisco, CA 94110
Dr. Judith A. Graham
HERL (MD-51)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
xvn
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Dr. Jack Hackney
Environmental Health Services - Room 51
Rancho Los Amigos Hospital
7601 Imperial Highway
Downey, CA 90242
Dr. Carl Hayes
HERL (MD-55)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. Michael T. Kleinman
Department of Community and Environmental Medicine
University of California at Irvine
Irvine, CA 92717
Dr. Jane Koenig
Department of Environmental Health SC-34
University of Washington
Seattle, WA 98195
Dr. Jerry Last
Primate Center
University of California at Davis
Davis, CA 95616
Dr. Fred Lipfert
23 Carl! Court
Northport, New York 11768
Dr. Roger 0. McClellan
Lovelace Inhalation Toxicology Research Institute
P.O. Box 5890
Albuquerque, NM 87185
Dr. Robert Phalen
Community and Environmental Medicine
University of California at Irvine
Irvine, CA 92717
Mr. Charles Rodes
EMSL (MD-56)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. Neil Roth
Roth Associates
6115 Executive Boulevard
Rockville, MD 20850
xvm
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Dr. Jack Spengler
Harvard School of Public Health
Department of Environmental Science and Physiology
Building 1, Room 1305
665 Huntington Avenue
Boston, MA 02115
Dr. Bonnie Stern
LRTAP - Health Effects Section
Health Protection Building - Room 65A
Tunney's Pasture
Ottawa, Ontario, Canada K1A OL2
Mr. Robert Stevens
ASRL (MD-47)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
Dr. William E. Wilson
ASRL (MD-59)
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
OBSERVER
The following member of the Clean Air Scientific Advisory Committee
(CASAC) of EPA's Science Advisory Board attended the June 10-12, 1987 workshop
as an observer on behalf of CASAC.
Dr. Robert Frank
Professor of Environmental Health Sciences
John Hopkins School of Hygiene and Public Health
615 N. Wolfe Street
Baltimore, MD 21205
xix
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1. INTRODUCTION
The United States Clean Air Act and its 1977 Amendments require the U. S.
Environmental Protection Agency (U.S. EPA) to periodically review criteria for
National Ambient Air Quality Standards (NAAQS) and NAAQS themselves, and to
revise such criteria and standards as appropriate. This process led in 1982 to
the publication of the EPA document Air Quality Criteria for Particulate
Matter and Sulfur Oxides and an accompanying addendum to that criteria document
addressing further information on health effects. Subsequently, a second
addendum to the criteria document that updated the earlier document by evaluat-
ing new studies and their implications for determination of health-related
criteria for the PM and S02 NAAQS was published in 1986. In this process of
reviewing new scientific studies concerning health effects of PM and S02» it
became apparent that researchers had identified acid aerosols as one constituent
of the PM/S02 airborne mix that may be associated with observed PM/SC^ health
effects. The Clean Air Scientific Advisory Committee (CASAC) of EPA's Science
Advisory Board, accordingly, recommended that an acid aerosol issue paper be
prepared to evaluate newly emerging literature concerning health effects
directly associated with acid aerosols and to address the issue of possible
listing of acid aerosols as a separate criteria pollutant for regulation by
means of National Ambient Air Quality Standards. To this end, the present
report provides a concise review of the most relevant information to charac-
terize ambient concentration patterns and human exposures as well as possible
acute and chronic health effects of acid aerosols derived from available
animal, controlled human, and epidemiological studies. Considerations for the
possible listing of acid aerosols as a criteria pollutant are also presented.
The report concludes by highlighting research needs.
Atmospheric aerosols consist of two principal components: a gas phase
("air") and a solid or liquid particle phase in suspension. The discussion in
this document focuses on the major strong acid species that contribute to
aerosol acidity, primarily strong acid sulfates (particles at typical ambient
1-1
-------
conditions) and to, a lesser extent, nitric acid (a vapor at typical ambient
conditions) and other acidic species.
Strong acid sulfates - sulfuric acid (H2S04) and ammonium bisulfate
(NH^HSO^) - appear to be the main species of concern in ambient acid aerosols
and are the most studied species. Sulfuric acid in particular has been the
focus of many of the available studies, both in terms of ambient measurements
and health effects research. However, other acid species, especially nitric
acid, may be of concern in certain exposure situations, such as the acid fogs
of western coastal cities, or may influence neutralization reactions and thus
total aerosol acidity. Nitric acid is completely scavenged to droplets in
fogs. Weak acids may also be present in the atmosphere, but these have not
been measured in conjunction with strong acid aerosol at ground base monitors.
Only limited data are available by which to characterize acid aerosols and
their concentrations in ambient air. Chapter 2 of this document discusses the
available information on this subject and possible human exposures as well.
The chapter first examines the chemical and physical properties of acid aero-
sols, meteorology, emission densities and distribution of the major species
contributing to atmospheric acidity, and historic acid levels. Following that
discussion, another section examines the various measurement methodologies and
the final section of the chapter examines recent data on atmospheric concen-
trations and "events."
Chapter 3 examines the deposition and fate of inhaled acid aerosols in the
respiratory tract. Important concepts discussed include hygroscopic growth and
neutralization by airway secretions and ammonia.
Chapters 4, 5, and 6 examine the available health effects information for
acid aerosols. The bulk of the animal and controlled human studies involve
acid sulfates, primarily submicrometer H2S04. There are no animal data, and
very limited controlled human exposure data, for larger droplets that would be
typical of acid fogs. Few data are available for nonsulfur constituents of
acid fogs or other acidic atmospheres, such as nitric acid. Most of the
pertinent epidemiological studies do not have direct acid measurements, but are
suggestive of human health effects being associated with air pollution
exposures where there is good reason to believe that high ambient acid
concentrations existed. Only a very limited set of epidemiological studies
have either subsequent or concurrent acid measurements.
1-2
-------
Chapter 4 discusses the toxicology of acid aerosols in experimental
animals. Available studies indicate effects from both acute and chronic
exposures. This chapter examines mortality, pulmonary function, respiratory
tract morphology and biochemistry, and respiratory tract defenses. The effects
of mixtures containing acid aerosols are also reviewed.
Available controlled human exposure studies for acid aerosols are dis-
cussed in Chapter 5. These studies have looked at the effects of acute expo-
sure on pulmonary function and respiratory tract clearance mechanisms in both
normal and asthmatic subjects and on blood biochemistry. Such studies have
also evaluated the effects of mixtures of acids with other pollutant gases or
aerosols.
Chapter 6 discusses relevant epidemiological studies, including acute
effects studies from historical episodes, acute exposure of children, acute
exposure to sulfate, and a European acid event of 1985; and chronic effects
studies from acid mist exposure in Japan, sulfate and SCL exposures, nitrogen
oxide exposures, and chronic occupational exposures.
Chapter 7 of this document, authored by the Office of Air Quality Planning
and Standards, assesses and integrates the available information by which to
address the central question of whether there is sufficient and compelling
evidence to proceed with the separate listing of acid aerosols as a criteria
air pollutant under Section 108 of the Clean Air Act. The major considerations
discussed include: (1) characterizing and defining acid aerosols as a
pollutant entity for purposes of regulation and their ambient concentrations;
(2) possible health effects of acid aerosols at current ambient levels; and
(3) the sources of acid aerosols. Each of these elements is of central
relevance for listing decisions under Section 108 of the Act. The final
section of this chapter presents alternative courses of action based on the
assessment of the available information.
The final chapter of this document (8) presents research needs that
reflect deficiencies of the data base identified in Chapters 2 through 6.
Lastly, the Report of the Clean Air Scientific Advisory Committee (CASAC) that
reviewed this document and made recommendations to EPA as well as the CASAC
Report on Acid Aerosol Research Needs are included as Appendices.
1-3
-------
-------
2. STRONG ACID AEROSOLS: CHARACTERIZATION AND EXPOSURE
2.1 INTRODUCTION
The information available on the concentration patterns and human exposure
to atmospheric acidic aerosol is meager, and many of the studies were not
designed to measure human exposure but rather were part of a program or research
directed at characterizing the ambient atmosphere. Nonetheless the information
is useful in pointing directions for future work, as well as in estimating the
exposure to acidic species for specific conditions. This chapter attempts to
summarize the data available on acidic aerosol species with special emphasis
on acid sulfate species which represent the major acidic species in ambient
acid aerosols and the most studied species to date for both aerometric levels
and health effects. The characteristics of the compounds of primary concern
in this chapter are shown in Table 2-1. Episodic situations are also
emphasized. An analysis of historical data accumulated in London, England,
during the 1960's is also presented.
Many of the major formation mechanisms for sulfuric acid were previously
examined in the Particulate Matter-SO Criteria Document (U.S. Environmental
J\
Protection Agency, 1982a); therefore, only recent advances and that information
necessary for understanding the potential for human exposures will be described.
Since there is no reference method for acid sulfate species, another major area
of concern is the multitude of techniques that have been used to detect various
acid species in the environment. These techniques are summarized along with
some discussion of their pertinent strengths and weaknesses. A discussion on
nitric acid and related fog processes is also included in the text.
In this chapter H+ is the ion associated with particulate cloud
or_acid rain species and the concentration is determined by [H ] =
10 H . Titratable acidity is the acid content neutralizable by
addition of strong base to a solution and is called titratable strong
acidity at a low pH endpoint (pH=2). At a high pH endpoint (pH=7)
this quantity becomes total strong and weak acidity.
2-1
-------
TABLE 2-1. PHYSICAL CHARACTERISTICS OF COMPOUNDS
ASSOCIATED WITH MAJOR ACID AEROSOL PRECURSORS
AND PRODUCTS
Sulfuric Acid
Ammonium Bisulfate
Ammonium Sulfate
Nitric Acid
Sulfur Dioxide
Ammonium
Nitrogen Dioxide
Ammonium Nitrate
Formula
H2S04
NH4HS04
(NH4)2S04
HN03
S02
NH3
N02
NH4N03
Molecule
Weight
g
98.08
115.11
132.14
63.01
64.06
17.03
46.01
80.04
Density
g/i
1.841
1.78
1.769
1.5027
2.927(g)a
0.7710
1.449
1.725
Melting
Point
°C
10.36
146.9
235
-42
-72.7
-77.7
-11. 2b
169.6
Boiling
Point
°C
330 ± 0.
5
decomposes
-
83
-10
-33.35
21.1
210
a1.434 1
b,,
Liquid, solid forms largely as N204.
There has been no effort to determine the reliability of the methods used
in acid aerosol studies or the uncertainty associated with a particular set of
measurements. Almost all studies described have been subject to peer review by
journals, indicating a certain degree of confidence in the data. Some of the
most recent data which, in some cases, are the most closely associated with
actual measurements of exposure, are undergoing peer review and are cited as
personal communications.
One important note of caution must be identified for the reader. The
detection of acidic sulfur species by the variety of methods described in this
chapter has usually resulted in data being available in one of two forms:
(1) the compound sulfuric acid or (2) the titratable strong acid hydrogen ion.
At present there are no techniques available to detect the intermediate acid
species, ammonium bisulfate (NH^SO^), although there have been two attempts to
infer the ammonium bisulfate concentration when hydrogen ion and sulfuric acid
measurements were made simultaneously (Morandi et al., 1983; Lioy and Lippmann,
1986). To place the results from each study in a context, in each case where
only hydrogen ion measurements were measured, the concentrations are expressed
as apparent sulfuric acid. Thus the values are probably an over estimate of
2-2
-------
the actual sulfuric acid concentration since in both urban and rural areas
sulfate is usually in a partially neutralized form. Weak acids may also be
present in the atmosphere, but these have not been measured in conjunction with
strong acid aerosol at ground based monitors.
2.2 CHEMICAL AND PHYSICAL PROPERTIES OF ACID AEROSOLS
2.2.1 Particle Size of S0^2and H+
Sulfate is in the fine particle size range (<2.5 urn) and is in the acidic
fraction of the atmospheric aerosol as shown in Table 2-2. The seasonal and
annual size segregation results from the nine Class I Sulfate Regional Experi-
ment (SURE) sites located in the Eastern U.S. from 1977 through 1987 show that
80 percent of the S04 is in the fine particle range (Mueller and Hidy, 1983).
The percentage varied from 50 to 100 percent, depending upon the site and the
month of the year with the lowest percentages occurring in the fall and the
winter.
Size distribution data have been acquired for sulfate and hydrogen ion by
Pierson et al. (1980b) and Keeler (1987) in two separate investigations at
Allegheny Mt., PA during July and August of 1977, and August in 1983. The
cumulative mass equivalent size distributions for the respective studies are
shown in Figures 2-1 and 2-2. The mass median equivalent diameters were
+ —?
0.84 urn and 0.7 urn for H and SO^ , respectively. Since these data were taken
in the Eastern U.S., the potential for having high relative humidity in the
summer would increase the particle size of the sulfate species above that found
initially by gas-phase or liquid-phase reactions. In the 1977 study the
average relative humidity was 79 percent and the average nighttime relative
humidity was 91 percent. The presence of large particle acid in the size
distribution suggests the formation of fog during the sampling periods, which
would be consistent with the high relative humidity during the night.
In California, two types of sulfur particle mass size distributions have
been noted and each is illustrated in Figure 2-3 (Friedlander, 1980). The
Pasadena, CA sulfate distribution in Figure 2-3 (top) appears to be similar to
that observed by Pierson et al. (1980b) and Keeler (1987) with most of the mass
found centered around 0.5 urn. Friedlander has classified this as a coastal
sulfur aerosol (multiply by 3 to approximate sulfate mass). The distribution
shown in Figure 2-3 (bottom) shows the sulfur mass having a mode which is
shifted down to between 0.1 and 0.2 urn. This was classified as desert type
2-3
-------
TABLE 2-2. CLASSIFICATION OF MAJOR CHEMICAL SPECIES ASSOCIATED WITH
ATMOSPHERIC PARTICLES
Fine Fraction
Coarse Fraction
Both Fine and
Coarse Fractions
Variable
S042, C (soot)
Organic (condensed
vapors)
Pb, NH4, As
Se, H , acids
Fe, Ca, Ti, Mg
K, P043, Si, Al
Organic (pollen,
spores, plant
parts)
Bases
Zn, Cu, Ni, Mn
Sn, Cd, V, Sb
Source: Air Quality Criteria for Particulate Matter and Sulfur Oxides
(U.S. Environmental Protection Agency, 1982a).
aerosol that appeared to be formed from homogeneous reaction mechanisms but did
not grow appreciably in the arid atmosphere. The concentration of the desert
3
sulfate aerosol was less than 2.0 pg/m . This could have contributed to the
smaller sizes since there would have been less coagulation of particles
in dispersed conditions. No information on the distribution of aerosol acidity
was available in either of these cases. However, a recent study conducted by
the California Air Resources Board measured the distribution of strong acid
found and found it to be in the size range <1.5 pm, Dae, in diameter (Fujita
et al., 1986).
2.2.2 Atmospheric Acid Fogs
Fog and clouds are a special type of atmospheric aerosol. While aerosols
are generally composed of crystalline, aquated salt, or other solid particles,
fogs and clouds are the suspension of liquid water droplets in the air. Such
droplets form by condensation of water vapor on preexisting fine aerosol
particles called condensation nuclei. However, this occurs only when the atmos-
phere is saturated with water vapor (i.e., relative humidity >100 percent).
From nuclei of 0.1 to 1.0 pm, droplets grow to diameters between 2 to
100 urn, although the majority of droplet mass occurs in the range of 5 to
30 urn. In contrast, raindrops are in the range of 200 to 2,000 pm. In fogs and
clouds, the mass of liquid water is typically 0.01 to 0.5 g/m ; the number
3
concentration of droplets is generally 10 to several 100/cm .
2-4
-------
15
10
8
E
tf
s«
Q.
1
0.8
0.6
0.41—
i—i r
H+
i i i i
1 2 5 10 20 40 60 80 90 98
MASS IN PARTICLES SMALLER THAN STATEDp^d. percent
Figure 2-1. Particle size distributions of H; and SO/ at the tower on Allegheny Mountain,
2000 EOT 24 July to 0800 EOT 11 August, 1977.
Source: Pierson era/. (1980b).
99
2-5
-------
10
8
— • H
E
1
0.8
0.6
0.4
I T
NH
I
10
50 90 99
MASS IN PARTICLES SMALLER THAN STATED SIZE, percent
99.8
Figure 2-2. Log probability plot of H*, NH*4, and SOJ- size distribution at the tower on Allegheny
Mountain, August 12-17,19-22, and 28.
Source: Keeler (1987).
2-6
-------
w
a.
•a
TOTAL MASS LOADING '
10.6 fZg/m3
1 —
5.0 10
0.01 0.05 0.1 0.2 0.5 1.0 2.0
Aerodynamic Diameter, dp,
Figure 2-3a. Aerosol sulfur mass distribution, Pasadena, CA,
Dec. 26, 1978. Average of two samples from 1428-1600 PST.
2.0
1.5
•&1.0
8
0.5
I 1 T
TOTAL MASS LOADING =
1.42/lg/m3
0.01 0.05 0.1 0.2 0.5 1.0 2.0 5.0 10
Aerodynamic Diameter, dp, p.m
Figure 2-3b. Aerosol sulfur mass distribution, Trona, CA
May 13,1978, from 0946-1145 PDT.
Source: Freidlander (1980)
2-7
-------
The presence of condensation nuclei, composed of both soluble and non-
soluble material, is essential to the formation of atmospheric water droplets.
The effects of surface tension and the chemical potential of the aquated
solutes are important; these raise and lower the saturation vapor pressure
near the droplet surface, respectively. Accretion or evaporation of water to
the condensation nucleus or droplet is forced by the difference between the
ambient and local (i.e., surface) humidities. Droplet growth equations have
been derived by coupling microscale heat and mass transfer at the aerosol sur-
face. The principal terms depend on: (a) atmospheric relative humidity;
(b) droplet surface tension; and (c) solute activity.
In many respects, fog is simply a ground-level cloud in which processes
such as nucleation, gas scavenging, and droplet growth are important. At the
same time, fogs consist of discrete water droplets, and sedimentation and
inertia! impaction are dominant transport mechanisms due to the relatively
large sizes of these particles. However, since fog droplets may change size
continually, their transport behavior may be altered.
Fog droplets are highly effective at scavenging pollutant materials
present in the air. The overall fraction incorporated into fog droplets
depends upon two processes: nucleation scavenging (i.e., activation) of aerosol
and gas dissolution. The speciation of pollutant components present prior to
fog formation is therefore important. Furthermore, i_n situ chemical trans-
formations (e.g., oxidation of S02 to sulfuric acid) may alter this speciation
and the effectiveness of fog scavenging while the droplet phase is present.
The pollutant species of concern are often present as hygroscopic aerosol
(e.g., ammonium sulfate and ammonium nitrate). These will deliquesce to form
aquated condensation nuclei at high relative humidity (RH), growing to larger
equilibrium sizes as RH approaches 100 percent. Under droplet-forming condi-
tions, the larger and more soluble aerosol grow into droplets first; however,
these relationships are at best qualitative. This area of fog microphysics, the
size-composition relationship within droplet spectra, may strongly affect the
chemistry and deposition of fog-borne material. It remains an area in need of
further research.
Dissolution of gaseous species in fogwater is dependent on gas-aqueous
equilibria and the quantity of liquid water present. Temperature and pH are
the most important parameters that affect phase equilibria (e.g., aqueous,
gas-aqueous, etc.). Sulfur dioxide is fairly insoluble at low pH. Only at
2-8
-------
higher pH (7 and above) does dissociation of the gas in solution lead to
appreciable SO,, solubility. In contrast, nitric acid is completely scavenged
to droplets for fogs even at minimal liquid water content (LWC).
Under most conditions, the rate of gas transfer to fog-sized droplets by
molecular diffusion is sufficiently rapid for phase equilibria to be achieved
on the order of seconds or less under most conditions (Baboolal et al., 1981;
Schwartz, 1984).
The study,of fog has traditionally remained in the domain of atmospheric
physicists principally concerned with its effect on visibility or the
mechanisms of formation analogous to clouds. Yet, even the data of early
investigations of fog indicate that fogwater can be highly concentrated with
respect to a variety of chemical components (see Table 2-3). Cloudwater,
sampled aloft, has been found with similar composition, although not with the
same extreme values. On the other hand, rainwater compositions, when compared
to fogwater, are found to be far more-dilute. This makes sense, since fog
droplets are approximately 100 times smaller than raindrops, which form
partially by the further condensation of water vapor. Hence, fog and cloud
water should be more concentrated in solute derived from the condensation
nuclei. Furthermore, fog forms in the ground layer where gases and aerosol are
most concentrated. Most recent measurements have been made in California,
but Spengler et al. (1986) also found fog associated with a period of acid
aerosol in Watertown, MA.
The higher aqueous concentrations and extremes in acidity found in fog-
water are reason for concern. Fog-derived inputs have the potential to add
substantially to the burden of acid deposition caused by precipitation. Its
contribution can be disproportional to the sum of additional moisture because
of its higher concentrations. Perhaps more important, deleterious effects of
fog deposition may be associated with the intensity of solution acidity. For
instance, appreciable nutrient leaching (Scherbatskoy and Klein, 1983) and
damage to leaf tissue (Haines et al., 1980) have been noted with application of
acid fog or mists. An historical correlation of fog with the most severe air
pollution episodes in Meuse Valley, Donora and London provides additional cause
for concern (Hoffman, 1984). Identification of a link between urban fog events
and human injury was made even before detailed measurements of fog composition
(Firket, 1936).
2-9
-------
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2.2.3 Formation of Acid Sulfates
The mechanisms involved in the transformation of S02 were reviewed in the
Participate Matter and Sulfur Oxides Criteria Document and the Acid Deposition
Assessment Document (U.S. Environmental Protection Agency, 1982a; 1984), and
are listed with the reaction rates listed in Table 2-4. Included are both
heterogeneous and homogeneous reactions which produce H2S04 in the gas phase or
within the aqueous phase. Additional potential mechanisms involve metal
catalysts, carbon, and surface reactions. The reaction rates in the atmosphere
range from <0.5 percent to >100 percent per hour. Some of the values have a
greater degree of confidence associated with them than others. Although it is
not readily apparent from the table, all these reactions will not occur at the
same time. Rather each will be associated with particular environmental
conditions either near a source, in a plume, or in the general atmosphere. The
importance of a particular reaction scheme will depend on the season, geographic
location, time of day (night or daylight) and local or prevailing meteorology.
A summary of S02 reaction rates in plumes are found in the Acid Deposition
Assessment Document U.S. Environmental Protection Agency (1984), and for gas
phase processes these range from 0 to 15% hr"1. In urban plumes the values
ranged from 0-30% hr'1. As one example, Gillani et al. (1981) and Gillani
et al. (1983) have studied the oxidation of S02 in actual power plant plumes,
and the conversions were parameterized for relative humidities (RH) <75 percent
and >75 percent. For the <75 percent conditions, empirical relationships
derived from the measurements indicated that the most significant indicator
variables were ozone concentration, solar radiation, and plume size. In con-
trast, for RH >75 percent, the interaction of a plume with clouds significantly
enhanced the conversion of S02 to particulate sulfur. Each of these processes
will contribute to the regional levels of acidic sulfate. The basis for
significant accumulations of acid sulfate would be summertime photochemical
smog for the former (RH <75 percent) and the presence of a persistent cloud
cover or expanding (contracting) cumulus clouds during fair weather for the
latter (RH >75 percent).
Recently, Jacob et al. (1984) compared field data collected by five
groups on aqueous phase transformations of SD£. Depending on local conditions,
the rates can vary widely (Table 2-5). In a discussion by Schwartz and Newman
(1983), the rates in Table 2-5 from Hegg and Hobbs (1981, 1982) were criti-
cized on the basis of the method of calculation. However, the general results
2-12
-------
n
I. Gas Phase
HO radical
H02 radical
CH302 radical
0.3 -
0.4 -
0.3 -
1.3
2.0
1.5
a,b
a,b
II. Aqueous Phase
Mn (II) catalysis
Fe (III) catalysis
C (soot) catalysis
03 (40 ppb)
03 (120 ppb)
H202 (1 ppb)
H202 (10 ppb)
pH 1 pH 3
pH 5
0.1
5 x 10"5
30
2 x 10"8
6 x 10"8
0.02
0.2
10
0.5
30
2 x 10"6
6 x 10"6
0.03
0.2
1 x 103
5 x 103
30
2 x 10"4
6 x 10"4
0.03
0.3
b.c.d,
399
c , e , i
y y
c,q
^* 9 3
c.q
** 5 a
c,h
j * *
c,h
a. Typical range for daytime at northern midlatitudes during the summer.
b. This reaction rate is not well established.
c. Assumed that liquid water volume of aerosol = 50 x 10"12 ms/m3 CSOo) =
10 ppb. ' z
d. Assumed that Mn (II) mass concentration = 20 ng/m3; also, the Mn (II) is
/rMUm?rr^ be uniforn»JY dissolved in the liquid water of the aerosol
([Mn (II)] = 89 x 10 3 M). Rate calculation used the expression of
Neytzell-de Wilde and Taverner (1958).
e. Assumed that Fe (III) mass concentration = 2 ug/m3; also, the Fe (III)
is assumed to be uniformly dissolved in the liquid water of the aerosol
y- ,,.{: ^ ~ °'9 M^- Rate calculation used the expression of Neytzell-
de Wilde and Taverner (1958).
f. Assumed that C mass concentration = 10 ug/m3 and behaves as the soots
studied by Chang et al. (1979), whose expression was used for this
calculation.
g. Rate calculation was based on Equation 2-39, in criteria document
(U.S. Environmental Protection Agency, 1982a).
h. Rate calculation was based on Equation 2-43, in criteria document
(U.S. Environmental Protection Agency, 1982a).
i. Influence of inhibitors has been ignored, but they are likely to suppress
the rate by orders of magnitude.
Source: Adapted from the U.S. Environmental Protection Agency Air Quality
Criteria for Particulate Matter and Sulfur Oxides (1982a).
2-13
-------
TABLE 2-5. AQUEOUS S02 OXIDATION RATES IN THE ATMOSPHERE
Location
K (Percent h"1)*
Reference
Western Washington
(wave clouds)
Western Washington
(clouds)
Los Angeles
(aerosol, summer)
Los Angeles
(aerosol, winter)
Bakersfield (fogs)
0 - 300
-600 ± 1,000 to 1,900 ± 1,900
6.0
2.0
0.9 ± 5.5
Hegg and Hobbs (1981)
Hegg and Hobbs (1982)
Cass (1981)
Cass (1981)
Jacob et al. (1984)
*K is a pseudo first-order rate constant expressing sulfate production as a
percent of [S02(g)].
Source: Adapted from Jacob et al. (1984).
from the Jacob et al. (1984) analyses indicate a need to continue research on
aqueous phase reactions since at present the rates of reaction can range from
<1 percent to >100 percent/h. The application of particular aqueous S02
oxidation mechanisms for particular locations and times of the day requires
further research.
An important conclusion that can be drawn from Table 2-4 is that there
are two types of possible conversion processes. In the presence of catalysts
(Mn, Fe and C) in liquid water droplets, conversion can be very fast. These
are local reactions. These reactions do not require sunglight nor warm
temperatures. Thus these reactions could lead to the production of acid
sulfates in the historic fog episodes in the Meuse Valley, Donora, and London.
They also may be occurring in the European winter episodes, in the Yokkaichi
area of Japan, and on the east coast as reported by Spengler et al. (1986).
In the absence of catalysts, and in the presence of various photochemically
produced radicals, with or without liquid water, the maximum reaction rates are
2% per hour or less. This implies long reaction times and therefore long
distance transport before substantial amounts of acid sulfate are formed. This
is clearly the pathway for most of the summer, and is associated with long
distance transport acid events, such as those observed in the camp studies and
the Ontario hospital admissions studies described in Chapter 6 of this document.
2-14
-------
This distinction is important in evaluating the epidemiologic studies,
as the presence of acid aerosols must be imputed in these studies based upon
the meteorology and assumed pollution mix.
2'2-3-1 Phase Equilibrium. The particles with diameters less than approxi-
mately 2.5 |jm contain most of the SO~2,H+, and NH/, and these particles will
interact more strongly with H20 vapor. The most important sulfate components
are^hose^of H_2S04, NH4HS04 and (NH4)2$04. Most aqueous systems contain H+,
NH4 ; S04 , N03 and Cl and these species are usually present in sufficient
mass to influence the liquid water concentration and the phase transition
points of particles as a function of relative humidity. Presently, phase
diagrams for this multicomponent system are not available for conditions
relevant for tropospheric particles. However, from the Criteria Document
(U.S. ^Environmental Protection Agency, 1982a) the phase diagram for the
H -NH4 -S04 -H20 system at equilibrium is shown in Figure 2-4. In this
diagram, the dry pure crystals of (NH4)2S04, letovicite (NH4)3H(S04)2 and
(NH4)HS04 are indicated as points A, B, and C, respectively. If (NH4)3H(S04)2,
is exposed to relative humidities starting at 0 and increasing to 100 percent,
its behavior can be described in terms of the locus BO in Figure 2-4. From
0 percent relative humidity the salt immediately enters the 3-phase zone
consisting of (NH4)3H(S04)2, (NH4)£S04 and some liquid solution of H+, NH/
and S04 . At point D, the locus intersects a phase boundary for (NH4)3H(S04);>
and a partial deliquescence occurs. Between point D and the intersection with
curve EEp solid (NH4)2S04 remains; however, at the intersection of EE-,, a
second and complete deliquescence occurs. From EE-j^ to point 0, only the
solution phase is present. In similar fashion, equilibrium paths for salts
subjected to various compositions and relative humidities can be traced. The
locus EE2 demonstrates the dependence of the complete deliquescence point
relative humidity on the weight percent of H2$04. As the system's acid compo-
sition changes from 0 to 35 percent, the complete deliquescence point relative
humidity changes from 80 to 39 percent, Thus, NH3 plays a key role in governing
the phase transition points.
The H2S04, (NH4)H(S04), (NH4)3H(S04)2 and (NH4)2$04 particle systems have
been characterized by Char!son et al. (1978), Tang (1976), Tang and Munkelwitz
(1977), and Tang (1980). Charlson et al. (1978) used an apparatus that measured
the light scattering coefficient of the aerosol as a function of the relative
humidity. They obtained good agreement between theory and experiment in observ-
ing the hygroscopic behavior of H2$04. However, they observed no deliquescence
2-15
-------
100
90
(NH^S
a;
O
i
Ul
(NH^HtSO^
B
(NHJ HS04
C
10
20
30 40
WEIGHT %H2SO4
50
70
Figure 2-4. Solubility diagram for the H*-NH/-SO42-H20 system at
equilibrium (30°C).
A = solid phase of (NH^SO,
B = solid phase of (NH^)3H(SO4)2
C = solid phase of (NHJHSO,
/ = liquid solution phase
a1 = fractional relative humidity
y = mole fraction of (NH4)2SO4
The numbers in parentheses are the fractional relative humidities for the complete
deliquescence points that are indicated.
Source: Tang (1980).
2-16
-------
point for NH4HS04 particles, and one at 38 percent r.h. for
particles. Further details are discussed in the Criteria Document (U.S.
Environmental Protection Agency, 1982a).
2.2.4 Formation of Nitric Acid
Formation. The basic 'mechanisms for photochemical smog formation include
the production of a number of free radicals. The primary pathway for the
atmospheric formation of nitric acid involves the OH (hydroxyl) radical which
is produced within the smog cycle. The reaction is:
OH + N02
HN03 (Tsang et al., 1977)
This reaction can occur in the general urban environment or downwind of power
plant plumes (U.S. Environmental Protection Agency, 1982b).
Another possible mechanism for the formation of nitric acid involves the
reaction of dinitrogen pentoxide (N20g) with water. The formation of N^Og
results from the reaction of Og with N02 according to the following:
N02
N03 + N02
N0
then in the presence of water:
N0
25
H20
2HNO,
Nitric acid formation mechanisms associated with nighttime chemistry
include nitrate radical reactions with aldehydes or alkanes (Russell et al.,
1986).
Nitric acid is a volatile acid, so that under ambient conditions it is a
vapor. The vapor will coalesce into a particle if it is neutralized by ammonia
to produce ammonium nitrate salt according to:
NH3(g) + HN03(g)
NH4N03(s)
2-17
-------
Details on this reaction equilibrium are found in Stelson et al. (1979).
This equilibrium is very sensitive to the temperature, such that for the range
from 20 to 30°C the mass concentration of the gas phase specie will increase
by greater than a factor for 3.
2.2.5 Neutralization
A key factor in determining the persistence of atmosphere acid sulfate
species is the potential for ammonia neutralization, which is controlled by the
reaction of ammonia with sulfuric acid, and the formation of ammonium salts
(NH.HSO. and (NH.VSO,). The principal sources of environmental ammonia appear
to be animals and humans, although there can also be significant contributions
from fertilizer manufacturing. For both animals and humans, the emissions are
primarily a result of excretion through the skin or from urea. Animals are
probably a much larger source due to the sewage treatment of human excrement.
The results of a regional mapping of domestic animal (cattle and pigs) and
human ammonium emissions by Husar (1982) are shown in Figures 2-5 and 2-6. The
regional distributions are quite different, with the animal ammonium emissions
centered in the midwestern U.S. and the human emissions keyed to the major
population centers. Husar and Holloway (1983) also added the emissions inven-
tory for fertilizer production and the final emissions estimates for ammonium
are shown in Figure 2-7. These emission estimates suggest that ammonia neutral-
ization will be dependent upon the land areas over which a sulfuric acid-laden
air mass travels, and whether the air mass is in contact with the surface.
At present, there are very few measurements of ammonia, but there are data
on the NHt ion, and usually these are linked to measurements of sulfate ion.
— O
One comprehensive study of SO. was the Sulfate Regional Experiment (SURE)
(Mueller and Hidy, 1983) which included measurements of these two ions for
nine sites in the eastern U.S. over a two-year period. The mass ratio of
SOT2/NHt was calculated for all sites, and the frequency of occurrence suggested
that 40 percent of the samples were a mixture of ammonium salts and 60 percent
could have contained free sulfuric acid. A scatter diagram from the SURE
(Mueller and Hidy, 1983) of the Hi-Vol mass ratio of SO~2/NH* versus sulfate
concentration is shown in Figure 2-8. (Please note that since these data were
taken with a high volume sampler, artifact formation could occur. They should
only be interpreted in a qualitative manner.) The distribution of the data
suggests that the highest percentages of acids are probably associated with
2-18
-------
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c\j in
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o
a
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i
I £
a a>
9
u.
2-19
-------
POPULRTION
*
Do. 10-0.25
Ho. 25-0. SO
Ho. 50-0.75
• >0.75
Figure 2-6. Annual average N-NH; emissions from humans.
Source: Husar (1982).
2-20
-------
in o in
c\j in r~
a
m
S
o
£
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2-21
-------
40
30
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en
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'vK v.. \ . *'
• [•*••».
....\ • «\« • ••»»
10
ACIDIC SPECIES-
(H2SO4 AND
AMMONIUM
ACID SALTS)
AMMONIUM
ACID SALTS'
I
10
20 30 40
SULFATE CONCENTRATION, /ug/m3
50
60
Figure 2-8. Scatter diagram of sulffate to ammonium mass concentration ratios as a
function of sulfate concentration for high volume samples. (Please note that these data
were taken with a high volume sampler, artifact formation could occur. They should
only be interpreted in a qualitative manner.)
Source: Muller and Hidy (1983).
2-22
-------
relatively low sulfate concentrations (5-10 ug/m ) and not with the extremely
high sulfate concentrations that are usually measured during the intense
portions of a photochemical smog episode. There are exceptions since acid
concentrations can reach in excess of 20 jjg/m .
Studies that have measured strong acid aerosol acidity directly have shown
+ -2 -2
that the highest H /SO. ratios will occur at the lowest SO, concentrations
(Pierson et al., 1980b; Keeler, 1987; and Morandi et a!., 1983). Since the
_2
percentage of acid sulfate species is lower with higher SO. , it could be
hypothesized that during the accumulation of sulfate during events the acid
species will have more time for contact with ammonia emissions and be subject
to neutralization reactions.
Morandi et al. (1983) examined the local character of the distribution of
acid species for a regional smog episode from August 27 through 29, 1980
(Table 2-6). It can be seen that the most acidic portion of this photochemical
episode occurred at the beginning and that with time the acidity decreased. In
a follow-up study at Fairview Lake, N.J. it was observed by Lioy et al. (1987)
that in the period from July 31 through August 3, 1984 the acid aerosol was
composed primarily of apparent NH.HSO. (based on calculations not measurements).
During the last day of this period, however, the levels of H9SOA increased from
3
approximately zero to 4 ug/m for 4 h in the afternoon. The conditions
described above for acid species accumulation must be examined more fully to
identify the distribution of possible situations when high values of acidic
species could be present in the atmosphere. Such research would include iden-
tifying the physical-chemical processes that contribute to the accumulation of
acidic species (e.g., free radical concentrations in summertime episodes,
plume downwash in nocturnal inversions or the breakup of nocturnal inversions
in the morning).
2.3 EMISSION DENSITIES AND DISTRIBUTION
2.3.1 Sulfur and Nitrogen Oxide Emission Densities
In the Eastern half of the United States, sulfur dioxide emissions are
highest in the area within the Ohio Valley from the .Mississippi River through
Southwestern PA, see Figure 2-9; This core area is surrounded with rural
and urban centers that have significant S02 emissions. In contrast, nitrogen
oxide emissions in the east are centered in the metropolitan corridor of
2-23
-------
TABLE 2-6. ESTIMATED H2S04 (NH4)HS04 AND (NH4)2S04 CONCENTRATIONS BASED
ON THERMAL ANALYSIS FLAME PHOTOMETRIC DETECTOR AND QUARTZ FILTER
MEASUREMENTS AT STERLING FOREST DURING THE
AUGUST 27 THROUGH 30, 1980 EVENT.
Date
27 Aug
28 Aug
29 Aug
Time
1980
1980
1980
09:15
09:15
09:15
- 21:15
- 21:15
- 16:05
H2S04*
5.2 ± 1.3
5.4 ± 1.3
1.3 ± 1.0
% NH4H(S04)* %
30
19
10
13.4
11.9
1.0
± 3.5
± 3.0
± 0.9
70
43
8
(NH4)2S04* %
10.5
11.0
± 1.5
± 4.1
38
82
tAs percent of total S042.
*umoles of S042/m3xlO~2.
Source: Morandi et al. (1983).
New York, New Jersey and Connecticut and the major urban areas such as Chicago
and Detroit, see Figure 2-10. The distribution of nitrogen oxide emissions is
more uniform throughout the country than is that of sulfur dioxide.
In the western half of the nation, S02 emissions are centered in specific
areas related to large stationary sources such as smelters. The nitrogen
oxides emissions in the west are distributed much more broadly and the actual
emission densities are much lower in specific instances.
2.3.2 Sulfate Distribution
Many studies and monitoring programs have routinely provided data on the
sulfate ion, which is relatively easy to measure and is a major constituent in
the ambient aerosol. Acid sulfate species represent the principal component of
most acid aerosols. Thus while the animal toxicology and human clinical
studies in this document provide data that strongly suggest that the health
effects are related to the hydrogen ion rather than the sulfate ion, sulfate
levels should correlate to some degree with acid aerosol levels.
Presence of high sulfate does not necessarily indicate the presence of a
highly acidic component in the sulfate aerosol. Examination of the extent to
which sulfate can be distributed in the environment does give some indication
of the possible spatial extent of acid sulfate in the worst possible case (i.e.,
little neutralization). The most extensive data base on the regional nature
of sulfate in the Eastern U.S. was acquired during the SURE Project.
~2
Figure 2-11 shows the monthly average SO, ' concentrations and the change over
2-24
-------
<100
100-500
500-1000
>1000
SCALE, km
250
Figure 2-9. Distribution of SO2 emissions in the SURE area tor summer (metric tons/day).
Emissions are based on data representative of 1977.
Source: Mueller and Hidy (1983).
2-25
-------
<100
100-500
500-1000
>1000
SCALE, km
250
Figure 2-10. Distribution of NOZ emissions in the SURE area for summer (metric tons/day).
Emissions are based on data representative of 1977.
Source: Mueller and HMy (1983).
2-26
-------
AUGUST, 1977
OCTOBER, 1977
JAN/FEB, 1978
APRIL, 1978
JULY, 1978
OCTOBER, 1978
804, /ng/m3
Figure 2-11. Monthly average distribution of 24-hour HIVOL paniculate sulfate concentrations
in the eastern United States.
Source: Mueller and Hidy (1983).
2-27
-------
the course of a year of the magnitude and the spatial extent of such concentra-
tions. The data also indicate that a significant portion of the Eastern U.S.
3
experiences average sulfate levels above 8 pg/m during the summer.
3
The peak sulfate values recorded in SURE were in excess of 25 ug/m at
most of their class I monitoring sites during the summer with lower values
found during the winter. The higher concentrations shifted to the southeast
during the winter. In the Airborne Toxic Elements and Organic Substances
(ATEOS) study conducted at four sites in New Jersey (Newark, Elizabeth, Camden,
o
Ringwood) during 1981-1983, mean values of approximately 10 ug/m were observed
3
at each site (Lioy and Daisey, 1986). Sulfate excursions were above 30 ug/m
3
during the summer, and above 20 pg/m on a few occasions during the winter.
The Particulate Matter - Sulfur Oxides Criteria document (U.S. Environmental
Protection Agency, 1982a) states that on the West Coast the area around Los
3
Angeles has annual average sulfate values above 8 pg/m . Hidy (1986) published
—2 3
data indicating a peak concentration of SO, of 24.3 pg/m in Los Angeles in
1977.
_2
The regional relationship between SO, and S0? present at the SURE
monitoring sites was examined using the ratio of sulfate sulfur to total
_2
airborne sulfur (SO. and S02). The results for each season are shown in
Figure 2-12. These findings indicate that the seasonal average of the
_o
SO. /Total S ratio for summer was much higher than ratios for the winter.
During the winter, the ratios were substantially lower in the northern part of
the SURE study area than in the southern and the coastal sections. ' These
differences were consistent with the expectation of both greater rates of
S02 conversion to S0~ and greater losses by dry deposition of S02 during the
summer months and in the south during winter months. During any of the seasons,
the maximum ratios usually occurred within 80 to 200 km of the major source
areas. The authors indicate that most of the conversion to SO
-2
or S02 dry
deposition were associated with mesoscale meteorology even during regional
sulfate events because the ratios declined with distances greater than 100 km.
This latter point suggests that concentrations of the acidic portion of the
_0
SO. aerosol may be enhanced in areas downwind of urban or stationary source
plumes. The work of Gillani (see Section 2.2.3) was strongly suggestive of the
formation of sulfur aerosol in a variety of plume conditions.
2-28
-------
50
'40
SUMMER
AUGUST, 1977
FALL
•f ° OCTOBER, 1977
\ / 0500-1000
-
WINTER
JAN/FEB, 1978
SPRING
APRIL, 1978
SUMMER
-30 JULY, 1978
10
FALL
OCTOBER, 1978
Figure 2-12. Geographical distribution of the ratio of sulfate sulfur to total airborne sulfur
for different seasonal periods (in percent).
Source: Mueller and Hidy (1983).
2-29
-------
2.4 METHODOLOGY FOR STRONG ACID MEASUREMENT
Atmospheric strong acids consist principally of sulfuric and nitric acids
derived from the oxidation of sulfur dioxide and nitrogen oxides emitted from
stationary and for NO mobile combustion sources (National Research Council,
/\
1983). Some evidence suggests that hydrochloric acid (HC1) may also be present
in the atmosphere (Rahn et a!., 1979) derived from primary, coal-fired utility
emissions or evolved due to interactions between sea salt and acidic sulfate
aerosols. Emissions of HC1 from municipal refuse energy recovery systems
(Rollins and Homolyn, 1979) and incineration of hospital waste (Allen et al.,
1986) have been measured. The acid species are neutralized principally by
atmospheric gaseous ammonia (the latter mostly originated from surface biogenic
and anthropogenic sources) and soil-derived particulate matter to produce the
composition of sulfate and nitrate aerosols and levels of nitric acid measured
in the atmosphere (Brosset et al., 1975; National Research Council, 1977).
Research efforts in progress on acid species are dependent on the develop-
ment and application in the last 10 to 20 years of techniques for rapid,
accurate, microscale determination of total strong acid and of individual
acidic species in atmospheric aerosol and gaseous samples. This section
details these technical developments, concentrating largely on acidic aerosols;
although, a brief section is provided on nitric acid measurements. These
techniques consist mostly of filter-based schemes but with some continuous
and/or real-time approaches. Sampling/analysis protocols are recommended that
minimize analytical complications.
2.4.1 Methodologies for Strong Acids and Sulfuric Acids
Descriptions of methodologies for strong acids in aerosols are arranged
according to the measurement principle: filter collection and post-collection
extraction, derivatization and analysis, or real-time, in situ analysis—and
further segregated according to whether total aerosol strong acid content is
measured or individual species are determined.
2.4.1.1 Sulfuric Acid
2.4.1.1.1 Filter collection. Thermal volatilization schemes were popular for
several years for speciation of acidic sulfate compounds in aerosols. Filter
samples were heated and HUSO, collected by microdiffusion (Scaringelli and
Rehme, 1969; DuBois et al., 1969) or determined directly by flame photometry
after volatilization from Teflon filters (Richards and Mudgett, 1974; Richards
2-30
-------
et al., 1978). In one method, H2S04 was distinguished from other volatile
sulfates (e.g., NH4HS04 and (NH4)2S04), and nonvolatile sulfates (e.g.,
Na2S04) by heating in sequence at two different temperatures (Leahy et al.,
1975). In another approach, 2-perimidinylammonium sulfate was formed from acid
sulfates and thermally decomposed to S02 for West-Gaeke analysis (Maddalone
et al., 1974).
These methodologies were attempts to analyze acidic sulfate aerosols for
individual species. However, due to serious recovery problems (Leahy et al.,
1975) and limited success in distinguishing the two major aerosol species
(NH4HS04 and (NH4)2$04) from each other (Thomas et al., 1976), the methods have
fallen into disfavor with three exceptions. One technique uses a temperature-
cycled diffusion denuder tube in connection with a real-time flame photometric
detector (FPD) to determine H2$04 in ambient aerosols (Tanner et al., 1980;
Allen et al., 1984). A related technique uses a series of denuder tubes at
varying temperatures to collect nitric acid, sulfuric acid and bisulfate
constituents separately for integrated analysis with several-hour time resolu-
tion (Slanina et al., 1981). Recently the heated denuder system has been mated
with a flame photometric detector to produce a computer-controlled system for
H2S04, ammonium acid sulfates and nonvolatile sulfate with time resolution of
5 min to 1 h depending on requisite sensitivity (Slanina et al., 1985). A
photoionization detector has also been used for the determination of HUS04
after preconcentration in a denuder and gas chromatographic separation
(Lindqvist, 1985). A related technique determines nitric acid by denuder tube
collection with subsequent decomposition to NO and determination by ozone-
/\
chemiluminescence (Klockow et al., 1982).
2.4.1.1.2 Extraction with pH measurement or H titration. Filter-collected
samples may be analyzed for net strong acid content by extraction into water or
dilute mineral acid. The extracted free acid content may be determined by
simple measurement of, pH and, in the absence of weak acids, equated to the
amount of strong acid originally present in the sample. However, this determi-
nation can be in error because of the potential presence of buffering agents
such as weak carboxylic acids or hydrated forms of heavy metal ions; e.g.,
Fe(III) and Al(III) (Commins, 1963; Junge and Scheich, 1971).
Titration procedures for strong acid employing a logarithmic display of
data points (Gran titration) were originated by Junge and Scheich (1971)
perfected by Brosset and co-workers (Brosset and Perm, 1978; Askne and Brosset,
2-31
-------
1972), and used widely by other groups (Stevens et al., 1978; and Liberti
et al., 1972). Coulometric generation of strong base for Gran titrations has
been used by several groups (Liberti et al., 1972; Krupa et al., 1976; Tanner
et al., 1977). Dissolution of filter samples in 0.1 mM mineral acid followed
by Gran titration with correction for the blank (Tanner et al., 1977) allows
for titration of 1 pmole levels of strong acid with precision and accuracy
better than ±10 percent (Stevens et al., 1978; Phillips et al., 1984).
The presence of partially dissociated weak acids, i.e., with pkgs (the
negative of the ionization constant of the acid) in the range of the aqueous
extract of aerosols can lead to overestimates of strong acid content (Lee and
Brosset, 1978). The extent of this error source was discussed by Keene and
Galloway (1985) for precipitation samples in which weak acids were preserved
from microbial decomposition. Standard protocols for aerosol collection and
strong acid determination do not include preservation, which explains the
absence of significant quantities of weak acids in atmospheric aerosol samples
(Ferek et al., 1983) and validates the use of Gran titration approaches with
continuous addition of titrant for strong acid quantisation in those samples.
2.4.1.1.3 Specific extraction of atmospheric acids. Most of the effort in
specific extraction of atmospheric acids has been related to aerosol I^SO^
analysis. Benzaldehyde has been shown to be specific for H^SO^ in dried
acidic aerosol sulfate/nitrate samples with analysis for sulfate in aqueous
back-extracts (Leahy et al., 1975). Isopropanol (Barton and McAdie, 1971)
quantitatively extracts H2SO. from quartz filter media but also removes
ammonium bisulfate phases (Leahy et al., 1975). The behavior of isopropanol
as an extractant is not well characterized for mixed nitrate/sulfate aerosols.
In addition, difficulties have been reported with quantitative removal and
selectivity of extraction using the benzaldehyde extraction technique (Appel
et al., 1980; Eatough et al., 1978). Since free H£S04 is not a common con-
stituent of ambient aerosols, use of specific extractant methodologies has
decreased in recent years in favor of generic strong acid determinations.
2.4.1.1.4 Specific extraction with derivatization. A method has been proposed
for derivatization of collected H2S04 by dry diethylamine followed by reaction
with CS? and cupric ion to form a colored complex for spectrophotometric deter-
mination (Huygen, 1975). This method suffers from a large ammonium bisulfate
interference. Likewise an approach in which filter-collected H2S04 is con-
verted to dimethylsulfate by reaction with diazomethane, with subsequent
2-32
-------
analysis by gas chromatography-flame photometric detection, does not specifi-
cally determine H2$04 in the presence of ammonium bisulfate and sulfate salts
(Penzhorn and Filby, 1976; Tanner and Fajer, 1981). A related method, by which
H2S04 and other aerosol strong acids are converted to 14C-labelled bis(diethyl-
ammonium) sulfate and analogs, is useful for determination of low levels of
strong acid in aerosols (Dzubay et al., 1979), but is also not specific for
H2S04.
2.4.1.1.5 Continuous and/or real-time analysis. Sulfuric acid may be deter-
mined using a continuous flame photometric detector (FPD) although such measure-
ment is not real-time and represents an average concentration over a few-minute
period (Tanner et al., 1980; Allen et al., 1984; Slanina et al., 1985). The
technique uses a diffusion denuder tube for S02 removal attached to an FPD,
identical to the instrumentation for a continuous aerosol sulfur analyzer as
described by a few groups (Huntzicker et al., 1978; Cobourn et al., 1978; Camp
et al., 1982; Morandi et al., 1983). However, the temperature of the denuder
tube or a zone just upstream therefrom is cycled between room temperature and
about 120°C. At ambient temperatures sulfuric acid remains in the aerosol
phase, but at 120°C, it is volatilized and removed in the denuder tube. The
difference in response between ambient temperatures and 120° represents ambient
H2S04 levels- The minimum cycle time and hence time resolution for the tech-
nique is about 6-8 min. Sensitivity-enhanced FPD measurements using SFg-doped
H2 fuel gas are required for ambient measurements (D'Ottavio et al., 1981).
Acidic sulfates including sulfuric acid may also be inferred using
humidograph techniques (Charlson et al., 1974) and recently developed
thermidograph variations (Larson et al., 1982; Rood et al., 1985). This latter
technique involves heating the aerosol-containing air stream progressively from
20°C to 380°C in 5 min cycles, rapidly cooling it to the dry bulb temperature
and measuring the light scattering at 65 to 70 percent RH with a nephelometer.
By comparing the results with the thermidograms of test aerosols, the frac-
tional acidity can be measured and level of H^SO. estimated.
The fraction of acidity in sulfate can also be determined using an
impactor: attenuated total reflectance (ATR), Fourier-transform infrared
(FTIR), spectroscopic technique (Cunningham and Johnson, 1976). Impactor
samples are pressed into a KBr matrix and the IR spectrum used to determine
the relative acid and qualitatively identify aerosols with molar H+/S072
ratios >1, the condition for the presence of HUSO, in the aerosol samples.
2-33
-------
2.4.1.2 Nitric Acid
2.4.1.2.1 Nitric acid sampling techniques. A summary of techniques presently
employed in nitric acid sampling is found in Table 2-7 (Stevens, 1986). All
are filter techniques that can include multiple hour or multiple day samples.
Research grade instrumental HN03 samplers are available that use chemilumi- .
nescence, tunable diode laser infrared spectroscopy, or Fourier transform
infrared spectroscopy as the operating principle.
Unlike the situation for acid sulfates, nitric acid technique intercom-
parisons were made in the Claremont, CA intercomparison study (Spicer et a!.,
1982). This particular intercomparison did not include the annular denuder
system described in Table 2-7. A second intercomparison involving eighteen
instruments was conducted at Pomona College, CA during September, 1985 (Hering
et al., 1988). The results from this particular experiment reported nitric
acid values that varied by a factor of two or more on all sampling days with
the differences increasing with loading. It appears that the technology for
making accurate nitric acid determinations still requires further examination
and testing before the development of a reference method can proceed.
2.4.2 Sampling Anomalies
Sampling anomalies have plagued the measurement technologies for atmo-
spheric strong acids present in the gas phase or as aerosols, justifying a
separate section on the nature of these artifact problems and suggested
sampling techniques to minimize their effects. These sampling problems
generally fall into two classes: (1) reversible or irreversible sorption
losses onto filter materials in integrative methodologies or onto sampling
lines in continuous and real-time techniques; (2) equilibrium-driven loss or
gain of species due to non-steady-state conditions in the sampled atmosphere
over the time period of the measurement. Both of these phenomena affect
sampling/analysis techniques for strong acids in the atmosphere and are
discussed below.
2.4.2.1 Sorption Losses. Studies of sorption losses on filters have centered
on three major areas related to measurement of strong acid content in atmos-
pheric samples. One area is the loss of strong acid in aerosol particles by
reaction with basic sites in the filter matrix used to collect the particles
(Appel et al., 1979). Filter matrices used for high-volume sampling include
glass fiber or cellulose. These media, particularly glass fiber filters of all
2-34
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types, are unsuitable for collection of acidic aerosol particles for subsequent
extraction and titrimetry (Tanner et al., 1977; Appel et a!., 1979; Coutant,
1977). This is true even if the glass fiber filters are pretreated with acid
as well as fired to high temperature, since subsequent rinsing exposes addi-
tional free basic sites in the glass, resulting in neutralization of the sample
(Tanner et al., 1977). High-purity quartz filters can be pretreated to remove
basic sites for high-volume sampling, hence, treated quartz and Teflon filter
media have generally replaced glass fiber or cellulose filters for sampling of
acid aerosols by high-volume and low-volume techniques, respectively.
The filter treatments described above also eliminate a positive source of
error in sulfate measurements - the artifact sulfate formed by base-catalyzed
oxidation of S02 (sorbed on the filter surface) to form sulfuric acid (Coutant,
1977; Pierson et al., 1976; Pierson et al., 1980a). The acid so formed is
neutralized on the filter surface, but the residual sulfate remains and is
measured using standard extraction/analysis techniques.
A third problem is the loss of strong acid contents by topochemical reac-
tions between co-collected basic and acidic particles on the filter surface.
This most frequently occurs as the result of coarse (>2.5 urn), alkaline, soil
derived particles interacting with fine (<2.5 jjm), acidic sulfate particles
(Camp, 1980; Spicer et al., 1978; Tanner et al., 1979). This problem can be
eliminated by sampling with a dichotomous sampler, by high-volume or low-volume
sampling with a cyclone to remove coarse particles, or by sampling for shorter
time durations. In connection with the latter solution, sampling in most
ambient environments for <3 h results in low enough surface coverage to prevent
topochemical reactions, but this procedure does not prevent neutralization
during subsequent extraction procedures. Carefully designed handling procedures
are required.
2.4.2.2 Equilibria-Driven Losses. Equilibria involving gas- and particulate-
phase species may lead to artifactual errors in sampling strong acids as well
as other species in the atmosphere under both steady-state and non-steady-state
conditions. Thermodynamic considerations suggest that aerosol sulfuric acid/
sulfate mixtures should be in dynamic equilibrium with atmospheric ammonia
(Lee and Brosset, 1979). Indeed, as noted initially, ammonia is believed to be
the principal neutralizing agent for sulfuric acid formed by heterogenous or
homogenous oxidation of SCy However, the equilibrium level of NH3 for even
slightly acid sulfate is much below the usually observed ambient NH3 levels.
2-36
-------
jThis suggests that a non-steady-state, mixing-limited situation normally exist
(Appel et al., 1979) or, alternatively, that mixed nitrate/sulfate salts are
usually present with their concomitantly much greater equilibrium NH3 concen-
trations. However, each of these needs confirmation since NH3 at high
^concentrations could include artifacts in that once acids are collected on
sfilters other processes can contribute to the loss of aerosol hydrogen ion.
This includes vaporization of NH^NOj and then the abstraction of the H+ to form
HN03, or the conversion of NH4C1 do HC1.
2.4.3 Suggested Protocols
2.4.3.1 Strong Acid Aerosols. The discussion above indicates that a method
for analysis of strong acid in aerosols is collection on inert filter media,
Ultrasonic extraction into weak acid (ca. 0.1 mM) and titration with base using
a Gran plot to determine the equivalency point. In some cases a pH measurement
of the extract can be sufficient. For sampling periods longer than a few hours
(depending on ambient levels), a virtual impactor-based sampler or annular
denuder system that collects particles on Teflon filter media could be used.
With shorter term sampling high-volume apparatus with acid-treated quartz
filters and a cyclone pre-separator for coarse particle removal can be used.
Automation of the titration procedure using coulometric generation of hydroxide
is a practical necessity when large numbers of samples must be processed.
Precision and accuracy approaching ±10 percent is possible with careful flow
calibration and for sample sizes exceeding 0.5 ueq (>25 ug as H2SO«) (Phillips
et al., 1984). All samples must be collected using pre-separator denuders to
eliminate artifact formation or neutralization of acidic species by gases on
the collected samples.
2.4.3.2 Specific Determination of H?SO.. No method is fully satisfactory for
determining the low levels of HpSO* occasionally found in ambient aerosols.
Two approaches that may be used with reasonable success are the following.
Filter pack samples, collected on treated quartz filters that are then
thoroughly dried over desiccant, may be extracted into benzaldehyde, the
sulfate therein then back-extracted into water and determined by ion chroma-
tography or other soluble sulfate methodologies (Leahy et al., 1975; Tanner
et al., 1977). Careful drying of the filter is required, as noted above, to
prevent significant interference from ammonium bisulfate (usually present in
excess of H2SO«); in addition an impurity, benzoic acid, in the benzaldehyde
2-37
-------
may be present in amounts sufficient to interfere with ion chromatography or
other sulfate determinations. Sulfuric acid may also be determined by flame
photometry using a temperature-cycled diffusion denuder tube (Tanner et al.,
1980; Allen et al., 1984). Time resolution is limited by the minimum tempera-
ture cycle time of the denuder (5 to 10 min) and is quite adequate. However,
rt
the limit of detection, only about 1 ug/m H2$04 even with sensitivity enhance-
ment through use of SFg -doped H2 unless denuder concentration is used (Slanina
et al., 1985), is not adequate for many ambient applications. Direct denuder
tube collection of H2$04 in heated denuders is a viable alternative. The time
resolution is several hours if extraction and wet chemical analysis is used due
to the necessarily slow flow rate through denuder tubes.
2.4.4 Applications
The results from studies that have been conducted during the past 12 years
on strong acid sulfate and sulfuric acid are reported in the next section.
These studies have used a variety of quasi-continuous and integrated sampling
methods. Only the most recent studies have systematically used approaches
similar to those suggested in Section 2.4.3. The development of the suggested
techniques represent the advancements made by individual investigators. No
organized program exists to develop techniques; nor is any program currently in
place that evaluates the relative uncertainties of the methods employed in the
individual studies. Efforts to examine the national exposure to acidic aerosol
will require the development of a quality assurance program and a program to
examine which train of pre-collection devices (impactor and denuders) will be
necessary to minimize alteration of the acid concentration actually present in
the atmosphere.
2.5 HISTORIC ACID LEVELS
2.5.1 London Sulfuric Acid Data
A relationship between air pollution and mortality/morbidity was recognized
in England, especially after the severe London fog episode of December 5-8,
1952. Although sulfuric acid was considered one of the pollutants possibly
responsible for the increased mortality and morbidity (United Kingdom Ministry
of Health, 1954), routine air pollution monitoring conducted by local authori-
ties and other regulatory bodies did not have data for sulfuric acid. Some
2-38
-------
inferential information was available to implicate acids, however, from samples
collected in London on five consecutive days in 1934 (Mader et al., 1950).
Seven to 9.5 h average of apparent sulfuric acid concentrations were measured
that ranged from 0 to 148 ug/m3.
Following the episode, the Air Pollution Research Unit at St. Bartholomew's
Hospital started an elaborate research program on air pollution (Commins and
Waller, 1967). Their daily measurement of British Smoke and S02 started in
January 1954. The concentrations of some other pollutants, including sulfuric
acid calculated from net aerosol acidity, were also measured during episodes
and, later, on a daily basis. In their ten years of air pollution measurements
(1954-1964), sulfuric acid measurements were reported for episodes starting in
the winter of 1957/1958. The highest daily and highest hourly apparent
sulfuric acid concentrations recorded were 347 ug/m3 and 678 ug/m3, respec-
tively, on days in December 1962. The daily measurement of sulfuric acid was
begun during April 1963 (Figure 2-13). It was noted that the sampling site at
the Medical College was in a commercial area and that much of the sulfur
dioxide came from central heating installations in commercial buildings
(Commins and Waller, 1967).
The analytical method for the aerosol acidity measurements was reported in
detail by Commins (1963). The total particulate matter from the sampled air
was collected by filtration, and the filters were immersed in a known excess of
0.01 N sodium tetraborate and titrated back to pH 7 with 0.01 N sulfuric acid.
This procedure allowed the sodium tetraborate to neutralize the acid before it
was neutralized by the insoluble base on the filter (interference). The
interferences by acidic gases, basic gases; and other particulate acids were
reported to be negligible. These data still must be reviewed with caution
since artifact formation was likely to occur on these samples. There was no
fine particle size selection or denuders to eliminate NH3 or S02 which could
result in excess acid formation or neutralization depending upon the concentra-
tions present.
The daily apparent aerosol acidity values are plotted in Figure 2-13 and
averages, standard deviations, and maximums for years and winter months
(November 1 through February 29) are noted. It can be seen in Figure 2-13 that
H concentration was usually highest during the winter, probably due to
increased heating fuel usage and adverse meteorological conditions.
2-39
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2-40
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2.5.2 Los Angeles Data
In 1949 a study was conducted in Los Angeles, California to determine the
amount of free sulfuric acid in the atmosphere during periods of intense fog
and on clear days (Mader et al., 1950). The results for four separate 1-hour
sampling periods indicated a range in concentration from 0 to 157 pg/m3. There
O
were two days with levels above 150 ng/m and each occurred on a day with high
relative humidity.
2.6 ATMOSPHERIC CONCENTRATION
2.6.1 Atmospheric Acidic Sulfate Studies from 1974 to 1986
Results of field investigations of the surface concentration of acidic
sulfate species in the United States and Canada since 1974 are shown in
Table 2-8. A variety of sampling strategies and analytical methods were used,
and the individual sampling times ranged from 1 to 24 hours. In all cases that
used filter collection, no glass fiber filters were used to collect aerosols.
In some cases the sampling device collected lower volumes with pre-particle
selection. But in only the more recent studies were ammonia denuder systems
employed on a regular basis. Thus all filter results could be underestimates
of the actual H present. Similarly, the thermal analysis flame photometric
detector system only measured H2S04.
Most of the studies reported in Table 2-8 were conducted during the
summer. This is the season when large scale regional ozone and SOT smog
episodes, which last at least three days, can or have occurred in the eastern
U.S. and Canada (Wolff and Lioy, 1980; Wolff et al. , 1981). In addition,
photochemical smog episodes frequently occur in Los Angeles, CA (Hidy et al.,
1980) and Houston, TX (Beck and Tannahill, 1978). The magnitude of the winter-
time levels of acid sulfate species were derived from a more limited data base,
which is also described in Table 2-8. Spengler et al. (1989) reports daily
concentrations of H ion for a minimum of nine consecutive months in four
United States cities that show a seasonal pattern with lower concentrations in
the winter and higher levels in the summer months.
The ranges of S0~2, H+ (as H2$04) and/or H2S04 concentrations recorded in
these studies are shown in Table 2-9. It is apparent that a wide range of
S04 values were encountered in acid aerosol studies with the peak concentra-
tion being 75 |jg/m for an 8 h period in Toronto, Canada (Waldman et al. , 1988).
2-41
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TABLE 2-9. CONCENTRATION RANGES OF SO?, H+
(in ug/m3) MEASURED IN VARIOUS LOCATIONS
(as H2S04) AND H2S04
IN NORTH AMERICA
Sample
Duration
Study Hours
Glasgow, IL
1977
St. Louis, MO
1977 Summer
1978 Winter
Lennox, CA
Smokey Mountains
High Point, NJ
Brookhaven, NY
RTP, NC
Allegheny Mt, PA
Shenandoah
Valley, VA
Tuxedo, NY
Mendham, NJ
Houston, TX
New York City
St. Louis, MO
St. Louis, MO
Los Angeles, CA
Harriman, TN
Watertown, MA
Fairview Lake,
NJ
Warren, MI
12
1
1
2-8
12
6
3
2,4
12
12
1-12
4,20
12
6
QC
QC
12
QC
QC
QC,4
24
Concentration
Range ug/m3)
SO?
- 7-48
5-60
3-24
1.2-18
6.2-17.4
3.0-36.6
1.0-23.7
3.6-19.8
1-32.5
2-40
1-41
1-37.3
2-32.4
3-28
3-25
<5-43
3-10
9-47
5-31
13-27
.4-36.7
H2S04
0-39
0-28
0-12
0-11
2.8-9.6
2.2-17.8
0.3-10.2
0-9.8
0-20
0-23
1-8.7
0-6.3
0-7.6
nm
0-7
0-34
0.6-3.2
0-18
0-14
0-12
.8-8.7
Reference
Tanner and Marlow (1977)
Cobourn (1979)
Cobourn and Husar (1982)
Appel et al. (1982)
Stevens et al. (1980)
Lioy et al. (1980)
Lioy et al. (1980)
Stevens et al. (1978)
Pierson et al. (1980b)
Stevens (1983)
Morandi et al. (1983)
Lioy and Lippmann (1986)
Stevens (1983)
Lioy et al. (1980)
Huntzicker et al. (1984)
Ferris and Spengler (1985)
John et al. (1985)
Spengler et al. (1986)
Spengler et al. (1986)
Lioy and Lippmann (1986)
Cadle (1985)
(continued on the following page)
2-44
-------
TABLE 2-9. (continued)
Study
Whiteface Mt. ,
MW
Sample
Duration
Hours
24
Concentration
Range (ug/m3)
S042 H2S04
0-58.9 0-14
Reference
Kelly et al. (1985)
Nova Scotia
24
Toronto, Canada 8,16
Allegheny Mt., PA 7,10
Laurel Mt., PA 7,10
0-26 0-9 Smith-Palmer and Wentzell
(1986)
0-75 0-19.4 Waldman et al. (1988)
1.7-45.4 0.4-30.5 Pierson et al. (1989)
2.2-55.5 0.5-42.0 Pierson et al. (1989)
nm, not measurable
QC, quasi-continuous
-2
At other times, each study recorded S04 decreases to as low as 0-2 fjg/m .
The peak H2S04 value, measured with a flame photometric detector (FPD), was
41 |jg/m (1 h average) in 1984 at a site in St. Louis, MO (Ferris and Spengler,
1985).
4. o
A H concentration (as equivalent H2S04) of 39 |jg/m was observed in 1975
just northeast of St. Louis in Glasgow, IL (Tanner and Marlow, 1977). The
features of the Glasgow data were: (1) the H+ was measured in the fine particle
size range; (2) the measurements were 12 hour duration samples, and (3) the
visibility maps indicate the development of an urban plume from St. Louis. A
comparison of the {H+}/({H+} + {NH4+}) ratio on July 29, 1975 indicated that
the aerosol in Glasgow, IL contained both NH4HS04 and H2S04.
A number of other studies also indicated the presence of both H2S04 and
NH4HS04 species (Tanner and Marlow, 1977; Morandi et al., 1983; Huntzicker et
al., 1984; Lioy and Lippmann, 1986). Pierson et al. (1989) completed a study
at both Allegheny Mountain and Laurel Mountain in 1983 with observed peak H+
(as apparent H2S04) concentrations of 30.4 and 42.0 jjg/m3 at the respective
sites.
As stated previously, work by Morandi et al. (1983) included an attempt
to infer the distribution of acidic species from coincident instrumental FPD
measurements of H2S04 and filter analyses for H+. The results of that study
indicated there was no evidence of the presence of any strong acids (pka <2)
2-45
-------
other than NH4HS04 or H2$04. On the basis of this observation, and using
data from the FPD and filter samples, the SO^2 associated with H2S04 and
NH4HS04 was inferred from the molar differences between the H+ and the
simultaneously measured H2S04 by the FPD (i.e., using equivalent average time
periods for the latter data). The results of the analysis showed:
1. The species H2S04, NH4HS04 and (NH4)2S04 can occur simulta-
neously in a present-day polluted atmosphere.
2. On occasion, S042 will be associated only with H2S04 and NH4
HS04.
3. During a period of sustained sulfate concentrations (2 to
3 days) the sulfates change in composition from acid to basic
species, (Table 2-6).
The latter observation was made during a large scale regional episode that
affected the northeastern U.S. at the end of August 1980.
The 1984 Fairview Lake, N.J. study reported by Lioy et al. (1987) was con-
ducted in a manner similar to Morandi et al. (1983). The species distribution
and concentration again showed that the occurrence of HpSO. is quite variable
and is usually limited in extent, while NH^HSO. was found over a series of days.
The approximate 1 h peak of H2S04 was 12 \ig/m .
The 1977-1978 St. Louis, MO study by Cobourn and Husar (1982) showed that
2
levels of H2S04 in excess of 1 to 2 pg/m occurred sporadically, but most of
the time the occurrence of H^SO. was rare. From July 15-18, 1977 St. Louis was
influenced by a highly stagnant southerly maritime tropical air mass. The
o
observed 1 h H9SO. was about 6 pg/m for much of July 17 and 18. In two 1 h
3
intervals, the levels exceeded 20 ug/m . In 1979, a short study (8 days) by
Huntzicker et al. (1984) also examined summertime H^SO. in St. Louis. The
period of increased acid occurred within a single day, and in this case was
determined to be associated with a local power plant, approximately 17 km away.
Winter measurements during the Cobourn and Husar (1982) study were made
in 1978. During the period, H2S04 was measured consistently in February and
March, but at lower peak levels than observed during the summertime.
(Table 2-9.)
For each of the other summertime studies, peaks of H2S04 and/or H were
observed sporadically, and based upon the meteorological data, were associated
with the presence of a slow moving hazy summertime high pressure system. A
2-46
-------
major acid sulfate event occurred over the period from August 1 through
August 12, 1977 (Lioy et a!., 1980). The daily variation of the six hour
particulate sulfate, hydrogen ion samples, and the daily maximum ozone
concentrations are shown in Figure 2-14. In the multi-site analyses of this
period the results of Lioy et al. (1980) for High Point, N.J. and Brookhaven,
Long Island, N.Y. showed peak excursions of H+ at High Point and Brookhaven
(separated by 160 km) with the passage of SO^2-laden air masses on a number of
days. In contrast, on one day, August 4, 1977, both High Point and Brookhaven
were affected by air parcels that had passed over different geographical areas,
and only the High Point site recorded high H+ and SOT2.
New York City data for the same period were reported by Tanner et al.
(1981). They did not record any acidity during August 4 or on any other of the
fifteen sampling days. This suggested that after passing High Point, N.J.,
the flux of NH3 emanating from the metropolitan area neutralized the air
parcels that contained acidic sulfate particles. The values of H+ measured at
Brookhaven, L.I., N.Y., were consistently lower than the values measured at
High Point, suggesting partial neutralization and/or fresh acid production over
the New York metropolitan area. Such changes in concentration suggested that
complex relationships exist among S02 emissions, acid aerosol formation, and
the availability of NH3 for neutralization.
Suggestive information on the regional nature of the acid in rural areas'
was also provided by Lioy et al. (1980) in comparisons of acid events (>5 pg/m3
for at least 1 hr) occurring at Allegheny Mountain, PA during the same period
as photochemical smog in High Point, NJ (Pierson et al., 1980b). On August 4,
1977 the concentrations of H+ (as H2S04) were 17.0 and 10.4 ug/m3 for the
periods 8 p.m. (August 3rd) to 8 a.m. (August 4th) and 8 a.m. to 8 p.m.
(August 4th) respectively at Allegheny, Mtn., which coincide with the peaks
observed at High Point, N.J. (320 km east). Similar coincidence observations
of H were found at both sites for the period August 6 through August 10. An
independent study in Research Triangle Park, N.C. by Stevens et al. (1978) was
conducted simultaneously with another part of the Pierson et al. (1980b) study.
On July 31, 1977, the last day of the North Carolina study, the peak H+ con-
centrations observed by Stevens et al. (1978) occurred simultaneously with an
H event at Allegheny Mountain, PA.
Later studies by Stevens et al. (1980), in the Great Smokey Mountains, TN;
by Stevens (1983) and Ferman et al. (1981) in the Shenandoah Valley, VA and by
2-47
-------
150
6 8
DAYS IN AUGUST, 1977
10
12
Rgure 2-14.6-hour SO4= and H+, and 6-hour max. O3 samples collected during August, 1977
at High Point, NJ.
Source: Lioy and Waldman (1989).
2-48
-------
Lioy and Lippmann (1986) In Mendham, NJ show the presence of acidic species in
other nonurban areas within the Eastern U.S. Other results by Stevens (1983)
indicated the presence of acidic species in Houston, TX, and were supported by
semi-quantitative recent humidographic data from Waggoner et al. (1983).
In 1984 Spengler et al. (1986) initiated H2$04 studies at two of the
Harvard Six-Cities Health Study sites, Harriman, TN (coal burning area), and
Watertown, MA (suburb of Boston). Using the FPD system for H^SO* measurement
they classified acid events. Data from their study shows the H^SO, concentra-
tions and the duration of events with HpSO, >1 ug/m for at least two hours
(Table 2-10). This is a rather low threshold for classifying events, but the
study gives one of the few comparisons of acidity in two different environments.
TABLE 2-10. ACID CONCENTRATIONS MEASURED ABOVE
H2S04 £1 ug/m3 for £2 h
Watertown, Massachusetts
(N = 72)
Duration Concentration
(hr) (ug/m3)
Harriman, Tennessee
(N = 65)
Duration Concentration
(hr) (ug/m3)
MEAN
SD
75 percent
90 percent
MAX
7.2
5.2
8.0
17.7
24.0
2.2
1.4
2.2
4.4
7.4
8.4
6.4
10.0
17.4
41.0
3.0
1.5
3.8
4.7
9.5
N = Number of samples.
Duration = time intervals when H2S04 was above ^1 ug/m3 H2S04.
Source: Spengler et al. (1986).
Those that occurred in the coal burning area of Harriman, TN were of longer
duration and higher concentration than at Watertown, MA. In Watertown, MA, the
events were usually associated with local power plants located within 20 miles
of the monitoring site. In Harriman, TN, the events were associated with
regional and local H^SO* production. For both of these sites, the total strong
acidity was probably underestimated since the ammonium bisulfate concentrations
could not be measured by the FPD.
In another investigation by Harvard (Ferris and Spengler, 1985) a high
o
HSO- concentration (41 ug/m for 15 minutes) was observed in St. Louis. In
2-49
-------
this case, wintertime conditions were studied, and the results suggested an
association with power plant plumes.
A study by Appel et al. (1982) at Lennox in the Los Angeles basin was
conducted for the period July 10 to July 17, 1979. A four hour maximum of
O
11 ug/m of H2S04 was observed on July 16 apparently associated with the
daytime oxidation of local S09 emissions. Three other acid events were
-? 3
measured during this interval, although S04 was above 10 ug/m throughout the
sampling interval. Recently, a study was conducted by John et al. (1985) in
Los Angeles in which the apparent H2S04 was lower during this week-long study.
They used two sites, and the downwind location, east of LA, recorded acid
concentrations above 2 ug/m .
Cadle (1985) reported the results of acidity measurements (H+) at a
suburban site in Warren, MI from June 1981 through June 1982. The results were
consistent with the growing body of information on apparent hLSCh. The most
frequent excursions occurred during the summer with six 24 h samples exceeding
4 |jg/m . However, the highest H2$04 value occurred during the winter.
Two recent rural investigations, one in Whiteface Mt., NY (Kelly et al.9
1985), and one in Nova Scotia, Canada (Smith-Palmer and Wentzell, 1986), focussed
on acidic sulfate aerosol. In each case, there was at least one period during
which the apparent H2$04 concentration exceeded 9 ug/m3.
To date, there have been a couple of studies in which the acid sulfate
species were measured at two or more sites located <45 km apart (Waldman et al.,
1988; Pierson et al., 1989). One study was conducted in Toronto, Canada during
the summer of 1986 and on July 25th, H+(as H2+S04) was observed at all three
sites (one in downtown Toronto and two in the suburban areas). The 8 h average
peaks at each site were 8.3, 14.4, and 19.4 ug/m3. On the same day H+ measure-
ments of 28 ug/m (as H2S04) were made at Dunnville, ONT, which is approximately
30 km south of Toronto. The other study, the 1983 Allegheny-Laurel Experiment,
was conducted at sites 36 km apart. Nine-hour average H+ (as hLSOA) concentra-
3
tions of 30 and 42 ug/m were observed at these Pennsylvania sites on August 17,
1983 (Pierson et al., 1989).
A distinct diurnal pattern of acidity is shown in studies which report
6 hour or finer time resolution over a 24-hr period. Three studies provide
information on the diurnal cycle. Cobourn and Husar (1982) reports semi-
continuous measurements of H2S04 in St. Louis with a peak in H2S04 clearly
occurring between noon and 6 p.m. Inspection of a four-day period suggests
2-50
-------
that the diurnal pattern is more pronounced during periods of high acidity.
Tanner et al. (1981) report 6-hour measurements of strong acidity by titration
at three sites near New York City. The acidity peaks in the noon to 6 p.m.
quarter at all three sites. Waggoner et al. (1983) report summertime measure-
ments of HpSO,, HSO." and S0.~ from Houston, TX and Shenanadoah (rural VA).
The acidity index, moles NH, /moles SO^", and the sulfate concentrations show
distinct diurnal patterns with acidity and sulfate concentration peaking
between noon and 6 p.m. (Figure 2-15).
This diurnal pattern is important. If measurement techniques do not have
at least a 6-hour resolution the peak acid concentrations will be averaged out
to lower values. The reason for this pattern probably has to do with conversion
of S02 to HpSO. during the peak photochemical activity, and/or with processes
involving (a) neutralization of H^SO* by NH, from ground level sources and
removal of HUSO, by dry deposition during the night and (b) mixing downward of
unneutralized HpSCK from the upper part of the well-mixed layer as the height
of the mixed layer goes up during the day. Both exposure models and air
quality models will need to account for this diurnal variation. This may be
especially important for exposure estimates since children tend to be outdoors
during the peak concentration periods. There may be instances however, when
peaks occur at night. This was seen by Pierson et al. (1980b) and Keeler
(1987) for two elevated sites (>1000 ft) in Western, PA. Such situations will
require further research concerning nighttime or nonphotochemical smog
processes.
The preceding discussion was limited to the data presently available on
acid sulfate species. The studies were highly skewed to the summertime.
Although large segments of the population could be affected by these acid
events, data and information are not available on the types of situations
for other season where people could be exposed to high concentrations of acid
species (e.g., downwind of industrial and power plant plumes). The conditions
conducive to high acid exposure in the other seasons must be examined, as well
as the spatial distribution of acid sulfate (e.g., southeast and the mid-east
during the winter).
The studies of Pierson et al. (1980b), Lioy et al. (1980), and Stevens
et al. (1978) suggest that large areas of the northeast can be affected by acid
aerosol during the summer. Recent work by Thurston and Waldman (1987) also
suggest that these events can extend into Canada. Since the population
2-51
-------
g
To
k_
.23
o
Shenandoah
Diurnal Plots
i i i i
.
T
I
Acidity Peak
'
i t
— (NHJ.SO.
i , ** t •*
less acidic than
more acidic than
NH4H S04
-L H,SO.
0 3 6 9 12 15 18 21 24
Time of Day (EOT)
g
to
? 1
.03
O
1 I
Houston Univ.
Diurnal Plots
i i i i
.
T
il
Acidity Peak
l I
less acidic than
more acidic than 4 4
0 3 6 9 12 15 18 21 24
Time of Day (CDT)
- H2S04
Figure 2-15. Diurnal variation. The molar ratio of ammonium to sulfate ion
shows an acidity peak between noon and 6 pm.
Source: Waggoner et al. (1983).
2-52
-------
potentially affected could be large, well focused studies on regional exposure
to acid sulfate aerosol may be necessary. In contrast, the Los Angeles, CA
study of John et al. (1985) only found limited acid aerosol concentrations at
two sites.
2.6.2 Acid Sulfate Exposure and Events
The field studies described in the previous section measured a wide range
of acid sulfate concentrations in the atmosphere. Most of the I-USO,, or H (as
3 3
H2S04) values were below 5 ug/m, although events above 5 ug/m occurred at
least once over the course of each study. At present, there is no way to
define an acid event systematically as an episode, since, as previously noted,
periods of high acid sulfate do not necessarily coincide with periods of
_2
highest S(L concentrations; e.g., photochemical haze or smog. Therefore, the
definition of an acid sulfate episode would be quite arbitrary.
In the context of the following exposure assessment, a signifi-
cant pollution excursion for acid sulfate will be defined, as an event
in which the measurement of free sulfuric acid or H (as H^SO^
reaches levels above 5 ug/m3 for at least 1 h. No relationship to
possible health effects is intended or implied in using the words
significant, episode, or event and in some cases the exposure may be
overestimated, e.g., 24 hrs, because the actual amount of time spent
outdoors and the penetration of acid indoors were not quantified in
each study.
Research recently conducted at Camp Kiawa in Southern Ontario by Spengler
et al. (1989) considered exposure to acids on a 12-h basis for H and as 1-h
averages for HpSO*. For the same event described by Thurston and Waldman
(1987) and Waldman et al. (1988), a 1-h maximum sulfuric acid concentration of
o
50 ug/m was measured at the camp. The entire 36-h event had measured 12-h
sequential H+ (as H2$04) of 120, 336, and 150 (ug/m3)-h. This is within the
range of exposures that evoked responses in controlled human studies by Koenig
et al. (1983) and Utell et al. (1983), and supports the development of exposure
estimates for individual acid sulfate episodes.
With the preceding criteria and information, some of the studies listed in
Table 2-8 were selected for estimating the frequency of events, and the poten-
Q
tial for exposure to acid sulfates as (ug/m )*,h (Lioy and Waldman, 1989).
2-53
-------
It must be emphasized that the exposure (concentration x time)
calculation will only be applied for determination of exposures that
can occur during an event. At the present time annual average
calculations of exposure are inappropriate. Event exposure calcula-
tions may be of some biological significance since it has been shown
in a controlled human study that exposures to 100 (jg/m3 for more than
one hour will yield greater effects on mucocilliary clearance than a
one hour exposure. (Spektor et al., 1989; Schlesinger, 1989). For
the purposes of the following discussion, however, the exposure
values (|jg/m3)-h should be interpreted as the maximum potential expo-
sure during an event, and not the biologically effective dose to an
individual.
Because of the lack of a single approach to measuring acid sulfates, the
studies examined in Table 2-11 have been grouped by sampling duration. In the
case of studies with direct I-^SO^ measurements the total hydrogen ion exposure
will be underestimated, and in the case of studies with H+ measurements the
actual HgSO^ exposure probably will be overestimated.
The exposure and event results shown in Tables 2-11 through 2-15 and are
divided into representative studies with sample collection times of 24 h, 12 h,
6 h, 1 h, and a combined sampling time (Lioy and Waldman, 1989). Unfortunately,
the locations for the studies with the twelve hour samples, Table 2-12, and for
the other sampling times, Table 2-13 through Table 2-15, were different from
those examined for the 24-h studies, Table 2-11. Thus the results are not
necessarily comparable specially.
For the 24 h studies, Table 2-11, the events lasted a maximum of 24 h,
which was the sample duration. This may be an underestimate of the length
of the episode since the portion of the next or preceding 24-h period may have
been above 5 ug/m and could not have been detected. The exposures for the
24-h episodes ranged from 120 to 336 (|jg/m3)-h. For the day of the study,
however, exposures were isolated instances of high acid sulfate.
The acid sulfate events for the 12--h samples reached 36-h in duration
and recorded peak exposures of 511 and 925 (|jg/m3)-h. An interesting feature of
the 12-h studies was that each was conducted for a period of one month or less,
and each had at least one event with acidic sulfate exposure above
100 (ug/m )*h. Obviously, the frequency of occurrence of acid events can not
be described in this analysis. Longer duration studies covering all seasons
would be required in each location.
The 6 h analyses yielded information similar to the 12 h samples since
0
the two examples had calculated exposures above 100 (jjg/m )«h during intervals
2-54
-------
TABLE 2-11. EPISODIC ACIDIC AEROSOL DATA AND ESTIMATES OF PERSONAL EXPOSURE
FROM SELECTED ACID SULFATE CLASSIFIED BY SAMPLING TIME. ONLY INTERVALS OF
TIME WHERE CONCENTRATIONS EXCEEDED 5 ug/m3 DURING THE MINIMUM SAMPLING
PERIOD OF APPARENT H2S04 ARE CALLED AS EVENTS
24 HOUR SAMPLES
Study
(Period)
Whiteface Mt.*
(85 samples
collected
over 1 yr)
Nova Scotia**
(23 days)
Warren, MI***
(1 yr)
St Louis, MO****
(9 months)
Kingston, TN****
(9 months)
Date
1984
July
August
August
1983
September 6
1981
July
July
July
July
August
August
November
February
1985/1986
September
1985/1986
May 30
June 3
July 6
July 17
July 22
August 5
August 18
Mean
(ug/m3)
8.2
10.0
14.0
9.0
9.0
6.5
7.5
6.7
5.0
5.0
6.5
10.0
6.1
7.7
5.9
5.4
11.1
8.3
6.1
14.3
Exposure
(ug/ms)-h
197
240
336
216
216
156
180
161
120
120
156
240
146
185
142
130
266
199
146
343
*Kelly et al. (1985).
**Smith-Palmer and Wentzell (1986).
***Cadle (1985).
****Koutrakis et al. (1988).
of sampling that encompassed less than two weeks. However, the intensity and
duration of the High Point, N.J. (Lioy et al., 1980) exposures were quite
different. In the period from August 5 through 12 there were almost continuous
2
exposures to acidic sulfate above 100 (ug/m )-h. On some of the days there
were 6 h periods when H (as H_SO.) was not above 5 (jg/m , but these were the
exception rather than the rule.
2-55
-------
TABLE 2-12. TWELVE HOUR ACID AEROSOL SAMPLES AND ESTIMATES OF EXPOSURE
Study
Tuxedo, NY*
(31 days)
Glasgow, IL**
(8 days)
Smokey Mts***
(6 days)
Houston, TX****
(9 days)
*Morandi et al.
**Tanner et al.
***Stevens et al.
****Stevens (1983)
TABLE 2-13.
Study
High Point, NJ*
(11 days)
Date
1980
August 2
August 8
August 27
1975
July 22
July 26
July 28, 29
1978
September 20-21
September 21-22
September 24-26
1980
September 11
September 12
September 13
(1983).
(1977).
(1978).
•
SIX HOUR ACID AEROSOL
Date
1977
August 1
August 3
August 4-5
August 5-6
August 7-9
August 10
August 11-12
Mean
((jg/m3)
8.0
8.0
14.2
9.3
5.2
25.7
5.7
8.2
8.6
6.4
6.7
7.6
SAMPLES AND
Mean
(ug/m3)
11.6
5.8
9.0
10.1
7.4
6.5
8.3
Duration Exposure
(h) (Hg/m3)-h
12
12
36
12
12
36
12
12
36
12
12
12
ESTIMATES OF
Duration
(h)
6
6
24
30
36
18
24
96
96
511
112
62
925
68
98
310
77
81
91
EXPOSURE
Exposure
(ug/m3)-h
70
35
216
303
266
117
199
Shenandoah Valley** 1980
(7 days)
August 29-
September 1
14.6
24
350
*Lioy et al. (1980).
**Stevens (1983).
2-56
-------
TABLE 2-14. ONE HOUR H2SO. DATA AND ESTIMATES OF EXPOSURE*
Study
St. Louis, MO**
(61 days)
(59 days)
Harriman, TN***
(7 days)
Watertown, MA***
(7 days)
Date
1977
July 15
July 16-17
July 17
1978
February 9-10
February 10
February 10
February 11
February 11
1984
August 13
August 14
August 15
August 16
August 17
August 18
August 19
1984
August 9
August 10
August 12
Mean
(ug/m3)
7.0
9.2
13.0
7.0
6.0
7.0
7.5
8.5
6.0
6.5
8.5
6.3
5.8
8.0
5.2
7.0
7.5
7.0
Duration
(h)
3
7
4
13
1
3
4
20
7
13
16
4
5
11
2
6
12
8
Exposure
(ug/m3)-h
21
64
52
91
6
21
30
170
42
85
136
25
29
88
10
42
90
56
*A11 measurements were for H2S04 alone
**Cobourn (1979).
***Spengler et al. (1986).
TABLE 2-15. FOUR-, EIGHT- AND SIXTEEN-HOUR ACID AEROSOL DATA AND
ESTIMATES OF EXPOSURE
Study
Toronto
(6 weeks) (Site 1)
(Site 1)
(Site 2)
(Site 3)
Date
1986
July 19
July 25
July 25
July 25
Mean
(pg/m3)
6.4
14.1
13.4
8.3
Duration
(h)
13.4
18.8
25.3
7.5
Exposure
(ug/m3)-h
86
265
339
62
Source: Waldman et al. (1988).
2-57
-------
The examples of 1-h sample studies, all of which made direct H2S04
measurements showed the duration of an acid episode ranging from 1 to 20 h.
In contrast to the locations examined previously, there were only two instances
during which exposures to H2S04 were above 100 (ug/m3)-h and three above
80 (ug/m )-h. In the case of St. Louis, this was puzzling, since the sampling
included an entire year, and there are major sources of S02 in the area (Husar
et a!., 1978). The work, however, of Ellestad (1980) and the previously cited
work of Tanner and Marlow (1977) may explain part of this lack of frequent high
excursions in H2SO..
Even though St. Louis has major sources of S02, the main
impact was probably at some distance downwind. During the 1975 Midwest Inter-
state Sulfur Transformation and Transport (MISST) study at Glasgow, IL, Ellestad
(1980) measured particle light scattering downwind of the St. Louis urban and
power plant plumes and found aerosol production during the summer. The Tanner
and Marlow (1977) summertime H measurements indicated very high exposures
o
(>900 ug/m -h) at this same location. Thus the main acid impact from the plume
in this case was downwind. In the future, studies will require careful con-
sideration of where major plume impacts will occur, and their potential for
producing high acid concentrations and exposures.
In the Toronto, Canada study, Waldman et al. (1988) used a scheme which
involved collection of samples for a variety of time intervals, depending on
whether a sulfate episode was in progress-see Table 2-15 (Thurston and Waldman,
1987). The exposure analyses completed for the three sites across a metro-
politan area of 2.5 million people showed that there was one period, July 25th,
o
during which exposures at two of the three sites were above 100 (ug/m )-h. At
the third site, the levels were much lower, probably because of local neutrali-
zation. Thus, the potential for local differences in acid sulfate is present
and will have to be examined in the future to assess where maximum exposures
occur.
The above analyses suggest that during acidic sulfate events there were
instances where the conditions were conducive to exposures above 100 ug/m «h.
These must be evaluated further with an emphasis on identifying comparable
exposure conditions in controlled human studies, and identifying situations
where such exposures can occur routinely and could be the focus of epidemiolo-
gical investigations.
2-58
-------
2.6.3 Atmospheric Nitric Acid Concentration
Ambient data on nitric acid in the atmosphere are available from Spicer et
al. (1982) for Claremont, CA, Figure 2-16. Another study conducted in Los
Angeles, California by Sickles et al. (1986) measured levels of nitric acid
3
that ranged from 0.2 to 32 ug/m . Other data collected in the Ohio Valley,
in North Carolina, and in the Los Angeles, California Basin are shown in
Table 2-16 and Figures 2-17 and 2-18.
2.7 METEOROLOGY
Much has been written in the scientific literature about the development
of sulfate ion events (Hidy et al., 1978; Wolff et al., 1984; Samson, 1980;
Dutkiewicz et al., 1983; Lioy et al., 1980; Galvin et al., 1978; Whelpdale,
1978; Rahn and Lowenthal, 1985; Thurston and Lioy, 1987). However, very few
studies have addressed the conditions conducive to the formation of local or
regional acid sulfate events. The data available on meteorological conditions
for acid events will be described for eight of the studies discussed in this
chapter, but these should not be considered inclusive, in fact, for the cases
reported the meteorological data are very limited. As stated previously, most
acid aerosol studies have been conducted during the summertime. Thus, the
nature of acidic aerosol events that can occur in different types of locales
and during the remaining three seasons must be identified in future chemical
characterization and human exposure studies.
In the Kelly et al. (1985) White Mountain, NY study summertime aerosol
_o
acidity was closely associated with SO. levels that resulted from the trans-
port of pollutant laden air masses from industrial regions (the air flow was
from southerly to westerly directions). The temporal pattern of acid events
did not vary with other seasons, however, a seasonal variation of precursor S0?
_p *-
and NO and the secondary products S04 and HN03 was detected. This variation
was attributed to seasonal variation in the oxidation process. Homogeneous
photochemical oxidation was reduced during the winter months. Heterogeneous
oxidation by H,09 or 0, in aqueous solution was also reduced due to the low
£, £- *5
concentration of the oxidants.
In the 1983-1984 Antigonish, Nova Scotia study by Smith-Palmer and
Wentzell (1986), acid events were associated with synoptic scale transport and
moved north and east by high pressure systems that passed over the center of
the eastern United States and central Canada. No local sources of acid or acid
2-59
-------
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Figure 2-16. Nitric acid measurements taken at Claremont, CA, August and September 1979.
Source: Spicer et al. (1982).
TABLE 2-16. RESULTS OF COLUMBUS AMBIENT AIR SAMPLING
Date
10-17-79
10-18-79
10-19-79
10-20/22-79
10-22/23-79
10-23-79
10-24-79
10-25-79
10-26-79
10-27/28-79
10-29-79
10-30-79
10-31-79
11-2-79
11-19-79
11-28-79
Day Of
Week
W
Th
F
S-M
M-Tu
Tu
W
Th
F
s-s
M
Tu
W
F
M
W
Total
Inorganic
Nitrates
(ug/m3)
0.30
2.40
3.40
1.90
1.26
<0.50
3.43
3.37
2.10
4.66
7.83
5.39
2.28
3.11
2.32
2.11
(|jg/m3)
0.30
1.10
2.16
1.07
0.78
<0.50
3.10
2.36
0.60
3.00
3.15
2.04
0.54
2.22
0.65
1.53
HN03
(ug/m3)
<0.30
1.31
1.24
0.82
0.48
<0.50
0.33
1.01
1.50
1.66
4.67
3.35
1.74
0.90
1.67
0.59
so?s
<0.30
1.01
14.02
0.87
0.60
2.52
3.31
0.56
0.78
3.80
0.76
4.49
2.57
2.75
1.84
0.53
HC1
(H9/m3)
-
-
-
-
—
—
—
-
—
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~
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—
—
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(continued on the following page)
2-60
-------
TABLE 2-16. (continued)
Date
12-4-79
12-11-79
12-18-79
1-3-80
1-8-80
1-16-80
1-21-80
1-28-80
2-11-80
2-19-80
2-25-80
3-3-80
3-10-80
3-17-80
3-24-80
3-31-80
4-9-80
4-14-80
4-21-80
4-28-80
5-12-80
5-21-80
5-28-80
6-3-80
6-9-80
6-14/15-80
6-23-80
6-30-80
7-7-80
7-8-80
8-12-80
8-25-80
9-2-80
9-11-80
9-15-80
9-22-80
9-30-80
10-5-80
10-15-80
10-21-80
10-29-80
Day Of
Week
Tu
Tu
Tu
Th
Tu
W
M
M
M
Tu
M
M
M
M
M
M
W
M
M
M
M
W
W
Tu
M
s-s
M
M
M
Tu
Tu
M
Tu
Th
M
M
Tu
M
W
Tu
W
Total
Inorganic
Nitrates
(ug/m3)
3.29
1.92
2.81
2.57
3.89
1.68
5.92
7.86
4.97
3.89
4.59
2.66
1.06
4.32
2.14
3.06
9.54
1.43
2.80
5.03
4.20
9.26
7.78
3.54
1.57
4.66
6.79
2.03
3.99
4.24
3.27
8.92
4.35
3.84
2.17
1.77
2.40
4.20
4.11
3.88
1.79
NO;
(ug/m3)
2.28
0.78
2.51
1.20
3.41
0.54
5.15
6.43
3.21
1.61
3.92
0.36
0.47
3.30
0.68
1.15
9.17
0.29
0.96
3.62
2.72
1.48
2.09
0.90
0.82
1.55
2.32
0.70
1.44
1.98
1.06
5.24
3.66
2.20
1.58
0.96
1.43
3.19
2.38
2.52
1.42
HN03
(ug/m3)
1.02
1.14
0.30
1.38
0.48
1.14
0.77
1.43
1.76
2.28
0.67
2.31
0.59
1.02
1.46
1.91
0.38
1.14
1.85
1.41
1.48
7.78
5.69
2.64
0.75
3.10
4.46
1.33
2.54
2.27
2.43
3.67
0.68
1.64
0.60
0.81
0.97
1.01
1.73
1.35
0.37
S042
(ug/m3)
1.08
0.72
3.65
0.84
3.05
15.27
3.90
4.40
7.15
1.09
6.18
2.01
0.47
0.51
5.63
0.33
2.27
<0.28
<0.32
1.58
3.64
12.41
2.94
3.36
0.88
6.52
12.32
1.12
3.76
3.72
0.40
31.20
9.69
5.54
5.16
1.16
6.04
7.13
5.30
2.23
1.73
HC1
(ug/m3)
• —
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1.41
1.52
0.05
0.39
0.21
0.54
0.18
0.25
2-61
-------
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DATE (1986)
Figure 2-17. Dinural variation in nitrate concentration, Raleigh, NC, 1985.
Source: Stevens (1986).
2-62
-------
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2-63
-------
precursors were noted in their analyses. Warm and hazy weather with air mass
trajectories over water for long distances characterized the acid events. Air
mass trajectories over water minimized the availability of NH, from sources on
land. Acid aerosol events during the winter were of longer duration but had
lower acid levels than summer events. Winter events had narrow peaks above
3 3
5 |jg/m and otherwise low acid levels well below 1 pg/m .
A sulfate pollution event (>15 yg/m of sulfate ion) associated with the
transport of pollutants in the Washington, D.C. to New York City corridor in
the summer of 1980 was studied by Morandi et al. (1983). South to southwest-
erly wind flows appeared to bring air masses from the industrial regions of the
eastern United States. In the northeast U.S. these southwesterly wind flows
typically occur during the summer season. Sulfate events were associated with
slow-moving high pressure systems that accumulated secondary acid sulfate
particles in the atmosphere. However, the percent acid species did not neces-
sarily increase throughout the event.
The Glasgow, II study by Tanner et al. (1979) showed acid events associ-
ated with urban and power plant sources approximately 17 km west in the
2
St. Louis vicinity. Events which produced a peak 12 h average of 39 |jg/m of
H+(as HpSO*), occurred during daylight hours and were attributed to homogeneous
photochemically induced sulfuric acid formation. Conversely, ammonia levels
were higher during the nighttime.
The Lioy et al. (1980) analyses for 1977 found sulfate and acid levels
well correlated at High Point, NJ. Sulfate concentrations in excess of
15 [jg/nr were associated with westerly winds that carried precursor S02 from
sources in the midwest, Ohio Valley or western Pennsylvania and or south-
westerly winds through the Washington, D.C. to Boston corridor. These
occurred with southerly to westerly flow on the backside of high pressure
systems that moved slowly across areas of major emissions of S02. Ozone
concentrations in excess of 120 ppb have also been recorded under these
meteorological conditions. High acid was detected in the lower visibility
sections of the hazy air mass.
From the year-long investigation in St. Louis (1977-1978) by Cobourn
(1979), the summer acid events occurred with haze, stagnation, high tempera-
ture, high humidity, and cloudless skies. Elevated surface levels were due to
long distance transport of hazy air masses associated with maritime tropical
systems. High acid levels during the afternoon hours were attributed to
2-64
-------
enhanced photochemical gas phase reactions and vigorous mixing of pollutants in
the atmosphere. This area of the country had been studied previously by
Char!son et al. (1974) using a humidograph technique and they found that
particles were more acid when associated with maritime trajectories.
Winter events occurred with slow moving wind trajectories from the north-
east, implicating emissions from the industrial northeastern United States.
Recent work by Ferris and Spengler (1985) implicated local plume emissions with
the occurrence of high acidic sulfate (41 ug/m3 of apparant H2$04 for 15 min)
in St. Louis, MO.
In the St. Louis, MO investigation by Huntzicker et al. (1984) in August,
1979, acid events occurred with a high pressure system characterized by light
surface winds from the southwest. In addition, high daytime temperatures and
absolute humidity were indicative of a maritime tropical air mass and could
also be deficient of ammonia since the major NH- emission areas are to the west
and north of St. Louis. Two types of acid events were distinguished: one
occurring during the afternoon resulting from gas phase oxidation, and the
other early in the evening.
2.8 INDOOR AIR
Studies that focused on the indoor concentrations of acid aerosol species
have been conducted by Meranger et al. (1987) and Leaderer et al. (1988).
Meranger et al. (1987) showed that on average the indoor values were only 24%
of the outdoor values (2.77 ug/m ). The indoor data was not taken in a home
with a indoor source of acid. In contrast, Leaderer et al. (1988) conducted an
emission study of kerosene heaters in a large room chamber and found acid
o
aerosol concentrations in excess of 74 ug/m for a 12 h period for
radiant-radiant units. For convective, convective-radiant and radiant heaters
the concentrations were 17.2, 1.4 and 16.9 ug/m3, respectively. These two
studies suggest that acid will be present indoors, but the magnitude and extent
of the contribution of the indoor environment to personal exposure and popu-
lation exposures needs to be quantified, especially since the peak exposures
o
for the kerosene study were 895 (ug/m )-h.
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2.9 SUMMARY
The level of knowledge about the frequency, magnitude and duration of acid
sulfate particle events/episodes is insufficient, although acid aerosol events
appear to occur sporadically. Efforts must be made to gather more data, but
these should be done in such a way that situations where maximum human exposures
may occur are the focus of the research. In addition, further data are required
on the mechanisms of formation of H2$04, and on what factors can be used to
predict acid sulfate episodes. New studies must focus primarily on selecting
areas where there can be conditions for exposure which may yield an adverse
health effect, and not the establishment of a diffuse monitoring program. The
high exposures calculated for some of the documented data were not from studies
necessarily designed to examine high as well as low human exposures. Most were
basically designed to investigate the characteristics of the atmosphere. Thus
situations with potentially higher exposure could be present in North America.
From the studies identified and discussed, it appears that two potential
exposure situations are possible. Those related to: (1) regional stagnation
and transport conditions, and (2) local plume impacts.
o
Levels of apparent H2$04 in excess of 20 to 40 ug/m have been observed
for time durations ranging from 1 to 12 hours, and these were associated with
~2 3
atmospheric SO. levels in excess of 40 ug/m and with possible exposures
3
during episodes of >900 (ug/m )-h. Earlier London studies suggested that HLSO,
3
in excess of 100 ug/m can be present in the atmosphere, and exposures
>2,000 (ug/m3)-h were possible.
It is apparent that the two types of outdoor conditions mentioned above
can lead to a number of possible situations for conducting epidemiological and
human exposure studies. The first would be studies conducted during major
summertime haze episodes, where large populations in the eastern U.S. could be
affected periodically by high acid sulfate levels. The exposure could be
manifested by high FLSO. and/or NH.HSO, accumulated over periods of one hour or
more throughout a day or sequence of days. Because these haze episodes occur
in the summer, large segments of the population will be participating in
outdoor activities in the rural and suburban areas. These individuals would be
most at risk during regional events, and would be the focus of opportunities
for epidemiological studies.
The second type of exposure would be confined to places downwind of a
power plant plume or urban plume during any season of the year. Obviously, the
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greatest potential for population exposure would still be during the summer;
however, exposures could still occur during all of the other seasons. The
latter would be confounded by variable levels of outdoor activity, and degree
of penetration of the acid sulfate into the home. It should be noted that the
highest acid concentrations observed in the cited studies appear to be
associated with direct plume impacts. Therefore, these types of locations
warrant considerable attention in long-term health effect epidemiological
studies. In considering locations for investigations on exposures to acid
aerosols, locations outside the United States and Canada should be considered.
Space heating with open kerosene heat sources can lead to significant
emissions of acid aerosols indoors. This potential acid exposure situation
must be considered for study as well as personal monitoring studies for
situations that could be associated with indoor/outdoor contributions to
exposure.
At present there are a few studies that have included the measurement of
nitric acid vapor. As the use of samplers such as the annular denuder become
more common, the concentrations of the H+ in both the vapor phase and the
particulate phase will be more easily compared. Further research on the tech-
niques for nitric acid determinations is also necessary.
Most research on acid fog has been limited to rural and in mountainous
areas outside of California. A better data base on fog is necessary,
especially in terms of the potential for enhanced aerosol acidity after the fog
evaporates.
2.9.1 Implications for Atmospheric Pollution Studies
Many of the technique limitations and the implications derived from
measurement of strong acids in atmospheric aerosols have already been
introduced in the preceding sections. A summary of these limitations and
implications is included below.
Most of the strong acid content of the atmospheric aerosol
derives from partially NH3-neutralized sulfuric acid aerosol.
Regional levels of acid sulfate aerosols are predominantly
formed by secondary oxidation processes in the atmosphere, with
only a small fraction from primary emissions.
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Techniques now exist for hydrogen ion determination that are in
large part sufficiently sensitive and selective for ambient
measurements with adequate time resolution for surface measure-
ments. Improvements are still needed for certain airborne
applications, and a quality assurance program should be
developed for candidate sampling and analysis techniques.
No practical technique exists that distinguishes ammonium
bisulfate from ammonium sulfate in either internal or external
mixtures in ambient aerosols, and is required to accurately
quantify the major acid sulfate species.
The role of local and regional ammonia concentrations in con-
trolling the surface levels of atmospheric strong acids to which
populations are exposed must be examined. Additional
measurements of this important species are recommended.
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3. DEPOSITION AND FATE OF INHALED ACID AEROSOLS IN THE RESPIRATORY TRACT
3.1 INTRODUCTION
This chapter first reviews the deposition of inhaled aerosols in the
respiratory tract for both humans and experimental animals. The special case
of hygroscopic aerosols is then addressed. Finally, an important factor
modifying the response to inhaled acids, namely neutralization by airway
surface fluid buffers or by endogenous ammonia, is assessed.
The respiratory tract is the major route of exposure to ambient acid
aerosols. In order to elicit any response, these aerosols must first deposit
on airway surfaces. The deposition of inhaled particles on the internal
surfaces of the airways defines the delivery rate to the initial contact
site(s) and, for materials that exert their action upon surface contact such
as irritants, is a major predicator of response. Deposition is controlled by
various physical mechanisms that are influenced by particle characteristics,
respiratory mechanics, airflow patterns and rates, and respiratory tract
anatomy. An understanding of deposition is essential for interpretation of the
results of the animal toxicologic and human health effects studies discussed
later.
Biological effects of aerosols are often related more to the quantitative
pattern of deposition within specific respiratory tract regions rather than to
total deposition. In regard to particle deposition, three main anatomic
regions can be considered: (1) the upper respiratory tract, which includes the
airways extending from the nose or mouth through the larynx; (2) the tracheo-
bronchial tree, which includes the conducting airways from the trachea through
the terminal bronchioles; and (3) the pulmonary or gas-exchange region, which
includes the respiratory bronchioles, alveolar ducts, alveolar sacs, and alve-
oli. Although there are numerous data on regional deposition of particles in
humans, many types of exposure protocols require use of experimental animals,
with the ultimate goal being extrapolation to humans. To apply results of
toxicologic studies adequately in risk assessment, it is essential to consider
differences in deposition patterns, since various animal species exposed to
3-1
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the same aerosol may not receive identical doses in comparable sections of the
respiratory tract.
3.2 PARTICLE DEPOSITION MECHANISMS AND PATTERNS
The deposition of inhaled particles in the respiratory tract occurs by
similar physical mechanisms in humans and experimental animals. There are five
significant mechanisms by which deposition may occur: impaction, sedimentation,
Brownian diffusion, interception, and electrostatic precipitation.
Impaction is the inertia! deposition of a particle onto an airway surface.
It occurs when the particle's momentum prevents it from changing course when
there is a change in the direction of bulk airflow. Impaction is the main
mechanism by which particles having aerodynamic diameters (D ) >0.5 pro deposit
in the upper respiratory tract and at or near tracheobronchial tree branching
points. The probability of impaction increases with increasing air velocity,
rate of breathing, particle density and size.
Sedimentation is deposition due to gravity. When the gravitational force
on an airborne particle is balanced by the total of forces due to air buoyancy
and air resistance, the particle will fall out of the air stream at a constant
rate, known as the terminal settling velocity. The probability of sedimenta-
tion is proportional to the particle's residence time in the airway and to
particle size and density, and decreases with increasing breathing rate.
Sedimentation is an important deposition mechanism for particles with diameters
(DQe) >0.5 urn that penetrate to those airways where air velocity is relatively
low, e.g. mid to small bronchi and bronchioles.
Submicrometer-sized particles, especially those with physical diameters
<0.2 urn, acquire a random motion due to their bombardment by surrounding air
molecules; this motion may then result in contact with the airway wall. The
displacement sustained by the particle is a function of a parameter known as
the diffusion coefficient, which is inversely related to particle cross-
sectional area. Brownian diffusion is a major deposition mechanism in airways
where bulk flow is low or absent, e.g., bronchioles and alveoli. However,
extremely small particles may deposit by diffusion in the upper respiratory
tract, trachea and larger bronchi.
Interception is a significant deposition mechanism for elongated parti-
cles, i.e., fibers, and occurs when the edge of the particle contacts the
airway wall. The probability of interception increases as airway diameter
3-2
-------
decreases, and fibers that are long (e.g,, 50 to 100 urn) but thin (e.g.,
0.5 urn) can penetrate into distal airways before depositing.
Some freshly generated particles can be electrically charged, and may
exhibit enhanced deposition over what would be expected from size alone. This
is due to image charges induced on the surface of the airway by these particles
and/or to space-charge effects, whereby repulsion of similarly charged parti-
cles results in increased migration towards the airway wall. The effect of
charge on deposition is inversely proportional to particle size and airflow
rate. Since most ambient particles become neutralized naturally due to air
ions, electrostatic deposition is generally a minor contributor to overall
particle collection by the respiratory tract; it may, however, be important in
laboratory studies.
Various techniques may be used to measure particle deposition in the
respiratory tract. However, different procedures and assumptions inherent in
their use has resulted in large variations in reported values. Direct measures
of total respiratory tract deposition may be obtained by two procedures. In
one, the concentration of test particles in inhaled air is compared with that
in exhaled air which is collected after each breath; the difference represents
the total amount deposited. In another technique, radioactively-tagged tracer
particles are administered and scintillation detector systems used to measure
deposition. Total deposition is estimated by summing the activity in the chest
and head regions immediately after exposure, while regional deposition is
usually defined functionally on the basis of subsequent clearance of deposited
particles. For example, it is commonly assumed that any tracer particles
remaining in the chest area by 24 hr after exposure originally deposited in the
pulmonary region, while those deposited in the tracheobronchial tree were
cleared prior to this time.
Experimentally determined values for particle deposition within the human
respiratory tract as a function of the median size of the inhaled aerosol are
presented in the top panels of Figures 3-1 to 3-4. All values are expressed
as percentage deposition of the total amount of aerosol inhaled (i.e., deposi-
tion efficiency). The obvious variability is due to a number of factors, two
of which are anatomical variation between subjects and the use of different
experimental protocols in different studies. Figure 3-1 shows the pattern for
total respiratory tract deposition. This is characterized by a minimum for
particles with diameters of ~0.3 to 0.5 urn. As mentioned, particles with
3-3
-------
100
80
60
40
v O
c
20
I I
O HUMAN (ORAL)
• HUMAN (NASAL)
o°c>
H 100
8
a.
UJ
Q
80
• 60
40
20
ORAT
D MOUSE
A HAMSTER
OGUINEA PIG
VDOG
O
V
I
I
0.01 0.1 1.0
PARTICLE DIAMETER, Mm
10
Figure 3-1. Deposition efficiency (percentage deposition of amount inhaled)
In humans and experimental animals for total respiratory tract.
Source: Schlesinger (1988).
3-4
-------
100
80
60
40
20
percen
p 100
§
a.
LU
Q 80
60
40
20
I I I
O HUMAN (ORAL)
_ • HUMAN (NASAL)
—
:
<
r •
In* I i 1* |J
_
j<
• 41
4
4
•
«
>
«
r»
<
i
/
r
i
—
b
1 1 1 1
i p t- OO
I
ORAT
a HAMSTER
A MOUSE
O GUINEA PIG
V DOG
0.01 0.1 1.0
PARTICLE DIAMETER, jtm
10
Figure 3-2. Depostion efficiency (percentage deposition of amount inhaled))
in humans and experimental animals for upper respiratory tract.
Source: Schlesinger (1988).
3-5
-------
60
40
20
-------
60
40
20
03
a.
y 0
O HUMAN (ORAL)
• HUMAN (NASAL)
I
go
Ll
00
O
H
CO
O
a.
60
40
20
0.01
O RAT
O HAMSTER
A GUINEA PIG
.O MOUSE
V DOG
T
i
w
I
0.1 1.0
PARTICLE DIAMETER, jum
Figure 3-4. Oepostion efficiency (percentage deposition of amount inhaled)
in humans and experimental animals for pulmonary region.
Source: Schlesinger (1988).
3-7
-------
diameters >0.5 urn are subject to impaction and sedimentation, while the deposi-
tion of those <0.2 pm is diffusion dominated. Particles with diameters between
these values are minimally influenced by all three mechanisms, and tend to have
relatively prolonged suspension times in air. They undergo minimal deposition
after inhalation, and most are, therefore, exhaled.
Studies of deposition in humans generally employ either oral or nasal
breathing, and the effect of breathing mode upon deposition is evident from
Figure 3-1. Inhalation via the nose results in greater total deposition than
does oral inhalation for particles with diameters >0.5 urn; this is due to
enhanced collection in the nasal passages. On the other hand, there is little
apparent difference in total deposition between nasal or oral breathing for
particles with diameters between 0.02 to 0.5 pm. Oronasal breathing (partly
via the mouth and partly nasally) deposition is discussed in United States
Environmental Protection Agency, (1986).
Figure 3-2 (top) shows the pattern of deposition in the human upper
respiratory tract. Again, it is evident that nasal inhalation results in
enhanced deposition. The greater the deposition in the head, the less is the
amount available for removal in the lungs. Thus, the extent of collection in
the upper respiratory tract affects deposition in more distal regions.
Figure 3-3 (top) depicts deposition in the tracheobronchial tree. The
available data base indicates that deposition efficiency rapidly increases as
particle size increases, for particles greater than 1 pm.
Deposition in the human pulmonary region is shown in Figure 3-4 (top).
With oral inhalation, deposition increases with particle size to a maximum at
about 3-4 urn, after a minimum at about 0.5 pro. With nasal breathing, on the
other hand, deposition tends to decrease with increasing particle size above
about 4 urn. The removal of particles in more proximal airways determines the
shape of the pulmonary curve. For example, increased upper respiratory and
tracheobronchial deposition would be associated with a reduction of pulmonary
deposition; thus, nasal breathing results in less pulmonary penetration of
larger particles, and a lesser fraction of deposition for entering aerosol than
does oral inhalation. Thus, in the latter case, the peak for pulmonary deposi-
tion shifts upwards to a larger sized particle, and is more pronounced. On the
other hand, with nasal breathing, there is a relatively constant pulmonary
deposition over a wider range of sizes.
3-8
-------
Since much information concerning responses to inhaled acids is collected
using experimental animals, the comparative regional particle deposition in
these animals must be considered to help interpret, from a dosimetric view-
point, the implications of animal toxicological results to humans. However,
it is difficult to systematically compare interspecies deposition patterns
obtained from various reported studies, because of variations in experimental
protocols, measurement techniques, definitions of specific respiratory tract
regions, and so on. For example, tests with humans are generally conducted
under protocols that standardize the breathing pattern, whereas those using
experimental animals involve a wider variation in respiratory exposure condi-
tions (for example, spontaneous breathing versus controlled breathing as well
as various degrees of sedation). Much of the variability in the reported data
for individual species is due to the lack of normalization for specific respira-
tory parameters during exposure. In addition, the various studies have used
different exposure techniques, such as nasal mask, oral mask, oral tube, or
trachea! intubation. Regional deposition fractions may be affected by the •
exposure route and delivery technique employed.
The bottom panels of figures 3-1 to 3-4 show deposition in commonly used
experimental animals. Although there is much variability in the data, it is
possible to make some generalizations concerning comparative deposition pat-
terns. The relationship between total respiratory tract deposition and particle
size is relatively the same in humans and most of these animals; deposition
increases on both sides of a minimunij which occurs for particles of 0.2 to
0.9 pm. Interspecies differences in regional deposition efficiencies occur due
to anatomical and physiological factors. In most experimental animal species,
deposition in the upper respiratory tract nears 100 percent for particles
>2 pm, indicating greater efficiency than that seen in humans. In the tracheo-
bronchial tree, there is a relatively constant, but lower, deposition efficiency
for particles of >1 urn in all species compared to humans. Finally, in the
pulmonary region, deposition efficiency peaks at a lower particle size (~1 pm)
in the experimental animals than in humans (2 to 4 urn).
In evaluating studies with aerosols in terms of interspecies extrapola-
tion, it is not adequate to express the amount of deposition merely as a
percentage of the total inhaled. Since overall respiratory tract deposition
for the same size particle may be quite similar in humans and many experimental
animals, it follows that deposition efficiency is independent of body size
3-9
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(McMahon et a!., 1977; Brain and Mensah, 1983). Different species exposed to
identical particles at the same exposure concentration will not receive the
same initial mass deposition. If the total amount of deposition is normalized
to body weight, smaller animals would receive greater initial particle burdens
per unit weight per unit exposure time than would larger ones.
3.3 HYGROSCOPIC AEROSOLS
Most deposition studies tended to focus on insoluble and stable test
aerosols whose properties do not change during inhalation. Ambient aerosols,
however, usually contain deliquescent or hygroscopic particles that may grow
while in transit in the humid respiratory airways. Such particles will deposit
according to their hydrated, rather than their initial, size (Blanchard and
Willeke, 1984; Cavender eta!., 1977). In general, the larger the initial
particle size, the less is the absolute growth and growth rate; in any case,
the deposition pattern of a specific hygroscopic aerosol can usually be related
to its growth characteristics. A comprehensive review of those factors affect-
ing the deposition of hygroscopic aerosols has been provided by Morrow (1986).
Because of dynamic changes in particle size, it is likely that deposition
of an acid particle may not be predictable from data on nonhygroscopic aerosols
inhaled at the same size. For example, a 1 pm (Dae) particle of H2S04 may grow
to nearly 3 pm (D ) while in the nasal passages, increasing total respiratory
tract deposition by a factor of 2 or more over that expected for the original
1 urn particle; this is due to an increase in both upper respiratory tract and
tracheobronchial deposition. Concomitantly, there would be a decrease in
pulmonary deposition. However, actual differences in deposition may vary,
depending upon the initial size of the acid droplet. For example, the rela-
tionship between total respiratory tract deposition and inhaled particle size
for humans (Figure 3-1) suggests that hygroscopic particles inhaled at <0.5 pm
would actually show a decrease in total deposition if they grow no larger than
0.5 urn, and will only begin to show an increase in deposition if the final
diameter reached is >1 urn. On the other hand, 0.3 to 0.5 (jm hygroscopic
particles may show substantial changes in their deposition probability.
Particles >5 urn may minimally grow in one respiratory cycle, and may not show
an increase in deposition at all compared to similarly sized nonhygroscopic
particles (Ferron etal., 1987). Analytical deposition models developed
3-10
-------
specifically for hygroscopic sulfate particles (Martonen and Patel, 1981a,b)
also indicate that total respiratory tract deposition efficiencies for such
particles in humans should be greater than those for nonhygroscopic particles
if the sulfate originates from particles having diameters larger,than 0.1 to
0.3 urn. But even if the total deposition of hygroscopic and nonhygroscopic
particles of the same initial size is the same, regional deposition may differ
(Martonen et al., 1985).
The deposition of acid sulfate aerosols has been examined in experimental
animals. Dahl and Griffith (1983) assessed the deposition of I^SO^ aerosols in
guinea pigs and rats. Upper respiratory tract and lung, as well as total
respiratory tract, deposition of aerosols ranging in size from 0.4 to 1.2 urn
(MMAD) was found to increase with increasing initial droplet size. Although
the lung deposition of 0.5 pm acid particles was similar to that for 0.5 urn
nonhygroscopic particles, 1 urn FUSO, particles deposited much more effectively
than did 1 urn nonhygroscopic particles. On the other hand, Dahl et al. (1983)
examined the deposition of similarly sized H^SO, aerosols in dogs, and found
the deposition pattern at two relative humidities (20 percent and 80 percent)
to be similar to that of nonhygroscopic aerosols having the same size. The
interindividual variability of deposition in these animals was greater than the
differences due to relative humidity. It was suggested that hygroscopicity was
not a dominate determinant of deposition site in this larger mammal. Thus, the
relative effect of hygroscopicity on ultimate deposition pattern is not resolved,
since results using ideal models and those from actual experiments may not
agree; in addition, the extent of the effect on deposition may depend upon the
animal species.
3.4 NEUTRALIZATION BY AIRWAY SECRETIONS AND ABSORBED AMMONIA
Two important chemical defenses against inhaled acid include endogenous
ammonia and airway surface liquid buffers. Acids may react with ammonia to
produce ammonium salts or may be buffered by airway secretions. The capacity
to buffer or neutralize inhaled acid may thus be an important factor in the
eventual toxicity to the organism.
3.4.1 Airway Surface Liquid Buffering
The acid-base equilibrium of airway surface fluids may be altered by
buffer content, secretion rate, and presence of inflammation and may differ
3-11
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according to the region of the lung from which the airway secretions are
obtained (Lopez-Vidriero et al., 1977). Reported mean values of airway pH
from mammals range from 6.6 to 7.5. Changes in pH of airway secretions alter
the properties of the mucus macromolecules and hence the viscosity of the mucus
gel layer. Secretion of sulfated mucins (sulfomucins) may be partially respon-
sible for alterations in pH.
Airway surface fluid pH has been estimated by measuring the pH of sputum,
a mixture of saliva and airway mucus, usually only obtainable from smokers or
individuals with airway disease associated with mucus hypersecretion. A more
direct approach has been to immerse a micro-pH probe, in vivo, into airway
surface fluids. Sputum is not typically available from individuals with normal
healthy lungs. Caution should be exercised in the interpretation of sputum pH
since the individuals from whom sputum is obtained may have abnormal mucus
secretion or infection and thus sputum pH may not be an appropriate surrogate
for mucus pH. Furthermore, there may be considerable differences in mucus
secretion rates and mucus transport rates among individuals and between various
species.
Gatto (1981) measured the pH of the mucus gel surface layer in rats using
a surface pH probe inserted through a trachea! "window." The pH averaged
7.52. Cholinergic stimulation caused a decrease to 7.46, presumably due to
increased secretion of acidic glycoproteins and sialic acid in the mucus.
The effect of alterations of pH on ciliary motility and on the morphology
of the airway mucosa was examined by Hoi ma et al. (1977). These authors
reported that previous studies of cilia from invertebrates, fundamentally
similar to human cilia, show that not only the pH but also the ionic composi-
tion of the medium influence ciliary motility. Ciliostasis occurs in mammalian
respiratory tract cilia at pH's ranging from 5.2 to 6.4.
Human bronchial pH was measured with a surface pH electrode inserted via a
bronchoscope. This yielded i_n situ measurements of mucus pH (Guerrin et al.,
1971). Normal values ranged from 6.5 to 7.5 with a mean of approximately 6.9.
These investigators also showed that hypercapnia (respiratory acidosis) was
associated with a reduction in mucus pH. Inflammation and infection was
associated with considerably more acidic mucus pH's (5.2 to 6.2). Tracheal pH
measured in rabbits averaged about 6.6, slightly more acidic than in the
humans.
Bodem and co-workers (1983) measured endobronchial pH using a flexible pH
probe passed through a bronchoscope and wedging it in a peripheral bronchus.
3-12
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Measurements made in normals and 18 patients revealed a mean pH of 6.6 (range
6.44 to 6.74). The presence of pneumonia in the patients was associated with
a slightly lower (6.48) pH. The average endobronchial pH in a group of five
dogs was 7.1.
Mucus is converted from a gel to a sol at a pH of about 7.5. Holma et al.
(1977) indicate that the mucus is secreted in an alkaline form (and thus as a
gel) and is subsequently acidified by carbonic acid formed by C02 dissolved in
the mucus layer. It was suggested that acidification of the gel layer by
inhaled acids or acid forming gases (S02, C02) would cause increased mucous
viscosity and hence increased clearance, provided the pH is not reduced suf-
ficiently to reduce ciliary motility.
Ciliary motility of isolated bovine trachea! strips was studied. Normal
ciliary activity was observed in the pH range of 6.7 to 9.7. FLSCL was used
for acidification and complete ciliostasis was observed at pH 4.9. Further-
more, at acid pH, epithelial cells "loosened from each other and from the
basement membrane." Since normal motility is maintained to pH 6.7 (in cows),
Holma et al. (1977) concluded it was unlikely that ambient levels of S0? would
cause sufficient acidification of the mucus layer to alter ciliary motility.
Ciliostasis was typically preceded by intracellular edema.
In a more recent study, Holma (1985) examined the buffer capacity and
pH-dependent rheological characteristics of human sputum, expectorated airway
mucus. The pH of sputum is influenced by airway C02; the normal mucus pH of
about 7.4 is established by the mucus buffering system. Sputum equilibrated
with 5 percent C02 at 37°C and 100 percent RH was titrated with H2S04 to pH 3.
Although buffer capacity was variable depending on the sputum sample, depres-
sion of sputum pH from 7.25 to 6.5 required the addition of approximately
6 [jmol of H per ml of sputum. Sputum from asthmatics had a lower initial pH
(6.8; range 6.3 to 7.4) and reduced buffering capacity. Sputum viscosity was
minimal at a pH of 7.5 and was increased as the sputum was acidified. Recent
work by Holma (Holma, 1989) demonstrates a minimal value for mucus viscosity at
a pH of 7.0. Viscosity increased with acidification or alkalinization of the
mucus. Since the capacity of mucus to buffer H+ is reduced in asthmatics, this
provides another reason to be concerned with acid aerosol exposure of this
sensitive group.
Assuming a tracheobronchial mucus volume of 2.1 ml, between 8 and 16 umol
of H , if evenly distributed throughout the airways, would be required to depress
3-13
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the pH to 6.5 from 7.4. Since 1 ug H is obtained from 49 ug of H^SO,, between
390 and 780 ug of HpSO. would be needed to cause this depression of pH. Assum-
ing exposure duration of 30 min, ventilation of 20 L/min and 50 percent
3 +
deposition of 100 ug/m H2SO. (1M), 0.6 umol of H would be deposited in the
lung (50 percent x 100 ug/m3 x (600 L -f 1,000 L/m3) = 30 ug - -3 umol H2$04 or
0.6 ug of H ).
The distribution of submicron acid aerosol particles in the respiratory
tract is not uniform and therefore larger changes in pH might be anticipated on
a regional basis in lung regions with high deposition of acid. If, for example,
30 ug of acid deposited in 0.2 ml of surface liquid, a much larger pH change
would be expected.
Fine et al. (1987) hypothesized that buffered acid aerosols (with a
greater "hydrogen ion pool") would cause more bronchoconstriction than
unbuffered acid aerosols of the same pH. Since the airway surface fluids have
a considerable capacity to buffer acid, it was suggested that the buffered
acid would cause a more persistent decrease in airway surface pH. If a change
in pH is the primary mechanism that triggers bronchoconstriction following
inhalation of acid aerosol, then it follows that buffered acids would be more
potent bronchoconstrictive agents. The subjects were 8 nonsmoking clinically
mild asthmatics whose medications included theophylline and p-sympathomimetic
bronchodilators. Their asthma was stable throughout the study and there were
no significant deviations in baseline SR .
clW
Subjects were first administered aerosolized solutions of unbuffered
hydrochloric acid (producing HC1 vapor) and sulfuric acid of progressively
increasing acidity (pH's were 7, 5, 4, 3, 2). The osmolarity of the aerosolized
solutions was about 300 mOsm (i.e., isoosmolar). Only one subject experienced
a demonstrable increase (120 percent) in SR at pH = 2 with HC1; the mean
cLW
increase was 28 percent for HC1 at pH = 2 and 15 percent for H2S04 at pH = 2.
With aerosols generated from glycine buffered acid solutions at pH = 2 all
subjects (except one with H2S04) experienced at least a 50 percent increase in
SR (the mean change is not reported since the test was terminated at different
clW
levels of titratable acidity for each subject depending on his or her response).
Most subjects experienced cough during the acid aerosol challenges.
These studies demonstrate that the potential for these aerosols
to stimulate cough and bronchoconstriction is related to the acidity of
the solution used to generate them. More specifically, these responses are
3-14
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related to the total available hydrogen ion (titratable acidity), not just the
pH. Since airway surface fluids are capable of buffering small amounts of
hydrogen ion, the minimal response to unbuffered acids is presumably related to
•a transient change in airway surface pH. These observations suggest the
possibility that persistent effects of acid aerosols (reported in other studies)
may be related to persistence of changes in pH of airway surface fluids.
Since most acid fogs are likely to have a low osmolarity, Balmes and
colleagues (Balmes etal., 1988a; Balmes etal., 1988b) investigated the
hypothesis that increased acidity could potentiate the known effects of
hypoosmolar aerosols to cause bronchoconstriction (Sheppard et al., 1983) in
subjects with asthma. Subjects were administered increasing quantities of five
different aerosols (5.2 to 6.3 urn): hyposmolar saline (HS), HS + H2SO.,
HS + HN03, HS + H2S04 + HN03, and issomolar H2$04. Aerosolized solutions of
saline and nitric acid separate into saline and nitric acid vapor. All acid
solutions were adjusted to pH 2 prior to generation of the aerosol. Response
to the aerosols was assessed by giving subjects a series of increasing aerosol
concentrations. The amount of aerosol required to increase airway resistance
by 100 percent was determined by making a series of SR measurements after
each dose of aerosol.
The three acid hypoosmolar aerosols caused a 100 percent increase in SR
at a lower aerosol concentration than did the hypoosmolar saline. There were
no differences in responses related to acid composition of the aerosol.
Isoomolar H?SO. aerosol did not cause a 100 percent increase in SR even at
o aw
the highest dose, estimated to be 43.5 mg/m .
The results of this study support one of the conclusions of Fine et al.
(1987), namely that the H+, not SO" or N0~ anion, is the stimulus for broncho-
constriction. However, this study also demonstrates that H+ is a more potent
stimulus to bronchoconstriction when administered in a hypoosmolar aerosol.
Nevertheless, as the authors point out, both the water content and the acid
content of the aerosols were much higher than would be seen even in the worst
case acid fog situation.
Potential risk groups sensitive to acid deposition would include individ-
uals with "acid-saturated" mucus (i.e. low initial pH), individuals whose
mucus has a low buffering capacity, or those who may have an incompletely
developed mucociliary system (i.e. infants).
3-15
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3.4.2 Reactions of Inhaled Acid With Airway Ammonia
Ammonia is present in the expired air of man and animals. Kupprat et al.
(1976) reported in man expired volumes of 2 pi at rest and 6 ul during exercise,
approximately equivalent to 0.2 ppm or 138 ug/m3. Robin et al. (1959) reported
levels of 0.38 ppm or 262 ug/m3 in dogs given intravenous NH4HC03 solution.
Larson and co-workers (1977) presented the hypothesis that expired ammonia
from the respiratory tract could react with a significant portion of inhaled
acid aerosol to produce ammonium sulfate and ammonium bisulfate. They used a
variety of sampling techniques to determine the source(s) of the respiratory
ammonia in a group of 16 subjects. When gas was sampled from the mouth, the
median NH3 concentration ranged from 130 to 210 ug/m3. Samples taken from the
nose or directly from an endotracheal tube had a median concentration of 21 to
2
29 ug/m . It was suggested that the mouth was a major source of expired
ammonia, possibly from the bacterial decomposition of salivary urea. One
microgram of NH3 can convert 5.8 ug of H2$04 to ammonium bisulfate or 2.9 ug of
sulfuric acid aerosol to ammonium sulfate. It was determined that with the
range of respiratory ammonia levels (up to 520 ug/m3) a maximum of 1,500 ug
H2S04 could be converted to (NH4)2S04. The extent to which respiratory ammonia
can react with sulfuric acid aerosol depends not only upon the production of
respiratory ammonia but also upon the inspiratory flow rate and the time within
the airways that elapses prior to impaction or sedimentation of the aerosol.
Larson et al. (1979a) extended their observations in a group of 10 subjects
and observed a higher mean value for ammonia concentration sampled at the mouth
o
of 690 ppb or 475 ug/m . These results are comparable to the mean value of
o
790 ppb (544 ug/m ) reported by Hunt and Williams (1977). The increase in
ammonia levels reported by Larson et al. (1979a) in their second report was
apparently due to an improvement in the sampling method.
Larson et al. (1979b) also reported measurements of expired ammonia in the
3 3
dog. Ammonia concentration at the mouth was 130 ug/m but was only 41 ug/m
This again suggested the importance of the oral
when measured in the trachea.
cavity as a source of ammonia.
Barrow and Steinhagen (1980) found an average expired NH, level of 78 ppb
3
in nose-breathing rats, or 54 ug/m . This is only slightly higher than results
Trachea! cannulated rats had NH- levels
for nose breathing humans, ~25 ug/m .
3
of 286 ppb or about 197 ug/m . Thus, these results suggest that the nose is a
sink for NH3 in the rat.
3-16
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Vollmuth and Schlesinger (1984) measured expired ammonia levels in a
3
group of 5 rabbits. They noted an average expired level of 185 ug/m . When
the rabbits underwent an oral cleansing and tooth brushing regimen prior to
measurement, the NH, levels decreased to 126 ug/m , indicating a significant
oral source of ammonia. Fasting, with oral hygiene, caused a further
3
reduction in expired ammonia to 68 ug/m . It was concluded that fasting
probably further reduced the oral sources of ammonia and was not associated
with reduced amino acid metabolism. Using the model of Larson et al. (1982)
it was estimated that about 14 percent of inspired 0.3 urn hygroscopic sulfuric
o
acid aerosol would be converted to (NH,)2SO. with an NhU level of 185 ug/m and
an oral cavity residence time of 200 msec.
•3
Larson et al. (1982) measured expired ammonia levels of 31 ug/m (45 ppb)
and 57 ug/m (82 ppb) from dogs breathing through the nose or mouth respec-
tively. Ammonia concentration in the trachea averaged 28 ug/m (40 ppb).
They calculated that the concentration of NhL that would be in equilibrium with
blood NH* was 38 ug/m3.
In addition, NHL levels were measured at the trachea for air drawn
3
unidirectional through either the nose or mouth. Similar levels of ~83 ug/m
were seen regardless of whether the air entered via the nose or mouth.
Neutralization of inhaled acid aerosol was linearly related to the concentra-
tion of NH3 at the level of the larynx; approximately 60 percent of inhaled
0.5 urn sulfuric acid aerosol was neutralized with laryngeal ammonia levels of
~135 ug/m and a flow rate of 0.1 L/s. The authors made estimates of
3
neutralization of 100 ug/m HUSO, in humans using a model based on this study.
These authors assumed a residence time of 0.2 seconds and a relative humidity
of 90%. They estimated that, with oral levels of ammonia, particles less than
0.2 urn would be fully neutralized by ammonia prior to entering the trachea;
only about 30 percent of 0.5 urn particles would be neutralized under similar
conditions. Larson et al.'s estimates indicate a slightly less efficient
neutralization of inhaled acid than the model of Cocks and McElroy (1984).
There appears to be considerable variability in expired ammonia levels
from one species to another. The mode of breathing or the location from which
ammonia is sampled is also the source of considerable variation. It is
important to establish whether these differences are true species differences
or methodological differences.
3-17
-------
The probability that endogenous ammonia reacted with inspired acid aerosols
to produce ammonium sulfate and bisulfate has been an issue in a number of
investigations. Some of the factors implicated in neutralization of acid
aerosols have been discussed by Larson et al. (1978). The likelihood of
neutralization of acid aerosols depends upon:
1.
2.
3.
particle size
neutralization
concentration
-- small particles are subject to more rapid
than large particles with the same acid
concentration of ammonia in the airways
concentration of acid in the aerosol - this is partially depen-
dent on hygroscopic growth of the aerosol in the airways
4. residence time of the aerosol in the airways.
It appears that ammonia concentrations are not uniform throughout the respira-
tory tract, and thus neutralization is also dependent on the avenue of inhala-
tion of acid aerosols; oral inhalation offers the greatest potential for
neutralization by ammonia.
Loscutoff et al. (1978) exposed dogs to various levels of sulfuric acid
aerosol. With 1 or 3.5 mg/m3 H2S04, they reported that all expired sulfate
was in the form of an ammonium salt. Such measurements, of course, provide no
indication of the fate of H2S04 that is deposited within the lung.
Utell et al. (1986) discussed the effects of oral ammonia in a recent
o
symposium presentation. They exposed asthmatics to 350 pg/m sulfuric acid
aerosol via mouthpiece under conditions of low (69 ug/m3) or high (340 ug/m3)
expired ammonia levels. Exposure lasted 10 min while subjects performed light
exercise. The reduction in FEV-, Q was significantly greater if the subjects
were exposed when the oral ammonia levels were lower. The higher oral ammonia
level has the potential (i.e., if the reaction goes to completion and uses up
all the ammonia) to convert over 900 ug of H^SO. to (NH.)2SO/,, while the lower
ammonia concentration could convert only about 190 ug. These data strongly
support the hypothesis that oral or respiratory ammonia may play an important
role in the airway toxicity of sulfuric acid aerosol.
However, a recent study by Avol et al. (1986; 1988), showed a similar
response to acid aerosols in subjects who gargled acidic grapefruit juice
prior to exposure and those who did not. The efficacy of the grapefruit juice
3-18
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gargle in reducing oral ammonia was not reported. A similar acidic juice
gargle (lemon concentrate) was used by Utell et al. (1986) to successfully
lower oral ammonia levels. Based on the small differences in lung function
responses between acid aerosol and sham exposures in the Avol et al. (1988)
study, it is unlikely that the study design had sufficient statistical power
to detect an effect of differing oral ammonia levels if one existed.
Cocks and McElroy (1984) have recently presented a model analysis of
neutralization of sulfuric acid aerosols in human airways. The acidity of the
particles is a function of dilution by particle growth and neutralization by
absorbed ammonia. With acid concentrations of 0.14 M and humidity 99.5%,
droplet growth does not occur, because the droplet is already at equilibrium
with lung conditions, and neutralization is determined principally by ammonia
absorption. At higher acid concentrations, droplet growth dilution is a major
factor in determination of pH (See Table 3-1).
Table 3-1 presents selected results of the model analysis of Cocks and
McElroy (1984). Data are presented for 5.0 (acid fog) and 0.5 |jm and 1.0 urn
Q
(acid aerosol) particles at both 500 (oral) and 50 (nasal) ug/m ammonia, at
times of 0.1 and 1.0 s, and for three different acid concentrations.
For 0.5 urn particles with H9SO, concentration of 3M, aerosol mass concen-
3 3
tration of 100 ug/m and ammonia of 500 ug/m , neutralization is complete in
o
0.3 s. With NH3 levels of only 50 ug/m , neutralization requires 3 s. With an
acid concentration of 0.14M, where no particle growth occurs, neutralization
proceeds more rapidly. The authors concluded that, even with nasal levels of
ammonia, substantial neutralization of droplets less than 0.5 urn would occur.
With droplets in the "acid fog" size range and with relatively higher pH,
neutralization is rapid, especially with high ammonia levels. However, the
typically dilute solutions in acid fog droplets lend themselves to rapid
neutralization such that the reaction of 5 urn particles with oral levels of
ammonia would be complete in less than 1.0 s with aerosol mass concentration
o
as high as 100 ug/m . However, at the inspiratory flow rates achieved during
exercise, the residence time of a particle in the oral cavity will be much
less than 1.0 second.
Larson (1989) recently presented a model analysis which considered both
airway deposition and ammonia neutralization. This analysis indicates that
virtually no acid fog particles will successfully traverse the nasal airway
whether ammonia is present or not. During mouth breathing, acid fog particles
3-19
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TABLE 3-1. MODEL ESTIMATES OF NEUTRALIZATION OF 0.5, 1.0 AND 5.0 urn
PARTICLES BY "ORAL" AND "NASAL" LEVELS OF AMMONIA
(Adapted from Cocks and McElroy, 1984)
H2S04
7.0mM
0.14M
3.3M
Aerosol
Initial acid mass NH3
RH ug/m3 |jg/m3
99.973 1,000 500
(oral )
50
(nasal)
100 500
50
99.5 1,000 500
50
100 500
50
80 1,000 500
50
100 500
50
MMAD
urn
5.0
5.0
5.0
5.0
5.0
1.0
5.0
1.0
5.0
1.0
5.0
1.0
1.0
0.5
1.0
0.5
1.0
0.5
1.0
0.5
% Neutral
O.ls
100
11.7
100
22.1
11.7
100
1.2
12.6
12.1
1.2
1.2
27
19.1
68.5
1.9
6.9
20.4
90.2
2.0
9.0
ized in
1.0s
100
14.4
100
100
81.9
100
8.2
14.4
100
100
11.7
100
99.9
99.6
12.3
14.2
100
99.9
25.7
81.3
Note: with 1000 ug H2S04 and 50 ug NH3, maximum neutralization is
approximately 15%.
could reach the larynx and trachea but they are largely neutralized by oral
ammonia. Using calculations from this model, the effect of ammonia in decreas-
ing acid deposition of small aerosols with a higher acid concentration was
much less than for the large fog droplets because of the greater surface area
to acid-mass ratio (as distinct from the surface to volume ratio) of the larger
more dilute droplets. Larson also discussed that a soluble acid gas such as
HNOo in fog, would be expected to deposit in the nose where it would be
removed as a gas or else be removed by impaction of fog droplets in the proxi-
mal trachea-bronchial region.
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3.5 CONCLUSIONS
The respiratory tract is a target for inhaled particles, as well as a
portal of entry by which other organs may be affected. When aerosols are
inhaled by humans or experimental animals, different fractions of the inhaled
materials deposit by a variety of mechanisms in various locations in the
respiratory tract. Particle size distribution and other particle properties,
respiratory tract anatomy, and airflow patterns all influence deposition.
Impaction, gravitational settling, and diffusion dominate the deposition
of particles in the respiratory tract, with electrostatic attraction and
interception being of relatively minor importance. Diffusivity and the inter-
ception potential of a particle depend on its geometrical size, whereas the
probability of settling and impaction depend on its aerodynamic diameter.
Gravitational settling accounts for deposition in the tracheobronchial and
pulmonary regions, while impaction contributes to deposition in the upper
respiratory tract and tracheobronchial regions. Diffusion primarily affects
respiratory tract deposition of particles with diameters smaller than 0.2 urn.
Hygroscopicity is a major particle characteristic which affects deposition.
Hygroscopic particles change in size once inhaled, and may have different
patterns of deposition when compared to nonhygroscopic particles of the same
size; the difference is a function of the initial particle size and composition.
Some portion of inhaled acids will be transformed into the ammonium salts
as the acid enters the respiratory tract. Acid that is deposited in the
airways prior to reaction with ammonia will be buffered by airway surface
fluids. The extent to which these two processes will influence the ultimate
fate of the acid will depend upon a number of factors. Larger particles in the
"acid fog" size range (5 urn) will be slower to be neutralized but more likely
to impact upon the airway walls. Smaller particles (~0.5 urn) are subject to
more rapid chemical transformation by ammonia.
The total capacity to buffer or "neutralize" acid is substantial. How-
ever, regional capacities vary considerably. For example, the surface liquid
buffering capacity of the non-ciliated airways and alveoli is probably quite
low. Furthermore, alveolar ammonia levels are lower than in the oral cavity.
It is therefore likely that the physiologic effects of inhaled acid aerosols
are due to either accumulation of acids at specific sites that overwhelms the
neutralization/buffer capacity or to accumulation in lung regions that have a
low neutralization/buffer capacity.
3-21
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3.6 REFERENCES
Avol, E. L.; Linn, W. S.; Hackney, J. D. (1986) Acute respiratory effects of
ambient acid fog episodes [final report]. Downey, CA: Rancho Los Amigos
Medical Center, Environmental Health Service; EPA grant no. ES03291-02.
Avol, E. L.; Linn, W. S.; Wightman, L. H.; Whynot, J. D.; Anderson, K. R.;
Hackney, J. D. (1988) Short-term respiratory effects of sulfuric acid in
fog: a laboratory study of healthy and asthmatic volunteers. J. Air
Pollut. Control Assoc. 38: 258-263.
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4. TOXICOLOGICAL STUDIES OF ACID AEROSOLS
4.1 INTRODUCTION
The goal of toxicologic studies is the estimation of risk to humans.
Often, this is done empirically with the use of animal models. These serve to
identify the nature of responses to toxicant exposure and the range of doses
over which such responses occur, and to provide information on mechanisms of
potential human toxicity and the pathogenesis of disease. Although studies
with experimental animals allow planning of future human studies and are, thus,
often done prior to initiating testing with humans, they are also needed for'
protocols which cannot be used with humans at all, e.g., chronic or repeated
exposures which may result in delayed and/or nonreversible changes; such
studies serve to assess how the duration, and other conditions, of exposure
affect response. In addition, the use of destructive endpoints, such as patho-
logic assessment, requires animal models even with acute exposure protocols.
This chapter reviews and evaluates the toxicology of acid aerosols in
experimental animals. Almost all of the available data have been derived from
studies using acid sulfates, i.e., ammonium sulfate ((NH4)2S04), ammonium
bisulfate (NH4HS04), and sulfuric acid (H2S04). The bulk of the studies
included involve exposure via inhalation; the effects of acids administered by
other routes have been discussed only when they help to assess the mechanisms
underlying responses to inhaled aerosols.
Although acid aerosols may be constituents of ambient atmospheres, they
are not the only pollutants present. Thus, the toxicologic effects of pollutant
mixtures are of concern in assessing the relative biological significance of
ambient acid aerosols. In this section, only studies in which a specific acid
is a primary component of the pollutant mix are discussed; those in which the
only acid present is formed secondarily due to chemical reaction in the exposure
atmosphere have not been included.
It will be evident from this survey of the data base that there is a great
deal of variation, both qualitatively and quantitatively, in observed responses
to inhaled acids. One major reason involves response differences between
4-1
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species, or between strains of the same species, due to inherent sensitivity
differences, or differences in age, health status, aerosol deposition patterns,
and respiratory tract NhL levels. But even within the same species or strain,
variability may be quite large among various studies; this is likely due to
the lack of standardization in exposure protocols. A number of experimental
variables may impact upon the observed results. Differences in median acid
particle size as well as in size distribution affect the extent of aerosol
penetration into the respiratory tract, with resultant differences in the
mechanism or degree of toxic action at the site of initial contact and, per-
haps, the extent of neutralization by respiratory tract NHg. Hygroscopic
growth is also dependent upon the initial size of the acid droplets. Relative
humidity of the exposure atmosphere is another important factor affecting the
size of the inhaled acid particle and, therefore, the extent and rate of
subsequent particle growth. In addition, the nominal acidity of a droplet may
be altered by hydration after inhalation, or in the exposure system itself.
Other reasons for variability may involve the lack of adequate characterization
of the exposure atmosphere at the animal's breathing zone, the failure to
validate that the exposure system is dosing the animals as expected, or even
differences in the manner in which data are analyzed.
A single major confounding factor in assessing acid aerosol toxicology, and
a likely explanation for at least some of the wide variations in response even
within one species, is neutralization by both endogenous or exogenous NHg
(Chapter 3). The former may be affected by factors such as the time between the
last feeding and acid exposure and the normal bacterial flora of the respiratory
tract, while a major factor influencing exogenous levels is the particular mode
of exposure.. For example, a greater potential for neutralization exists with
whole body chamber exposures, due to the possible release of NH3 from excrement.
In any case, the result of neutralization would be delivery to the animals of
less strong acid than anticipated; but without knowing the extent of conversion
to less acidic, or neutral, products, the exact composition of the resultant
exposure atmosphere is not certain. Thus, in many studies, the actual relation
between sulfuric acid levels as measured in the generation or exposure atmos-
phere and dose to target site is difficult to evaluate. Mode of exposure may
also impact upon relative regional deposition and rate of hygroscopic growth.
Thus, multiple factors are involved in determining the responses observed in any
study, and these factors may interact with each other, accounting for the
variations in response to inhaled acid aerosols seen in the current data base.
4-2
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4.2 MORTALITY
A number of studies have examined the acute lethality of acid aerosols,
mainly H2S04. As will be evident with other toxicologic endpoints, large
interspecies differences occur. Treon et al. (1950) ranked species in terms of
their sensitivity, based upon exposures (chamber) of various duration (15 min
to 7 h/d for 5d) to 87 to 1,610 mg/m H2$04 aerosols consisting of particles
with diameters mostly <2 urn; the ranking, in order of decreasing sensitivity,
was as follows: guinea pig, mouse, rat, rabbit.
Within a particular species of experimental animal, the H2$04 concentra-
tion required for lethality may be dependent upon animal age and exposure
aerosol particle size. In terms of the former, Amdur et al. (1952) determined
the H2S04 (1 urn, MMD) concentration to produce 50 percent mortality (LC™) for
an 8-hr exposure (chamber) in guinea pigs to be 18 mg/m3 for 1 to 2 mo old
O
animals, and 50 mg/m for 18 mo old animals. The effect of particle size on
lethal concentration is shown in Table 4-1. Although the actual LC5Q may
differ at similar sizes in different studies, the data show that in any one
study, smaller particles are less effective than are larger ones.
TABLE 4-1. EFFECT OF H2S04 PARTICLE SIZE ON MORTALITY
Particle Size
(urn)
0.8 (MMD)
2.7 (MMD)
0.4 (MMAD)
0.8 (MMAD)
LC50a
(mg/m3)
60
27
>109
30.3
References
Pattle et al. (1956)
Pattle et al. (1956)
Wolff et al. (1979)
Wolff et al. (1979)
Based upon 8-hr exposures (chamber) of guinea pigs.
Various environmental factors may confound the response to H~SO.. For
example, Pattle et al. (1956) noted an increase in H2S04 lethality in guinea
pigs when exposure was performed at a cold temperature (0°C), compared to room
temperature. This effect was ascribed to the direct action of cold on the
constrictive response, i.e., an added stress. On the other hand, temperature
differences may also have affected the hydration of the acid particles, which
may have altered deposition patterns.
4-3
-------
Fairly high concentrations of H2S04 are required for lethality, even in a
species as sensitive as the guinea pig. Amdur et al. (1952) found no deaths
with 8-hr exposures in 1 to 2 mo old guinea pigs at 8 mg/m3 (1 Mm, MMD).
Thomas et al. (1958) found no deaths in guinea pigs exposed (in chambers)
continuously (24 hr/d) for 18 to 140 days to 4 mg/m3 (0.59 to 4.28 (jm, MMAD);
exposures to 26.5 mg/m3 (0.59 pm) for 18 to 45 days also resulted in no mortal-
ity. Finally, Schwartz et al. (1979) reported an LD5Q of 100 mg/m3 H2$04 (0.3
to 0.4 jjm, MMAD; ag, ~1.5) for continuous, 7 d exposures (chamber).
The cause of death due to acute, high level H2S04 exposure is laryngeal or
bronchial spasm. As the concentration is reduced, more deep pulmonary damage
occurs prior to death. Lesions commonly seen are focal atelectasis, hemor-
rhage, congestion, pulmonary and perivascular edema, and epithelial desquama-
tion of bronchioles; hyperinflation is also often evident (Amdur, 1971; Wolff
etal., 1979; Cavender etal., 1977b; Rattle and Cullumbine, 1956). Since
death appears to be due largely to an irritant response, differences in the
deposition pattern of smaller and larger acid droplets may account for the
observed particle size dependence of lethal concentration; larger particles
would deposit to a greater extent in the upper bronchial tree, within which the
bulk of irritant receptors are located.
A major concern in toxicologic assessment is the relative role of concen-
tration^) and exposure duration(T) in producing a response. Unfortunately,
there are few data available to allow analysis of C x T relationships for acid
exposure. Amdur et al. (1952) did examine this in guinea pigs, and found
o
that exposure for 72 h to 8 mg/m H^SO. did not increase mortality percentages
over those observed due to 8-h exposures to the same concentration. Thus,
lethality appeared to depend on concentration rather than on the duration of
exposure. On the other hand, the extent of any histological damage appeared to
be related to cumulative exposure (Amdur et al., 1952).
There are few data to allow assessment of relative LCr« for acid aerosols
other than H2$04.
However, Rattle et al. (1956) noted that if sufficient
ammonium carbonate was added into the chamber in which guinea pigs were exposed
to H2SO. to give excess NH3, protection was afforded to acid levels that, in
the absence of NH3, would have produced 50 percent mortality. This infers that
H2SO. is more acutely toxic than its neutralization products, i.e., NH4HS04
and/or (NI-L)2SO.. Repelko et al. (1980) exposed rats (chamber) for 8 h/d for
3 days to (NH4)2$04 at 1,000 to 2,000 mg/m3 (2 to 3 pm, MMAD); no mortality
4-4
-------
resulted. On the other hand, 40 percent and 17 percent mortality was observed
in guinea pigs exposed once for 8 h to 800 to 900 or 600 to 700 mg/m3,
respectively, of similarly sized-particles; no mortality was observed at levels
<600 mg/m . Death was ascribed to airway constriction. As with H2S04, guinea
pigs are more sensitive to the lethal effects of (NH,)2S04.
The embryotoxic potential of H2$04 has been examined in three species.
Hoffman and Campbell (1977) exposed chick embryos continuously, from the 1st
through the 14th day of development, to H2S04 at 6.06 mg/m3 (0.2 to 0.3 urn,
MMAD). There was no effect on survival rate nor on organ/body weight ratios,
but embryonic weight was slightly, but significantly, reduced, as was serum
lactic dehydrogenase activity. This latter was suggested to reflect a delay in
normal development. In another study, Murray et al. (1979) exposed pregnant
mice and rabbits daily for 7 h, during the major period of organogenesis, to
o
up to 20 mg/m HgSO^. There was no evidence of any teratogenic effect, at
least based upon histological examination.
4.3 PULMONARY FUNCTION
The earliest studies examining the toxicology of inhaled acid aerosols at
sublethal levels used changes in pulmonary function as indices of response. A
survey of the data base is presented in Table 4-2.
One of the major exposure parameters that affects response is particle
size. In terms of altering pulmonary mechanics, specifically pulmonary resis-
tance in guinea pigs, studies by Amdur (1974) and Amdur et al. (1978a,b) have
found the irritant potency of H2$04, (NH4)2$04, or NH4HS04 to increase with
decreasing particle size, i.e., the degree of response per unit mass of S04~ at
any specific exposure concentration increased as particle size decreased, at
least within the range of 1 to 0.1 urn. If this is compared to the relationship
between particle size and mortality, it is evident that the relative toxicity
of different particle sizes also depends upon the exposure concentration; at
concentrations above the lethal threshold, large particles are more effective
in eliciting response, while at sublethal levels, smaller particles are more
effective. There is, however, some indication that even with pulmonary func-
tion as the endpoint, a greater response may be obtained with large particles
at high concentrations. Thus, Amdur (1958) found that in a series of 1 hr
3
exposures to -2 to ~40 mg/m H2SO. at sizes of 0.8 or 2.5 pro, the latter size
resulted in a greater response only at the highest exposure concentration used.
4-5
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Pulmonary functional responses to H2$04 suggest a major site of action to
be the conducting airways, as evidenced by exposure induced alterations in
resistance and compliance. However, some data also suggest that high exposure
levels may affect more distal lung regions. Changes in pulmonary diffusing
capacity (DLCQ), which could indicate damage to the gas-exchange region of the
lungs, were noted in dogs exposed at 0.889 mg/m3 (Lewis et a!., 1973); they
were not found in guinea pigs exposed at 0.1 mg/m3 (Alarie et a!., 1973). How-
ever, deep lung effects of H2$04 are also evident from studies of morphologic
and lung defense endpoints, discussed in subsequent sections.
The particle size of the acid aerosol appears to affect the temporal
pattern of response. For example, Amdur (1958) observed that changes in
pulmonary resistance in guinea pigs following an acute exposure to 0.8 urn HpSO.
began immediately, while a delay in the onset of response was observed when
2.5 urn particles were used. In a subsequent study also with guinea pigs (Amdur
et al., 1978a), resistance was found to return to control levels by 1/2 hr
after exposure to 0.1 mg/m3 H2$04 when the particle size was 1 urn, but exposure
to the same mass concentration of 0.3 urn particles resulted in the maintenance
of elevated resistance through this same time. Thus, the response to 0.1 mg/m3
at 1 urn was slight and rapidly reversible, while that with 0.3 urn droplets was
greater and more persistent. At any particular size, however, the degree of
change in resistance and compliance in guinea pigs was observed to be concen-
o
tration related, and at exposure concentrations >0.1 mg/m with either 1 or
0.3 pm particles, resistance remained elevated at the 1/2 h post-exposure meas-
urement time.
Although the studies by Amdur and colleagues appear to provide a reason-
able picture of the relative effects of acid particle size and exposure concen-
tration on the bronchoconstricive response of guinea pigs at sublethal exposure
levels, there is some conflict between these results and reports by others.
Whereas the former work supports a concentration dependence for respiratory
mechanics alterations, i.e., animals in each exposure group responded uniformly
and the degree of response was related to the exposure concentration, others
(Wolff et al., 1979; Silbaugh et al., 1981b) have found that individual guinea
pigs exposed to HpSO. will show an "all-or-none" constrictive response, i.e.,
in atmospheres above a threshold concentration, some animals will manifest
major changes in pulmonary mechanics ("responders"), while others will not be
affected at all ("nonresponders"). As the exposure concentration is increased
4-9
-------
further, the percentage of the population that is affected, i.e., the ratio of
responders to nonresponders, will increase, producing an apparent concentration-
response relationship. However, the magnitude of the change in pulmonary
function is similar for all responders regardless of exposure concentration.
Sensitivity to this all-or-none response may be related to an animal's airway
caliber prior to HUSO, exposure, since responders had higher pre-exposure
values for resistance, and lower values for compliance, than did nonresponders.
In any case, the threshold concentration for the all-or-none response is fairly
high (>10 mg/m3 HgSO^); in the study of Silbaugh et al. (1981b), deaths of some
responders occurred at X24.3 mg/m .
Reasons for the discrepancy with the studies of Amdur and colleagues are
not known; they may involve differences in guinea pig strains, ages, health
status, or other exposure conditions. In any case, the dyspneic response of
the guinea pig responders is similar to asthma attacks in humans, in both its
rapidity of onset and in the characteristic obstructive pulmonary function
changes with which it is associated.
Another approach which has been reported for evaluation of the acute
pulmonary functional response to HpSO. in guinea pigs involves co-inhalation of
C02 (Wong and Alarie, 1982; Matijak-Schaper et al., 1983; Schaper et al.,
1984). This procedure assesses the response to irritants by measuring the
decrease in tidal volume (Vy) which is routinely increased above normal by
adding 10 percent C02 to the exposure atmosphere. Although the exact mechanism
underlying a reduction in C02 response is not known (e.g., it may be due to
changes in resistance or compliance) the assumption is that the change in
ventilatory response after irritant exposure is due to direct stimulation of
irritant receptors. An exposure concentration dependent decrease in response
to C02 has been found following 1-hr exposures (head-only) to H2S04 (~1 urn,
MMD) at levels >40.1 mg/m3 (Wong and Alarie, 1982). Subsequently, Schaper et
al. (1984) exposed guinea pigs (head-only) for 0.5 h to H^O^ at 1.8 to
54.9 mg/m3 (0.6 urn, AED, erg = 2.9). At concentrations >10 mg/m , the level of
response (i.e., the maximum decrease in ventilatory response to C0?) increased
3
as a function of exposure concentration. However, below 10 mg/m , there was no
relation between exposure concentration and response; in these cases, the
effect was transient, with a decrease in C02 response occurring at the onset of
acid exposure, but subsequently fading.
4-10
-------
The results of the studies with C02 differ from those of both Silbaugh
et al. (1981b) and Amdur and colleagues, in that there was neither an "all or
none" response as seen by the former, nor was a concentration-response rela-
tionship observed at H2$04 concentrations <10 mg/m3 as reported by the latter.
In addition, Amdur and colleagues observed sustained changes in lung function,
rather than a fading response, at low concentrations. The reasons for these
differences are unknown, but may partly reflect inherent sensitivity differ-
ences of the experimental techniques and/or animal strains used.
The relative potency of various sulfates to alter resistance or compliance
in guinea pigs with acute exposure was examined by Amdur et al. (1978b). They
found that the percentage increase in resistance per unit mass of SO/" (at
equivalent particle, sizes) was greater for HpSO, than for either (NH.^SO, or
NH4HS04. However, NH4HS04 was found to be less potent than was (NH.^SO.. The
greater irritancy of (NH4)2$04 compared to NH4HS04 is unexpected, since the
former is less acidic. This particular ranking was not found in pulmonary
function studies in humans (Utell et al., 1982) nor in mucociliary transport
studies in rabbits (Schlesinger, 1984). Using an acidic NO salt, i.e.,
}\
NhLNO.,, Loscutoff et al. (1985) found no changes in pulmonary mechanics in rats
or guinea pigs exposed to 1 mg/m (0.6 urn) for 6 h/d, 5 d/wk for up to 20 d;
(NH4)?S04 was more potent in this regard.
The specific mechanism underlying acid induced pulmonary functional
changes is not known, but irritant receptor stimulation may occur due to direct
contact by deposited particles or due to mediators released as a result of
exposure. In terms of the latter, a possible candidate in mediation of the
bronchoconstrictive response, at least in guinea pigs, is histamine. Charles
and Menzel (1975) incubated guinea pig lung fragments with various salts,
including (NH4)2$04, NH4N03, NH4C1, NaCl, and Na2S04. The first three resulted
in histamine release in proportion to their concentration ((NH4)2S04 was the
most effective), while no histamine release was found with the latter two.
Since SO/~ itself appeared not to be involved in the response (no effect was
seen with Na2S04) and NH4+ was apparently needed for sulfate-mediated histamine
release, this mechanism would not seem to explain the bronchoconstrictive
effects due to H?SO. exposure. However, in whole animal studies, similar
pulmonary function responses were found in guinea pigs exposed to histamine or
H2S04 (Popa et al., 1974; Silbaugh et al., 1981b), and H2$04 exposure resulted
in degranulation of mast cells (Cavender et al., 1977a). Whether histamine is
4-11
-------
Involved in other species of animals is not certain. Interspecies differences
in response to histamine do exist; perhaps this is one factor accounting for
interspecies response differences to HpSO,.
Evidence for a direct response to HgSO^ in altering pulmonary function is
found using the C02 coinhalation procedure. Schaper and Alarie (1985) noted
that the responses to histamine and HgSO^ differed in both their magnitude and
temporal relationship, suggesting direct action of the inhaled acid.
There are few data to allow an interspecies comparison of acid aerosol
induced pulmonary function response, but examination of the available evidence
(Table 4-2) suggests that guinea pigs are more sensitive than the other species
examined. An exception is the study by Loscutoff et al. (1985), in which rats
were more affected by exposure to (NH-^SO* than were guinea pigs; this was not
supported by the (NH4)2$04 mortality study of Pepelko et al. (1980). The
reason for this discrepancy is unknown.
The results of pulmonary function studies indicate that HUSO, is a
bronchoactive agent that will alter lung mechanics of exposed animals primarily
by constriction of smooth muscle; however, the threshold concentration for this
response is quite variable, depending upon the animal species and measurement
procedure used. But although changes in resistance and compliance are markers
of exposure, the health significance of these in normal individuals is unknown.
On the other hand, all subgroups of an exposed population may not have equal
sensitivity to inhaled pollutants. In fact, some may be especially sensitive.
For example, in humans increased hospital admissions in summer for acute respi-
ratory disease, including asthmatic attacks, may be related to ozone, sulfate
and temperature (Bates and Sizto, 1986). These investigators speculate that
the Oo and sulfate may be surrogates for other pollutants; it has been
suggested that one possibility for the latter is H^SO* (Lippmann, 1985). Some
lung diseases, the most notable of which is asthma, involve a change in airway
"responsiveness", i.e., an alteration in the degree of reaction to exogenous
(or endogenous) bronchoactive agents, resulting in increased airway resistance
at levels of these agents which do not affect normal individuals. Such altered
airways are called hyperresponsive. The use of pharmacologic agents capable of
inducing smooth muscle contraction, a technique known as bronchoprovocation
challenge testing, can assess the state of airway responsiveness after exposure
to a nonspecific stimulus such as an inhaled irritant.
The ability of HpSO* aerosols to alter airway responsiveness has been
assessed in two studies. Silbaugh et al. (1981a) exposed guinea pigs (chamber,
4-12
-------
80 percent RH) for 1 hr to 4 to 40 mg/m3 H2$04 (1.01 ym, MMAD, ag = 1.3-1.7)
and examined the subsequent response to inhaled histamine. Some of the animals
showed an increase in pulmonary resistance and a decrease in compliance at
H2S04 concentrations >19 mg/m and without histamine challenge; only the
animals showing this constrictive response during acid exposure also had major
increases in histamine sensitivity, suggesting that airway constriction
may have been a prerequisite for the development of hyperresponsivity. In
another study, Gearhart and Schlesinger (1986) exposed rabbits (nose-only,
80 percent RH) to 0.25 mg/m3 H2S04 (0.3 urn, MMAD; ag = 1.6) for 1 h/d, 5 d/wk,
and assessed airway responsiveness after 4, 8, and 12 mo of exposure, using
acetylcholine administered intravenously. Hyperresponsivity was evident at
4 mo, and a further increase was found by 8 mo; the response at 12 mo was
similar to that at 8 mo, indicating a stabilization of effect. Unlike the
previous results in guinea pigs, there was no change In baseline resistance
(i.e., measured prior to bronchoprovocation challenge) at any time during the
acid exposures. Thus, repeated exposures to H2S04 resulted in the production
of hyperresponsive airways in previously normal animals; this may then
"sensitize" the airways to further acid exposure, or to exposure to other
airborne materials.
The mechanism that underlies sulfuric acid-induced airway hyperrespon-
siveness is not clear. Neither is its relation to airway disease. Although
hyperresponsivity is associated with specific diseases, its pathogenetic
significance is not understood. Human asthmatics and, to some extent, chronic
bronchitics typically have hyperresponsive airways (Ramsdell etal., 1982;
Ramsdale et a!., 1985; Simonsson, 1965), but it is not known whether this state
is a predisposing factor in clinical disease, or merely a reflection of other
changes in the airways that precede it. At this point, circumstantial
evidence supports the hypothesis that an increase in airway responsivity may be
a risk factor in development of obstructive airway disease (Fish and Menkes,
1984). More work is clearly needed to resolve this issue.
From the previous discussion, it is possible that one particular group
of individuals that may have altered response to pollutants are those with
respiratory disease. Unfortunately, there are very few data to allow examina-
tion of the effects of different disease states in experimental animals upon
response to acid aerosols. Rats and guinea pigs with elastase-induced pulmonary
emphysema were examined to assess whether repeated exposures (6 h/d, 5 d/wk,
4-13
-------
20 d) to (NH4)2S04 (1 mg/m3, 0.4 ym MMAD) or NH4N03 (1 mg/m3, 0.6 pm MMAD)
would alter pulmonary function compared to saline-treated controls (Loscutoff
et a!., 1985). Similarly, dogs having lungs impaired by exposure to N02 were
treated with H2S04 (0.889 mg/m3, 21 h/d, 620 d) (Lewis et al., 1973). Both of
these studies indicated that the specific disease states induced did not enhance
the effect of acid aerosols in altering pulmonary function; in some cases, there
were actually fewer functional changes in the diseased lungs than in the
unimpaired animals. It is, however, possible that other types of disease states
could result in enhanced response to inhaled acid aerosols; as mentioned, asthma
is a likely one.
4.4 RESPIRATORY TRACT MORPHOLOGY AND BIOCHEMISTRY
Morphologic damage associated with exposure to lethal levels of acid
aerosols has been previously discussed. Of greater concern, perhaps, are those
changes associated with sublethal exposures. A survey of these, as determined
microscopically, is provided in Table 4-3.
Single or multiple exposures to H2S04 at fairly high levels (»1 mg/m ) is
associated with a number of characteristic responses, e.g., alveolitis,
bronchial and/or bronchiolar epithelial desquamation, and edema. However, the
sensitivity of morphologic endpoints to these exposure levels is dependent upon
the animal species. Comparative sensitivity of the rat, mouse, rhesus monkey
and guinea pig was examined by Schwartz et al. (1977) using mass concentrations
o
of H2S04 >30 mg/m at comparable particle sizes. Both the rat and the monkey
were quite resistant, while the guinea pig and mouse were the more sensitive
species. The nature of lesions in the latter two were similar, but differed in
location; this is, perhaps, a reflection of differences in the deposition
pattern of the acid droplets. Mice would tend to have greater deposition in
the upper respiratory airways than would rats (Schlesinger, 1985), which could
account for the laryngeal and upper trachea! location of the lesions seen in
the former. The relative sensitivity of the guinea pig and relative resistance
of the rat to acid sulfates is supported by results from other morphological
studies (Busch et al., 1984; Cavender et al., 1977b; Wolff et al., 1986).
As mentioned previously, the severity of lung histologic damage appears to
depend upon some combination of concentration and length of exposure, rather
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-------
than concentration alone. For example, guinea pigs exposed to 8 mg/m3 FUSO.
for 72 hr (C x T = 576 (mg/m )«h showed more extensive tissue damage than did
those exposed at 20 mg/m3 for 8 h (C x T = 160 (mg/m3)-h. There was no
mortality at the first condition, but 50 percent at the second (Amdur et al.,
1952).
With mortality and pulmonary mechanics as endpoints, the particle size of
the acid droplet plays a role in relative toxicity. There are conflicting data
in this regard with morphologic alteration, although the reasons for this are
unclear. Thomas et al. (1958) exposed guinea pigs for 5 mo to >1 mg/m3 H2$04
at three sizes, 0.59, 0.93, and 4.28 urn (MMAD). At nonlethal levels, the
midsize particle appeared to be the most effective in producing a morphologic
response. More recently, however, Cavender et al. (1977b) exposed guinea pigs
to 20 mg/m3 H2S04 for 7 to 28 d at three particle sizes, 0.53, 0.99, and
1.66 urn (MMD). There was no apparent size-related difference in response.
Similarly, Alarie et al. (1975) noted no size dependence (<1 urn to 5 urn) for
O
the histopathologic effect of >1 mg/m H2S04 exposures in monkeys.
Repeated or chronic exposures to H2$04 at concentrations <1 mg/m3 produce
a response characterized by hypertrophy and hyperplasia of epithelial secretory
cells. In morphometric studies of rabbits exposed to 0.25 to 0.5 mg/m3 H2S04
(0.3 pm) for 1 h/d, 5 d/wk, increases in the relative number or density of
secretory cells have been found to extend to the bronchiolar level (Schlesinger
et al., 1983; Gearhart and Schlesinger, 1988), where these cells are normally
rare or absent. The changes began within 4 wk of exposures, and persisted for
up to 3 months following the end of exposure. Persistently increased secretory
cell number in peripheral airways is significant, since an excess of mucus in
this region, a likely consequence of this increase (Jeffery and Reid, 1977), is
associated with chronic bronchitis (Hogg et al., 1968; Matsuba and Thurlbeck,
1973).
A shift in the relative number of smaller airways in rabbits was found
o
after 4 mo of exposure to 0.25 mg/m (0.3 urn) for 1 hr/d, 5 d/wk (Gearhart and
Schlesinger, 1988). Changes in airway size distribution due to irritant
exposure, specifically cigarette smoke, has been reported in humans (Petty
et al., 1983; Cosio et al., 1978); in these cases, the size change is ascribed
to inflammation. It is, therefore, of interest that the response seen in the
acid-exposed rabbits was not accompanied by inflammation. In any event, size
change seems to be an early change relevant to clinical small airways disease.
4-19
-------
Damage to the respiratory tract following exposure to acid aerosols may be
determined by methods other than direct microscopic observation. Analysis of
bronchopulmonary lavage fluid obtained from exposed animals can also provide
valuable information. For example, levels of cytoplasmic enzymes, such as
lactic dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6-PD), are
markers of cytotoxicity; an increase in 'lavageable protein suggests increased
permeability of the alveolocapillary barrier; levels of membrane enzymes, such
as alkaline phosphatase, are markers of disrupted membranes; the presence of
fibrin degradation products (FDP) provides evidence of general damage; and
sialic acid, a component of mucoglycoprotein, may be an indicator of mucus
secretory activity.
Henderson et al. (1980b) exposed rats (chamber) for 6 h to H9SOA (0.7 urn,
Q fc T"
MMAD) at 1.5, 9.5, and 98.2 mg/m and found FDP in blood serum after exposure
at all concentrations. No FDP was found in the lavage fluid, but since the
washing procedure did not include the upper respiratory tract (i.e., anterior
to and including the larynx), the investigators concluded that the FDP observed
in the serum was an indicator of upper airway injury. An exposure concentra-
tion dependent increase in sialic acid content of the lavage fluid was also
observed; this was ascribed to increased secretory activity in the tracheo-
bronchial tree.
Wolff et al. (1986) exposed both rats and guinea pigs for 6 h to H^SO.
(0.8 to 1 Mm, MMAD), at levels of 1.1 to 96 mg/m3 for the former and 1.2 to
o
27 mg/m for the latter. No changes in LDH, lavageable protein nor sialic acid
content of lavage fluid was found in the rat. However, some of the guinea pigs
3
exhibited bronchoconstriction after exposure to 27 mg/m , and only these
animals showed increased levels of lavageable protein, sialic acid and LDH. No
change in lavageable protein was found in the lungs of rats exposed for 3 d
(23.5 h/d) to 1 mg/m3 (0.4 to 0.5 pm, MMAD) H2$04 (Warren and Last, 1987), nor
for 2 d (23.5 h/d) to 5 mg/m3 (0.5 pm, MMAD) (NH4)2$04 (Warren et al., 1986).
The hydroxy pro line content of the lungs may provide an index of collagen
deposition or degradation. No change in total lung synthesis or content of
hydroxy pro line was found in rat lungs after exposure for 7 d (23.5 h/d) to
3
SO, nor due to a 7 d exposure to 1 mg/m
4.84 mg/m (0.5 pro, MMAD)
(0.5 urn) H£S04 (Last et al., 1986).
4-20
-------
A series of studies by Last and colleagues assessed the synthesis of
collagen by minces prepared from rat lungs after iji vivo acid sulfate expo-
sure; this is a possible indicator of the potential for pollutants to produce
fibrosis. Exposure for 7 d (23.5 h/d) to H2$04 at 0.04, 0.1, 0.5, and 1 mg/m3
(0.4 to 0.5 urn, MMAD) resulted in no increase in collagen synthesis rate
(Warren and Last, 1987). No effect on collagen synthesis by rat lung minces
was found due to 7 d exposures to (NH4)2$04 at 5 mg/m3 (0.8 to 1 urn, MMAD)
(Last et a!., 1983).
Another parameter of damage and/or inflammation is change in lung DNA, RNA
or total lung protein. No significant changes in any of these were found in
rats after exposure to 1 mg/m3 H2$04 (<1 urn) for 3 d (Last and Cross, 1978),
nor in tissue protein content in rats exposed for up to 9 d to a similar
concentration of H2$04 (Warren and Last, 1987).
The data base concerning morphological alterations shows that acid
sulfates are both upper airway and deep lung irritants. But the specific
pathogenesis of acid-induced lesions is not known. As with pulmonary mechan-
ics, both a direct irritant effect of deposited acid droplets on the epithelium
and/or indirect effects, perhaps mediated by humoral factors such as histamine,
may be involved. Similar lesions have been produced in guinea pig lungs by
exposure to either histamine or H2$04 (Cavender et al. , 1977a); however, the
former appears to initiate the lesions, and once they are so initiated, further
acid exposure produces necrosis more rapidly than does further histamine
exposure. In addition, some lesions may be secondary to reflex bronchocon-
striction, to which guinea pigs are very vulnerable, rather than primary
effects separable from constriction. Thus, damage at the small bronchi and
bronchiolar level may be due not only to direct acid droplet-induced injury,
but to indirect reflex-mediated injury (Brownstein, 1980).
The mechanism underlying secretory cell hyperplasia at low HpS04 exposure
levels is also unknown; it may involve an acid-induced increase in division of
existing cells, or transition from a different cell type. Other irritants
(e.g., tobacco smoke and S02) have been shown to result in the conversion of
one epithelial cell type into another, e.g., serous cell to goblet cell, or
Clara cell to goblet cell (Reid et al., 1983; Phipps, 1981; Reid and Jones,
1979).
4-21
-------
4.5 RESPIRATORY TRACT DEFENSES
The response to air pollutants often depend upon interaction with an array
of nonspecific and specific respiratory tract defenses. The former consist of
nonselective mechanisms protecting against a wide variety of inhaled materials;
the latter require immunologic stimulation for activation. Although these
systems may function independently, they are linked; for example, response to
an immunologic insult may enhance subsequent response to non-antigenic materi-
als as well. The overall efficiency of lung defenses determines the local
residence times for inhaled deposited material, which has a major influence
upon the degree of pulmonary response; furthermore, depression or over-activity
of these systems may be involved in the pathogenesis of lung disease.
Studies of altered lung defenses due to inhaled acid aerosols have concen-
trated on examination of conducting and respiratory region clearance function;
there are only a few studies of effects upon immunologic competence.
4.5.1 Clearance Function
Clearance, a major nonspecific defense mechanism, is the physical removal
of material that deposits on airway surfaces. The mechanisms involved are
regionally distinct. In the conducting (i.e., tracheobronchial) airways,
clearance occurs via the mucociliary system, whereby a mucus "blanket" overly-
ing the ciliated epithelium is moved by the coordinated beating of the cilia
towards the oropharynx. The mucus cover is actually bilayered, at least in the
central airways. It consists of a lower hypophase (sol) overlying the
epithelium and bathing the cilia, and an upper epiphase (gel) resting on top of
the cilia.
In the respiratory (i.e., alveolated) region of the lungs, clearance
occurs via a number of mechanisms and pathways, but a major one for both
microbes and nonviable particles is the alveolar macrophage. These cells rest
on the fluid lining of the alveolar epithelium, where they move by ameboid
motion. Via phagocytic ingestion of deposited particles, macrophages help
prevent penetration through the alveolar epithelium and subsequent transloca-
tion to other sites. These cells contain proteolytic enzymes, allowing
digestion of a wide variety of organic materials, and they also kill bacteria
through peroxide-producing oxidative mechanisms. In addition, macrophages are
involved in the induction and expression of immune reactions. Thus, the
macrophage provides a link between the lung's nonspecific and specific defense
4-22
-------
systems. Macrophages may be cleared from the respiratory region along a number
of pathways, but the primary one is via the mucociliary system after these
cells reach the distal terminus of the mucus blanket (Bowden, 1984).
4.5.1.1 Conducting Airways - Mucociliary Clearance. The assessment of effects
upon mucociliary clearance due to inhaled acid aerosols often involved examina-
tion solely of mucus transport rates in the trachea, since this is a readily
accessible airway and tracheal mucociliary clearance measurements are more
straightforward to perform than are those aimed at assessing clearance from the
entire tracheobronchial tree. Table 4-4 outlines reported studies of acid
aerosol effects upon tracheal mucociliary clearance; all of the available data
are for sulfate compounds.
Although many of the studies involved fairly high concentrations of acid
aerosols, most demonstrated a lack of effect. The most likely explanation for
this is that the size of the aerosol used precluded significant tracheal
deposition. This is supported by noting that Wolff et al. (1981) found
tracheal transport rates in dogs to be depressed only when using 0.9 (jm H?S04,
while no effect was seen with a 0.3 pm aerosol at an equivalent mass concen-
tration. In any case, the use of tracheal clearance rate as a sole toxicologic
endpoint may be misleading, inasmuch as other studies (Schlesinger et al.,
1978, 1979) have demonstrated changes in bronchial clearance that were not
associated with any change in tracheal transport.
The results of studies assessing the effects of acid aerosols upon
bronchial mucociliary clearance are outlined in Table 4-5. Observed responses
to H2$04 indicate that the direction of clearance change, i.e., slowing or
speeding, following acute exposure is dependent upon both exposure concentra-
tion (C) and exposure time (T) (Schlesinger, 1989); stimulation of clearance
occurs at low CxT values, and retardation at higher levels. However, the
actual value needed to produce an observed acceleration may be dependent upon
the region within the bronchial tree from which clearance is being measured, in
relation to the region that is most affected by the deposited acid (Leikauf
eta!., 1984). Thus, in effect, low H2$04 exposure concentrations, i.e.,
~0.1 to 0.3 mg/m for 1 hr, accelerate clearance from the large proximal
airways, where there is little deposition, while slowing clearance from the
distal ciliated airways, where there is greater acid deposition. At higher
exposure concentrations, i.e., > -0.75 mg/m3 for 1 hr, mucociliary clearance
from both proximal and distal conducting airways is depressed.
4-23
-------
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4-25
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Comparison of responses to H2S04 suggest that there are possible inter-
species differences in responsiveness of mucociliary clearance to inhaled acid
aerosols (Wolff et al., 1986). As an example, the speeding of trachea! trans-
port in the rat with ~100 mg/m3 H2$04 seems anomalous since, in other species,
levels >1 mg/m produce mucociliary depression. The reasons for this observa-
tion are not known. The rat is less susceptible to the lethal effects of
H2S04, and it does not have strong bronchoconstrictive reflex responses
following H2S04 exposures. These characteristics, together with the lack of
effect of H2S04 on bronchial clearance at fairly high exposure levels
(3.6 mg/m for 4 hr), suggest that the mucociliary system of the rat may also
differ in sensitivity from most of the other species studied. Although the
lack of response of trachea! transport in the guinea pig at H2SO, levels
>1 mg/m is also surprising, its response at 1 mg/m3 is also different from
that of the rat and more in line with other species (Wolff, 1986). As with all
studies, however, it should be borne in rnind that differences in experimental
variables, such as aerosol particle size, may contribute to some extent to
apparent response differences between species.
The relative irritant potency of acid sulfate aerosols, in terms of
altering mucociliary clearance, is likely related to their degree of acidity.
Schlesinger (1984) exposed rabbits for 1 h to submicrometer aerosols of NH.HSCL,
(NH4)2S04 and Na2S04. Exposure to -0.6 to 1.7 mg/m3 NH4HS04 produced a signif-
icant depression of clearance rate only at the highest level. No significant
effects were observed with the other sulfate compounds at levels up to
~2 mg/m . When these results are compared to those from a study using H2S04
(Schlesinger et al., 1984), the ranking of irritant potency is found to be
H2S04
> NH4HS04 > (NH4)2S04, Na2S04; this strongly suggests a relation between
C- T *T t , t £. t C. t ~
the hydrogen ion (H ) concentration (total acidity) and the extent of bronchial
mucociliary clearance alteration. In another study, Schlesinger et al. (1978)
found bronchial clearance to be altered in donkeys exposed to H2S04 for 1 hr at
levels above ~0.2 mg/m3, while exposures to (NH4)2S04 at up to 3 mg/m3 produced
no response.
The mechanism by which deposited acid aerosol may alter clearance is not
certain. The effective functioning of mucociliary transport depends upon
optimal beating of the cilia and the presence of mucus having appropriate
physicochemical properties. Both ciliary beating and mucus viscosity may be
affected by the deposition of acid (Hoima, 1985). Normally, tracheobronchial
4-2(
-------
mucus has a pH of -6.5 to 8.2 (Kwart et al., 1963; Guerrin et al., 1971; Gatto,
1981; Holma et al., 1977). In vitro studies have shown that, at alkaline pH,
mucus is more fluid than at acid pH; the inflection point occurs at a pH between
7.5 to 7.6 (Breuninger, 1964). A small increase in viscosity which may occur
due to deposited acid could "stiffen" the mucus blanket, perhaps promoting the
clearance mechanism and, thus, increasing its efficiency (Holma et al., 1977).
Such a scenario may occur at low H2S04 exposure concentrations, where ciliary
activity would not be directly affected by the acid, and is consistent with
clearance acceleration observed at these concentrations with acute exposure.
However, the exact relation between mucus viscosity and transport rate is not
certain; differential alterations in rheological properties of the sol or gel
layers may have different effects upon the system (Puchelle and Zahm, 1984).
Higher exposure concentrations of H2$04, in addition to altering mucus
viscosity, may also affect ciliary beating. Schiff et al. (1979) and Grose
et al. (1980) found that 2- to 3-h rr\ vivo exposures of hamsters to ~0.9 to
1 mg/m H2S04 resulted in a depression of ciliary beating frequency in trachea!
explants prepared after exposure, ^n vitro studies indicate that complete
ciliostasis will occur if the pH is low enough (Holma et al., 1977); however,
regional ciliostasis, presumably with a change in clearance function, may occur
at pH values above this critical level. Thus, a H+-induced depression of
ciliary beating, due to a direct impact upon the cilia and/or to a change in
mucus viscosity, could account for the observed retardation of clearance
observed at high concentrations of H2$04 (or NH4HS04) with acute exposures.
There is some evidence, however, that the response to H2S(L may not be
entirely due to the free H+. Schiff et al. (1979) exposed hamster trachea!
rings ui vitro to H2S04 in medium for 3 h and examined ciliary beat frequency
and cytology; the pH of the medium was ~5. There was no effect upon beat
frequency when the tissue was examined within 1 h after exposure, although
morphological damage was evident at this time; at 24 h after exposure, beat
frequency was depressed. They then exposed trachea! explants for 3 h to the
same medium as above, but with the pH adjusted to 5 using hydrochloric acid
(HC1). Exposure under this condition resulted in a reduction in beat
frequency, but no change in cell morphology. When these latter explants were
transferred to fresh culture medium, the cilia resumed beating at their normal
frequency. According to the investigators, these results indicated that medium
at pH 5 itself produced no lasting morphological effects, and that acidity
4-27
-------
alone (at least as measured by pH) was not responsible for the observed morpho-
logical and functional effects produced by the H2$04. Fine et al. (1987) have
suggested that response is due to total H concentration rather than pH.
Another (or an additional) mechanism by which deposited acid may affect
mucociliary clearance is via alteration in the rate and/or amount of mucus
secretion. A mild, irritant induced increase in the quantity of mucus, to
which the mucociliary system adapts by speeding transport, is consistent with
the initial increase in bronchial clearance rates observed following acute
exposures to low concentrations of H2S(L. Direct evidence for hypersecretion
is limited. In a study that examined secretory rate, Last and Cross (1978)
showed that exposure of rats for 23.5 h/d for 3 days to submicrometer H2$04 at
~1 mg/m did not affect the secretion of mucus glycoprotein from trachea!
explants prepared after exposure; however, the effect on secretion from smaller
conducting airways was not examined. On other hand, Henderson et al. (1978),
using analysis of lavage fluid to detect responses in the lungs of rats exposed
o
to 1, 10, or 100 mg/m H^SO. for 6 h, showed a concentration related increase
in sialic acid content, which the authors suggested to indicate increased mucus
secretion. Although mild irritation may increase clearance rate, at some
point, oversecretion due to higher exposure concentrations will likely result
in an overloading of the clearance system, and a retardation in transport rate
(Wolff, 1986; Albert eta!., 1973). This likely occurs with repeated or
o
chronic exposures, even to lower (0.1-0.25 mg/m ) acid concentrations.
The airways actively transport ions, and the interaction between trans-
epithelial ion transport and consequent fluid movement is important in the
maintenance of the mucus lining. A change in ion transport due to deposited
acid particles may, for example, alter the depth and/or composition of the sol
layer (Nathanson and Nadel, 1984), perhaps affecting clearance rate. Although
no data are available regarding acid sulfates, Stutts et al. (1981) found that
ammonium nitrate (NH.NO,) altered sodium and chloride transport across canine
+ -
trachea! epithelium. The response was ascribed to NH4 rather than to N03 .,
since sodium nitrate (NaN03) had no effect; mucociliary transport was not
examined.
The pathological significance of transient alterations in bronchial
clearance rates in healthy individuals is not certain, but such changes are an
indication of a lung defense response. On the other hand, persistent impair-
ment of clearance may lead to the inception or progression of acute or chronic
4-28
-------
respiratory disease and, as such, may be a plausible link between inhaled acid
aerosols and respiratory pathology.
Short-term exposures to acid aerosols may lead to persistent clearance
changes. Schlesinger et al. (1978) demonstrated that weekly 1-h exposures of
donkeys to submicrometer H2$04 at 0.2 to 1 mg/m3 produced a transient slowing
of bronchial clearance in 3 of 4 animals. However, two of the four (including
one that did not respond after any individual test) developed persistently
slowed clearance after about 6 of the exposures; this slowing persisted for two
months after all acid exposures had ceased.
The development of persistent alterations after a relatively small number
of 1-h weekly exposures emphasizes that, in order to evaluate fully the impact
ambient acid aerosols might have upon the inception and progression of respira-
tory disease, it is essential to consider the effects of intermittent exposures,
especially at low exposure concentrations. Thtts, as a follow-up to the above
study, Schlesinger et al. (1979) exposed the two donkeys that had shown only
transient responses, as well as two previously unexposed animals, to 0.1 mg/m3
H2S04 for I n/d» 5 d/week for 6 months. Within the first few weeks of exposure,
all four animals developed erratic clearance rates. The two previously
unexposed animals developed persistently slowed bronchial clearance during the
second three months of exposure, and during four months of follow-up clearance
measurements, while the two previously exposed animals adapted to the new
exposures in the sense that their clearance times fell consistently within
the normal range during the last few months of acid exposure. However, after
the end of the exposure series, their clearance rates were significantly faster
than prior to any acid exposures, and remained so for the entire follow-up
period (Lippmann et al., 1982).
Schlesinger et al. (1983) exposed rabbits to 0.25 to 0.5 mg/m3 H^SO.
(0.3 ym, MMAD) for 1 h/d, 5 d/wk for 4 weeks, during which time bronchial
mucociliary clearance was monitored. Clearance was accelerated on specific
individual days during the course of the acid exposures, especially at
0.5 mg/m . In addition, clearance was significantly faster, compared to
preexposure levels, during a 2-week follow-up period after acid exposures had
ceased.
The longest-term exposure at relatively low H2S04 levels for examination
of effects on bronchial clearance was the study of Gearhart and Schlesinger
(1988). Rabbits were exposed to 0.25 mg/m3 H2S04 for 1 h/d, 5 d/wk for up to
4-29
-------
52 wk, and some animals were also provided a three month follow-up period.
Clearance was slower during the first month of exposure and this slowing was
maintained, and became progressive, throughout the rest of the exposure period.
After cessation of exposure, clearance became still slower (a phenomenon seen
in the donkey study, above), and did not return to normal by the end of the
follow-up period. No significant change in clearance was observed in sham
control animals. Differences in the direction of clearance change between
this study and that of Schlesinger et al. (1983) were due to differences in
exposure protocol, i.e., in the earlier study, clearance was measured immedia-
tely after acid exposure while in the later one, it was measured 24 hr after
exposure. In both studies, however, histologic analysis indicated the develop-
ment of increased numbers of epithelial secretory cells, especially in small
airways, the likely consequence of which would be an increase in mucus produc-
tion. In addition, the slowing of clearance seen by Gearhart and Schlesinger
(1988) was associated with a shift in the chemistry of mucus towards a greater
content of acidic glycoproteins; this would tend to make mucus more viscous.
See also related discussion in chapter three.
4.5.1.2 Respiratory Region
a. Antimicrobial Activity
The development of an infectious disease requires both the presence of
the appropriate pathogen and host vulnerability. The alveolar macrophage
represents the main defense against pathogenic organisms depositing in the
respiratory region of the lungs. The ability of acid aerosols to modify
resistance to infection could result from a decreased ability to clear
microbes, and a resultant increase in their residence time, due to alterations
in normal macrophage function. To test this possibility, the rodent bacterial
infectivity model has been used (Gardner and Graham, 1977). In this technique,
mice are challenged with a bacterial aerosol after exposure to the pollutant
of interest; mortality rate and survival time are then examined within a
particular postexposure time period. Any decrease in the latter or increase in
the former indicates impaired defense against respiratory infection. Studies
that have used the infectivity model to assess effects of acid aerosols are
outlined in Table 4-6. It is evident that these aerosols are apparently not
very effective in enhancing susceptibility to bacterial-mediated respiratory
disease. The only study that demonstrated any response was that of Coffin
4-30
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(1972), and increased mortality occurred only at an extremely high exposure
level that likely resulted in extensive morphological damage.
In a related type of study, Fairchild et al. (1975b) examined the
clearance rate of viable bacteria from the lungs of mice, using a colony count
assay involving culturing ground lung tissue. They found that exposures
(chamber) to 1.5 mg/m3 of submicrometer (0.6 urn, CMD) H2S04 for 1.5 h/d for
4 days prior to, or for 4 h after, exposure to a bacterial aerosol produced no
alteration in the physical removal of this aerosol from the lungs. Since the
bulk of microbial clearance was likely due to macrophage activity, these
results are another, albeit indirect, indication that H2S04 exposures at modest
levels produce no measurable effect on bacterial infectivity.
Macrophages are also involved in antiviral defense, but there are no data
directly examining effects of acid on viral infectivity. In a study that
examined this indirectly, macrophages harvested from mice exposed to submicro-
meter H2S04 at very high levels (125 to 154 mg/m3) for 10 to 14 days showed
decreased interferon titers in the culture media (Schwartz et al., 1979); this
suggests impaired resistance to viral infection.
b. Respiratory Region Clearance
There are only a few studies that examined the ability of acid aerosols
to alter clearance of nonviable particles from the respiratory region. Rats
exposed (nose-only) to 3.6 mg/m3 H2S04 (1 urn, MMAD) for 4 h showed a signif-
icant delay in clearance when the relative humidity of the exposure atmosphere
was low (39%); no change in clearance was found when humidity was raised to
85% (Phalen et al., 1980). On the other hand, acceleration of clearance was
seen in rabbits exposed for 1 h to H2S04 at 1 mg/m3 (80% RH; 0.3 urn, MMAD;
erg = 1.6) (Naumann and Schlesinger, 1986).
Some studies involving repeated exposures to acid aerosols have been
o
reported. In one, rabbits were exposed (nose-only) to 0.25 mg/m (0.3 urn,
MMAD; ag = 1.7) H2S04 for 1 h/d, 5 d/wk, and tracer particles were administered
on days 1, 57, and 240 following the start of the acid exposures (Schlesinger
and Gearhart, 1986). Clearance (measured for 14 d after each tracer exposure)
was found to be accelerated during the first test, and this acceleration was
maintained throughout the acid exposure period. In another study (Schlesinger
and Gearhart, 1987), rabbits were exposed (nose-only) 2 h/d for 14 days to
0.5 mg/m3 H2S04 (0.3 urn MMAD); retardation of respiratory region clearance of
tracer particles administered on the first day of exposure was found.
4-32
-------
Schlesinger (1989) exposed rabbits to H2S04 (0.3 pro, MMAD) at 0.25-1 mg/m3 for
1-4 hr/d for 14 d. The results of this and the other two studies suggest a
graded response which is dependent upon both exposure concentration and time;
low values of CxT accelerate respiratory region clearance and high levels
retard it, such as is seen with mucociliary transport following acute HLSO.
exposure (Schlesinger, 1989) and with respiratory region clearance after
repeated exposures to other inhaled pollutants (Ferin and Leach, 1977; Driscoll
et al., 1986).
The mechanisms responsible for the altered respiratory region clearance
patterns seen in the above studies are not known. Observed clearance is the
net consequence of a number of underlying responses; these likely include
inflammation, epithelial lesions, release of specific mediators, and/or altered
functioning of alveolar macrophages. The effects of acid aerosols on lung
tissue have been previously discussed. There are only a few studies examining
the response of macrophages, or the induction of inflammation following acid
aerosol exposures.
In order to perform their role in clearance adequately, macrophages must
be competent in a number of functions, e.g., phagocytosis, mobility, and
attachment to a surface (Gardner, 1984). Alterations in any one, or combina-
tion, of these individual factors could perhaps result in altered clearance.
Naumann and Schlesinger (1986) noted a reduction in surface adherence and an
enhancement of phagocytosis in macrophages obtained by lavage from rabbits
<3
following a 1-h exposure (oral tube) to 1 mg/m (0.3 pm, MMAD; erg = 1.6)
H2SCV ^ne acid exposure produced no change in the viability or numbers of
recoverable macrophages. This is not surprising, since Coffin (1972) found no
change in the number of recoverable macrophages from mice exposed to 300 mg/m3
H2S04 for 3 h.
In the only study with repeated H2$04 exposures, macrophages were
recovered by lavage from rabbits inhaling (nose-only) 0.5 mg/m3 H2S04 (0.3 |jm,
MMAD) for 2 h/d for up to 13 days (Schlesinger, 1987). Macrophage counts were
increased after 2 of the daily exposures, but returned to control levels
thereafter. Neutrophil counts remained at control levels throughout the study,
indicating there to be no inflammatory response. Random mobility of macro-
phages was decreased after 6 and 13 of the exposures. The number of
phagocytically active macrophages and the level of such activity was increased
after 2 exposures, but phagocytosis became depressed by the end of the exposure
4-33
-------
series. Although such studies demonstrate that H2$04 can alter macrophage
function, they have not as yet been able to provide a complete understanding of
the cellular mechanisms that may underlie the changes in respiratory region
clearance observed with exposure to acid aerosols.
The relative potency of the acid sulfate aerosols in terms of altering
respiratory region clearance was examined by Schlesinger (1989). Rabbits were
exposed for 2 h/d for 14 d to 2 mg/m3 (NH4)2S04 and to 0.5-2 mg/m3 NH4HS04.
None of these exposures altered the clearance of tracer particles from the
respiratory region measured during the exposure period. This contrasts with
Q
the retardation of clearance observed using similar exposures to 0.5 mg/m
H9SOA (Schlesinger and Gearhart, 1987), suggesting that the response was likely
+ +
due to H . However, the H associated with the H,,S04 appeared to be more
"potent" than that associated with NH4HS04.
The role of relative acidity in altering macrophages has not been examined
in any detail. Aranyi et al. (1983) found no change in total or differential
counts of free cells lavaged from mice exposed (chamber) to submicrometer
(NH4)2S04 at 1 mg/m3 for 3 h/day for 20 days. Changes with H2S04 were
discussed above.
4.5.2 Immunologic Defense
Little is known about the effects of acid aerosols on humoral (antibody)
or cell-mediated immunity. Since numerous antigens may be present in inhaled
air, the possibility exists that air pollutants may enhance immunologic reac-
tion and, thus, produce a more severe response and one with greater pulmonary
pathogenic potential. Pinto et al. (1979) found that mice that inhaled H2S04
(chamber; neither mass concentration nor particle size was specified) for
30 min daily and were then exposed weekly to a particulate antigen (sheep red
blood cells) exhibited higher serum and bronchial lavage antibody titers than
did animals exposed to the antigen alone. Other sulfate compound aerosols may
also have this effect. Although none have been directly examined, S02 appears
to have an adjuvant effect on antibody production (Matsumura, 1970). Pinto
et al. (1979) also noted that the combination of acid with antigen produced a
histopathologic response, characterized by mononuclear cell infiltration around
the bronchi and blood vessels, while exposure to acid or antigen alone did not.
Thus, the apparent adjuvant activity of H2$04 may have been a factor promoting
lung inflammation.
4-34
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Osebold et al. (1980) exposed mice (chamber) to 1 mg/m3 H2$04 (0.04 urn,
CMD; 0g = 1.86) to determine whether this enhanced the sensitization to an
inhaled antigen (ovalbumin). The exposure regime involved intermittent 4 d
exposures, with up to 16 total days of exposure; no increase in sensitization
compared to controls was found. Kitabatake et al. (1979) exposed guinea pigs
(head-only) to 1.91 mg/m3 (<1 urn, MMAD) at 30-min intervals, twice per week,
for 4 weeks, followed by up to 10 additional paired treatments with the H2$04
for 30 min each, then exposure to aerosolized albumin for another 30 min. The
breathing pattern of the animals was monitored for production of dyspnea,
i.e., an "asthmatic attack." Enhanced sensitization was found after ~4 of the
albumin exposures. A subsequent challenge with acetylcholine suggested hyper-
responsive airways.
Acid aerosols may mediate the production of lung tumors. Godleski et al.
(1984) examined the effect of inhaled (NH4)2$04 on benzo[a]pyrene (BaP)-induced
carcinogenesis in hamster lung. Animals were exposed (chamber; 39 percent RH)
to -0.2 mg/m3 (NH4)2$04 (0.3 pm, MMD; ag = 2.02), with or without instilled
BaP, for 6 hr/d, 5 d/wk, for 15 wk; they were observed for an additional 2 yr.
Exposure to (NH4)2$04 resulted in a significant reduction in tumor incidence
during the first 6 mo of observation but, by 2 yr, there were no differences
between those groups receiving BaP alone or BaP plus (NH4)2S04. These results
indicated some interaction between BaP and sulfate, but not one that provided
long-term protection against tumor development. Other studies have shown that
S04 administered by routes other than inhalation enhanced the development of
tumors induced by other carcinogens (Blunck and Crowther, 1975; DeBaun et al.,
1970; Cohen and Bryan, 1978). These latter likely involved different metabolic
and/or chemical reaction pathways.
4.6 EFFECTS OF MIXTURES CONTAINING ACID AEROSOLS
Most of the toxicological data concerning effects of acid aerosols are
derived from exposures using single compounds. Although these data are essen-
tial, it is also important to study responses that result from inhalation of
typical combinations of materials, since general population exposures do
involve mixtures. Toxicological interaction provides a basis whereby low
concentrations of ambient pollutants may be damaging in combination. Thus, the
lack of any toxic effect following exposure to an individual pollutant should
4-35
-------
always be interpreted with caution, since mixtures often behave differently
than expected from the same pollutants acting separately. In this regard, the
effects of acid aerosols may be influenced by various co-pollutants. Table 4-7
presents a survey of studies examining various endpoints following exposures to
mixed atmospheres containing acid aerosols. Most of the studies listed
involved inhalation of atmospheres containing only two pollutants. Investiga-
tions using more complex atmospheres are discussed separately.
The occurrence or extent of any toxicological interaction involving acid
aerosols depends on the endpoint being examined, as well as on the co-inhalant.
For example, in most studies that employed acid with 03, the response was due
solely to the latter rather than to the former. The major exceptions are the
studies of Last and colleagues (see Table 4-7), in which Og and H2$04 were
synergistic in altering lung protein content and collagen synthesis, and that
of Osebold et al. (1980), in which the inclusion of H2S04 potentiated the
response to inhaled antigen seen with 0, alone. This latter study suggests
that inhalation of pollutant mixtures containing acid aerosols may increase
the number of sensitized individuals, or augment a reaction in those already
sensitized. These studies are highly suggestive that H2S04 acts by increasing
the effective dose of 03 delivered to its target site(s) in the lungs.
Although most interaction studies involve simultaneous exposure to more
than one pollutant, exposure to one substance may alter the response to another
subsequently inhaled. Thus, the order of exposure to inhaled materials may be
important in eliciting a toxic interaction. For example, using sequential
exposures (chamber), Gardner et al. (1977) found an additive increase in
infectivity when mice were exposed to 0.1 ppm 0, for 3 h immediately before
o o
exposure to 0.9 mg/m (0.2 urn, VMD) H2S04 for 2 h; no difference from control
was found when the H2S04 was administered prior to the 0,. On the other hand,
Silbaugh and Mauderly (1986), using bronchoconstriction as the endpoint, found
that a 2 h exposure (chamber, 65 to 72 percent RH) of guinea pigs to 0.8 ppm
Og did not alter the response to a subsequent 1-hr exposure to 12 mg/m
(0.63 pm, MMAD) H2S04. Grose et al. (1980) exposed hamsters (chamber) to
0.1 ppm 03 for 3 h followed by 1.09 mg/m3 (0.3 urn, VMD) H2$04 for 2 h. A
reduction in ciliary activity in isolated trachea! cultures was observed, but
the magnitude of the change was significantly less than that found with
exposure to the H2S04 alone; 03 alone produced no change at all.
4-36
-------
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Another factor which may influence the interaction between acid aerosols
and other inhaled materials is the particle size of the former. Using pulmo-
nary resistance in guinea pigs as the endpoint, Amdur (1957) found a synergis-
tic response following a 1-h inhalation (head-only) of 82 ppm S02 with
19 mg/m3 of 0.8 urn (MMD) H2$04; on the other hand, no synergism was seen when
inhalation involved a 2.5 urn acid droplet. Last et al. (1986) observed a
synergistic response on biochemical indices in rat lung with exposure (chamber,
80 percent RH) to H2$04 (1 mg/m3) and 03 (0.6 ppm) when the droplet size was
0.5 pm (MMAD), while no potentiation of 03 response was seen with a droplet
size of 0.03 urn. Apparently, in this case, the aerosol that had greater
deposition in the terminal-respiratory bronchiolar region (the major site of
03 deposition) was most interactive with 03>
The pollutant atmosphere in most environments is a complex mix of more
than two materials. A few studies have attempted to examine the effects of
multicomponent atmospheres containing acid particles. Mannix et al. (1982)
examined the effects of a 4 h exposure (chamber) of rats to a S02~sulfate mix,
consisting of S02 (5 ppm) plus 1.5 mg/m3 (0.5 prn, MMAD, ag = 1.6) of an aerosol
containing (NH4)2$04 and Fe2(S04)3. No change in particle clearance from the
tracheobronchial tree or respiratory region was found. Aranyi et al. (1983)
exposed mice (chamber; 48 to 54 percent RH; 5 h/d, 5 d/wk for 103 d) to
mixtures of 03 (0.1 ppm), S02 (5 ppm) and (NH4)2$04 (1.04 mg/m3; 0.39 pm MMAD;
ag 2.42), and noted enhanced bactericidal activity of macrophages, compared to
Oo alone. This same exposure regime also resulted in a greater (compared to
Oo alone) degree of i_n vitro cytostasis to tumor target cells cocultured with
peritoneal macrophages obtained from exposed mice. The investigators suggested
that these results indicated possible macrophage activation by the complex
atmosphere.
Hyde et al. (1978) studied dogs exposed (in chambers) for 16 hr/d for
68 mo to pollutant mixtures as follows: H2$04 (0.09 mg/m , <0.5 pm) + S02
(0.4 ppm); H2S04 (0.09 mg/m3) + S02 (0.46 ppm) + auto exhaust; H2$04
(0.11 mg/m3) + S02 (0.4 ppm) + irradiated auto exhaust (which results in pro-
duction of oxidants); nonirradiated auto exhaust; or irradiated auto exhaust.
The animals were examined for morphological damage 32 to 36 mo after exposures
ended. Although there was no evidence of any interaction between auto exhaust
and sulfur oxides, most groups including the H£S04 and S0£ group showed
enlargements of air spaces in proximal acini and hyperplasia of bronchiolar
4-41
-------
cells. Pulmonary function changes were also observed in these animals (Stara
et a!., 1980). During the "clean air" post exposure period, pulmonary function
continued to deteriorate. Unfortunately, the individual component(s) of the
mixtures causing these effects could not be determined.
Kleinman et al. (1985a,b) exposed rats (nose-only) for 4 h to atmospheres
consisting of various combinations of 03 (0.6 ppm), N02 (2.5 ppm), S02 (5 ppm)
and aerosol. The latter consisted of 1 mg/m3 (0.2 pm, MMAD) of either
(NH4)2S04 or H2S04, laced with iron and manganese sulfates. The metallic salts
act as catalysts for the conversion of sulfur (IV) into sulfur (VI), and the
incorporation of gases into the aerosol droplets. The respiratory region was
examined for morphological effects. A confounding factor in these studies was
the production of nitric acid in atmospheres that contained 03 and N02, and
nitrate in those that contained 03 and (NH4)2$04 but not N02- Nevertheless, a
significant enhancement of tissue damage was produced by exposure to atmo-
spheres containing H2$04 (or HN03) compared to those containing (NH4)2$04. In
addition, there was a suggestion that the former atmospheres resulted in a
greater area of the lung becoming involved in lesions, which were characterized
by a thickening of alveolar walls, cellular infiltration in the interstitium
and an increase in free cells within alveolar spaces. Exercise seemed to
potentiate the histological response to the complex mixture containing H2S04
(Kleinman et al., 1989).
Mautz et al. (1985) examined the effects of complex mixtures upon pulmo-
nary mechanics in exercising dogs. Exposures (nose-only) were for 200 min to
atmospheres consisting of 03 (0.45 to 0.7 ppm), S02 (4.8 to 5.2 ppm), H2S04
(0.8 to 1.2 mg/m3, 0.2 pm MMAD), and catalytic salts (iron and manganese
sulfates). A greater increase in resistance and decrease in compliance was
found with the complex atmospheres containing the sulfate compounds than with
03 alone. Although this was ascribed to the presence of the H2S04, synergism
could not be definitively concluded since the mixture was not tested without
°3'
Most of the toxicologic data base for H2S04 consists of studies aimed at
assessing the effects of exposure to submicrometer aerosols such as would be
formed secondarily in the atmosphere from S02. Recently, the response to
sulfuric acid coating the surface of metallic oxide particles was examined by
Amdur and Chen (1989); this was intended to simulate primary emissions from
coal combustion processes. Guinea pigs were exposed for 3 hr/day for 5 days
4-42
-------
to ultra-fine (0.05 urn CMD, ag = 2) aerosols of zinc oxide (ZnO), which
3
contained a surface coating of HpSO.. Levels as low as 0.02-0.03 mg/m as
equivalent H2$04 delivered in this manner resulted in significant reductions in
total lung volume, vital capacity, and CO diffusing capacity. The effects
appeared to be cumulative, in that their severity increased with increasing
days of exposure. These exposures also resulted in an increase in the protein
content of pulmonary lavage fluid (an index of lung damage) as well as an
increase in neutrophils (and index of inflammation). The investigators found
that much higher exposure levels of pure HUSO. aerosol were needed to produce
comparable results. This suggests that the physical state of the associated
acid in pollutant mixtures is an important determinant of response.
It is apparent from this survey of the data base that toxicologic interac-
tions with acid aerosols may be antagonistic, additive, or synergistic. The
latter poses the greatest threat in terms of potential health effects.
There are various mechanisms by which synergism may occur. One is physi-
cal, the result of adsorption of one material onto the acid particle and
subsequent transport to more sensitive sites, or sites where this material
normally would not deposit in concentrated amounts. The acid particles, thus,
essentially act as carriers. A second mechanism involves dissolution and
reaction within an acid droplet, forming some secondary product(s) that may be
more toxicologically active than the primary materials.
A third mechanism may involve an acid induced change in the local micro-
environment of the lung, enhancing the effects of the co-inhalant or vice
versa. This was proposed by Last and colleagues based upon a series of studies
(Last et al., 1983, 1984, 1986; Last and Cross, 1978; Warren and Last, 1987;
Warren et al., 1986) in which rats were exposed to sulfate aerosols (H2S04,
(NH4)2S04, Na2S04) with and without oxidant gases (03 or N02), and various bio-
chemical endpoints examined. Acidic sulfate aerosols alone did not produce any
response at levels that caused a response in conjunction with 03 or N02- The
investigators suggested that the deposition of the acid aerosol produced a
shift in local pH within the alveolar milieu; this shift then resulted in a
change in the reactivity or residence time of reactants (e.g., radicals)
involved in oxidant-induced pulmonary effects. Further evidence that the toxic
interaction was due to acidity was the finding that neither Na,,S04 nor NaCl was
synergistic with 03 (Last et al., 1986).
4-43
-------
4.7 SUMMARY AND CONCLUSIONS
The bulk of the toxicologic data base on acid aerosols involves sulfate
compound particles, primarily submicrometer FUSO^,. There are no data for larger
HgSO^ droplets that would be constituents of acid fogs, and few data for other,
nonsulfur constituents of such fogs or other acidic atmospheres, e.g., nitrogen
compounds such as HN03. However, the available evidence indicates that the
observed responses to acid sulfates are likely due to H+ rather than to S04=.
Thus, H2S04 may be considered to be a "model" acidic irritant and the observed
effects seen for this pollutant likely apply, at least qualitatively, to other
acid aerosols having similar deposition patterns in the respiratory tract.
However, it has been suggested that the irritant potency of an acid may be
related more to its total H+ concentration, i.e., titratable acidity, rather
than to its free H concentration as measured by pH (Fine et al., 1987). This
implies that the specific chemical composition of different acids may be a
factor mediating the quantitative response. In any case, the toxicity of
H2SO^ is likely due to the direct irritant action of deposited acid droplets
and/or to the subsequent release of humoral mediators such as histamine.
A survey of the data base for H2S04 toxicology shows what often appear to
be contradictory or, at the least, variable results.' There are a number of
possible explanations for these. A major one involves response differences
between animal species (or strains) due to intrinsic sensitivity differences,
or differences in age, aerosol deposition pattern, and respiratory tract NH,
levels. Various experimental variables (e.g., relative humidity), mode of
exposure, aerosol particle size, exogenous NH3 levels, also differ in different
studies. But in spite of such differences, a number of generalizations regard-
ing the toxicology of H^O* may be made, based upon relative consistencies in
similar studies.
The available evidence indicates that H2SO. exerts its action throughout
the respiratory tract, with the type and magnitude of response dependent upon
particle size, mass concentration, and, for most endpoints, exposure duration.
o
At very high concentrations (>15 mg/m ), mortality will occur following acute
exposure, due primarily to laryngeal or bronchoconstriction; larger particles
are more effective in this regard than are smaller ones. Somewhat lower
exposure levels will also result in death, but this is due to extensive
pulmonary damage, including edema, hemorrhage, epithelial desquamation, and
atelectasis. But even in the most sensitive species, levels needed for lethal-
3
ity are quite high (>8 mg/m ).
4-44
-------
Both acute and chronic exposure to H^SO* at levels well below lethal ones
will produce functional changes in the respiratory tract. The pathological
significance for some of these is greater than for others. Acute exposure will
alter pulmonary function, largely due to bronchoconstrictive action. However,
attempts to produce changes in airway resistance in healthy animals at levels
below 1 mg/m3 have been largely unsuccessful, except in the guinea pig. The
lowest effective level of H0SOA producing bronchoconstriction to date in the
3
guinea pig is 0.1 mg/m (1 h exposure). In general, the smaller-size droplets
were more effective in altering pulmonary function, especially at low concen-
trations. Yet even in this species, there are inconsistencies in the type of
response exhibited towards acid aerosols. Some studies show an exposure-
concentration response beginning at 0.1 mg/m , while others show an all-or-none
response beginning only at concentrations much higher than this, and no
response at lower levels. Chronic exposure to I^SO^ is also associated with
alterations in pulmonary function, e.g., changes in the distribution of
ventilation and in respiratory rate in monkeys. But, in these cases, the
3
effective concentrations are >0.5 mg/m .
The relationship between the above changes in pulmonary function and
disease is unclear. But the development of hyperresponsive airways in healthy
animals due to acid aerosols, at levels below those producing any change in
lung functional indices without bronchoconstrictor challenge, does have impli-
cations for the pathogenesis of airway disease due to nonspecific irritant
exposure. Hyperresponsive airways have been induced in rabbits with repeated,
1 h daily- exposures to 0.25 mg/m3 H2SOA; the effects on responsivity of long-
term exposure to lower levels are not known.
Severe morphologic alterations in the respiratory tract will occur at high
acid levels. At low levels, and with chronic exposure, the main response seems
to be hypertrophy and/or hyperplasia of mucus secretory cells in the epithelium;
these alterations may extend to the small bronchi and bronchioles, where
secretory cells are normally rare or absent and may persist after exposures
end. Whether these persistent changes are permanent is not known. The observed
changes in secretory cells likely result in an increase in secretory rate and
mucus volume in such airways, which is a possible factor in the pathogenesis of
obstructive lung disease.
The lungs have an array of defense mechanisms to detoxify and physically
remove inhaled material, and available evidence indicates that certain of these
4-45
-------
defenses may be altered by exposure to H2S04 at levels <1 mg/m3. Defenses such
as resistance to bacterial infection are not altered even by acute exposure to
o
concentrations as high as 150 mg/m . However, the bronchial mucociliary
clearance system is very sensitive to inhaled acids; much lower levels of
O
H2S04 ^ mg/'m ^ Produce alterations in mucociliary transport rates in healthy
animals. The lowest level shown to have such an effect, 0.1 mg/m3 with repeated
exposures in the donkey, is well below concentrations that result in other
physiological changes in most experimental animals, and also resulted in a
persistent change in clearance in some of the animals. Furthermore, exposures
to somewhat higher concentrations that also alter clearance have been associated
with various morphometric changes in the bronchial tree indicative of mucus
hypersecretion.
Limited data also suggest that exposure to acid aerosols may affect the
functioning of alveolar macrophages; the lowest level examined in this regard
is 0.5 mg/m HgSO^. Although the pathogenic implications of such effects are
not certain, they likely play some role in altering removal of material from
the respiratory region. Respiratory region particle clearance is affected by
repeated H2S04 exposures to as low as 0.25 mg/m3.
Effective clearance mechanisms are critical in reducing the residence time
of inhaled, deposited materials, and alterations in clearance, especially due
to chronic acid aerosol exposure, may be associated with lung disease.
Mucociliary efficiency influences the development of acute infectious disease
(Proctor, 1979; Niederman et a!., 1983), and there is accumulating evidence
that dysfunction of bronchial clearance plays a role in the pathogenesis of
chronic bronchitis (Albert et al., 1973; Schlesinger et al., 1983) and may be
an early indication of disease in otherwise asymptomatic individuals (Mossberg
and Camner, 1980; Goodman et al., 1978).
The role of acid aerosols, specifically HpSO., in the development of
chronic bronchitis is supported by a comparison of results from studies of
submicrometer hLSO, mist and cigarette-smoke exposures (Lippmann et al., 1982);
the latter are known to be involved in the etiology of human chronic bronchi-
tis. Since the effects of both agents on bronchial mucociliary clearance
patterns were found to be essentially the same following either single or
intermittent exposures in experimental animals and humans, H?SO. may be involved
in the development of this disease.
4-46
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The pathogenic implications of alterations in clearance from the respira-
tory region are more speculative than those for mucociliary clearance, but
clearance rates are reduced in humans with chronic obstructive lung disease and
in cigarette smokers (Bohning et al., 1982; Cohen et al., 1979). This suggests
some relation between altered defense and chronic lung disease development in
these latter individuals; the results of toxicologic assessments suggest the
former precedes the latter.
The assessment of the toxicology of acid aerosols requires some examina-
tion of potential interactions with other air pollutants. Although such
interactions may be antagonistic, additive, or synergistic, the exact mechanism
by which they occur is not well defined, and evidence for them may depend upon
the sequence of exposure as well as on the endpoint examined. Low levels of
o
HUSO* (0.04 mg/m ) have been shown to react synergistically with 03 in simul-
taneous exposures using biochemical endpoints. In this case, the HUSO^ enhanced
the damage due to the 03. This is common in studies with 03, while H2S04 toxic
effects themselves may be more directly manifest with other, less potent,
co-inhalants. There is some evidence that sulfuric acid existing as a sulfate
coating on other particles may be more potent than the acid existing as a
sulfate droplet. The most realistic exposures are to multicomponent atmos-
pheres, but the results of these are often difficult to assess due to chemical
interactions between the components and a resultant lack of precise control
over the ultimate composition of the exposure environment.
In conclusion, the effects of acid (i.e. H2$04) inhalation involve, at
high levels, bronchoconstriction and, at lower levels, alterations in the
rate of clearance from the tracheobronchial tree and pulmonary region. In
some cases, changes in tracheobronchial clearance were found to persist for a
few months after exposure ended. The toxicologic data base allows for specula-
tion that the potential does exist for the production of chronic lung disease
due to long-term inhalation of acid aerosol, i.e., H2$04. Although the concen-
trations associated with persistent changes, which may be related to chronic
disease, are above those found as peaks in ambient air. The diseases which
would most likely be associated with acid exposures are asthma and chronic
bronchitis. The greatest potential health threat due to pollutant interactions
likely involves 0,, since synergism has been found with combinations of peak
ambient levels of 03 (0.2 ppm) and H2$04 (0.04 mg/m3); in this case, the
4-47
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associated disease is speculated to be pulmonary fibrosis. However, the lowest
level of acid capable of eliciting responses (alone or in combination with
other pollutants) is currently not known.
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« ?' F'; Gray' .R' H<; Center, R. L. ; Hahn, F. F.
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•*• * •
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5. CONTROLLED HUMAN EXPOSURE STUDIES OF ACID AEROSOLS
5.1 INTRODUCTION
The effects of inhaled acid aerosols were studied initially because of
interest in occupational exposures. These early studies, conducted in the
1950's, have been followed by a more extensive series of investigations, most
of which have been completed since 1977. The sparse data on environmental
levels of airborne acidity have hindered the design of human exposure studies.
The majority of studies have been conducted using sulfuric acid aerosol and its
salts, although the effects of nitrates and nitric and hydrochloric acid vapor
have also been examined. A broad range of concentrations of these aerosols
have been studied ranging from 10 |jg/m3 to more than 1,000 ug/m3. The "dose"
of inhaled aerosol has been varied by using exposures of different durations
(from 10 minutes up to 4 hours) or by increasing the venti'latory exchange by
incorporating exercise. In addition to these rather straightforward considera-
tions, the delivered "dose" is also affected by the upper airway path traversed
by the aerosol and the size of the particles as well as their potential for
hygroscopic growth in the respiratory tract, as discussed in Chapter 3.
The studies reported in this section have been conducted on both normal
and asthmatic subjects; the latter group represents a potentially "susceptible"
population. Several different types of measurements have been made following
exposure. In most cases, some measures of lung function such as spirometry or
plethysmography have been made. In addition, the effects of acid aerosols on
airway reactivity and on mucociliary clearance have been studied rather exten-
sively. Another area of investigation has been the influence of aerosol
acidity and the potential for neutralization of acid by ammonia or by airway
surface fluid buffers. The size of aerosols given in the text is their mass
median aerodynamic diameter (MMAD) unless otherwise stated.
Human subjects have been exposed to acid aerosols either in an environ-
mental chamber or directly via a mouthpiece or facemask. In a chamber, the
subjects may be free to breathe as the^ld in the ambient environment.
5-1
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When aerosols are delivered by a closed system, the subject is often required
to breathe through either the mouth or the nose which will impact respiratory
tract deposition. As discussed in Chapter 3, the capacity for the formation of
ammonium salts may differ considerably depending on whether the subject breathes
via the nose or the mouth. The type of atmosphere used as a "control" may be
important in interpretation of responses. Clean ambient air may not be the
most appropriate "control" since there may be a physiological 'response to a
"control" aerosol such as sodium chloride or distilled water (Lippmann et al.s
1977). Various procedures have been used prior to exposure, to reduce levels
of oral ammonia including tooth brushing, gargling with a bacteriostatic
mouthwash, or gargling with acidic fruit juices. The efficacy of such proce-
dures in reducing oral ammonia levels has been verified in at least one study
(Utell et al., 1986).
The relative humidity in the chamber or aerosol delivery system has an
important effect on particle size. The increase in size of an inhaled hygro-
scopic particle will depend, to some extent (see Chapter 3), upon the ambient
humidity. This rate of particle growth will then be one of the determinants of
the pattern of deposition of the aerosol.
The first investigation into the effects of acid aerosols on human lung
function was conducted by Amdur and co-workers in 1952 (Amdur et al., 1953).
Using a group of 15 subjects, they studied the retention of inhaled sulfuric
acid aerosol, the changes in respiratory pattern induced by the acid aerosol,
and the sensory threshold for olfactory detection of sulfuric acid mist.
The aerosol was generated from fuming H2S04; the particle size was reported
to be 1 urn. Calculated respiratory tract aerosol particle retention averaged
77 percent and ranged from 50 percent to 87 percent in the exposure concentra-
O Q
tion range of 0.4 to 1.0 mg/m . Aerosol concentrations of less than I mg/m
could not be detected by either odor or taste and apparently caused no irrita-
0
tion. All subjects were able to detect a concentration of 3 mg/m . At
o
5 mg/m , a deep breath usually produced coughing.
Changes in respiratory pattern were reported at 0.35 to 0.50 mg/m H2S04.
A reduction in both maximum inspiratory (-15 percent) and expiratory (-20 per-
cent) flow was accompanied by a modest tachypnea (+35 percent increase in
respiratory frequency) and a decrease (-28 percent) in tidal volume. These
findings were interpreted as a typical response to respiratory irritants. This
study did not, unfortunately, generate the necessary interest at the time for a
5-2
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large number of subsequent investigations of the effects of acid aerosol
exposure in man.
One subsequent study, conducted by Sim and Pattle (1957), reported the
responses to relatively high concentrations of large-particle sulfuric acid
aerosols. Because of the high concentrations used and the somewhat uncon-
trolled nature of the exposures, this study provided little useful information.
The next reported study of human exposure to sulfuric acid aerosol was
that of Larson et al. (1977). This paper reported the first evidence that oral
ammonia could effectively neutralize a portion of the inhaled acid aerosol; it
is discussed in more detail in Chapter 3. Although interest in sulfuric acid
aerosol as an air contaminant dates back to the "fog" episodes, virtually all
of the studies that address human health effects, which are relevant to
ambient exposures, have been published since 1977. This important study served
as a lead-in to a number of subsequent studies of the effects of acid aerosols.
The studies described in this section deal with human experimental expo-
sures to inhaled acids and their salts; such studies are frequently referred to
as human "clinical" studies. The methods used in these studies are similar to
those used in experimental studies of criteria pollutants such as ozone, NOp,
and S02> A detailed discussion of the methodology is beyond the scope of the
chapter but some points may be important in evaluating the studies discussed
subsequently.
Inhaled substances may be breathed directly through a mouthpiece or from
air within an environmental chamber or a facemask. One of the major consider-
ations is that air breathed orally bypasses the nose, which removes soluble
pollutants from the air and humidifies the incoming air. On the other hand,
air breathed nasally encounters greater flow resistance and bypasses a potential
source of ammonia in the mouth. The volume of air exchanged is a function of
the metabolic rate or level of activity of the exposed individual; exercising
subjects will therefore inhale more of the pollutant gas or aerosol. The
temperature and humidity of the inspired air may be an important factor,
especially for asthmatics. Of course, the duration of the exposure and the
concentration of pollutant are essential in quantitating the exposure.
5.2 PULMONARY FUNCTION EFFECTS OF H2$04 IN NORMAL SUBJECTS
The effects of sulfuric acid aerosol have been studied extensively in
healthy subjects without history of respiratory disease. Such subjects are
5-3
-------
typically young adult males whose atopic status has usually not been deter-
mined. Studies completed since 1978 include exposures to a range of concen-
trations from 75 to 1,500 ug/m with a variety of aerosol particle sizes from
0.1 to 1.5 urn. This section includes only the data from "normal" subjects.
If data on asthmatics or other types of subjects were also included in a
report, these data are discussed separately in the appropriate subsection
(Section 5.6). Many of the details of the experimental procedures are presented
in the tables to avoid a cumbersome text.
o
Newhouse et al. (1978) exposed 10 subjects to 1,000 ug/m sulfuric acid
aerosol (0.5 urn) under temperate (22°C), humid (70 percent RH) conditions for a
period of 2 h. The exposure period included a total of 20 min of heavy
exercise (70 to 75 percent of maximal aerobic power); oral breathing was
obligatory throughout exposure. There were no significant changes in VC,
FEV, Q, or MMFR as a result of this exposure.
Sackner et al. (1978) reported the results of a series of exposures of
both normal and asthmatic humans to sulfuric acid aerosol concentrations
Q
ranging from 10 to 1,000 ug/m . These studies involved a total of 17 normal
subjects of mixed age and gender and were performed with oral breathing at
rest. There were no significant effects of up to 1,000 ug/m sulfuric acid
aerosol of any of the extensive series of tests of lung function performed
after exposure in these subjects.
o
Six subjects exposed to 75 ug/m sulfuric acid aerosol were studied by
Avol and associates (1979). Exposures included light intermittent exercise and
lasted for 2 h. There were no significant respiratory function effects of
this exposure in these subjects.
In a study primarily designed to examine the effects of sulfuric acid
aerosol on mucociliary clearance, Leikauf et al. (1981) exposed 10 healthy
o
nonsmokers for one hour to 110, 330, and 980 ug/m of 0.5 urn sulfuric acid
aerosol via nasal mask. There were no significant effects of H2$04 exposure
on airway resistance, partial maximum expiratory flow at 25 percent of vital
capacity (V25; partial expiratory flow-volume test), or on an index of
distribution of ventilation based on multiple breath nitrogen washout.
2
Kerr et al. (1981) examined the effects of a longer exposure to 100 ug/m
sulfuric acid (0.1 to 0.3 urn). Two groups of 14 subjects each, one consisting
of smokers (11 M, 3 F) and the other of nonsmokers (8 M, 6 F) were exposed for
4 hr in an environmental chamber; •moderate exercise was performed for two
5-4
-------
15-min periods during exposure. There were no significant alterations in lung
function (forced expiratory tests, single breath nitrogen washout, airway
resistance, or pulmonary compliance).
In a study using a similar protocol, Horstman et al. (1982) confirmed the
absence of significant change in pulmonary function following exposure to low
sulfuric acid aerosol levels (108 ug/m3 of 0.5 urn aerosol). A control group of
17 and an experimental group of 18 male subjects were exposed on two consecu-
tive days for 4 h including two 15-min periods of moderately heavy exercise.
Each group received a clean air exposure on the first day. On the second
exposure day, the control group received clean air and the experimental group
received H2$04. The exposure had no effect on breathing pattern, spirometry,
or airway resistance.
Horvath et al. (1982) exposed 11 male subjects to clean air and to 233,
418, and 939 ug/m of 0.9 urn sulfuric acid aerosol. Exposures lasted 2 hr and
included four 15-min periods of mild intermittent exercise. A small decrease
(101 ml; -2.1 percent) in FEV-j^ Q was reported for the 939 ug/m3 exposure.
Since this change was similar in relative magnitude to other spirometry mea-
surements in the study, it is quite possible that the "significance" of this
result occurred by chance (i.e., a total of 12 measurements were tested for
significance at the P <0.05 level, which increases the likelihood of finding a
"significant" response by chance alone). Although there was no convincing
evidence of pulmonary function effects, symptoms of cough and dry or irritated
throat were more prevalent at the highest (939 ug/m3) concentration and were
noted mainly at the beginning of the exposure period. The occurrence of
significant symptoms suggests that the significance of the small change in
FEV1.0 reP°rted at tne 939 M9/m concentration could be real. However, Avol
et al. (1986) noted increased symptoms, in the absence of changes in spirometry
at both 1,000 and 2,000 ug/m3 of H2$04 "acid fog" aerosol.
Utell et al. (1982) exposed normal volunteers to 100 and 1,000 ug/m3 of
0.5 to 1.0 urn "dry" sulfuric acid aerosol for 16 min via mouthpiece breathing.
This resting exposure produced no significant effect on airway conductance yet
induced "quite small" but significant changes (magnitude not reported) in
maximum expiratory flow on maximum expiratory flow volume curves (MEF60%TLC)
and partial expiratory flow volume curves (PMEF60%TLC, PMEF40%TLC) after the
1,000 ug/m exposure.
5-5
-------
From a comprehensive exposure study including several pollutants, Stacy
et al. (1983) reported results for 11 subjects exposed to 100 pg/m3 sulfuric
acid aerosol. The 4-h exposure, which included 30 win of moderate exercise,
produced no significant effects on pulmonary function..
Utell et al. (1984) reported results of a study in which 14 normal sub-
o
jects were exposed to 100 and 1,000 ug/m sulfuric acid aerosol for 16 min;
there were no effects on SGaw, FEV1 Q, or V60%TLC.
During a study examining the effects of ozone plus H9SOA, Horvath et al.
3
(1987) exposed 9 men to a range of 1,200 to 1,600 ug/m sulfuric acid aerosol
for 2 h. In contrast to their previous study (Horvath et al., 1982), an
extremely fine aerosol (<0.1 urn) was used. The exposures were conducted under
warm, humid conditions and included a total of 60 min of moderate intermittent
exercise. There were no significant changes in FVC, FEVj Q, ft? 25-75% or Raw
attributable to sulfuric --acid aerosol exposure. Although evaluation of subject
symptoms was apparently conducted, the symptom results were not included in
their report.
Avol et al. (1986, 1988) have exposed subjects to 0, 500, 1,000, and
2,000 ug/m of acid fog (see details in 5.6 or Table 5-1). In the healthy
normal subjects, there was no indication of pulmonary function effects after
any of the exposures. However, upper and lower respiratory symptoms increased
o
after all exposures but most notably after the 2,000 ug/m exposure. Airway
reactivity to methacholine was unchanged after the exposures.
The results of the above 11 studies, which investigated the effects of
sulfuric acid aerosols over a broad range of particle sizes (0.1 to 10 urn) and
under a variety of exposure conditions (duration, temperature, humidity,
inhalation route, activity level), consistently demonstrated that there were no
pulmonary function effects of up to 500 ug/m sulfuric acid aerosol for dura-
tions up to 4 hr. Although there is some suggestion that pulmonary function
3
effects may begin at concentrations of approximately 1,000 ug/m , the demon-
stration of responses is confined to only a few of many studies and the effects
were very small in magnitude and not consistently demonstrated across a variety
of exposure conditions. However, symptoms of upper respiratory discomfort were
3
reported after exposure to 1,000 ng/m in two studies of normal subjects.
Unfortunately there are no data available for acid aerosol exposure of
non-asthmatic adolescents or children.
5-6
-------
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5.3 EFFECTS OF ACID AEROSOLS ON BLOOD BIOCHEMISTRY
Chaney and co-workers (1980a) examined the effects of sulfuric acid
aerosol exposure on blood biochemical markers. Twenty subjects were exposed to
O
100 ug/m of 0.5 pm sulfuric acid aerosol for 4 h at rest on two consecutive
days. Blood samples were taken immediately before and after exposure, and
then again one day after exposure. There was no effect of acid aerosol
exposure on any of the measured blood parameters: glutathione, red blood cell
(RBC) glutathione reductase, RBC glucose-6-phosphate dehydrogenase, lysozyme,
SGOT (serum glutamic-oxaloacetic transaminase), serum vitamin E, and 2,3-
diphosphoglycerate (DPG).
The above study was repeated (Chaney et al., 1980b) using a slightly
modified experimental design and an exposure protocol that incorporated
exercise. (The exercise protocol is identical to that described in Section 5.2
for Horstman et al., 1982). The blood parameters measured were the same as in
the resting study except that G6PD was omitted. This study demonstrated no
effects of sulfuric acid aerosol exposure on these human blood biochemical
markers.
5.4 EXPOSURE TO MIXTURES OF ACID AEROSOLS WITH OTHER POLLUTANT GASES
In the ambient environment, many pollutants coexist. When individuals are
exposed to two or more inhaled pollutants, either simultaneously or sequen-
tially, there is potential for an additive or interactive effect. These
possible combined effects have been studied for sulfuric acid aerosol in
combination with 03, S02, and NO,,. Although a variety of pollutant combina-
tions have been utilized, rarely, if ever, are the ambient conditions approxi-
mated. More consideration of actual ambient conditions is required, especially
consideration of the gas and aerosol concentrations in areas impacted by
plumes.
Kleinman et al. (1981a) studied the effect of the combination of ozone
(0.37 ppm), S02 (0.37 ppm), and sulfuric acid aerosol (100 ug/m ) under warm,
humid conditions in an environmental chamber. Nineteen subjects participated
in the 2-h intermittent exercise exposures using a non-randomized exposure
sequence: exposure to the pollutant was always preceded several days earlier
by a clean air "sham" exposure. Exposure to the pollutant mixture caused
significant reductions in FVC (-2.8 percent), FEV^g (-3.7 percent), and other
5-13
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spirometric measurements. There was a trend for symptoms to increase during
the exposures but the symptoms reported during the pollutant mixture exposures
were not significantly different from those reported during the clean air
exposures. The authors indicated that more than 90 percent of the H2$04 had
been converted to ammonium bisulfate. The decrease in FEV-, Q (-3.7 percent)
was only slightly larger than for a previous group of subjects exposed to ozone
alone (FEV, Q; -2.8 percent), using a similar exposure protocol. It was
therefore concluded that the presence of sulfuric acid aerosol did not enhance
the effects of ozone-SOp mixtures.
Kulle et al. (1982) reported the results of a study in which subjects were
exposed first to 0.3 ppm ozone for two hours and then immediately thereafter to
sulfuric acid aerosol for a period of 4-h. Twelve nonsmokers participated in
o
this study in which the effects of 0.3 ppm ozone and 100 ug/m of 0.13 urn
sulfuric acid aerosol were studied individually and then sequentially. The
order of exposures was identical for all subjects: ozone, sulfuric acid
aerosol, and ozone plus sulfuric acid aerosol, each exposure separated by one
week. The exposures each included one 15 min period of moderate cycling
exercise. None of the exposures produced significant changes in spirometry or
plethysmography. The authors suggested that the bronchial reactivity to metha-
choline may have decreased following sulfuric acid aerosol exposure but the
apparent difference was not statistically significant. It was concluded that
the prior exposure to ozone did not enhance the response to sulfuric acid
aerosol (or at least did not help to induce a response where none was previously
evident). It was nevertheless suggested that the use of a larger-particle-size
sulfuric acid aerosol may have produced different results since a larger aerosol
would tend to deposit, by impaction, to a greater extent on the larger airways,
the apparent site of the symptomatic effects of ozone.
In a study involving a total of 231 subjects, Stacy et al. (1983) examined
3
the effects of 4-h exposures to sulfuric acid aerosol (100 ug/m ), ammonium
3 3
sulfate aerosol (133 ug/m ), ammonium bisulfate aerosol (116 ug/m ), and
3
ammonium nitrate aerosol (80 ug/m ) in combination with ozone (0.4 ppm), N02
(0.5 ppm) and S02 (0.75 ppm). In addition to exposures to each individual
pollutant, there were a total of 12 combination exposures to a mixture of
one of the four aerosols and one of the three gaseous pollutants. There were
two 15-min periods of moderately heavy exercise during the exposure. With
the exception of the ozone plus aerosol exposures, none of the aerosols or
5-14
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gas-aerosol mixtures caused any significant changes in plethysmography or
spirometry. Similarly, only subjects exposed to ozone reported symptoms
indicative of respiratory tract irritation (e.g., coughing or throat
irritation).
Kagawa (1986) recently reported the results of a series of studies of
exposure to air pollutant combinations, some of which included sulfuric acid
aerosol. The subjects were young adult Japanese; approximately half were
smokers. A 2-h intermittent exercise protocol was used which included four
15-min exercise periods at 50 W (300 kpm). Exposures to either 200 or
Q
400 ug/m sulfuric acid aerosol occurred in a body plethysmograph maintained
at 28 to 29°C and 50 to 60 percent RH. Unfortunately the data for individual
exposures to only sulfuric acid aerosol are omitted from the tables and
figures. The addition of sulfuric acid aerosol to exposure atmospheres —
most contained ozone (0.15 to 0.30 ppm) -- produced no obvious additional
effects on specific airway conductance over and above those caused by the
other pollutants. Airway reactivity to acetylcholine was determined after
one series of exposures to 200 ug/m of sulfuric acid aerosol; no effect on
airway reactivity was observed. In several different series of ozone plus
sulfuric acid aerosol exposures, the author observed no apparent health-
related synergistic effects of sulfuric acid aerosol with ozone.
Horvath and co-workers (1987) studied the effects of exposure to much
o
higher concentrations of sulfuric acid aerosol (1,200 to 1,600 ug/m ) in
combination with ozone. As indicated in Section 5.2, there was no effect of
the sulfuric acid aerosol alone on pulmonary function. The combination of a
"no-effect level" of ozone (0.25 ppm) with the sulfuric acid aerosol also
produced no significant changes in pulmonary function. Although the investi-
gators chose a somewhat conservative probability level for indicating signi-
ficance (P <0.01), their findings of no significance would also have held at
P <0.05.
The studies cited in this section examined the pulmonary function
responses to exposure to sulfuric acid aerosol, over a broad range of concen-
trations, in combination with various other pollutants including ozone,
nitrogen dioxide, and sulfur dioxide. There was no evidence to suggest an
interactive effect between sulfuric acid aerosol and the other pollutants.
However, these studies primarily used the physiological measurement endpoints
derived from spirometry or plethysmography which provide information about
5-15
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airway resistance and lung volume. Further studies using different endpoints,
including measurements of airway permeability or airway inflammatory responses
(using bronchoalveolar lavage) should be considered.
5.5 EXPOSURE TO OTHER ACID, AEROSOLS OR MIXTURES OF AEROSOLS
Human exposure to a number of aerosol species including sodium nitrate
(NaNOo), ammonium nitrate (NH*N03), ammonium bisulfate (NH^HSO,), ammonium
sulfate ((NH4)2SO.), zinc ammonium sulfate (ZnSO^-CNH^SO^), and ferric
sulfate (Fe2(SO~4)3) has been studied over the past several years. Ambient
levels of airborne nitrate salts are typically less than 5 ug/m and rarely
exceed 50 ug/m3 (Sackner et al., 1979).
5.5.1 Nitrates
A series of sodium nitrate and ammonium nitrate aerosol exposures in both
normals and asthmatics was performed by Sackner and colleagues (1979). Groups
of 5 or 6 normal or asthmatic subjects breathed NaCl or NaNO, aerosol at
3
concentrations ranging from 10 to 1,000 ug/m for 10 minutes while resting. In
the normal subjects, possibly significant differences in V
50%'
VC and SGaw
between NaNOg and NaCl exposures were observed. However, a decrease in flow
was accompanied by an increase in airway conductance. Because of the large
number of specific comparisons, the authors concluded that these observations
were probably due to chance alone. They concluded that NaN03 exposure up to
1,000 ug/m caused no acute effects on cardiopulmonary function.
Utell et al. (1979) studied both normal and asthmatic volunteers exposed
q
to 7,000 ug/m of 0.46 urn NaNO, aerosol for 16 min via mouthpiece. The major
health effect endpoints measured in their study included airway resistance,
both full and partial expiratory flow-volume curves, airway reactivity to
carbachol, and aerosol deposition. Aerosol deposition as a percentage of
inhaled aerosol averaged about 50 percent for normals and about 56 percent for
asthmatics; the group differences were not significant. The effect of exposure
to NaN03 aerosol was indistinguishable from the control NaCl exposure in
normals. Similarly, there were no effects of NaN03 exposure in asthmatics.
Utell et al. (1980) subsequently studied 11 subjects with influenza
exposed to the same NaN03 regimen as above. The subjects were initially
exposed at the time of illness and then reexposed 1, 3, and 6 weeks later.
5-16
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Aerosol deposition ranged from 45 to 50 percent over the four exposure
sessions. All subjects had cough and fever and 10 of 11 had viral or
immunologic evidence of acute influenza. Baseline measurements of FVC and
FEV., 0 were within normal limits and did not change throughout the six-week
period. There were small but significant decreases in airway conductance
following NaN03 inhalation. This difference was present during acute illness
and one week later but was not seen at 3 and 6 weeks post-illness. The
decrease in SGaw seen on the initial exposure was accompanied by a decrease in
partial expiratory flow at 40%TLC; this was also observed at the one week
follow-up exposure. This study suggests that the presence of an acute viral
respiratory tract infection may render humans more susceptible to the acute
effects of nitrate aerosols. Nevertheless, the concentration of nitrates used
in this exposure study exceeded maximum ambient levels by more than 100-fold.
In addition to NaN03 aerosols, NH^NOj exposure has been studied by
Kleinman and associates (1980). Twenty normal and 19 asthmatic subjects were
a
exposed to a nominal 200 pg/m of 1.1 urn ammonium nitrate aerosol. The 2-h
exposures included mild intermittent exercise and were conducted under warm
conditions (31°C, 40 percent RH). There were no significant physiologically
meaningful effects of the NH,N03 exposure in either subject group.
5.5.2 Other Sulfates
Linn et al. (1981) studied a group of 21 normal and 19 asthmatic subjects
exposed to 15 to 16 ug/m of zinc ammonium sulfate aerosol. Exposures lasted
2 h in an environmental chamber at 20°C and 85 percent RH and included light
intermittent exercise. Although there were some very small changes in function
between and within exposure conditions which apparently reached statistical
significance, there was no overall pattern of response which indicated that
zinc ammonium sulfate resulted in pulmonary dysfunction. The authors concluded
that this study "fails to demonstrate convincingly any effects of zinc ammonium
sulfate exposure important to health."
In a subsequent study wit.ii zinc ammonium sulfate, Kleinman and co-workers
(1985) exposed 20 normal subjects to a mixture of SO, (0.5 ppm), N09 (0.5 ppm),
3
and zinc ammonium sulfate (26 pg/m , 1.1 urn) combined with NaCl aerosol; these
2-h exposure sequences incorporated light intermittent exercise. There were
no significant pulmonary function effects of this exposure. Symptom data
suggested that the S0?-N0?- (NaCl aerosol-zinc ammonium sulfate) aerosol
5-17
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mixture was somewhat more irritating than the NaCl aerosol alone but the
difference was not significant. Only the total symptom score was reported and
thus the individual symptoms responsible for the increased score cannot be
ascertained from this report. This study confirms the absence of effect of
zinc ammonium sulfate observed in the prior Linn et al. (1981) study.
Another metal-sulfate aerosol that has been evaluated as a potential
respiratory irritant is ferric sulfate (Kleinman et al., 1981b). Twenty normal
and 18 asthmatic subjects were exposed to 75 ug/m3 of 2 urn Fe2(S04)3 aerosol.
In the presence of ammonia, ferric ammonium sulfate may be formed, which was
assumed to be the case in this study. There were no statistically significant
changes in the physiologic tests performed before and after the exposures
(these included spirometry, plethysmography, single breath nitrogen washout,
forced oscillation, and oxygen saturation). Neither normal nor asthmatic
groups reported a significant increase in symptoms as a result of the exposure
to ferric sulfate. Even when data were analyzed on an individual basis, there
was no consistent pattern indicative of dysfunction induced by the ferric
sulfate aerosol.
Kulle and co-workers (1984) examined the possibility that a mixture of
^
S02 (1.0 ppm) and ammonium sulfate (528 |jg/m , 1 urn) could produce greater
effects on the respiratory system than either pollutant alone. The exposures
lasted 4 h and included two 15-min sessions of moderate bicycle exercise.
Twenty subjects (10 M, 10 F) completed the study. There were no significant
changes in spirometry, plethysmography, or airway reactivity to methacholine
with either ammonium sulfate alone or ammonium sulfate plus S02- Nevertheless,
there were increased symptoms as a result of the combined exposure in particu-
lar, in which 9 of 20 subjects reported upper airway irritation. Only 4 of
20 subjects reported upper respiratory tract symptoms for S02 exposures alone.
This observation suggests that the upper respiratory symptoms observed in
normals after S02 exposure (Witek et al., 1985) could possibly be enhanced in
the presence of ammonium sulfate.
While testing the hypothesis that a carbon aerosol could potentiate the
conversion of S09 to sulfates and enhance the effect of SO,,, Kulle and
3
associates (1986) exposed subjects to a mixture of S02 (1 ppm) and 500 ug/m
of 1.5 urn activated carbon aerosol. Although it was demonstrated that most
of the S02 which was sorbed onto the carbon was converted to sulfate, the
sorption of S02 by carbon constituted only a very small fraction of the total
5-18
-------
SOp dose. The effects of S02, which are not of interest for the purposes of
the current document, were neither enhanced nor mitigated by the addition of
carbon aerosol. This study provided no evidence to support the hypothesis
that the inert aerosol worsened the effects of S02 in normal healthy subjects
as a result of sulfate formation.
These studies of exposure to a variety of sulfate and nitrate aerosols
point to the absence of an effect on spirometry, plethysmography, and various
other physiological indicators of pulmonary function in asthmatics and healthy
normal subjects. The only group of subjects that demonstrated a possible
effect were a group of normal individuals who had recently contracted
influenza. The health significance of the small alterations in pulmonary
function as a result of exposure to "massive" concentrations of NaN03 is
unclear at this time. Even at concentrations much higher than would be
anticipated in the ambient air, the nitrates and sulfates that have been
studied to date do not appear to produce any meaningful effects on pulmonary
function measurements in exposed individuals with "normal" lung function.
5.6 EFFECTS OF ACID AEROSOLS ON RESPIRATORY FUNCTION OF ASTHMATICS
The effects of sulfuric acid aerosol in asthmatics have been studied in a
number of laboratories in the past decade. There is considerable variability
in the results of these studies, much of which may be attributed to variability
in severity of asthma, in the procedures for withholding or continued use of
medication, and in exposure conditions. Asthmatics represent a "sensitive
subgroup" who are potentially more susceptible to the effects of several air
pollutants. One of the more obvious examples is the approximately tenfold
greater sensitivity of asthmatics to S02, a gas that not only is a precursor
of sulfuric acid aerosol but is also likely to coexist with H2S04. Asthmatics
also show increased airway resistance as a result of other stimuli such as
exercise, or from breathing cold air, dry air, or hypoosmolar aerosols.
The cause of increased resistance is often presumed to be in large
conducting airways (bronchoconstriction). However, constriction of the larynx
or of smaller airways may make an important contribution to increased airway
resistance. The regionalization of changes in airway resistance is not
typically evaluated.
Characteristics of the asthmatics who participated in the studies reported
in this section are shown in Table 5-2.
5-19
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Sackner and associates (1978) performed a series of sulfuric acid aerosol
exposure studies in a diverse group of 17 asthmatics exposed to 10, 100, and
o
1,000 ug/m . Most of the asthmatics were taking theophylline, prednisone, or
both. The exposures to 0.1 to 0.3 urn sulfuric acid aerosol lasted for 10 min.
None of the physiological tests performed showed evidence of significant
dysfunction resulting from the exposures.
2
Avol et al. (1979) exposed 6 asthmatic subjects to 100 ug/m sulfuric acid
aerosol for 2 h on two consecutive days. These subjects were also exposed to
ammonium sulfate and ammonium bisulfate. There were no significant group
effects on lung function that could be attributed to any of the aerosols. It
was noted, however, that two of the asthmatics exposed to sulfuric acid aerosol
showed "possibly meaningful changes in respiratory resistance." Because these
changes were observed on both sulfuric acid aerosol exposure days, it is
unlikely that the responses were due to chance alone. There was a tendency for
group mean symptom responses to increase on the sulfuric acid aerosol exposure
days. Nevertheless, the authors concluded that there were "no obvious group or
individual reactions."
Utell et al. (1982, 1983a) studied 17 asthmatics (none requiring steroid
therapy) exposed to a variety of aerosols including NaCl, NaHS04, (NH4)2$04,
NH4HS04,
and
The aerosols were submicrometer (0.5 to 1.0 urn) and
concentrations were 100, 450, and 1,000 ug/m°. The relative humidity was
maintained below 25 percent. H2$04 deposition ranged from 54 to 62 percent of
the inhaled aerosol. All asthmatics were initially reactive to carbachol
inhalation challenge. Following the 16-min exposures to any of the sulfate
aerosols none of the asthmatics reported symptoms at any of the concentrations.
The low-concentration (100 ug/m ) exposure produced no significant group
3
changes. After exposure to 450 ug/m sulfuric acid aerosol, there was a
19 percent drop in SGaw, compared with only a 3 percent decrease after NaCl
aerosol. None of the other pulmonary function parameters was affected by the
exposure. Exposure to NH4HS04 aerosol decreased SGaw but the other forms of
sulfate aerosol had no significant effect on lung function at the 450 ug/m
level. Following the 1,000 ug/m exposure series, there was a 21 percent
decrease in SGaw with sulfuric acid aerosol and a 13 percent decrease with
NH4HS04 aerosol (Figure 5-1). Neither NaHS04 or (NH4)£S04 produced significant
effects. In addition, 1000 ug/m3 H2S04 aerosol caused a 5 percent decrease in
FEV., Q. Both 1000 ug/m3 H£S04 and NH4HS04 exposures resulted in significant
decreases in flow on both maximum and partial expiratory flow-volume curves.
5-21
-------
30
25
I
I
o
20
Ul
CD
I 15
U
10
1. SIGNIFICANTLY DIFFERENT FROM PRE-EXPOSURE VALUES:
*-p<0.001
**- p< 0.005
***= p<0.050
2. SIGNIFICANTLY DIFFERENT FROM VALUES AFTER
~" EXPOSURE TO NaCI.
+ - p<0.001
++ = p<0.05
+-H--p<0.01
* +
1000
**+++
450
NaCI
100
AEROSOL SULFATE CONCENTRATION, /ig/m3
Figure 5-1. Mean percent change in specific airway conductance (SGaw) produced
by a 16-mlnute inhalation of sulfate aerosols by asthmatics.
Source: Utell et al. (1983a).
5-22
-------
Ten adolescent asthmatics were exposed via mouthpiece to 110 ug/m of
0.6 |jm sulfuric acid aerosol by Koenig et al. (1983). In contrast to the work
of Utell et al. (1983a), the studies were carried out under humid conditions
(>75 percent RH). The exposure sequence involved 30 min of rest followed by
10 min of moderate exercise (VV = 40 1/min); NaCl aerosol was used as a control
exposure. The regular medication of most subjects included theophylline and
a sympathomimetic bronchodilator (2 subjects used cromolyn sodium, 2 used
antihistamines, and 1 used prednisone). The hypothesis that there was no
difference between the NaCl aerosol and the sulfuric acid aerosol was
originally tested by the use of repeated t-tests. These data have been
subsequently reanalyzed by the authors (Koenig, 1987) using an analysis of
covariance for repeated measures. There was a tendency for FEV-, Q, VmaxcQS
V
max75
to decrease after exposure, both to NaCl aerosol and sulfuric acid
aerosol. FEV-, Q was decreased 8 percent when measured 2 to 3 min after
exercise while breathing sulfuric acid aerosol but was decreased only 3 percent
after NaCl aerosol. The analysis of covariance confirmed the significant
decreases in FEVn n, Vmnv rn, and Vmav 7I- immediately (2-3 min) postexposure.
JL. U HlaX OU maX / 0
FEV-, Q was also significantly reduced 4-5 min after exposure; the flow
variables also tended to be reduced after 4-5 min but the changes did not
attain statistical significance. The results of the analysis of covariance are
presented in Table 5-3.
There was also a 40 percent increase from preexposure to postexposure in
the forced oscillation measurement of total respiratory resistance (Ry).
The magnitude of this change, associated with sulfuric acid aerosol exposure,
was primarily due to an unusually low preexposure baseline value in comparison
to other exposure conditions for the same group of subjects. The difference in
postexposure measurements between NaCl and HgSO^ was only 15 percent, which
is within the measurement error of this test. The results of this study were
compared with a previous study (Koenig et al., 1982) of exposure to 0.5 ppm
S02 in seven subjects who participated in both studies; the effects of the
0.5 ppm S02 exposure were similar to those seen with sulfuric acid aerosol.
The investigators concluded that, in this group of adolescent asthmatics,
exposure to 100 ug/m of sulfuric acid aerosol accompanied by exercise led to
significant changes in pulmonary function.
In a study aimed primarily at the effects of sulfuric acid aerosol on
mucociliary clearance, Spektor and associates (1985) also reported effects on
5-23
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TABLE 5-3. ANALYSIS OF COVARIANCE OF TEN ADOLESCENT ASTHMATICS EXPOSED
VIA MOUTH PIECE TO 110 pg/m3 SULFURIC ACID AEROSOL
Pulmonary
Function Time of
Value Measurement
FEVi
Vmax50
Vmax75
JlluA
RT
I
2-3 min post exp.
4-5 min post exp.
later points
2-3 min post exp.
later points
2-3 min post exp.
later points
4-5 min post exp.
later points
also N.S.
F
20.
7.
10.
6.
3.
46
85
23
64
21
Tail Prob
0
0
0
0
0
.0019
.0231
N.S.
.0126
N.S.
.0328
N.S.
.1107
H2S04
H2S04
H2S04
H2S04
H2S04
Adjusted Mean
= 2.
= 2.
= 1.
= 0.
= 7.
68;
79;
81;
66;
32;
NaCl
NaCl
NaCl
NaCl
NaCl
_ f\
= 2.'
= 2.
= 0.
**" 0 •
91
92
12
80
52
Source: Koenig et al. (1987).
pulmonary function. Ten asthmatics (6 M, 4 F) were exposed to 110, 319, and
971 ug/m of 0.5 urn sulfuric acid aerosol via nasal mask at 27°C and 47 percent
RH. Six mild asthmatics who used no regular medication were designated
group I. Four subjects who regularly used methylxanthine and sympathomimetic
bronchodilators were designated group II (one of these subjects also used
steroids). Following the series of three 20 min inhalations of 1,000 ug/m of
sulfuric acid aerosol in the group I subjects, airway conductance, FEV-, Q/FVC,
FEFpc-ycvj and V «s were significantly decreased. When measured 3 hours
after the exposure, the magnitude of these decreases had become greater; SGaw
was decreased 5 percent immediately after exposure and 10 percent after
3 hours. There were no effects of the two lower H^SO. concentrations on
respiratory mechanics in these subjects.
In a second study of adolescent asthmatics, Koenig et al. (1985) exposed a
3
different group of 10 subjects to 100 ug/m sulfuric acid aerosol either via
mouthpiece or facemask. Although the intent of the study, in part, was to
examine the differences in response to su'Jfuric acid aerosol between oral and
oronasal breathing, this comparison was not made because the subjects reported
that they breathed mostly through the mouth (rather than oronasally) when
wearing the mask. In addition to other measures of pulmonary function, nasal
work of breathing and nasal "power" were calculated from nasal flow-pressure
5-24
-------
measurements. Resting exposures of 30 min were followed by 20 min of moderate
treadmill exercise (V£ = 43 1/min). Although associated S02 (0.5 ppm) exposures
indicated an effect on nasal "power," there was no change in this measurement
following sulfuric acid aerosol exposure. FEV^ 0 was decreased by 7 percent
and 8 percent following the two sulfuric acid aerosol exposures but these
changes were slightly less than the 9 percent decrease observed with filtered
air and considerably less than the 16 to 24 percent decrease after the S0?
exposure. Although there were significant pre- and pbstexposure changes in
Vmax50 and Vmax755 there were also large nonsignificant changes in clean air of
similar or greater magnitude against which these data were not compared. The
use of the repeated t-test in this repeated measures design obscures the effect
of changes in respiratory function which occurred with clean air exposures and
which are presumably due to modest exercise-induced bronchoconstriction. The
results from this study are summarized in Table 5-4.
In more recent work, Koenig et al. (1988) indicated that 68 ug/m3 sulfuric
acid aerosol produced a 5.9 percent decrease in FEV, Q (p <0.05). Exposure to
a mixture of H2S04 (68 ug/m3) and S02 (0.1 ppm) produced slightly smaller
changes in FEV-^g (-3.5 percent) (p <0.01). A small decrease was also observed
with clean air exposures; the decrease with H2$04, after correction for the air
exposure, was 4.1 percent. Similarly, FEF^ was decreased by 13.4 percent
(8.2 percent after correction) after sulfuric acid aerosol.
Linn et al. (1986) studied 27 young adult asthmatics exposed to 0.6 urn
sulfuric acid aerosol at three different concentrations (122, 242, and
410 ug/m ). Studies were conducted in an exposure chamber at 22°C and
50 percent RH; each exposure lasted 60 min and included three 10-min periods of
moderate exercise (V^ = 42 L/min). The subjects were a diverse group of
asthmatics but all would be considered clinically mild with the exception of
one subject who used inhaled steroids. All were sensitive to either cold air
inhalation challenge (24 of 27) or 0.75 ppm S02 inhalation challenge (23 of
27), and most were sensitive to both challenges. Only 7 of the 27 subjects
used regular oral or inhaled medication and all were able to withhold medica-
tion prior to exposure (48 h antihistamine, 12 h oral bronchodilators, 8 h
inhaled bronchodilators, 8 h steroids). In addition to pre- and postexposure
measurements, pulmonary function was also measured after the first 10-min
exercise period. In all exposures to sulfuric acid aerosol and clean air there
was a significant main effect of time; specifically, pulmonary function tended
5-25
-------
TABLE 5-4. A SUMMARY OF THE PERCENTAGE CHANGE IN PULMONARY FUNCTIONAL
VALUES AFTER 10 MINUTES OF MODERATE EXERCISE TO 100 ug/m3 H2S04
Pulmonary
Function Value
RT
FRC
^max50
^max75
FEVi
Air
+24 percent
NS
+8 percent
NS
-10 percent
NS
-23 percent
NS
-9 percent
p <0.005
Exposure Mode
Mouthpiece (H2S04)
+45 percent
p <0.05
+5 percent
NS
-22 percent
p <0.005
••18 percent
p <0.005
-7 percent
p <0.005
Mask (H2S04)
+35 percent
p <0.05
+4 percent
NS
-16 percent
p <0.005
-16 percent
p <0.010
-8 percent
p <0.005
NS = nonsignificant.
P = values are for paired t-test, pre- vs post-exposure not adjusted for air
exposure response.
Source: Koenig et al. (1985).
to worsen with time of exposure regardless of exposure atmosphere. There
was no significant effect of sulfuric acid aerosol exposure at any of the
concentrations tested. Even when the subjects were divided into reactive and
nonreactive groups, there were no apparent differences that could be attributed
to acid aerosol exposure. Symptom scores were not significantly affected by
the sulfuric acid aerosol exposures, but in the week following the exposure to
410 ug/m , the symptom score was "noticeably higher." This observation of an
apparently delayed response is in accord with the observations of Utell et al.
(1983b) and Spektor et al. (1985). The authors concluded that these subjects
experienced modest exercise induced bronchoconstriction during these exposures
and that these responses were modified only slightly, if at all, by sulfuric
acid aerosol inhalation. A preliminary summary of these findings was also
reported by Hackney et al. (1986).
o
Utell et al. (1987) exposed two groups of asthmatics to 100 or 450 pg/m
sulfuric acid aerosol either via mouthpiece or while freely breathing in a
3
chamber. There were no effects of exposures to 100 pg/m sulfuric acid
o
aerosol. Resting exposures to 450 ug/m lasted 16 min and resulted in a
5-26
-------
19 percent decrease in SGaw. Chamber exposures to 450 ug/m3 lasted 1 hr and
included 10 min of exercise at a power output of 50 watts; SGaw decreased
22 percent after these exposures. The authors estimated, using aerosol deposi-
tion models, that the tracheobronchial deposition of aerosol was 27 ug for
mouthpiece and 36 ng for chamber exposures, respectively. Despite the con-
siderable differences in overall respired aerosol mass between the two exposure
conditions (72 micrograms — mouth; 230 micrograms — chamber), the similarity
between the airway responses and the tracheobronchial sulfuric acid aerosol
deposition suggested, to the authors, that a possible causal relationship
existed between sulfuric acid aerosol deposition and decreased airway conduc-
tance.
Horstman and colleagues (1986) have presented preliminary information of a
study in which mild asthmatics were exposed to a combination of sulfur dioxide
(0.75 ppm) and sulfuric acid aerosol (100 ug/m3) to determine if small amounts
of sulfuric acid aerosol could influence the asthmatic's response to SOp. The
subjects were exposed in a chamber to S02 alone, sulfuric acid aerosol alone,
and the combination of sulfuric acid aerosol and S02, as well as to clean air.
Subjects exercised throughout the 20-min exposures at a ventilation of 40 to
44 1/min. under warm (26°C) and humid (70 percent RH) conditions. Because the
study was only partially complete when the report was prepared, the investiga-
tors did not present statistical analyses of the data. The exercise performed
during the exposure produced a modest 75 percent increase in SRaw and a
3.9 percent decrease in FEV-^ Q. The increase in SRaw and the decrease in
FEV-^ Q were slightly smaller after the H2S04 exposure than after air. After
S02 exposure, SRaw increased from 7.5 to 29.0 cmH20-s. After H2S04 plus S02
exposure, SRaw increased from 7.1 to 33.1 cmH20-s. Changes in FEV-, Q were also
larger after S02 or S02 plus H2S04, averaging 0.50 and 0.55 liters respectively.
Preliminary examination (Horstman, 1988) of the data since completion of the
study does not substantiate the preliminary observation of worsening of response
with the combination of pollutants. Symptom responses followed a similar
pattern to the spirometry and plethysmography measurements in that they were
most pronounced with the two exposures involving S02>
Avol et al. (1988) have studied the effects of "acid fog" in both normal
and asthmatic subjects. They exposed subjects to nominal concentrations of
0, 500, 1,000 or 2,000 ug/m3 of sulfuric acid "fog" aerosol (10 urn) under
"fog" conditions (10°C and 100 percent RH). Three 10 minute periods of exercise
5-27
-------
post exposure.
o
2,000 ug/m exposure.
(Y£ = 43 L/min) were performed during the one hour chamber exposure. Half the
subjects gargled grapefruit juice prior to exposure in order to minimize oral
ammonia levels. The efficacy of this procedure in reducing oral ammonia was
not reported. All asthmatics were clinically mild; less than half used regular
medication. The only significant effect of the acid fog exposure appeared to
be a decrease in peak expiratory flow after exposure to 2,000 ug/m3. There
was a trend for FEV-j^ Q and FVC to decrease after the 2,000 ug/m3 exposure
but these trends were not significant. There were no significant effects
attributable to gargling acidic juice prior to exposure. Symptoms classified
as "lower respiratory" were significantly increased during acid fog exposures,
3
especially at 2,000 ug/m . These symptoms were largely resolved at one hour
"Upper respiratory symptoms" also increased during the
Airway reactivity to methacholine was not changed
following exposure to any of the concentrations of acid fog. The responses of
the asthmatics were similar to those of normals. In this study, it was
demonstrated that with larger aerosols, which deposit in the major thoracic
and extra-thoracic airways, asthmatics were not more reactive than healthy
normal subjects.
Hackney et al. (1989) recently presented additional studies of adult
asthmatics exposed to nominal concentrations of 500, 1,000, and 2,000 ug/m3 of
0.9 urn sulfuric acid aerosol. (Actual high concentration was closer to
o
1,500 ug/m ). Whereas the acid fog studies (Avol et al., 1986) showed increased
respiratory symptoms in the absence of changes in spirometry, subjects exposed
to the smaller aerosol (i.e., 0.9 urn vs 10 urn in acid fog) experienced signifi-
cant changes in FEV^ and increased lower respiratory symptoms. The symptom
responses displayed a concentration-response relationship and were progressively
increased with increasing acid concentration. However, FEV-. was unchanged
3
with exposure to 500 ug/m when compared to air exposure. At the two highest
o
acid concentrations, (approximately 900 and 1500 ug/m ) FEV^ was decreased.
These observations are in accord with aerosol deposition models which would
predict substantially greater intrathoracic deposition of the smaller aerosol.
Utell et al. (1986) summarized the importance of three factors that affect
the responses of asthmatics to sulfuric acid aerosols. One of these factors,
exercise, is known to exacerbate the effects of most inhaled pollutants due to
the increase in ventilation and is also known to produce bronchoconstriction in
asthmatics. The mode of breathing (i.e., nasal, oronasal, or mouthpiece)
5-28
-------
affects the tracheobronchial deposition of inhaled aerosols; the extent to
which deposition patterns are altered depends in part upon the initial particle
size, the ambient temperature and relative humidity, and the velocity of
airflow. Within the size range of ambient sulfuric acid aerosol (0.2-0.6 urn),
the deposition is only slightly higher with nasal than with oral breathing.
A third factor that appears to be specifically related to acidic aerosols is
the observation that oral and/or respiratory ammonia may mitigate the response
to inhaled acid aerosol, because of neutralization of the acid.
Bauer and colleagues (1988) studied 8 asthmatics and 11 COPD patients
exposed to either NaCl aerosol or 75 |jg/m of sulfuric acid aerosol for 2 H in
an environmental chamber. Four ten minute periods of moderate exercise were
included in the exposure. There were no significant differences between air
and acid exposures for FVC, FEV-, or SGai( in the COPD patients. In the asthmatic
J. uW
subjects, there were no statistically significant differences between NaCl and
acid aerosol exposure for FVC, FEV-,, or SG . The authors noted however that
-L o.W
there was a trend for the exercise associated decrease in FEV-, to be slightly
larger after three of the four exercise periods in HpSO..
In another recent report, Balmes et al. (1988) compared the effects of
large and small H2$04 and NaCl aerosols in a group of 11 asthmatics. The
aerosols were inhaled via mouthpiece during resting breathing. The concentra-
tion of H2S04 was 2900 ug/m3 in the 6 urn (MMAD) aerosol and 2800 ug/m3 in the
1 urn aerosol. The pH of the acid aerosols was 2.0 and of the NaCl aerosols was
5.6. The osmolarity of all aerosols was approximately 30 mOsm. All aerosols
caused a modest decrease in airway resistance but there was no significant
difference between H2S04 and NaCl aerosols. A large (6 u"0 isoosmolar H2$04
aerosol produced similar responses. Brief exposure to these high concentra-
tions of sulfuric acid aerosol caused no bronchoconstriction in this group of
asthmatics.
These studies on acid aerosol exposure of asthmatics indicate that
asthmatics are more reactive than normals to inhalation of these aerosols. The
observation was made in several studies (Avol et al., 1979; Utell et al., 1983b)
that symptoms tended to increase immediately and also with some time delay
after sulfuric acid aerosol exposure. It appears that these delayed symptom
responses may be more likely to occur after longer exposures, when the capacity
of the respiratory surface liquids to buffer the hydrogen and sulfate ions
present in the aerosols may possibly be overwhelmed. The most acidic sulfate
5-29
-------
aerosols (i.e., F^SO^ and NH^HSO.) tended to be the ones that caused the
greatest pulmonary function effects. Pulmonary function responses in adult
3
asthmatics have been observed after exposure to 400 to 1,000 ug/m sulfuric
acid aerosol; no pulmonary function effects have been reported for normals
3 3
below 900 ug/m . Responses for adolescent asthmatics exposed to 68 ug/m have
been reported but these results need to be confirmed. Studies of adult asth-
o
matics at these lower acid levels (75 ug/m ) tend to support the observations
made on adolescents. However, more work is needed to confirm these studies.
Folinsbee (1989) summarized the effects of various concentrations of
sulfuric acid aerosol on changes in FEV-, Q in asthmatics. Data from several
studies of asthmatics exposed to acid aerosols are illustrated in Figure 5-2.
The change in FEV-, Q (corrected for the effect of the sham exposure) is plotted
against the acid aerosol exposure expressed as log of nanomoles of acid. This
figure was developed from data presented in Table 5-5. A wide range of
responses is evident. As discussed in Chapter 3, the quantity of acid aerosol
delivered to any specific region of the respiratory tract is dependent not only
on the duration of exposure, the acid concentration, and the volume of air
breathed (which determine the amount delivered to the external airway opening)
but also upon the airflow velocity, particle size, particle growth within the
airway, airway dimensions, and the extent of neutralization. Furthermore, it
is known that only a fraction of the "exposure dose" is actually deposited
within the respiratory tract; this fraction depends, in part, upon the particle
size and breathing pattern and volume during exposure. Only the former three
variables are considered in developing Figure 5-2; no estimate of delivered
dose to the lung is implied. Studies of asthmatics exposed to "acid fog", even
at high sulfuric acid aerosol concentrations do not so far indicate that
asthmatics are more reactive than normal subjects to these larger aerosols.
5.6.1 Effects of Nitric Acid Vapor in Asthmatics
The only study of near ambient levels of nitric acid vapor is a recent
abstract of Koenig et al. (1988). Nine adolescent asthmatics with allergic
asthma and/or exercise induced bronchospasm were exposed to filtered air,
50 ppb HN03, 100 ppb HNOg, or 50 ppb HNOg plus 68 ug/m3 H£S04. The authors
reported that a significant decrease in
exposures when compared to filtered air.
indicated.
^ Q
occurred in all three acid
The magnitude of the change was not
5-30
-------
o
u
LL
0
LLJ
LL
-5
-10
Avol et al., 79
Horstman et al., 86 •
Koenig et al., 85 •
Avol et al., 88
Utell et al., 83a
Koenig et al., 88
Koenig et al., 83
Hackney et al., 89
Spektor et al., 85
103
104
105
Log nano Mole/of Acid Aerosol * 104
Concentration • Ventilation • Duration Product
Figure 5-2. Change in FEV, in asthmatics exposed to various concentrations and
particle sizes of acid aerosols for varying durations and activity levels. The FEV1
percent change is corrected for the change observed in the control or sham expo-
sure. The exposure was calculated as the product of the acid aerosol concentration,
average ventilation, and the exposure duration. With the exception of the Koenig et
al. studies of adolescent asthmatics, the subjects were adult asthmatics. Aerosol
MMAD ranged from 0.5 to 1.0 urn except in Avol et al. 1988 study of 10 \im acid fog
aerosol.
5-31
-------
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CCTJfO I_3£-X 4JCOI- tnmoSi 'oJTJ TJ
«T3PJ= Uluiin rHCU)> '""j-O. PZ3P-r-QJ
nj-r-m+J O J3I- .i-.r-(tJ 4JO ^-v.;- U) !-
r--r- a.cnroj=a*E tnojcoSTJ >>P
TJQ)3S XO Q* PI- t.'-ECOC-t-T?
3T3 UJ= JZ-r-UJ . '—.CTJ ^-l'(O^-v.-rHLn"~ in
u
>fl3i-roooo ^t— s*s^-J^=3ca"-
3 a. i i i i i i i
tn &^ O* to to III III
Q)
Z; rH CM
5-32
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5.7 EFFECT OF ACID AEROSOL INHALATJON ON PULMONARY CLEARANCE MECHANISMS
Inhalation of acid aerosols has been shown to alter the pulmonary defense
mechanisms, in particular mucociliary clearance and alveolar macrophage func-
tion. Animal studies have indicated that the relative potency of sulfates in
altering mucociliary clearance [H2S04 > NH4HS04 > (NH4)2S04 > Na2S043 is
related to their acidity (Schlesinger, 1985).
Acid aerosols could alter mucociliary clearance by altering the physico-
chemical properties of the mucociliary blanket, influencing mucus production,
or by altering the beat frequency of the cilia. Physical damage to the cells
that produce mucus or damage to the cilia that move the mucous layer would also
alter clearance. A reduction in pH of the surface liquid of the trachea and
bronchi results in an increase in mucus viscosity and a decrease in the beating
frequency of cilia (Schlesinger, 1985) (see Section 4.5.1 and 3.4.1).
Sulfuric acid can either stimulate or inhibit mucociliary clearance,
depending on the regional airway dose and the region of the lung being evalu-
ated. Low doses of acid in the central airways (trachea and major bronchii)
tend to stimulate mucociliary clearance possibly due to a slight increase in
mucus viscosity which may permit the mucus layer to be moved more easily. With
increased deposition of acid in the airway, the airway pH is eventually depres-
sed and this causes a reduction in ciliary motility which depresses clearance
(Lippman, 1985). These concepts are also discussed in section 4.5.1.1.
Differences in regional airway deposition and the role of ui vivo acid neutral-
ization are discussed in Chapter 3. The effects of acid on mucociliary
clearance may vary from region to region within the respiratory system depending
upon the quantity of acid delivered and the resultant change in local pH.
Regional deposition depends on several physical properties of the aerosol
including particle size and hygroscopicity as well as characteristics of
ventilation and airway size. This latter point is of considerable importance
in interpretation of the results. Clearance is typically measured by following
the clearance of radioactively labelled particles that have been deposited in
the lung by inhalation. External detectors are used to measure the amount of
remaining test aerosol at various times following inhalation (see Clarke and
Pavia, 1980, for discussion of methodology).
In 1978, Newhouse et al. (1978) examined the effects of threshold limit
value (TLV) levels of SO,, (5 ppm) and H2S04 (1,000 \jtg/m , 0.5 pm) on mucociliary
clearance of healthy adults. They measured clearance using a 3 pm aerosol of
5-33
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Tc-AIbunnn in saline administered by a bolus technique intended to achieve
deposition in the large airways. The subjects were exposed to either sulfuric
acid aerosol or distilled water aerosol in a chamber. Mouth breathing was
obligatory throughout. The exposure lasted 2.5 h and consisted of 30 min
rest, 30 min intermittent heavy exercise (4X5 min at 70 to 75 percent of
maximum aerobic power, estimated ventilation 60 to 90 L/min), and 90 min rest.
Bronchial clearance was 15 percent faster following the H^SO^, exposure than
following water aerosol exposure. With the small acid aerosol used in this
study, it is likely that the central airways deposition was minimal. Further-
more, oral breathing would promote neutralization of the sulfuric acid aerosol
by ammonia. The combination of a small aerosol MMAD and high levels of oral
ammonia would result in a minimization of hydrogen ion deposition in the
central airways. Since the test aerosol was intended to measure central airway
clearance, the measurements were made at a site different from that where the
sulfuric acid aerosol was deposited. It is known that small amounts of sulfuric
acid aerosol can stimulate central airways clearance but the effects of sulfuric
acid aerosol on peripheral airways clearance in the subjects of Newhouse et al.
(1978) was not assessed.
Leikauf et al. (1981) studied the responses of 10 healthy nonsmokers to
distilled water aerosol (sham) or 110, 330, or 980 pg/m3 of 0.5 urn sulfuric acid
aerosol administered via nasal mask (see Figure 5-3). Following these 1-hr
resting exposures, clearance of Fe203 raclioactively labelled with 99mTc (which
was administered prior to exposure) was followed for 7 to 10 hours and then
measured again at 24 hours. In addition to measurements of bronchial clearance
from the right lung by counting the lung fields, tracheal mucociliary transport
rates were also determined by focusing on the head and neck region. There was
no effect of sulfuric acid aerosol exposure on tracheal mucociliary transport
3
rates. At the lowest exposure concentration (110 ug/m ), the bronchial muco-
ciliary clearance rate (BMCR) was accelerated (clearance half-time was reduced
o
38 percent). At the highest exposure concentration (980 ug/m ), BMCR was
apparently significantly slower (clearance half-time increased 48 percent).
However, there was a marked variability in the response and the data were
analyzed by the use of a paired t-test, which is not appropriate in the case of
a repeated measures design such as used in this study. The evaluation of the
significance of the paired t-test was not adjusted for multiple comparisons
(e.g., Bonferroni), and furthermore- the t distribution for one-tailed tests was
5-34
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used. If the more appropriate two-tailed distribution is used, only the change
(i.e., increased clearance) at 110 ug/m3 is significant using a t-test. A
follow-up test on the four subjects with the most rapid baseline clearance was
performed. Because much of the clearance in these subjects would have been
completed before the sulfuric acid aerosol exposure ended, the tagged FepCU was
administered after rather than before the 1,020 ug/m3 sulfuric acid aerosol
exposure. Three of these four subjects had previously demonstrated an apparent
acceleration, rather than a depression, of clearance after the 980 ug/m3
exposure. After the 1,020 ug/m exposure, evidence of slowing of mucociliary
clearance was seen in three of these four subjects. This study suggested that
sulfuric acid aerosol at TLV levels (approximately 1,000 ug/m3) causes a
depression of mucociliary clearance in healthy nonsmokers. However, the
results of this study cannot be considered conclusive because of the inappro-
priate data analysis methodology and the unfortunate choice of experimental
design that probably caused the investigators to miss the effects of 980 ug/m3
sulfuric acid aerosol exposure in subjects with normally rapid clearance.
The effect of sulfuric acid aerosol on clearance was clearly an acute response
since there were no differences in 24-h retention of the marker aerosol
regardless of the sulfuric acid aerosol exposure concentrations.
An earlier report of the above study was presented by Lippmann et al.
(1977) at the Fourth Inhaled Particles Symposium. The above study and a series
of animal studies with both cigarette smoke and sulfuric acid aerosol exposures
were summarized by Lippmann et al. (1982) (see Chapter 4).
The test aerosol ( mTc labeled Fe203) used to measure mucociliary clear-
ance in the initial Leikauf et al. (1981) study had a MMAD of 7.6 urn and
deposited primarily in the large bronchi and trachea. However, the 0.5 urn sul-
furic acid aerosol deposited primarily in the more peripheral airways. In order
to determine the effect on peripheral airway clearance, Leikauf et al. (1984)
performed a second study using a smaller Fe^O, test aerosol (MMAD =4.2 urn)
(see Figure 5-3). Five never smokers and three light ex-smokers participated
in this study; one ex-smoker had previously contracted pneumonia and one
never-smoker had experienced two previous episodes of bronchitis. One-hour
exposures via nasal mask were performed in three 20-min segments with brief
(3 min) measurement periods interposed between exposure segments. The sulfuric
o
acid aerosol concentrations studied were 0, 110, 310, and 980 ug/m of 0.5 urn
aerosol. The test aerosol (Fe«0-) was administered immediately before the
5-35
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CD
£
CD
Q.
c
g
*H—•
CD
«
DC
Is
o
c
E
JQ
O
CD
1
100
80
60
40
20
0
100
80
60
40
20
0
J>, J i I I I
A. 7.6 |nm Fe2O3
SI Exposure Period
II
1 T
, " -'' Source: Leikaufetal. (1981).
..».Jr..J I I I I I I
I I I I I
B. 4.2 |im Fe2O,
T
\>- ^ /
•"-/- -4
,;-;-Vl-
7t:-|:^ Source: Leikauf ei al. (1984).
'?.^i.^.i^ i i i L
90 180 270
Time, min
360
Figure 5-3. Effect of H2SO4 aerosol during and after a 60 min exposure
on group mean tracheobronchial mucociliary retention of "Tc-labeled
Fe2O3 particles. A: The response of ten healthy subjects who inhaled a
7.6 jim Fe2O3 aerosol before a 1-hour H2SO4 aerosol exposure and
B: The response of eight healthy subjects who inhaled a 4.2 jim Fe2O3
aerosol before a 1-hour H2SO4 aerosol exposure.
5-36
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sulfuric acid aerosol exposure. Trachea! mucus transport rate (TMTR) was not
significantly altered by any of the sulfuric acid aerosol exposure concentra-
tions, which confirms their (Leikauf et al., 1981) previous observation; TMTR
for the 0, 110, 330, and 980 exposures were 5.7, 5.9, 5.0, and 5.5 mm/min,
respectively. Tracheobronchial mucociliary clearance rate (TBMC) was assessed
by T5Q, the time for 50 percent of the initial test aerosol to clear the lung,
and the mean residence time (MRT), defined as the area under the tracheo-
bronchial retention curve (i.e., the graph of percent retention of marker
aerosol versus time). The 980 ug/m3 H2$04 exposure caused marked slowing of
TBMC as indicated by the increase in the TRn from 80 to 142 min. Clearance was
increased to 110
50.
similarly slowed after the 110 and 330 ug/nr exposures (T5Q
and 106 min respectively) although only the increase in T5Q at 110 ug/m3 was
statistically significant. Mean residence time increased in for all three
exposure conditions but was significant for only the 330 and 980 ug/m3 expo-
sures. There was no evidence for a concentration-response relationship between
sulfuric acid aerosol concentration and either T5Q and MRT, the indices of
mucociliary clearance. However, there was a small subject population (n=8) and
the inter- and intrasubject variability of mucociliary clearance measures is
quite large.
The results of these two studies by Leikauf and co-workers (1981, 1984)
suggest that while none of the tested levels of sulfuric acid aerosol affect
tracheal mucus transport velocity, low levels (<200 ug/m3) may stimulate
clearance in large conducting airways (i.e., less than ninth generation) but
may at the same time depress clearance in small conducting airways; the
regional anatomical location where stimulation ends and depression begins
obviously cannot be determined with precision. Higher concentrations, of sub-
micrometric sulfuric acid aerosol, on the order of 1,000 ug/m3 and possibly
lower, inhibit clearance in both large and small conducting airways but not,
apparently, in the trachea.
To determine whether subjects with hyperreactive airways would demonstrate
similar effects on mucociliary transport following sulfuric acid aerosol
exposure, Spektor et al. (1985) studied a group of 10 asthmatics exposed to
sulfuric acid aerosol levels which were similar to those used for the normal
subjects of Leikauf et al. (1981, 1984). Four of the subjects (designated
group II) required daily medication (either aminophylline or isoproterenol);
one took corticosteroids. All subjects withheld medication for six hours prior
5-37
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to the study except for the steroid-dependent subject. FEV, Q/FVC ranged from
46 percent to 87 percent. The asthmatics not requiring daily medication
(FEV-j/FVC range, 48-87%) were designated group I; two of these subjects were
current smokers. The exposure techniques were similar to those used by Leikauf
et al. (1981, 1984). Resting nasal mask exposures to 0.5 pm sulfuric acid
3
aerosol concentrations of 0, 110, 319, and 971 pg/m lasted for a total of one
hour (three 20-min inhalation periods separated by 3-min measurement periods).
Trachea! mucus transport rates were within the same range as those reported by
Leikauf et al. (1981, 1984) for healthy nonsmokers. There was no significant
effect of sulfuric acid aerosol at any of the tested levels on TMTR. For the
six subjects who did not require daily medication, TBMC was reduced after
3
exposure to the highest concentration (917 pg/m ) of sulfuric acid aerosol.
Mean retention time of the test aerosol was unaffected by sulfuric acid aerosol,
indicating a transient or short-lasting depression of clearance rate. For the
subjects requiring daily medication (FEV../FVC range, 46-77%) there was no clear
pattern of response, although clearance tended to be accelerated rather than
depressed. Abnormally low FEV,/FVC ratios are likely to be associated with
significant asymmetry in regional deposition which adds to the difficulty of
interpreting these studies.
The authors concluded that the mucociliary clearance of the Group I
subjects (mild asthmatics not dependent on medication) was slowed in a concen-
tration dependent manner as a result of the sulfuric acid aerosol exposure.
2
This conclusion was based on the regression (R not given) of the group mean
values for clearance at each of the four concentrations. However, examination
of the individual data indicated that an individual concentration-response
relationship was apparent for only one of the six subjects (who also happened
to be a smoker). Mucociliary clearance (T50; time to clear half the aerosol)
tended to be slower in the asthmatics than in previously tested normals although
mean retention times and TMTR were similar for normals and asthmatics. These
results suggest a possible increased risk for asthmatics from the transient
reductions of mucociliary clearance since their normal baseline mucociliary
clearance tends to be somewhat compromised. The added reduction of clearance
as a result of sulfuric acid aerosol exposure resulted in a clearance rate that
was less than 50 percent of the baseline clearance rate of normal healthy
nonsmokers. However, since two of the six subjects in Group I were current
smokers, this comparison may not be valid because of the possible direct or
interactive effects of smoking on clearance.
5-38
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Spektor et al. (1989) have recently completed a study which addresses
many of the confounding factors or uncertainties in earlier studies of the
effects of acid aerosol on mucociliary clearance. Ten healthy normal subjects
were exposed to 100-110 ug/m3 of 0.5 Mm H2$04 aerosol for 1 hour and 2 hours on
separate occasions. A control exposure to distilled water aerosol was also
conducted. The gamma-labelled tracer aerosols, used to measure clearance, were
varied in size for each subject (range 4.0 to 5.8 urn MMAD) in order to achieve
a similar initial deposition pattern of approximately 30 percent alveolar and
70 percent tracheobronchial. A controlled respiratory pattern was used to
ensure reproducible deposition of tracer aerosol. Two tracer aerosols were
administered to each subject, one tagged with 198Au and the other with 99mTc.
The gold-198 tagged aerosol was administered before exposure to H2S04 and the
technetium-99m tagged aerosol was administered following acid exposure.
Clearance was measured during and for 5 hours after exposure. It should be
noted that the group mean clearance half-time of the subjects in this study was
shorter than for previous groups of subjects from this laboratory (Leikauf
et al., 1981, 1984). However, this difference presumably represents the broad
range of normal clearance rates since the two control measurements were highly
reproducible.
There was no difference in tracer aerosol deposition, whether inhaled
prior to or after the acid aerosol exposure. This is an important observation
for future studies since it demonstrates that the tracer may be administered
following exposure provided there were no significant alterations in respiratory
mechanics, as observed in this study. Furthermore, the tracheobronchial
clearance measurements indicated a greater effect on clearance when the tagged
aerosol was administered after acid exposure. After a 1 hour acid aerosol
exposure, average clearance half times increased 100 percent. After a two hour
exposure, half time was elevated 162 percent relative to the control. The
authors suggested that there was an approximate 40 min delay, after the beginn-
ing of acid aerosol inhalation, before there were noticeable alterations in
clearance. There was a considerable difference in the persistence of the
alterations in clearance, depending on exposure duration. After a 1 hour
exposure, clearance was approaching normal rates within 2-3 hours. However,
with the 2 hour exposure, the clearance rate continued to slow for at least
3 hours after the completion of acid aerosol inhalation. These studies clarify
and extend previous observations of slowing of tracheobronchial mucociliary
5-39
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clearance after acid aerosol exposure. They indicate that the response depends
not only on acid concentration but also on duration of exposure.
As part of a summary of human acid aerosol exposure studies, Folinsbee
(1989) presented a figure summarizing changes in clearance half-time as a result
of exposure to varying concentrations of sulfuric acid aerosol (Figure 5-4).
5.8 EFFECTS OF SULFURIC ACID AEROSOL ON AIRWAY REACTIVITY
Many inhaled substances, including air pollutants, can alter the response
of the airways to pharmacologic (e.g., histamine, methacholine, carbachol) or
physical (e.g., cold and/or dry air) stimuli that induce bronchoconstriction.
The normal range of reactivity to agents that provoke bronchoconstriction is
quite large. Although there are marked group differences between normals and
asthmatics, there is considerable overlap between the least reactive asthmatics
and the most reactive "normals". The mechanisms by which airway reactivity is
altered are still being elucidated and different inhaled substances may act in
different ways. Among other possibilities, sulfuric acid aerosols could
directly influence the responsiveness of smooth muscle, alter the sensitivity
of airway irritant receptors, produce airway edema and inflammation, or change
airway caliber. Bronchial reactivity has recently been reviewed by Boushey
et al. (1980).
Airway reactivity to methacholine was tested by Kulle et al. (1982) in
3
subjects who were exposed to 100 |jg/m sulfuric acid aerosol. There was a
trend for postexposure airway reactivity to decrease but this was not
significant.
The effects of sulfate exposure on airway responsiveness, in both
asthmatics and normals, were assessed by Utell et al. (1982). In normals,
3
exposure to both sulfuric acid aerosol and NH^HSO^ (1,000 pg/m ) caused greater
decreases in SGaw with carbachol challenge than was observed with carbachol
challenge after the control NaCl aerosol. The range of decrease in SGaw was
between 6 and 13 percent after NaCl exposure (+ carbachol). SGaw was reduced
17 percent and 22 percent respectively with NH4HS04 and sulfuric acid aerosol
(+ carbachol) respectively. In asthmatics, the increase in carbachol reac-
tivity following H2SO. exposure was greater than after the control (NaCl)
exposure. In addition, Utell et al. (1983a) reported that the decrease in SGaw
after control carbachol exposures (i.e., an index of baseline airway reactivity)
5-40
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200
150
CD
CO 100
CD
O
§
CO 50
O
O Leikaufetal. (1981)
a Leikaufetal. (1984)
A Spektoretal. (1985)
O Spektor et al. (1989) (1 hr)
s? Spektor et al. (1989) (2 hr)
0
200 400 600 800
Acid Aerosol Concentration,
jig/m3 x Duration, H
1000
Figure 5-4. Clearance half-time (i.e. time required to clear half the deposited
tracer aerosol) as a function of the exposure (concentration of acid aerosol x ex-
posure duration in hours). All exposures were for one hour to 0.5 |im sulfuric acid
aerosol, except for the one 2-hour exposure reported by Spektor et al., 1989.
Note the broad range of baseline clearance rates. Particle sizes of labeled aero-
sols were 5.2 jim (Spektor et al,. 1989); 7.6 (im (Leikauf et al., 1981); 4.2 jim
(Leikauf et al., 1984); and 3.9 jim (Spektor et al., 1985). All subjects were healty
normal males and females except in the Spektoret al., 1985 study of asthmatics.
All exposures conducted at rest and ventilatipnswere not reported.
5-41
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was well correlated with the decrease in SGaw after sulfuric acid aerosol
exposures (r = 0.90), suggesting that carbachol reactivity may be a good
predictor of the bronchoconstrictor response to sulfuric acid aerosol. However,
this relationship needs to be examined in a larger subject population with a
broad range of response to both carbachol (or another cholinergic agonist) and
sulfuric acid aerosol. It was also noted that the most acidic (i.e., H^SO- and
) sulfates produced the greatest response. Exposure to NaHS04 and
(NH4)2S04 caused no significant change in pulmonary function.
In normals exposed for 16 min to 100 to 1,000 ug/m of sulfuric acid
aerosol (as well as other sulfates), Utell et al. (1984) examined the airway
reactivity to carbachol following exposure. Airway reactivity was assessed by
comparing airway resistance and spirometry both before and after a five-breath
dose of a 1 percent carbachol aerosol. As in the study of Kulle et al. (1982),
no effects on airway reactivity were observed after exposure to 100 ug/m3
sulfuric acid aerosol. However, airway reactivity was increased after exposure
to 1,000 ug/m of either sulfuric acid aerosol or NH4HS04 aerosol. Using
similar exposure conditions, asthmatics were exposed to 100, 450, and
o
1,000 ug/m sulfate aerosols. Airway reactivity to carbachol was increased in
o
the asthmatics after both 1,000 and 450 ug/m sulfuric acid aerosol exposures.
Airway reactivity was not altered by NaHS04.
In a subsequent study (Utell et al., 1983b), the effects of 100 and
o
450 ug/m sulfuric acid aerosol on airway reactivity was reexamined. In this
study, normal subjects participated in 4-hour exposures that incorporated
three 10-min periods of mild exercise. Airway reactivity to carbachol was
measured immediately after exposure and again at 24 hours postexposure.
Immediately after exposure, airway reactivity was unchanged. However, 24 h
3
after the 450-ug/m exposure, carbachol reactivity was increased; the response
to the carbachol challenge was a -21 percent reduction in SGaw. Twenty-four
hours after NaCl aerosol exposure, the same carbachol challenge caused only
a -8 percent reduction in SGaw. In addition, at the 24-h test, 8 of the
14 subjects reported throat irritation that had first been noticed between
12 and 24 hr postexposure. As in the previous study, there were no immediate
or delayed effects on pulmonary function or respiratory symptoms from exposure
O
to 100 ug/m sulfuric acid aerosol. The results of the above studies were more
recently summarized by Utell and Morrow (1986).
5-42
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The airway reactivity to a cold air challenge following sulfuric acid
aerosol exposure in asthmatics was recently reported by Linn et al. (1986).
3
One-hour exposures to 0, 122, 242, and 410 ug/m sulfuric acid aerosol were
followed by a cold air challenge. The subjects breathed subfreezing air for
4 min, and the response was determined by the percent decrease in FEV1 «.
There was no difference in response among the four exposure conditions;
sulfuric acid aerosol did not exacerbate the bronchoconstriction caused by
breathing cold-dry air.
These reports of altered airway reactivity in both normals and asthmatics
exposed to sulfuric acid aerosol may indicate altered responsiveness of one or
more components of the bronchoconstriction reflex arc, such as airway receptors
or airway smooth muscle. The effects occurred at concentration levels similar
to those at which changes in airway conductance or spirometry have also been
demonstrated. Change in airway reactivity may be an indirect indicator of
inflammation in the airways or of disruption of the normal status of the airway
epithelium.
5.9 SUMMARY AND CONCLUSIONS
Normal subjects have been exposed to sulfuric acid aerosols ranging in
3
concentration from 10 to approximately 1,500 ug/m under both resting and
intermittent exercise conditions. No effects of spirometry or plethysmography
3
have been observed after exposure to concentrations of less than 500 ug/m .
Small changes in spirometry have been observed after exposures to approximately
3
1,000 ug/m but these changes have not been consistently observed.
Exposure studies in man have been conducted using a number of different
sulfate and nitrate aerosols. Studies of exposure to a variety of sulfate and
nitrate aerosols point to the absence of an effect on spirometry, plethysmo-
graphy, and various other physiological indicators of pulmonary function in
asthmatics and healthy normal subjects. Exposures to combinations of sulfates
with other pollutant gases, most notably ozone and SOp, have not demonstrated
any evidence of synergistic or interactive effects with endpoints that have
been measured in human exposure studies.
Asthmatics have been exposed to a range of sulfuric acid aerosol concen-
3
trations from 10 to 1,000 ug/m . Exposures to concentrations of approximately
3
400 to 1,000 ug/m typically produced modest bronchoconstriction and small
5-43
-------
decrements in spirometry. At aerosol concentrations as low as 68 ug/m , small
decrements in spirometry have been observed for adolescent, but not for adult,
asthmatics.
There is a suggestion in studies of normals and asthmatics that there
may be delayed responses to sulfuric acid aerosol in addition to the acute
responses measured immediately after exposure. 'These delayed responses may
include both symptomatic and functional effects that persist or worsen within
the 24-hour period following exposure. The delayed responses appear more
likely to follow longer duration exposures (i.e., 1 to 4 hours with exercise)
rather than brief resting exposures. These observations suggest that, while
small quantities of acid aerosol may react with ammonia or be buffered by
airway surface liquids, larger quantities of acid aerosol may cause more
persistent changes in airway surface pH and hence may be more toxic.
The effects of sulfate and nitrate aerosols appear to be related to their
acidity or more specifically their titratable acidity. High levels of oral or
respiratory ammonia tend to reduce the effects of inhaled acidic aerosols.
Furthermore, unbuffered aerosols have less effect than buffered aerosols of the
same pH, suggesting that alteration of airway surface pH may be one of the
stimuli provoking cough and bronchoconstriction.
o
Inhalation of high concentrations (1,000 ug/m ) of sulfuric acid aerosol
cause a reduced rate of mucociliary clearance in both normals and asthmatics.
This is an acute response and does not affect the overall retention of aerosol
(over a 24-hour period). The acid aerosol has no apparent effect on tracheal
mucociliary transport rates measured in the most proximal portion of the
trachea. Additionally, low concentrations of sulfuric acid aerosol may result,
initially, in an increased rate of mucociliary clearance in the major airways
of both normals and asthmatics. Effects of H9SOA on slowing of mucociliary
3
clearance in small airways begin at concentrations as low as 100 ug/m .
Airway reactivity to bronchoconstrictive drugs such as carbachol or
3
methacholine is increased after exposure to 1,000 ug/m of sulfuric acid
o
aerosol in both normal and asthmatic subjects. Administration of 100 ug/m of
H«SOA for up to 4 hours does not appear to alter airway reactivity in either
3
normals or asthmatics. Intermediate concentrations (~500 ug/m ) may result in
either immediate or delayed (post -24 h) increases in airway reactivity.
Several factors determine the delivered dose of an inhaled pollutant.
These include the concentration(C), the subject's ventilation(V), and the dura-
tion^) of exposure. The product of these factors, CTV, may explain some of
5-44
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the variability in response over several reported studies. Other factors
including solubility; particle size; chemical reactions in the vapor phase, the
aerosol, or airway surface liquids; air velocity; etc.; will also determine the
dose delivered to the target tissue. Based on a graphical presentation of the
data (Figure 5-2) it appears that within a given study, increased exposure to
acid, usually as a result of increasing the concentration of acid aerosol,
causes a greater decrease in FEV.^ or (in Figure 5-4) in mucociliary clearance.
However, at least for FEV, Q measurements from various laboratories, the
differences in magnitude of exposure expressed as CTV explain only a portion of
the observed differences in response. Other factors related to subject respon-
siveness, experimental procedures, or delivery of acid to the target tissues
may also play a role in the determination of responses. More data will be
required to evaluate the usefulness of the CTV product in predicting response
to acid aerosols.
5.10 REFERENCES
Amdur, M. 0.; Melvin, W. W.; Drinker, P. (1953) Effects of inhalation of
sulphur dioxide by man. Lancet 2: 758-759.
Avol, E. L. ; Jones, M. P.; Bailey, R. M. ; Chang, N.-M. N.; Kleinman, M. T. ;
Linn, W. S.; Bell, K. A.; Hackney, J. D. (1979) Controlled exposures of
human volunteers to sulfate aerosols: health effects and aerosol charac-
terization. Am. Rev. Respir. Dis. 120: 319-327.
Avol, E. L.; Linn, W. S.; Hackney, J. D. (1986) Acute respiratory effects of
ambient acid fog episodes [final report]. Downey, CA: Rancho Los Amigos
Medical Center, Environmental Health Service; EPA grant no. ES03291-02.
Avol, E. L.; Linn, W. S.; Wightman, L. H.; Whynot, J. D.; Anderson, K. R.;
Hackney, J. D. (1988) Short-term respiratory effects of sulfuric acid in
fog: a laboratory study of healthy and asthmatic volunteers. J. Air
Pollut. Control Assoc. 38: 258-263.
Balmes, J. R.; Fine, J. M.; Christian, D. ; Sheppard, D. (1988) Effect of
particle size on sulfuric acid aerosol-induced bronchoconstriction. Am.
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6. EPIDEMIOLOGY STUDIES OF HEALTH EFFECTS ASSOCIATED WITH
EXPOSURE TO ACID AEROSOLS
6.1 INTRODUCTION
To date, only limited epidemiological evidence has become available by
which to evaluate health effects associated with ambient acid aerosol exposures.
This sparsity of data is partly due to the absence of adequate ambient acid
measurement techniques until recent years and, therefore, few studies directly
relating health endpoint data to actual measured ambient aerosol concentrations.
Nevertheless, some evidence exists indicative of human health effects being
associated with exposures to ambient acid aerosols both (1) as derived from
reexamination of older, historically important data on air pollution episode
events in the U.S. and Europe; and (2) as can be deduced from certain recent
epidemiology studies carried out in the U.S., Canada, and Europe. This chapter
concisely reviews such evidence first as it relates to acute exposure effects
and then in relation to chronic exposure effects. The power of several of
these studies is discussed in the summary and conclusions section.
Because of the sparsity of concrete evidence, most of this chapter is
devoted to identifying studies of situations in which there is good reason to
suspect that high ambient acid concentrations existed in the evaluated study
areas. From these studies the nature of the observed health effects are
summarized as a basis for drawing tentative conclusions and suggesting
directions for future research. However, no clear quantitative relationships
are delineated because of the lack of sufficient ambient acid measurements by
which to define exposure-response effects levels. Hopefully, several ongoing
studies currently underway in Canada, the United States, and Europe may provide
useful information in the near future. These face the difficult task of
separating out effects due to relative contributions of various air pollutants
present (e.g., differentiating between 03 effects and between those of H+).
The extremely critical need for extensive additional research becomes evident
through the present examination of currently available information.
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6.2 ACUTE EFFECTS STUDIES
6.2.1 Acute Episode Studies
Some of the earliest indications that ambient air acid aerosols may be
associated with human health effects can be discerned upon reexamination of
historically important air pollution episode events. These include, for
example, the Meuse Valley (Belgium), Donora, PA (USA), and well-known London
(UK) episodes, as discussed below.
6.2.1.1 Meuse Valley. Firket (1931) describes the fogs of December 1930 in
the Meuse Valley and the morbidity and mortality related to them. A detailed
discussion of the causes is presented which concludes that the main component
of the fog that caused the health effects that occurred was sulfuric acid.
This conclusion was based both upon consideration of the emissions in the
valley, the weather conditions and the aerometric chemistry required for the
production of sulfuric acid. Additionally, the pathophysiology seen was
thought to relate to sulfuric acid exposure more so than to other possible
agents. More than 60 persons died from this acid fog and several hundred
suffered respiratory problems, with a large number becoming complicated with
cardiovascular insufficiency. The mortality rate during the fog was over ten
times higher than the normal rate. Those persons especially affected by the
fog were the elderly, those suffering from asthma, heart patients and the
debilitated. Most children were not allowed outside during the fog and few
attended school. Unfortunately, no actual measurements of acid aerosols in
ambient air during the episode are available by which to establish clearly
their role in producing the observed health effects versus the relative
contributions of other specific pollutants.
6.2.1.2 Donora. Schrenk et al. (1949) reported on the health effects and
atmospheric pollutants of the smog episode in Donora of October 1948. A total
of 5,910 persons (or 42.7 percent) of the total population of Donora experi-
enced some effect from the smog. The air pollutant-ladened fog lasted from the
28th to the 30th of October, and during a 2-week period 20 deaths took place,
18 of them being attributed to the fog. An extensive investigation by the U.S.
Public Health Service concluded that the health effects observed were mainly
due to an irritation of the respiratory tract. Mild upper respiratory tract
symptoms were evenly distributed through all age groups and, on the average,
were of less than four days duration. Cough was the most predominant symptom;
it occurred in one-third of the population and was evenly distributed through
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all age groups. Dyspnea was the most frequent symptom in the more severely
affected, being reported by 13 percent of the population, with a steep rise as
age progressed to 55 years; above this age, more than half of the persons
affected complained of dyspnea.
It seems reasonable to state that, while no single substance can be
clearly identified as being responsible for the October 1948 episode, the
observed health effects syndrome could have likely been produced by two or more
of the contaminants, i.e., sulfur dioxide and its oxidation products together
with particulate matter, as among the more significant contaminants present.
Hemeon (1955) examined the water soluble fraction of solids on a filter of an
electronic air cleaner operating during the smog in Donora and concluded that
acid salts were an important component.
6.2.1.3 London Acid Aerosol Fogs. Based on the mortality rate in the Meuse
Valley, Firket (1931) estimated that 3,179 sudden deaths would likely occur if
a pollutant fog similar to that in the Meuse Valley occurred in London. An
estimated 4,000 deaths did later indeed occur during the London Fog of 1952, as
noted by Martin (1964). During the fog of 1952, evidence of bronchial
irritation, dyspnea, bronchospasm and, in some cases, cyanosis is clear from
hospital records and from the reports of general practitioners. There was a
considerable increase in sudden deaths from respiratory and cardiovascular
conditions. The nature of these sudden deaths remains a matter for speculation
since no specific cause was found at autopsy. Evidence of irritation of the
respiratory tract was, however, frequently found and it is not unreasonable to
suppose that acute anoxia due either to bronchospasm or exudate in the
respiratory tract was an important factor. Also, the United Kingdom Ministry
of Health (1954) reported that in the presence of moisture, aided perhaps by
the surface activity of minute solid particles in fog, some sulfur dioxide is
oxidized to trioxide. It is probable, therefore, that sulfur trioxide,
dissolved as sulfuric acid in fog droplets, appreciably augmented the harmful
effects of sulfur dioxide and/or other particulate matter species.
Martin and Bradley (1960) reported increases in daily total mortality
among the elderly and persons with preexisting respiratory or cardiac disease
in relation to SOp and PM (British Smoke; BS) levels in London during the
winter of 1958-1959. The pathological findings in 12 fatal cases and the
clinical evidence of practitioners seem to indicate clearly that the harmful
effects of the fog were produced by the irritating action of polluted air drawn
into the lungs. These effects were more obvious in people who already suffered
6-3
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from a chronic respiratory disease and whose bronchi were presumably more
liable to bronchospasm.
Waller (1963) reported that sulfuric acid was one of the pollutants
considered as a possible cause of the increased morbidity and mortality noted
during the London fog of December 1952. As noted earlier in Chapter 2, follow-
ing the 1952 pollution episode daily measurements of BS and SO^ were made in
London starting in 1954. Concentrations of sulfuric acid, calculated from net
aerosol acidity, were also measured during air pollution episodes and, later,
on a daily basis, starting in 1963. No regular measurements of sulfuric acid
were made during the winter of 1955-1956 but some was detected at times of high
pollution. For example, Waller and Lawther (1957) detected the presence of
acid droplets in samples collected in January of 1956. Insufficient measure-
ments were made, however, during the rest, of the winter of 1955-1956 to study
the effects of the acid aerosol present. Waller (1963) later reported measuring
acid droplets in London in the winter of 1958-1959 with mass median diameter of
0.5 urn. Commins (1963) measured particulate acid in the city of London and
found concentrations especially high at times of fog reaching levels of 678 ug
o
(calculated as sulfuric acid)/m of air. Typical winter daily concentrations
3 3
were 18 pg/m compared to 7 pg/m in the summer. The sulfuric acid content of
the air in the city of London at the time could range up to 10 percent of the
total sulfur. As discussed in Chapter 2, all of these historical acid measure-
ments must be viewed with caution since artifact formation is likely for these
samples. For example, there was no attempt to remove NH3 or S02, which could
result in excess acid formation or neutralization depending upon the concentra-
tions present.
Lawther et al. (1970) reported an association between daily pollutant
levels (BS and SO,,) and worsening of health status among a group of over
1,000 chronic bronchitis patients in London during the winters of 1959-1960 and
1964-1965. A daily technique for self-assessment of day-to-day change in
health status was used. The concentration of acid aerosol rose with that of
smoke, and it may have been partly responsible for health effects observed in
these chronic bronchitic patients. Since many patients become worse even at
times of relatively low humidity, this suggests that small droplets of strong
acid may have had more effect than larger ones. An interesting study was also
conducted on a smaller sample of the patients during in the winters of 1964-1965
and 1967-1968 when pollutant levels were somewhat lower than in earlier years.
6-4
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Approximately 50 subjects selected for their susceptibility to air pollutant
effects formed the sample. Daily apparent sulfuric acid, measured at
St. Bartholomew Hospital Medical College, was reported as having a relatively
high correlation with health effects in the 1964-1965 winter. For 1967-1968,
all these correlation coefficients were, lower but still significant. The
authors comment that the patients selected must have been particularly sensitive
to pollution, since from past experience no correlation would have been expected
with such very low levels of pollution encountered by such a small group.
Relationships between London air pollution levels and mortality have been
extensively reexamined during recent years, using more sophisticated statis-
tical analyses techniques, e.g., time-series analyses and various "filtering"
approaches to deal with potential confounding by extraneous cyclical factors.
Several authors (Mazumdar et al., 1982; Ostro, 1984; Schwartz and Marcus, 1986)
have reported significant associations between BS and SOp levels and mortality
during 14 London winters (1958-72), with associations of mortality with BS
o
being much stronger than with SOp at levels below 500 ug/m. Thurston et al.
(1989) have also presented a preliminary report on exploratory reanalyses
of London mortality data for which daily direct acid aerosol measurements were
made at St. Bartholomew's Medical College (see Chapter 2). The data considered
in these analyses include pollution and mortality records collected in Greater
London during winter periods (November 1-February 29) beginning in November
1963 and ending in February 1972. The air pollution data were compiled from
o
one of two sources. First, BS and S02 data (in |jg/m ) were compiled as daily
means of seven sites run by the London County Council and spatially distributed
throughout London County. A second data set of BS, S09 and aerosol acidity
+ 3
(Hydrogen ion, H , calculated as ug/m sulfuric acid) was also compiled for one
central London site run by the Medical Research Council Air Pollution Research
unit at the St. Bartholomew's Medical College.
The Greater London mortality data was obtained from the London General
Register Office for winter periods (November-February) beginning in 1958, and
for all days commencing in April 1965. Total mortality, respiratory mortality,
and cardiovascular mortality were all compiled daily during these periods, but
only total mortality was considered in this work. The Greater London population
was fairly stable during the period considered in this research (1963-1972),
averaging about 8 million people. For example, in 1958 the Greater London
population was 8.2 million, dropping only 5 percent to 7.8 million by 1970.
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The pollution and mortality data for each of the nine winters of data
were combined into one data set for analysis. This is acceptable in this case
because the period under study, late 1963 to early 1972, is subsequent to the
implementation of the London smoke control zones (1961-1963) and is therefore
a period of fairly constant average winter pollutant concentrations. Prior
to combining the data, each year's total mortality data was also prefiltered
using a filter that weights the mortality data in a manner very similar to the
calculation of deviations from a 15-day moving average of mortality, except
that it eliminates the undesirable short-term cyclical fluctuations. The
resulting data set comprised a total of 921 observations of daily pollution,
total mortality, and filtered total mortality data for the nine-winter data
set.
The log of H2SO. measured at the central site was much more strongly
correlated with raw total daily mortality than any measure of BS or S02 espe-
cially when it is correlated with the next day mortality (r = .31). It is also
clear that the logarithm transformation "helps" the acid-mortality association
more than is true for BS or SCL. For the filtered mortality variable, however,
the HpSO- correlation is weakened versus raw total mortality (e.g., r = .19 for
log (HpSO.) with next day filtered mortality). Thus, the St. Bartholomew's
College hLSO. measurements appear to be correlated with Greater London mor-
tality, especially before the mortality data is filtered for slow moving
fluctuations. Mortality-pollution crosscorrelation analyses indicate
that mortality effects usually follow pollution in time.
The superiority of the log of H2S04 concentration versus the raw H^SO^
data in correlations with total mortality agrees with the previous analyses of
British Smoke-total mortality associations. This may imply that a "saturation"
of mortality effects is indeed occurring over two or more days, and that a
cumulative effect of several episode days may be more relevant than modeling a
single day effect alone. This may be due to avertive behavior, especially
since episode warnings were publicized at the time of high pollution. Not all
of the measured acids during fog episodes would necessarily be respirable,
reducing their health effects from that implied by the total H,,S04 concentra-
tion. Most likely, however, the "saturation" of effects is due to the
"harvesting" of the pollution susceptible population on prior moderate pollution
days.
6-6
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Although the filtered total mortality has largely removed slow moving
fluctuations in the mortality data, the winters of 1967-1968 and 1969-1970 are
still slightly nonstationary, probably due to influenza epidemics in those
years. It may be necessary to also (or instead) control for these effects by
considering an influenza epidemic dummy variable in subsequent regression
analyses of these data. Additional analyses using models that involve more
sophisticated time series methods are in progress and are needed in order to
provide more definitive confirmation of acid aerosol contributions to London
mortality.
In summary, the early historically important air pollution data discussed
above provide some limited evidence for mortality and morbidity effects being
associated with ambient air concentrations of acid aerosols. The calculations
and measurements of sulfuric acid levels (estimated to range up to 678 ug/m3)
during some London episodes in the late fifties provide plausible bases for
hypothesizing contributions of sulfuric acid aerosols to the health effects
observed during those episodes. The recent preliminary analyses by Thurston
et al. (1989) of daily direct acid aerosol measurements over a longer span of
time (1963-1972) in London are especially important in providing more direct
evidence for likely associations between ambient acid aerosols and mortality.
However, as noted above, several pollutants were elevated and the acid measure-
ments are difficult to interpret, therefore the results of these analyses must
be viewed with caution.
6.2.2 European Pollutant Event of 1985
In addition to evidence derived from the above historically important
data, indications of possible involvement of ambient acid aerosols in the
induction of human health effects can be discerned through recent analyses of a
1985 European air pollution episode. During January 1985, large parts of
Europe from western Germany to Great Britain experienced a pollution event.
This event was tracked by monitoring stations in several countries as it moved
from east to west, and then finally dissipated over the North Sea. While very
high levels of PM, S0? and NO were reported, very few measurements of ambient
£ /\
acidity are available. Long-range transport modeling data of de Leeuw and
van Rheineck Leyssius (1989) suggest, however, that sulfuric and nitric acid
o
levels may have exceeded 50 ug/m during this event.
6-7
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Wichmann et al. (1989) studied mortality, hospital admissions, ambulance
transports and outpatient visits for respiratory and cardiovascular disease in
West Germany during the 1985 event. During this time, daily suspended partic-
ulates reached 600 (jg/m3, S02 reached 830 MQ/m3, and N02 reached 410 pg/m3.
Total mortality rose immediately with the increase in pollution (January 16,
1985), and reached a maximum on January 18. The increase in mortality was
about 8 percent. Similarly, increases in hospital admissions (15 percent),
outpatient visits (12 percent), and ambulance transports (28 percent) were
seen.
The progress of the event was monitored by de Leeuw and van Rheineck
Leyssius (1989) as it passed through The Netherlands. The event started on
January 15 and ended on January 21, 1985. A study examining pulmonary function
in children was conducted during this episode in the Netherlands by Dassen
et al. (1986). 24-hour average measurements of TSP, RSP (D™ <3.5 pm), and
S02 at six station network all reached a range of 200-250 pg/ir T. There were no
direct acid measurements. Pulmonary function values were significantly lower
(3-5%) than baseline values measured 1-2 months earlier for the same subgroup
of children. Lung function parameters that showed significant declines on the
second day of the episode included FVC and FEV, as well as measures of small
airway function (e.g., maximum mid- expiratory flow, maximum flow at 50% of
vital capacity). Declines from baseline were observed 16 days after the
episode in a different subset of children, but not after 25 days in a third
subgroup. Shortly before the last set of measurements, 24-hour average TSP,
RSP, and S02 reached 100-150 ng/m3, suggesting that these levels were not
associated with observable function effects (U.S. Environmental Protection
Agency, 1986).
Ayres et al. (1989) studied respiratory morbidity in patients of general
practitioners in England during the same period. The S02 and PM concentrations
were much lower than they were in Holland. Although acute bronchitis rates
were elevated for children aged 14 or less during the third week of January,
1985, the rates during this period were also elevated in other years because of
the immediately preceding holiday period. As a result, no clear conclusions
could be drawn from the British data that relate health effects to the January
1985 episode.
Collectively the above analyses are indicative of notable increased health
effects occurring in several countries during the 1985 European episode.
Certain of the analyses, Wichmann et al. (1989) and Dassen et al. (1986),
6-8
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appear to provide clear linkages between the observed health effects and
measured air pollutants (e.g., PM, S02). The likely presence of elevated
acidic species (sulfuric and nitric acid) in the polluted air mass makes it
plausible that acid aerosols may have contributed to the observed health
effects, but the sparsity of actual acid measurements during and after the
event makes it difficult to, evaluate their potential role.
6.2.3 Acute Exposure Studies of Children
Several studies have recently been carried out in the United States and
Canada that examine the effects of exposures to air pollutants on pulmonary
function in children at summer camps. Some of the available data derived from
these studies allow evaluation of possible involvement of acid aerosols in the
health effects observed.
Lippmann et al. (1983) studied 83 nonsmoking, middle class, healthy chil-
dren (ages 8 to 13) during a 1980 2-week summer camp program in Indiana, PA.
The children were involved in camp activities which resulted in their exer-
cising outdoors most of the time. At least once, each child had height and
weight measured and performed spirometry on an 8 liter Collins portable
i
recording spirometer in the standing position without nose clip. During the
study, peak flow rates were obtained by Mini-Wright® peak flow meter at the
beginning of the day or at lunch and adjusted for both age and height. Ambient
air levels of TSP, hydrogen ions, and sulfates were monitored by a high-volume
sampler on the rooftop of the day camp building. Ozone levels were estimated
using a model that used ozone data from monitoring sites located 32 and 100 km
away. The hi-vol samples were collected on HLSO. treated quartz fiber filters
for the determination of the concentration of H+ and total suspended partic-
ulate matter (TSP). H+ was determined from filter extract using a Gran
titration. Peaks in acid concentration occurred on four days, when the acid
3
values ranged between 4 and 6.3 ug/m (as hLSO.). On many occasions there was
no HUSO, in the atmosphere. While effects were reported as being significantly
associated with exposure to ozone, no effects were found to be related to
exposure to HLSO. at the levels observed during the study.
Bock et al. (1985) and Lioy et al. (1985) examined pulmonary function of
39 children at a camp in Mendham, New Jersey during a 5-week period in July-
August, 1982. Ozone was continuously monitored using chemiluminescent
analysis. Ambient aerosol samples were collected on Teflon filters with a
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dichotomous sampler having a 15 pm fractionation inlet and a coarse/fine
cut-size of 2.5 urn (Sierra Mod 244-E). Aerosol acidity as measured by strong
acid (H+) content, was determined using the pH method. Highly significant
changes in peak expiratory flow rate (PEFR) were found to be related to ozone
exposure, as well as a baseline shift in PEFR lasting approximately one week
following a haze episode in which the 03 exposure exceeded the NAAQS for four
consecutive days that included a maximum concentration of 185 ppb. There was
no apparent effect of H+ on pulmonary function. The authors did state,
however, that the persistent effects associated with the ozone episode could
have been due to acid sulfates as well as, or in addition to, ozone but
additional uncollected data were needed to evaluate this possibility.
During a four-week period in 1984, Lioy et al. (1987) and Spektor et al.
(1988) measured respiratory function of 91 active children who were residing
at a summer camp on Fairview Lake in northwestern New Jersey. Continuous data
were collected for ambient temperature, humidity, wind speed and direction, and
concentrations of 03, H2$04, and total sulfates. Ozone was measured by U.V.
absorbance, and HgSO^ and total sulfates were alternately determined by a flame
photometric sulfate analyzer (Meloy Model 285) preceded by a programmed thermal
pretreatment unit. The ambient aerosol samples were collected on quartz fiber
filters with a dichotomous sampler having a 15 urn fractionating inlet (PM-,5)
and a coarse/fine cut-size of 2.5 pm (Sierra Model 244-E). Aerosol acidity, as
measured by strong acid (H+) content, was determined using the pH method. The
o
maximum values recorded for HpSCL and NFLHSO, were 4 and 20 ug/m respectively.
While effects were reported as being associated with exposure to ozone, no
effects were found to be related to exposure to the acid aerosol concentrations
experienced in this study.
Raizenne et al. (1987b) reported preliminary analyses on data from a
study in Ontario, Canada. In 1983, fifty-two campers (23 were asthmatics) at
a summer camp were studied to examine lung function performance in relation to
daily pollutant concentrations. The health assessment included a precamp
clinical evaluation, a telephone administered questionnaire on respiratory
health, daily spirometry and symptomatology measurements. Pollutants measured
included 0,, respirable particles, sulfates, N00, and S09. Respirable sulfates
O £ « C.
were highly variable and ranged from 10 to 26 ug/m . Sulfate as sulfuric acid
was usually very low. Raizenne et al. (1989) report that 03, sulfate and PMp 5
were associated with decrements in lung function of children. Evidence of
6-10
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decrements in specific lung function indices were related to current pollution
levels and to a 12 to 24 hour lag function for PM2.5, S04~2, 03 and temperature.
Although both asthmatic and non-asthmatic had similar data trends, only
responses in the non-asthmatic group reach statistical significance. The
authors note that all of the air pollutants were highly correlated, and thus
it was not possible to attribute unique health effects to a single pollutant.
Raizenne et al. (1989) studied 112 young girls who participated in one of
three two-week camp sessions at camp Kiawa, Ontario, Canada during June to
August, 1986. They examined the subjects in relation to four ambient acid
aerosol events (the highest H2$04 level was 47.7 ug/m3 during one event on
July 25, 1986). The influence of air pollution on lung function was evaluated
first by comparing responses on the day of a pollutant event (high acid and
ozone levels) to the mean of the responses on corresponding days of low pollut-
ant levels. For FEVp there was tendency for the lung function decrements on
the event day to be greater than the response on the corresponding control
days, except for the last event (when an increase in function was observed).
The largest decrements for FEV1 and PEF (48-66mL decline for FEV-.) were observed
on the morning after the highest H2$04 event on July 25, 1986. No analyses
were presented, however, that attempted to separate out pollutant effects of
H2S04 from those of 03.
Airway hyperresponsiveness was assessed using a methacholine bronchial
provocation test for 96 of the subjects in the Raizenne et al. (1989) study.
Children with a positive response to methacholine challenge .had larger decre-
ments compared to their nonresponsive counterparts. These preliminary results
do not allow definitive statements to be made on the susceptibility of metha-
choline sensitive subjects; however, there are indications in these data of
differential lung function profiles and responses to air pollutants in children
with and without airway hyperresponsiveness. Further analyses and research are
indicated.
At the same camp twelve young females (9 to 14 years old) performed pre-
and post-exercise spirometry on a day of low air pollution and at the peak of
an air pollution episode. Clinical interview, atopy, and methacholine airway
hyperresponsiveness tests were performed at the camp on the first 2 days of
the study. Seven subjects had positive responses to methacholine challenge
(+MC) and five did not (-MC). A standardized ergometric physical capacity test
was also administered, in which minute volume, heart rates, and total work
6-11
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achieved were recorded. Air monitoring was performed on site and, during the
episode, air pollution concentrations were: 03 exceeded 130 ppb; H2$04 exceeded
40 ug/m during a one hour period. Additional discussion of the aerometeric
monitoring is given by multivariate normal methods on the indicator of airway
hyperresponsiveness. For the entire group (N = 12), post exercise FVC and
FEV-j^ were observed to increase on the control day and decrease on the episode
day. On the control day, an average 40 mL increase in FVC due to exercise was
observed (p <.05) for the whole group, with a 71 ml increase in +MC subjects
and a 17 ml increase in +MC subjects. Although not statistically significant
at the 10 percent level, mean FVC for the entire group was 30 ml less on the
day of high pollution versus low pollution, and this difference was more
pronounced in -MC (-65 ml) than +MC (-4 ml) subjects. The effect of exercise
in the model was statistically significant (p <.05), whereas the pollution day
effect was not.
These results suggest that lung function responses to exercise differ in
+MC and -MC subjects under field research conditions and that the expected
normal FVC response to exercise in both groups is altered during periods of
elevated ambient pollution. However, no analyses were presented that evaluated
possible acid aerosol relationships to health effects.
It is of interest to compare results obtained in the summer camp studies
to findings of certain controlled human exposure studies or other epidemiology
studies. For example, Spengler et al. (1989) calculated that the children in
the Raizenne et al. (1989) study received an average one-hour respiratory tract
dose of 1050 nmoles of H ions, based on a exposure model which takes into
account not only the concentration of exposure but also minute ventilation
rate. Spengler et al. (1989) further noted that the asthmatic subjects in the
human clinical studies of Utell et al. (1983) and Koenig et al. (1983) had
experienced an airway dose of approximately 1,200 nmoles of H+, which evoked a
3 3
response at reported concentrations of 450 ug/m and 100 pg/m H^SO. respec-
tively. These calculations suggest that, because of differences in minute
ventilation rates, the peak levels occurring at Camp Kiawa during a ambient
acid aerosol event may have produced exposures similar to those seen in clinical
studies of asthmatic subjects. It remains to be determined as to what extent
comparable C x T total respiratory tract dose(s) for H ions may be effective
in producing pulmonary functions decrements beyond the short exposure times
employed in the controlled human exposure studies or in producing other types
6-12
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of effects. For example, Spektor et al. (1989) found that the effect of
doubling the length of exposure to sulfuric acid increased average tracheobron-
chial clearance half-time from 100 to 162 percent relative to control.
6.2.4 Acute Studies Relating Health Effects to Sulfates
Measured sulfate and nitrate (see Section 6.3.3) levels may represent
crude surrogates for acid aerosol levels; however, the appropriateness of use
of sulfate and/or nitrate concentrations as indices of exposure to acid aerosols
has not been well evaluated. In Chapter 2 it was indicated that sulfate
species represent the principal component of most acid aerosols. The problem
is that measurements of total sulfate and/or nitrate levels may not only
represent acid aerosol exposures but sulfate/nitrate exposures that are not
acidic as well. Thus, the studies discussed below which present sulfate and/or
nitrate data but not acid aerosol data may provide only limited insight into
the potential health effects that may be related to acid aerosol exposure.
Bates and Sizto (1983, 1986) reported results of an ongoing correlational
study relating hospital admissions in southern Ontario to air pollutant levels.
Data for 1974, 1976, 1977, and 1978 were discussed in the 1983 paper. The 1986
analyses evaluated data up to 1982 and showed: (1) no relationship between
respiratory admissions and S02 or COHs in the winter; (2) a complex relation-
ship between asthma admissions and temperature in the winter; and (3) a
consistent relationship between respiratory (both asthma and nonasthma) admis-
sions in summer and sulfate and ozone concentrations, but not to summer COH
levels. However, Bates and Sizto note that the data analyses are complicated
by long-term trends in respiratory disease admissions unlikely related to air
pollution, but they nevertheless hypothesize that observed effects may be due
to a mixture of oxidant and reducing pollutants which produce intensely
irritating gases or aerosols in the summer but not in the winter.
Bates and Sizto (1987) later studied admissions to all 79 acute-care
hospitals in Southern Ontario, Canada (i.e., the whole catchment area of
5.9 million people) for the months of January, February, July and August for
1974 and for 1976 to 1983. Means of the hourly maxima for Og, N03, S02,
coefficient of haze (COH), and aerosol sulfates were obtained from 17 stations
between Windsor and Peterborough. Sulfates were measured every sixth day.
Total admissions and total respiratory admissions declined about 15 percent
over the course of the study period, but asthma admissions appeared to have
6-13
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risen. Evaluating the asthma category of admissions is complicated by the
effects of a change in International Classification of Disease (ICD) coding in
1979. The analyses demonstrate that there is a consistent summer relationship
between (1) sulfates, ozone and temperature and (2) respiratory admissions with
or without asthma. This conclusion is strengthened by the continuing lack of
any association of these variables with non-respiratory conditions. The
present data raise the question of whether the association of increased
respiratory admissions in the summer in this region can be associated with
ozone or sulfates. It would be surprising for the effects to be related to
ozone since it is aerosol sulfates that, in summer, explain the highest percen-
tage of the variance in respiratory admissions; yet these are not correlated
with respiratory admissions in the winter. In view of this, the possibility
exists that the observed health effects might be attributable neither to ozone
nor to sulfates, but to some other air pollutant species that "travel" with
them over the region in the summer (but not in the winter).
Bates and Sizto (1987) note that recent observations suggest the presence
of peaks of H+ aerosol of small particle size in this region of Canada in the
summer, concomitant with elevated 0- and SOT levels. On two days in July 1986
in Eastern Toronto when ozone and sulfate levels were elevated, but not higher
than on other days, peaks of H+ acid aerosol lasting for up to two hours were
recorded at levels of 10 to 15 |jg/m3. The particle size was small (about
0.2 |am). Similar observations were recorded on the same days by another H+ air
sample operation west of Toronto. This raises the possibility that the types
of health effects noted above might be attributable neither to ozone, nor to
sulfates but rather perhaps to acid aerosols.
The evidence from Bates and Sitzo (1983, 1986, 1987, 1989) neither
conclusively relates sulfates nor ozone to hospital admissions. Instead, the
results suggest that some other pollutant(s) may be responsible, e.g., sulfuric
acid that has been measured in the region. More aerometric data will be
required, however, to confirm or disprove this possibility, and a new study is
underway to examine these factors.
6.3 CHRONIC EXPOSURE EFFECTS STUDIES
As was the case for acute exposure effects, only very limited
epidemiologic study data currently exist by which to attempt to evaluate
possible relationships between chronic exposures to ambient acid aerosols and
6-14
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human health effects. These include one study from Japan relating effects to
estimated or measured acidity and several other North American studies, which
relate effects to sulfate levels or other surrogate measures thought to roughly
parallel acid aerosol concentrations.
6.3.1 Acid Mists Exposure In Japan
Kitagawa (1984) examined the cause of the Yokkaichi asthma events (1960 to
1969) by examining the potential for exposure to concentrated sulfuric acid
mists and the location and type of health effects noted. He concluded that the
observed respiratory diseases were due not to sulfur dioxide but to
concentrated sulfuric acid mists emitted from stacks of calciners of a titanium
oxide manufacturing plant located windward of the residential area. This was
based on the fact that the S03/S02 ratio of 0.48 was much higher than the
normal range of 0.02 to 0.05. The higher ratio indicates a higher acid aerosol
level. The acid particles were fairly large (0.7 to 3.3 pm) compared with acid
aerosols seen in the United States of America (see Chapter 2). More than six
hundred patients with respiratory disease were found between 1960 and 1969 with
chronic bronchitis, allergic asthmatic bronchitis, pulmonary emphysema and sore
throat. In 1969, measures of acid aerosol exposures were obtained from litmus
paper measurements collected near the industrial plant which showed that acid
mist particles were distributed leeward of the industrial plant. The author
notes that the physiological effects of concentrated sulfuric acid mists
(estimated mass concentration) may be quite different from that of dilute
sulfuric acid mists formed by atmospheric oxidation of sulfur dioxide, and that
the distinction between the two types of acid mists is very important. It
should be noted that morbidity fell after the installation of electrostatic
precipitators which reduced H2$04 emissions.
6.3.2 Chronic Studies Relating Health Effects to Sulfates
Franklin et al. (1985) and Stern et al. (1988a) reported on a cross-
sectional epidemiological study investigating the respiratory health of children
in two Canadian communities that was conducted in 1983-1984, in Tillsonburg,
Ontario and Portage la Prairie, Manitoba. There were no significant local
sources of industrial emissions in either community. Seven hundred and thirty-
five children aged 7-12 were studied in the first town and 895 in the second.
Respiratory health was assessed by the measurement of the forced vital capacity
6-15
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(FVC) and forced expiratory volume in 1 second (FEV-j^ Q) of each child, and by
evaluation of respiratory symptoms and illnesses using a questionnaire self-
administered by the parents. Sulfur dioxide (S02) and inhalable particles
(PM1Q) differed little between the communities. Historical data in the vicinity
of Tillsonburg indicate that average levels of sulfates, total nitrates and
ozone (03) did not vary markedly in the 9-year period proceeding the study.
The results show that Tillsonburg children had statistically significant
(p <.001) lower levels of 2% for FVC and 1.7% for FEV-j^ Q as compared with
children in Portage la Praire. These differences could not be explained by
parental smoking or education, cooking or heating fuels, pollution levels on
the day of testing or differences in age, sex, height or weight. The
differences persisted when children with either cough with phlegm, asthma,
wheeze, inhalant allergies or hospitalization before age 2 for a chest illness
were excluded from analysis. With the exception of inhalant allergies, which
occurred more frequently in Tillsonburg children, the prevalence of chronic
respiratory symptoms and illnesses was similar in the two communities.
Stern et al. (1988b) reported on a Canadian survey assessing the effects
to transported acidic pollution on the respiratory health of children, regional
differences in respiratory symptoms and lung function parameters. A cohort of
over 4000 Canadian school children, aged 7-11 years, residing in five rural
communities in southwestern Ontario (high exposure area) were examined.
Respiratory health status was assessed through the use of parent-completed
questionnaires and standard pulmonary function tests performed by the children
in the schools. The levels of particulate sulfates and nitrates varied little
between communities within each region, with annual average sulfate readings
3 3
for 1980 of 1.9 ug/m and 6.6 ug/m in Saskatchewan and Ontario respectively.
After adjusting for the effects of parental smoking and education, no
differences in the prevalence of chronic cough, chronic phlegm, and wheeze most
days and nights were observed. Similarly, the incidence of doctor-diagnosed
asthma and bronchitis in the previous year did not differ between the regions.
Hospital ization before age 2 for a chest illness was more frequent in
Saskatchewan than in Ontario. Statistically significant decrements of 1.8% in
FVC and 1.3% in FEV.. Q were observed in Ontario children, as compared with
those in Saskatchewan. These decrements were associated with the weight of
the children, with heavier children showing larger regional differences than
lighter ones, after adjusting for age, sex and height. There were no regional
6-16
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differences in PEF, FEF25_?5, FEF?5_85, Vmax50 and Vmax25. Children reporting
a history of asthma, bronchitis, and wheeze most days and nights exhibited
significant decrements in all lung function parameters except FVC, as compared
with healthy children. Decrements in all lung function parameters except FVC
for asthmatic children and for those reporting bronchitis were larger in
Ontario than in Saskatchewan; the reverse was true for those children reporting
hospitalization before age two for a chest illness and wheeze most days and
nights. The influence of parental smoking on the prevalence of chronic respi-
ratory symptoms differed between the regions; stronger associations were found
in Ontario than in Saskatchewan. The significance of these findings are
discussed in relation to air pollution and other etiological factors that might
differ between the regions.
Ware et al. (1986) have reported results of analyses from the ongoing
Harvard study of outdoor air pollution and respiratory health status of
children in six eastern and midwestern U.S. cities. Between 1974 and 1977,
approximately 10,100 white preadolescent children were enrolled in the study
during three successive annual visits to the cities. On the first visit, each
child underwent a spirometric examination, and a parent completed a standard-
ized questionnaire regarding the child's health status and other important
background information. Most of the children (8,380) were seen for a second
evaluation one year later. Measurements of TSP, sulfate fraction, and S02
concentrations at study-affiliated outdoor stations were combined with data
from other public and private monitoring sites to create a record of pollutant
levels in each of nine air pollution regions during a one-year period preceding
each evaluation, and for TSP during each child's lifetime up to the time of
evaluation. Annual mean TSP levels ranged from 32 to 163 ug/m3. S0? levels
ranged from 2.9 to 184 ug/m , and sulfate levels ranged from 4.5 to 19.3 (jg/m3.
Analyzing data across all six cities, Ware et al. (1986) found that
frequency of chronic cough was significantly associated (p <0.01) with the
average of 24-h mean concentrations of all three air pollutants during the year
preceding the health examinations. Rates of bronchitis and a composite measure
of lower respiratory illness were significantly (p <0.05) associated with
annual average particle concentrations. However, within the individual cities,
temporal and spatial variation in air pollutant levels and symptom or illness
rates were not significantly associated. The history of early childhood
respiratory illness for lifetime residents was significantly associated with
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average TSP levels during the first two postnatal years within cities, but not
between cities. Furthermore, pulmonary function parameters (FVC and FEV-,) were
not associated with pollutant concentrations during the year immediately
preceding the spirometry test or, for lifetime residents, with lifetime average
concentrations. Ferris et al. (1986), however, reported a small effect on
lower airway function (MMEF) related to fine particle concentrations. Spengler
et al. (1986) report the occurrence of acid aerosol peak concentrations of
o
30 to 40 ug/m (1 hr average) in two of the cities during recent monitoring.
Overall, these results appear to suggest that risk may be increased for
bronchitis and some other respiratory disorders in preadolescent children at
moderately elevated levels of TSP, sulfate fraction, and S02 concentrations,
which do not appear to be consistently associated with pulmonary function
decrements. However, the lack of consistent significant associations between
morbidity endpoints and air pollution variables within individual cities argues
for caution in interpreting the present results.
In an hypothesis-generating discussion preceding a presentation of a new
multicity study (see Section 6.4 and 8.5), Speizer (1989) presents city-
specific bronchitis prevalence rates from four of the above six cities where H
concentrations were measured. Additional preliminary H concentration data
from Watertown, MA was provided by Dockery (1988), and the entire data are in
Table 6-1. While no direct aerosol acidity measurements were actually made
during or before the 1980/81 school year (when the children were examined),
Speizer (1989) utilized data that Spengler et al. (1989) gathered in
Kingston/Harriman and St. Louis from December 1985 through September 1986 and
in Steubenville and Portage from November 1986 to early September 1987. When
the city-specific bronchitis rates are plotted against mean H concentrations
instead of PM-,r, there is a relative shift in the ordering of the cities which
suggests a better correlation of bronchitis prevalence with H than with PM15
(see Figures 6-1 and 6-2).
Because there are only five points (Table 6-1) with data for both PM15
and H the data must be reviewed extremely cautiously. These points contain
variation from sources other than pollution. For example, illness and hospi-
tal izati on rates are known to vary across areas independent of health status
factors (Wennberg, 1987; McPherson et al., 1982). Thus the relationship of
bronchitis rates with H must be considered as being suggestive at this time.
6-18
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TABLE 6-1. ADJUSTED CITY-SPECIFIC BRONCHITIS
PREVALANCE RATES AND PM15 AND H
CONCENTRATIONS FOR HARVARD SIX CITY STUDIES
Portage
Topeka
Watertown
Kingston
St. Louis
Steubenville
(ug/m3)
12.7
11.8
17.7
25.7
22.0
36.7
H+ 2
(nmoles/m3)
8.5
(12. 3)4
36.1
10.3
27.1
3
Bronchitis
3.6
6.0
4.7
10.0
6.4
8.1
1Annual mean for year preceding 1980-81 health examinations.
2Mean from samples collected over ten months between 1986 and 1988.
3City-specific prevalence (%) during 1980-81 school year adjusted for sex,
age, parental education, maternal smoking and gas stoves.
Preliminary data for 10 months.
The potential role of acid aerosols in the development of bronchitis is
suggested by the results of animal studies discussed in Chapter 4. Results
o
from animal studies indicate that at levels near 250 ug/m and with chronic
exposure, hypertrophy and/or hyperplasia of mucus secretory cells occur in the
respiratory epithelium; these alterations may extend to the small bronchi and
bronchioles, where secretory cells are normally rare or absent. This could
result in an increase in secretory rate and mucus volume in such airways which
could be a possible factor in the pathogenesis of obstructive lung disease.
But no study documents an actual increase in secretory rate or mucus volume
after acid exposure. Although mucus hypersecretion is a characteristic of
obstructive lung disease, particularly chronic bronchitis, respiratory epide-
miologists have produced conflicting results regarding its importance in the
development of obstructive lung disease. Annesi and Kauffmann (1986) concluded
that the presence of chronic phlegm production was predictive of subsequent
mortality based upon their study of 1,061 men working in the Paris area
followed for a period of 22 years. Peto et al. (1983) concluded that mucus
hypersecretion is not a link in any important causal chain that accelerates the
development of air-flow obstruction based upon their study of 2,718 British men
in a 20 year follow-up study. Bates (1983) comments that the work of Peto and
his colleagues (1983) add an important epidemiological perspective to the
clinical and pathological observation supporting the thesis of probable
6-19
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11
10
to
P
E
I 8
cc
m
uj 7
u
UJ
I 6
111
cc
a.
I
K _
W
I
10
20
30 40
PM15
50
60 0
10
20
H"1", nmoles/m^
30
40
Figure 6-1. Bronchitis in the last year, children
10 to 12 years of age in six U.S. cities, by PM15.
(P=Portage, Wl; T=Topeka, KS; W=Water-
town, MA; K=Klngston, TN; L=St. Louis, MO;
S=Steubenville, OH.)
Source: Speizer (1989).
Figure 6-2. Bronchitis In the last year, children
10 to 12 years of age In five U.S. cities, by
hydrogen ion concentration. (K=Klngston, TN;
L=St. Louis, MO; P=Portage, Wl; S=Steubenv8lle,
OH; W=Watertown, MA.)
Source: Speizer (1989):, Dockery (1988)
6-2(1
-------
dissociation between the development of chronic air flow limitations and mucus
hypersecretion. Thus, new studies that may add to the data base on the natural
history of chronic bronchitis represent a basic epidemiology research need.
Dodge et al. (1985) reported on a longitudinal study of children exposed
to markedly different concentrations of S02 and moderately different levels of
particulate sulfate in Southwestern U.S. towns. In the highest pollution area,
the children were exposed to 3 hour peak S02 levels exceeding 2,500 ug/m3 and
annual mean particulate sulfate levels of 10.1 ug/m3. The prevalence of cough
(measured by questionnaire) correlated significantly with pollution levels
(chi-square for trend = 5.6, p = 0.02). No significant differences existed
among the groups of subjects over 3 years, and pulmonary function and lung
growth over the study were roughly equal over all groups. The results tend to
suggest that intermittent high level exposure to S02, in the presence of
moderate particulate sulfate levels, produced evidence of bronchial irritation
(increased cough) but no chronic effect on lung function or lung function
growth.
Chapman et al. (1985) report the results of a survey done in early 1976
that measured the prevalence of persistent cough and phlegm among 5,623 young
adults in four Utah communities. The communities were stratified to represent
a gradient of sulfur oxides exposure. Community specific annual mean S00
o £_
levels had been 11, 18, 36, and 115 ug/m during the five years prior to the
survey. The corresponding annual mean sulfate levels were 5, 7, 8, and
14 ug/m . No gradients for TSP or suspended nitrates were observed. The
analyses were made using multiple logistic regression in order to adjust for
confounding factors such as smoking, age and education. Persistent cough and
phlegm rates in fathers were about 8 percent in the high exposure community,
versus about 3 percent in the other communities. For mothers, the rates in the
high exposure community were about 4 percent as opposed to about 2 percent in
the other communities. Both differences were statistically significant.
Schenker et al. (1983) studied 5,557 adult women in a rural area of
western Pennsylvania using respiratory disease questionnaires. Air pollution
data (including S02 but not particulate matter measurements) were derived from
17 air monitoring sites and stratified in an effort to define low, medium and
high pollution areas. The four-year means (1975-1978) of S00 in each stratum
3
were 62, 66, and 99 ug/m respectively. Respiratory symptom rates were modeled
using multiple logistic regression', which controlled for several potentially
6-21
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confounding factors, including smoking. A model was used to estimate air
pollutant concentrations at population-weighted centroids of 36 study
districts. The relative risk (odds ratio) of "wheeze most days or nights" in
nonsmokers residing in the high and medium pollution areas was 1.58 and 1.26
(p = 0.02) respectively, as compared with the low pollution area. For
residents living in the same location for at least five years, these relative
risks were 1.95 and 1.40 (p <0.01). Also, the increased risk of grade 3 dyspnea
in nonsmokers was associated with SOp levels at p = <0.11. However, no signi-
ficant association was observed between cough or phlegm and air pollution
variables. The results of this study suggest that wheezing may be associated
with S02 levels, but these results must be viewed with caution since the
gradient between areas was small and there were no particle or other pollutant
measures. Lippmann (1985) suggested that it was plausible that the effects in
this study are associated with submicrometer acid aerosol which deposits
primarily in small airways, rather than with SO,, levels.
Jedrychowski and Krzyzanowski (1989) related S02 and PM levels to
increased rates of chronic phlegm, cough and wheezing in females living in and
near Cracow, Poland. The authors suggest that the effects may have been due to
hydrogen ions, but no measurements were available.
Several authors (Lave and Seskin, 1972, 1977; Chappie and Lave, 1982;
Mendelsohn and Orcutt, 1979; Lipfert, 1984; Ozkaynak and Spengler, 1985;
Ozkaynak and Thurston, 1987) have attempted to relate mortality rates to
sulfate and other pollution measurements using ecological or macroepidemio-
logical analyses. There are significant problems and inconsistencies in
results obtained across many of these analyses, as reviewed extensively by the
U.S. Environmental Protection Agency (1986, 1982). For example, Lave and
Seskin (1977) reported that mortality rates were correlated with sulfates.
Lipfert (1984), reanalyzing the same data, found that it was not possible to
conclude whether sulfates or total respirable particulate matter had a statis-
tically significant effect on total mortality.
In more recent extensive analyses employing a variety of model specifica-
tions and controls for possible confounding, Ozkaynak and Spengler (1985),
Ozkaynak et al. (1986), and Ozkaynak and Thurston (1987) have used more
sophisticated statistical approaches in an effort to improve upon some of the
previous analyses of mortality and morbidity associations with air pollution in
U.S. cities. The principal findings presented by Ozkaynak and Spengler (1985)
6-22
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concern cross-sectional analysis of the 1980 U.S. vital statistics and avail-
able air pollution data bases for sulfates, and fine, inhalable and total
suspended particles. In these analyses, using multiple regression methods, the
association between various particle measures and 1980 total mortality were
estimated for 98 and 38 SMSA subsets by incorporating recent information on
particle size relationships and a set of socioeconomic variables to control for
potential confounding. Issues of model misspecification and spatial auto-
correlation of the residuals were also investigated^ Results from the various
regression analyses indicated the importance of considering particle size,
composition, and source information in modeling of PM-related health effects.
In particular, particle exposure measures related to the respirable and/or
toxic fraction of the aerosols, such as FP (fine particles) and sulfates were
the most consistently and significantly associated with the reported (annual)
cross-sectional mortality rates. On the other hand, particle mass measures
that included coarse particles (e.g., TSP and IP) were often found to be
nonsignificant predictors of total mortality.
The Ozkaynak and Thurston (1987) results noted above for analysis of 1980
U.S. mortality provide an interesting overall contrast to the findings of
Lipfert (1984) for 1969-70 U.S. mortality data. In particular, whereas Lipfert
found TSP coefficients to be most consistently statistically significant
(although varying widely depending upon model specifications, explanatory
variables included, etc.), Ozkaynak and Thurston (1987) found particle mass
measures including coarse particles (TSP, IP) often to be nonsignificant
predictors of total mortality. Also, whereas Lipfert found the sulfate coeffi-
cients to be even more unstable than the TSP associations with mortality (and
questioned the credibility of the sulfate coefficients), Ozkaynak and Thurston
(1987) found that particle exposure measures related to the respirable or toxic
fraction of the aerosols (e.g., FP or sulfates) to be most consistently and
significantly associated with annual cross-sectional mortality rates. It might
be tempting to hypothesize that changes in air quality or other factors from
the earlier data sets (for 1969-70) analyzed by Lipfert (1984) to the later
data (for 1980) analyzed by Ozkaynak and Spengler (1985) and Ozkaynak et al.
(1986) may at least partly explain their contrasting results, but there is at
present no basis by which to determine if this is the case or which set of
findings may or may not most accurately characterize associations between
mortality and chronic PM or SO exposures in the United States. Ostro (1988)
6-23
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also reported a stronger association between several measures of morbidity
(work loss days, restricted activity days, etc.) and lagged fine particle
estimates than associations with prior 2-week average TSP levels in 84 U.S.
cities.
Taken as a whole, these analyses are suggestive of an association between
mortality or morbidity and fine particle or sulfate fraction levels found in
contemporary American urban airsheds. Much still remains to be done, however,
to evaluate the relative contribution of acid aerosols formed from .the fine
particles or sulfates to the reported health effects.
6.3.3 Chronic Studies Relating Health Effects to Oxides of Nitrogen
Studies evaluating nitrate (as a crude surrogate for acid aerosols)
effects on human health are of possible interest. The area surrounding the
city of Chattanooga, Tennessee provided a unique opportunity to study the
effects of the oxides of nitrogen without the high concentrations of other
pollutants usually associated with automotive and industrial pollution. A
large TNT plant, located northeast of Chattanooga, produced a substantial
proportion of all trinitrotoluene (TNT) made in the United States during World
War II and the Korean War. The plant was reopened in April, 1966 to supply
munitions for use in Vietnam. By the this time, the area surrounding the plant
had become an upper-middle-class residential neighborhood. Epidemiological
studies were done in the late 1960's and early 1970's. There were, however, no
measurements made of acidity and, furthermore, many of the N02 measurements
made using the Jacobs-Hochheiser method had a number of instrumental and
analytical problems. The measured levels of the oxides of nitrogen were
nevertheless clearly quite high. For example, annual averages of nitrogen
3
dioxide reached 412 ug/m near the arsenal, and nitrate fraction levels reached
3
4.1 ug/m at the downtown post office. It is likely that the elevated nitrogen
dioxide levels were accompanied with elevated nitric acid levels, although no
direct measurements were made. The U.S. Environmental Protection Agency (1971)
measured several factors related to ambient air pollution including corrosion
of zinc, steel and nylon. The corrosion levels in Chattanooga in 1967 and 1968
were among the highest, and in the case of nylon, were 10 to 100 times the
levels of most other cities. According to the report, the arsenal was known to
emit acid aerosols. Thus it is likely that any adverse health effects seen in
Chattanooga during this time period were associated either with N02 itself or
with the nitric acid rather than other oxides of nitrogen.
6-24
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Shy et al. (1970) reported the results of a lung function study done in
the same area during the 1968-1969 school year. Ventilatory lung function
(FEVn 7[-) was measured in elementary school children in four areas near
3
Chattanooga. Average annual nitrogen dioxide levels ranged from 412 ug/m in
o
the high exposure area to 59 ug/m in the low exposure area. Suspended nitrate
o O
levels ranged from 7.3 ug/m in the high area to 1.6 ug/m in the low area, but
the results were not completely consistent with the gradient.
Pearl man et al. (1971) reported the results of a respiratory disease
survey done in the Chattanooga area in 1969. The study reported illness rates
in children for the period June, 1966 to June, 1969. Higher rates of
bronchitis in school aged children were found in both the intermediate and high
exposure areas as compared with the low exposure area. The results were not
completely consistent with the gradient since the rate in the intermediate area
was just as high as the high pollution area.
Love et al. (1982) studied acute respiratory disease in the same area
during the years 1972 to 1973. Fathers, mothers, school children and preschool
children all showed significantly higher rates in the area designated as high
pollution area during the beginning of 1972. There were almost no significant
differences in rates during the periods September to December, 1972, and
January to April, 1973. During the period January to June, 1972 nitrogen
dioxide levels ranged from 60.2 ug/m3 in the high area to 28.9 ug/m in the low
area. However, by the second half of 1972, the exposures in all areas were
quite comparable because of reduced emissions. Thus the results of the study
tend, to confirm the chronic effect of nitrogen dioxide or its by-products on
acute respiratory disease, including quite plausibly nitric acid effects.
6.3.4 Chronic Exposure Effects in Occupational Studies
The last remaining type of information considered here concerns the
effects of chronic exposures to acid aerosols in occupational settings. Such
studies are discussed mainly in order to provide some perspective on the
variety of health effects associated with acid aerosol exposures, even at
extremely high concentrations not likely to occur in ambient air.
Gamble et al. (1984a) studied pulmonary function and respiratory symptoms
in 225 workers in five lead battery acid plants. This acute effect study
obtained personal samples of H2S04 taken over the shift. Most personal samples
were less than 1 mg/m3 H2S04. Mass median aerodynamic diameter of H2S04
6-25
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averaged about 5 urn. The authors concluded that exposure to sulfuric acid mist
at these plants showed no significant association with symptoms or with acute
effect on pulmonary function. The ability of the body to neutralize acidity
of HgSO^ was considered as a factor is this outcome. Additionally, the authors
speculated that tolerance to H2S04 may develop in workers habitually exposed.
In a related study of chronic effects of sulfuric acid on the respiratory
system and teeth, Gamble et al. (1984b) measured in the same workers respira-
tory symptoms, pulmonary function, chest radiographs, and tooth erosion.
Concentrations measured at the time of the study were usually 1 mg/m3 or less.
Exposure to the concentration of acid mist showed no significant association
with cough, phlegm, dyspnea, wheezing, most measures of pulmonary function, and
abnormal chest radiographs. Tooth etching and erosion were strongly related to
acid exposure. The authors noted that the absence of a marked effect of acid
exposure on respiratory symptoms and pulmonary function may be due to the size
of the acid particles. The range of the mass median diameter in the 5 plants
was 2.6 to 10 pro. The relative humidity of the lung may cause at least a
doubling of particle size, especially in the lower size range. Thus many acid
particles may be deposited in the upper respiratory tract. The particle size
distribution of acid mist in battery plants is larger than that observed in
ambient air pollutants (several micrometers in diameter compared to submicron
diameters). Finally the authors note that the lack of any convincing finding
in this study relating to the respiratory symptoms is not completely unexpected
because of the relatively low exposure (<1 mg/m ) compared to previous occupa-
tional studies.
Williams (1970) studied sickness absence and ventilatory capacity of
workers exposed to high concentrations of sulfuric acid mist in the forming
department of a battery factory (location not stated). Based on 38 observa-
tions made on two days, the forming department had a mean HoSO, concentration
3 3
of 1.4 mg/m , ranging from a trace to 6.1 mg/m . In a different forming
department, the mass median diameter of the acid particles was 14 pm. Compared
with control groups, men exposed to the high concentrations of sulfuric acid
mist in the forming department had slight increases in respiratory disease,
particularly bronchitis. There was no evidence of increased lower respiratory
disease, which might be explained by the large particle size. After adjusting
for circadian variations, there was no evidence of decreased ventilatory
function.
6-26
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El-Sadik et al. (1972) studied lung function, salivary pH, and dental
anomalies in 33 workers in the manufacturing department of two battery
factories (presumably in Egypt). Control subjects were taken from comparably
aged workers in the same plants who were not exposed to chemicals. Air samples
2
showed concentrations of sulfuric acid vapor ranging from 26 to 35 mg/m in one
3
plant, and from 12 to 14 mg/m in another. Changes were found in FEVp dental
lesions, tooth erosion, and pH of saliva, and bronchopulmonary diseases. These
changes were either not statistically significant, or were not tested due to
the small sample sizes. The results were suggestive, however.
6.4 SUMMARY AND CONCLUSIONS
As noted at the outset of this chapter, only limited epidemiological
evidence is presently available by which to evaluate health effects associated
with ambient acid aerosols exposures. The main studies where acid levels were
measured or where the presence of acid aerosols was likely based on the ambient
air mixture of other measured pollutants (e.g., sulfates) are summarized in
Tables 6-2 and 6-3.
Historically important fog episodes believed to contain high levels of
acids resulted in mortality and morbidity. The health effects are believed to
have resulted from intense local irritant action on the lungs, which may have
led to acute anoxia due to either bronchospasm or exudate in the respiratory
tract. Those persons especially affected by the fogs were those suffering from
asthma, chronic bronchitis and heart disease. Common symptoms were cough and
dyspnea. Limited estimates or actual measurements of acid levels present
during London episodes provide some indications of likely involvement of
ambient acid aerosols in producing reported health effects.
United States and Canadian acute summer camp studies measured H concen-
trations, all but the Razienne et al. (1989) study had acid (HgSO^) concentra-
tions less than 5 (jg/m . No changes in pulmonary function could be found
related to these lower levels. The one study with acid (HLSOA) levels above
3
40 [jg/m did not separate the effects of acids from copollutants such as ozone
(Raizenne et al., 1989). Further analysis may do this. Bates and Sizto (1983,
1986, 1987, 1989) related hospital admissions for respiratory diseases
(including asthma) to sulfate and ozone levels in the summer in Canada and
speculate that acid aerosols may be more directly related.
6-27
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TABLE 6-2. ACUTE EXPOSURE HEALTH EFFECTS SEEN UNDER CONDITIONS
OF MEASURED OR PRESUMED ACID AEROSOL EXPOSURE
Study
Exposure
Health Effects Seen
Lippmann et al. (1983) lung
function study of 83 chil-
dren aged 8 to 13 at a
summer camp in Indiana, PA
Bock et al. (1985) lung
function study of
39 children at summer
camp in Mendham, NJ
Lioy et al. (1985) lung
function study of
91 children at a summer
camp in Fairview Lake, NJ
Franklin et al. (1985)
lung function study of at
summer camp at Lake
Couchiching, Ontario,
Canada
Raizenne et al. (1989)
lung function study of
112 children at Camp
Kiawa, Ontario, Canada
Bates and Sizto (1983,
1986, 1987, 1989) hospital
admissions study in
Southern Ontario, Canada
H2S04 less than
5 ug/m3
Low levels of H
H2S04 less than
4 ug/m3
H2S04 less than
5 ug/m3
H2S04 exceeding
40 |jg/m3
Daily sulfate
levels as high
as 38 ug/m3
None related to H2S04
None related to H
None related to H2S04
No association reported
and PEF decrements
associated with air
pollutant events (high
acid and ozone levels)
Respiratory admissions
(e.g., for asthma)
significantly related
to sulfates and ozone
in the summer
Martin and Bradley (1960);
Waller (1963); Commins
(1963); Lawther et al.
(1970); Mazumdar et al.
(1982); Ostro (1984);
Schwartz and Marcus (1986)
analyses of London
mortality and morbidity
during 1950's to 1970's
Thurston et al. (1989)
reanalysis of London
mortality data for
1963-1972 winters
Typical daily acidity
concentration of
18 |jg/m3 (winter)
and 7.0 [jg/m3
(summer), but very
high acid droplet
levels ranging up
to 678 ug/m3 during
severe episodes
Daily direct acid
aerosol measurements
with maximum 24-hr
levels ranging up to
40-134 ug/m3 (as
H2S04 equivalent)
Bronchial irritation,
dyspnea, and other
symptoms. Deaths from
respiratory and car-
diovascular conditions
Stronger correlation
of acid aerosols with
unadjusted total
mortality than for
BS or S02, but associ-
ation remains to be
confirmed by more
sophisticated time-
series analysis
6-28
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TABLE 6-3. CHRONIC EXPOSURE HEALTH EFFECTS SEEN UNDER CONDITIONS
OF MEASURED OR PRESUMED ACID AEROSOL EXPOSURE
Study
Exposure
Health Effects Seen
Kitagawa (1984) study
of asthma episodes in
Yokkaichi, Japan from
1960 to 1969
Franklin et al. (1985)
Stern et al. (1988b)
chronic cross-sectional
study of 1,141 children
in Canada
Ware et al. (1986) six
city Harvard study of
children in the eastern
and midwestern U.S.
Speizer (1989) bron-
chitis prevalence rates
in 5 of Harvard's six
city study
Chapman et al. (1985)
four city study of
chronic disease in
young adults in Utah
Schenker et al. (1983)
study of respiratory
disease in women in
rural Pennsylvania
Dodge et al. (1985)
longitudinal study of
children in south-
eastern U.S. towns
Shy et al. (1970)
study of lung function
in children in
Chattanooga
Pearlman et al. (1971)
study of respiratory
disease rates in
children in Chattanooga
High S03/S02
ratios. Presumed
high levels of
H2S04
Sulfate, S02, N02,
, and N03
Annual sulfate
levels ranged from
4.5 to 19.3 |jg/m3
H , PM15 (measured
at different times)
Annual sulfate
levels ranged from
5 to 14
Four year average
S02 levels ranged
from 62 to 99 |jg/m3
Peak 3 hour S02
exceeded 2,500
|jg/m3. Sul fates
also present
Annual N02 levels
ranged from 59 to
412 ug/m3, nitrate
levels from 1.6 to
7.3 ng/m3, probably
HN03
Annual N02 59 to
412 |jg/m3, nitrate
1.6 to 7.2 ng/m3,
probably HN03
Increased asthma
episodes
Two percent decrease in
FVC
Chronic cough was
related to sulfates,
but lung function
was not
Better correlation of
bronchitis prevalence
with H than with PM15
Persistent cough and
phlegm were related
to S02 and sulfate
levels
Wheeze was associated
with increased S02,
but cough and phlegm
were not
Prevalence of cough
was related to inter-
mittent high S02 in
the presence of
sulfates
Inconsistent decreased
pulmonary function
related to both
pollutants
Inconsistent increased
bronchitis rates
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Several researchers examined the European pollutant event of 1985 which
extended from western Germany to Great Britain. However, no studies had
adequate acid aerosol data by which to attempt detailed analyses that might
demonstrate direct health effects relationships to acid levels.
Among the chronic studies, Kitagawa (1984) attempted to measure acidity in
the air of one city of Japan where chronic health effects episodes occurred.
The study found increased bronchitis, pulmonary emphysema, and mortality from
asthma and chronic bronchitis. Actual acid mist levels are difficult to
estimate from this study.
Franklin et al. (1985), Stern et al. (1988b) and Raizenne et al. (1987b)
report pulmonary function decrements for a pollution mix in Canada but not for
acid aerosols or sulfates alone. The Ware et al. (1986) study suggests that
sulfate levels are related to bronchitis and some other respiratory disorders
in young children, but sulfate levels are not related to pulmonary function
measures. Speizer (1989) notes that, in five cities of the Harvard six city
study where acid levels were determined at a time separate from health evalua-
tions, there was a better correlation of bronchitis prevalence with H+ than
with PM15. The Chapman et al. (1985) study suggests that S02 and sulfate
levels are related to persistent cough and phlegm in young parents. Dodge
et al. (1985) found that prevalence of cough in children correlated with S02
and sulfate levels. Ozkaynak and Spengler (1985) also found that mortality is
also more strongly related to fine particles and sulfate levels than to total
suspended particulate levels. Consistent with this are Ostro's (1988) reported
similar stronger associations between morbidity indicators and estimated fihe
particle levels versus TSP levels.
Elevated levels of oxides of nitrogen may also have been correlated with
elevated acid levels in Chattanooga, TN. Pearlman et al. (1971) found some
suggestion of increased bronchitis rates in school aged children associated
with N02 and nitrate fraction levels. Love et al. (1982) found that fathers,
mothers, school children, and preschool children all showed significantly
higher rates of acute respiratory disease in the areas with higher pollution
levels. Shy et al. (1970) found slightly decreased lung function in school
aged children in the areas of higher pollution, although the results were not
completely consistent.
Lioy and Lippmann (1986) comment that situations exist where atmospheric
HSO at current North American exposure levels may be the active agent in
6-30
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causing respiratory responses. There are at least two scales on which this may
occur: (1) locally, downwind of a plume, and (2) regionally, downwind of major
source areas. The highest acid concentrations observed appear to be associated
with direct plume impacts. Therefore, these locations warrant considerable
attention in future epidemiological studies.
From among the occupational studies, the Williams (1970) results are most
3
notable. This study found that men exposed to HpSO. levels of 1.4 to 6.1 mg/m
had increases in respiratory disease, particularly bronchitis.
When taken as a whole, the epidemiological studies can provide indications
that ambient acid aerosols have likely been associated with certain types of
observed health effects in some situations and the available results help to
highlight directions for future research. It appears that respiratory disease
effects such as asthma, persistent cough and phlegm, and bronchitis are easier
to detect than are decreases in pulmonary function. This is consistent with
the pulmonary function test results of the human clinical studies reported in
Chapter 5. Also, alterations in mucociliary transport rates seen in human
studies have also been seen with repeated exposures in animal toxicological
studies as discussed in Chapter 4, which may be related to the development of
chronic obstructive pulmonary disease (Lippmann et al., 1987). Lippmann
et al. (1982) have also shown that the effects of HUSO, and cigarette smoke are
essentially the same on bronchial mucociliary clearance patterns.
An additional problem of the few studies with acid measurements is their
lack of power. This is not a criticism of the researchers who performed the
studies, but rather a possible explanation of why so little is known about the
effects of ambient acids at this time. The power of a study depends on several
factors, including 1) the true difference in the health outcome between the
high and low exposure measurements; 2) the sample size; 3) the design of the
study (longitudinal, cross-sectional, etc.); and, 4) the reproducibility of the
health outcome measured. The true difference in health outcome will be a
function of several factors, but the primary factor should be the difference
in exposures. This explains part of the lack of power of several of the camp
studies, since their acid exposures were very low.
At the risk of making too many assumptions, consider the following very
rough power calculations for several of the camp studies. First, assume that
each study consisted of FEV-. measurements on one low exposure day, and one high
exposure day. Second, assume that the reproducibility (variance) was about the
6-31
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same as that in the Camp Kiawa study. Third, assume that the true mean in
health outcome difference resulting from these exposures was either 50 ml or
20 ml. Fifty ml is approximately what was seen in the Kiawa study, and 20 ml
is approximately the amount seen as the result of an upper respiratory illness.
Once the mean differences, variances, sample sizes, and significant difference
level (alpha) are specified, the power can be calculated directly using
standard formulas (assuming normality). Table 6-4 gives the power (in percent)
of each study to detect the specified difference at a 0.05 significance level.
Studies with a known power much less than 80 percent usually would not be
carried out. Of course, most studies measured the campers on several days, but
the number of days with highly elevated acid levels was limited. Certainly
most studies would have difficulty detecting differences in FEV^ of 20 ml if
acid levels causing that kind of difference occurred only once or twice.
TABLE 6-4. POWER OF VARIOUS CAMP STUDIES TO DETECT SPECIFIED DIFFERENCES
Study
Kiawa, Ontario
(Raizenne et a!., 1989)
Lake Couchiching, Canada
(asthmatics and normals)
(Raizenne et a!., 1987b)
Fairview Lake, NJ
(Lioy et al., 1987)
Indiana, PA
(Lippmann et al., 1983)
Medham, NJ
(Bock et al., 1985)
Sample Size
112
52
91
83
39
39
True Difference
(FEVp in ml)
50
20
50
20
50
20
50
20
50
20
Approximate
Power (%)
83
20
50
12
74
17
70
16
40
10
The one clear conclusion that can be reached from these studies is that
there is a compelling need for additional research. Although there are a few
new studies that may be published in the near future, it is likely that the
results of these studies will be inconclusive due to the sparsity of actual
measurements of ambient acidity levels. New studies using improved acid
6-32
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measurement technology and measuring some of the health endpoints described
earlier are critical in order to provide more definitive evaluations of health
effects associated with ambient acids. As one example, Speizer (1989) has
reported on a new large scale study just begun which would directly assess the
chronic effects of acid aerosols on the respiratory health of children. That
multi-city study is to be done collaboratively by Harvard University and Health
and Welfare, Canada. The study will have three sets of eight sites, with
approximately 700 children being examined at each site. Sites will be chosen
to represent gradients in ozone, hydrogen ions from sulfur oxides, and hydrogen
ions from nitrogen oxides. Hopefully, such measurements of acid aerosol
parameters will allow for critically needed direct evaluations of acid aerosol
effects on human health under ambient conditions.
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6-39
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7. CONSIDERATIONS FOR LISTING ACID AEROSOLS AS A CRITERIA POLLUTANT
7.1 INTRODUCTION
7.1.1 Purpose
This chapter assesses and integrates the most relevant scientific and
technical discussion in the preceding chapters that the EPA staff believes
should be considered for the possible listing of acid aerosols as a criteria
air pollutant. This assessment is intended to help bridge the gap between the
scientific review and the judgments required of the Administrator in a listing
decision. As such, particular emphasis is placed on identifying those conclu-
sions and uncertainties in the available scientific literature that the staff
believes should be considered in a possible listing decision.
Because this document is concerned only with the health risks of acid
aerosols, a discussion of the potential welfare effects of acid aerosols is
beyond the scope of this chapter.
7.1.2 Background
Section 108 of the Clean Air Act provides for the listing of certain
ubiquitous ambient air pollutants that are reasonably anticipated to endanger
public health. The Act states that listing is for purposes of establishing
National Ambient Air Quality Standards (NAAQS) and, once an air pollutant is
listed, Sections 108-109 of the Act require issuance of air quality criteria
and proposal of standards for the pollutant within 12 months. Section 110 then
requires the development of State implementation plans (SIPs) to implement the
standards.
In response to these requirements, EPA has listed a number of air
pollutants under Section 108, including particulate matter, sulfur oxides, and
nitrogen oxides; issued the requisite air quality criteria and NAAQS for these
pollutants; and approved or promulgated SIPs to implement the NAAQS. As a
result, acid aerosols and their principal precursors are currently regulated to
varying degrees by these existing national ambient air quality standards. In
general, the existing related standards are met throughout most of the U.S.,
7-1
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and levels of these pollutants in the ambient air have generally been stable or
declining in recent years. Major increases in emissions of such pollutants are
not anticipated in most areas of the country.
7.1.3 Approach
The approach used in this chapter is to assess and integrate information
derived from the preceding chapters in order to address the central question of
Whether the available information provides sufficient and compelling evidence
to proceed with the separate listing of acid aerosols. Particular attention is
drawn to those critical elements that the staff believes should be considered
in a decision whether to proceed with a separate listing of acid aerosols and
to those judgments that must be based on the careful interpretation of
incomplete or uncertain evidence.
Section 7.2 examines the major considerations for listing acid aerosols.
Section 7.2.1 discusses available data for characterizing and defining acid
aerosols. This section also examines possible exposure scenarios to support
discussions of the available health effects studies. Section 7.2.2 presents
information on health effects of concern aind of sensitive population groups,
and summarizes the most relevant animal, controlled human, and epidemiological
studies. Section 7.2.3 reviews the sources of acid aerosols and their
precursors. Section 7.2.4 examines briefly the implications of listing acid
aerosols for the ambient standards program.
The final section of the chapter (7.3) presents alternative courses of
action regarding a listing decision in light of the available scientific
information.
7.2 CONSIDERATIONS FOR LISTING ACID AEROSOLS UNDER SECTION 108 OF THE
CLEAN AIR ACT
7.2.1 Characterization of Acid Aerosols
Acid aerosols can be defined and measured in several ways. Chapter 2
discusses the available information to characterize atmospheric acids as well
as available monitoring techniques. Acid sulfates are the major species in
ambient acid aerosols; at times, sulfuric acid (H2S04) and ammonium bisulfate
(NH^HSO^) may account for all of the aerosol strong acidity (Morandi et al.,
1983). Other species, particularly nitric acid (HNOg), may be of importance in
certain exposure situations, such as acid fogs. Under typical ambient
7-2
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conditions in the absence of fog, nitric acid is a gas.
A number of different "indicators," defined by the measurement method
employed, have been used to characterize acid aerosols in the ambient air. As
discussed in Chapter 2, measurement methodologies have various degrees of
species resolution, time resolution, recovery abilities, neutralization
control, and sampling anomalies. Table 7-1 presents various indicators with
comments regarding the merits of each to characterize human exposures.
A key consideration in a decision to list acid aerosols is whether one of
these measures is sufficient and appropriate to define acid aerosols clearly,
and thus serve as the pollutant indicator for regulatory purposes. A stand-
ardized measurement method is essential, but to date no organized program
exists to develop recommended techniques or to systematically evaluate the
relative uncertainties of the available methods and data from individual
studies. These are, however, techniques that appear to be sufficiently sensi-
tive and selective for ambient measurements and with coordinated effort the
present uncertainties can be reduced, for example, by refining techniques to
determine possible artifact neutralization of particle (sulfate) related H+
after collection. In any event clearly the health effects data must provide
adequate information on toxicologically important acid species to identify an
indicator that best encompasses ambient exposures of concern.
Ambient monitoring data available to characterize spatial and temporal
relationships of acid aerosols are sparse and interpretation must be tempered
by the limitations of the diverse methodologies employed. Chapter 2 reviews
the available studies. Although limited, this information does yield the
following general conclusions regarding ambient levels of acid aerosols and
their spatial and temporal relationships.
1) A wide range of acid levels (H2S04 or H+ as H2S04) have been
observed in contemporary North American atmospheres (see
Table 2-9). Concentrations of H2S04 from zero to nearly
50 ug/m3, Ih maximum (Spengler eta!., 1989), have been
measured, with most levels <5 ug/m3. In studies where only
H2S04 was measured, total aerosol strong acidity is probably
underestimated; at times the majority of strong acid appears to
be associated with partially neutralized ammonium salts (i.e.,
NH4HS04) rather than H2S04 (Morandi et al., 1983; Thurston and
Waldman, 1987).
2) Ammonia neutralization plays a key role in determining the
persistence of atmospheric acids (see Section 2.2.5). Addition-
ally, ammonia sources may locally modify acid levels of regional
events (Thurston and Waldman, 1987).
7-3
-------
•r- 0)
2 S
•o o z
•i- O.3:
•i- -r- 0)
.0 1-
•r- O
* '!=
fr-,
ID
+J r— •!-
10 Q) r—
r- U (d •
g.
S4J i—
10 .0
1 -c
•a j= •
3 4->
•i- 10 *>
,5 5 -§.
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'
i— 0) 10 i-
U) >>
I :=
0) +J •!-
U) 0) <
(O -i- U)
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LO i— *r- »—
U ••- J= ••-
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•^ m ^-r-
(0 a) c
r— S- T-
15
-------
3) Levels of sulfates and H appear to be highest in the summer
(Ferek et al., 1983; Spengler et al., 1989). Large areas of the
Northeast, extending into Canada, may be affected by elevated
acid concentrations over extended periods at this time (Pierson
et al., 1980; Lioy et al., 1980; Stevens et al., 1978; Thurston
and Waldman, 1987).
4) Urban areas may be a significant source of ammonia and there is
evidence that acid levels are lower in large urban areas than in
rural or upwind areas, particularly during regional events
(Tanner et al., 1981; Thurston and Waldman, 1987, see also
Section 2.6.1). However, elevated acid levels and acid events
do occur in urban areas.
5) Acid levels will often show a pronounced diurnal cycle, with
peak levels during daytime (cf. Stevens et al., 1980; Cobourn
and Husar, 1982; Spengler et al., 1986). Ozone often has a
similar pattern and hence elevated levels of ozone and acid may
occur together, particularly in the summer. However, unlike
ozone, the photochemical production of acid can be relatively
slow (see Section 2.2.3). Hence, in some instances, daytime
acid peaks may result not only from oxidation processes, but
also from atmospheric mixing whereby midday mixing, drawing acid
down from aloft, exceeds ground level ammonia neutralization.
Further research is necessary to identify conditions conducive
to acid accumulation.
6) Sulfate events may show fairly rapid swings in acidity, varying
from mostly strong acid (H2S04) to mostly weakly acidic ammonium
salts ((NH4)2S04), over periods of hours to days; weak and
strong acid species, however, can occur simultaneously (see
Section 2.6.1).
7) There are very few ambient data for HN03, therefore it is
difficult to evaluate the nature and extent of nitric acid
exposure. In addition, nitric acid, a gas at typical ambient
conditions, may have different health consequences than acid
particles (see discussion on page 7-8). In any event, it
appears that nitric acid concentrations are typically less than
10 |jg/m3, although higher peaks may occur (see Section 2.6.3).
8) Nitric acid vapor can be neutralized by ammonia, coalescing into
particulate ammonium nitrate. The reaction is reversible and
the NH3/HN03/NH4N03 equilibrium is very sensitive to temperature
(see Section 2.2.4). In addition, ammonium nitrate can react
with sulfate as follows:
H2S04, NH4HS04, (NH4)3H(S04)2 + NH4N03 -- >(NH4)2S04 + HN03 (g)
These reactions may occur on filters of measurement devices and
contribute to artifact loss of H+ (see Section 2.4.2.2).
7-5
-------
9) Acid fogs, discussed in Section 2.2.2, are a special type of
atmospheric aerosol. Fog droplets are very effective at
scavenging pollutant materials from the air and can be highly
concentrated with a variety of chemical components including
acids (see Table 2-3).
Based on the available data characterizing ambient acid aerosols, the
primary human exposures of interest are: regional episodes, local plume
impacts, and acid fogs.
Regional episodes, manifested by high H2$04 and/or NH4HS04 occurring over
periods of one hour or more throughout a day or sequence of days, could poten-
tially involve very large numbers of people. Moreover, elevated ozone could
frequently be associated with these events. Since these episodes occur in the
summer when large segments of the population, children in particular, will be
participating in outdoor activities, elevated ventilation rates due to exercise
and prolonged exposures may be key variables to consider in assessing health
risk. Additionally, the penetration of acid aerosols indoors is estimated to
be about 80% at this time of year (Spengler et a!., 1989). Overall the data
are quite sparse to characterize spatial and temporal acid patterns, thus the
true extent of possible regional exposures is difficult to assess.
The second type of exposures are confined to areas downwind of strong
sources such as power plants, smelters, or combined sources in urban areas.
Exposures can occur throughout the year, although, with typical activity
patterns and indoor/outdoor pollutant ratios, summer may be the most signifi-
cant period. Plume impacts may be different from regional sulfate episodes in
having higher S02 and NOX levels, high particle levels, primary acid sulfates
dominated by H2S04 (i.e., recently formed and little neutralized), and possibly
other acids, such as HC1 as well.
Acid fogs will be associated with cool temperatures and diverse chemical
composition, which may be modifying factors for possible health effects of such
fogs. Nitric acid is effectively scavenged to droplets in fogs (see
Section 2.2.2), and thus may significantly affect acidity.
Limited data are available to characterize particle size of typical
ambient acid aerosols, yet it is clear that most mass is in the fine particle
fraction (<2.5 urn) and, in fact, most studies have shown mean or median mass in
the submicrometer range (see Section 2.2.1). Regional acid events and plumes
are probably dominated by these fine particles, whereas a key feature of acid
fogs is the relatively large particle size (most mass between 5-30 urn, see
7-6
-------
Section 2.2.2). Particle size has a significant influence on regional
deposition in the respiratory tract and possible health effects (see
Chapter 3).
Although most acid levels examined were quite high compared to known
ambient concentrations, animal studies (Chapter 4) and controlled human
exposure studies (Chapter 5) indicate that health effects may result from
acute, subchronic (or repeated peak), or chronic exposures. Similarly,
epidemiological studies (Chapter 6) are suggestive that acute or chronic
exposures may be associated with health effects. However, ambient data are
insufficient at this time to assess adequately the frequency, magnitude, and
duration of acid aerosol events; moreover the limited health effects data base
makes interpretation of available ambient data difficult. There is a great
need for focused research to quantify ambient exposures, including data on acid
sulfates, nitric acid and ammonia.
In summary, the level of knowledge to characterize ambient acid aerosols
is limited and represents one of the most pressing research needs. There has
been, as yet, no precise definition of acid aerosols, rather they are a class
of pollutants that may be considered to be a subset of pollutants already
regulated by existing NAAQS. Acid sulfates appear to be the major species of
concern, but other acids, both particles and vapors, may be important in
certain situations. There are several possible measurement techniques, but
there is no accepted "standard" method, which further complicates interpreting
the available quantitative data. However, there are techniques that appear to
be sufficiently sensitive and selective for ambient measurements, and, with
coordinated effort, more uniform and comparable approaches can be developed to
reduce the current uncertainties. In any event, it is difficult at this time
to assess exposures accurately. Nevertheless, there is the potential for large
segments of the population to be exposed to elevated acid levels, at times in
combination with high levels of other pollutants such as ozone, and there are a
few different possible exposure scenarios. These include regional events,
local plume impacts, and acid fogs. Intertwined with these exposures are
meteorological variables and atmospheric processes which influence acidity.
For example, summertime regional events, removed from significant pollution
sources, may be typified by relatively slow conversion of S02 and long distance
transport before substantial acid accumulates, whereas more localized impacts
may result when conditions favor rapid conversion to acidic species (See
Section 2.2.3). These may occur at any season, but local, relatively rapid
7-7
-------
formation of acid may explain cold weather events and the historic fog epi-
sodes. The significance of ambient exposures in terms of health effects,
however, is unclear, as will be discussed next.
7.2.2 Available Health Effects Data on Acid Aerosols
To make the decision to list acid aerosols under Section 108 of the Act,
the Administrator must conclude that current ambient levels of acid aerosols
may reasonably be anticipated to endanger public health. Such a judgment
requires a sufficient body of supporting evidence that includes data on health
effects of concern, sensitive populations, and concentration-response informa-
tion from appropriate studies to measure against expected ambient exposures.
The bulk of the quantitative health effects data base for acid aerosols
involves acid sulfates, primarily submicrometer hLSO.. There are no animal
data, and limited controlled human data, for larger droplets that would be
typical of acid fogs. Few data are available for nonsulfur constituents of
acid fogs or other acidic atmospheres, such as nitric acid. It is essential to
have a clear idea of which acid species are toxicologically important to direct
efforts aimed at quantifying ambient exposures and before possible regulatory
action is taken. As indicated in Chapters 4 and 5, it appears that
toxicological potency is related to the strength of the acid, i.e., HpSCL >
NH4HS04 > (NH4)2S04. However, Amdur et al. (1978b) found that (NH4)2S04 had a
greater effect than NI-LHSO* on respiratory function in guinea pigs, whereas
Schlesinger (1989) provides evidence that the H associated with hUSO. may be
more "potent" for altering respiratory region clearance than that associated
with NH^HSO-. There is a need to explore concentration-response relationships
further in controlled studies, for example by examining different acid species
and mixtures with the same pH or the same titratable acidity.
In some instances, ambient acid vapor may exceed acid in particles.
Nitric acid appears to be the principal strong acid gas of concern in the
ambient air. As mentioned above, however, there are very few health effects
data for nitric acid. This highly soluble gas will likely have different
respiratory tract deposition than is true for typical fine mode acid particles.
The toxicologic implications of this for the range of possible health endpoints
is not clear. It may be that all forms of airborne acid are relevant for some
effects, but, given the current lack of data for nitric acid, the bulk of the
discussion of health effects below will focus on acid particles.
7-8
-------
At present, the best quantitative exposure-response data for acid aerosols
comes from controlled laboratory studies. The use of distinct acid species
(singly or in mixtures of pollutants) under well defined exposure conditions
(i.e., concentration, particle size, time and route of exposure) are strengths
of these studies.
Animal studies in particular are valuable to provide data on the full
range of possible effects, and are especially valuable for the study of chronic
effects, providing information generally unavailable from epidemiological or
controlled human studies. However, quantitative extrapolation to humans is a
major limitation of animal studies; with acid aerosols some unique problems
exist. Initial particle size, hygroscopic growth, ammonia neutralization,
airway buffering capacity, and regional deposition, in addition to species
sensitivity, may influence dose-response relationships and hence extrapolation
of the data. As discussed in Chapter 4, neutralization by both endogenous and
exogenous ammonia in particular may be a key variable in animal studies and may
explain some of the wide variation in response among the available studies.
Controlled human studies, in addition to the advantages of controlled
exposure conditions, avoid extrapolation problems of animal studies, yet they
are limited inasmuch as they may not characterize the most sensitive popula-
tions (e.g., elderly, most reactive asthmatics, individuals with preexisting
respiratory disease). Moreover, these studies generally examine specific,
predetermined endpoints (for acid aerosols these have included respiratory
function and symptoms, blood biochemistry, mucociliary clearance, and airway
reactivity—see Chapter 5) and do not include invasive endpoints, such as
evaluation of lung structure, or address chronic exposures.
Lastly, controlled animal or human studies focus on single pollutants or a
limited mixture of pollutants, whereas typical ambient exposures often involve
a complex and changing mixture of pollutants.
In any case, the available animal and controlled human studies provide
clear evidence that at high enough concentrations of acid aerosols health
effects will occur. However, these studies are limited at this time for
assessing ambient exposures. In general, most used concentrations well above
known peak ambient levels. Nevertheless, epidemiology provides suggestive
evidence that current ambient levels of acid aerosols may be associated with
health effects.
7-9
-------
Some of the most interesting epidemiological studies show health effects
associations with plausible surrogate acid indices (e.g., sulfates, particles)
in contemporary North American environments and in areas where elevated acid
levels have been found in subsequent monitoring efforts (e.g., Bates and Sitzo
(1987) report the presence of elevated H+ in the region while Speizer (1989)
indicates that the prevalence of bronchitis in the 6-city study suggests a
better correlation with subsequently measured H data than PM15 data). It has
been speculated that H+ may be a more likely causal agent, traveling with the
measured surrogate pollutants, to explain the effects seen in some of the
available epidemiological studies (Bates and Sizto, 1987; Lippmann, 1989).
However, sulfates or other surrogates do not consistently relate to aerosol
acidity and thus these studies are limited for specific inferences regarding
current ambient levels of acid aerosols. Moreover, the exposures consisted of
a mixture of pollutants, making it difficult to identify the contribution of
any single pollutant to the effects seen. The few epidemiological studies that
have measured atmospheric acidity have often found low acid concentrations and
no effects clearly attributable to acid aerosols (see Section'6.2.3) or
recorded elevated ozone concurrently (Raizenne et a!., 1987, 1989) and it is
difficult to separate the effect of acid from ozone for the endpoint measured
(pulmonary function).
The available health effects data indicate that acid aerosols have the
potential to deposit and act throughout the respiratory tract. As a result,
there is a broad range of health effects associated with exposure to acid
aerosols from both acute and chronic exposures at various concentrations; these
include effects on respiratory mechanics and symptoms, alteration of clearance
and other host defense mechanisms, morphological and biochemical alterations,
aggravation of existing disease or illness, and mortality. The discussion of
these effects below will focus on animal and controlled human studies with
o
exposures <1,000 ng/m , and pertinent epidemiological studies.
7.2.2.1 Respiratory Mechanics and Symptoms. A number of functional measures
are used to indicate altered mechanical and flow attributes of the respiratory
tract following pollutant exposures (A glossary of terms can be found in
Appendix A of this document). Interpretation of respiratory function changes
in relation to exposure to airborne pollutants is complicated by several
factors including interindividual variability, superposition of both transient
effects of acute exposures and the cumulative effects of chronic exposures,
7-10
-------
and the inherent day to day variability of effort dependent indices (Lippmann,
1988). Moreover, the "clinical" significance of various transient, apparently
reversible effects can be uncertain. Mild effects in normal subjects may
indicate potentially more serious responses in more sensitive subjects. In
addition, function or symptom responses may at times only crudely reflect
underlying changes of perhaps greater health significance.
For acid aerosols, animal, controlled human and epidemiological studies
show mixed results for effects of acute exposures on respiratory mechanics and
symptoms at concentrations <1,000 [jg/m3 (Table 7-2). Most animal studies have
shown no effects following acute acid sulfate exposures at these levels. Amdur
and colleagues, however, have observed changes in pulmonary function in guinea
pigs following 1-hour exposures to various acid sulfates alone, and in
mixtures, with significant changes as low as 100 ug/m3 H2S04, Recently these
investigators have examined the effect of H2$04-coated ultrafine zinc oxide
particles (Amdur and Chen, 1989); levels as low as 20-30 ug/m3 H2$04 delivered
in this manner resulted in significant changes in pulmonary function and
produced increased bronchial hypersensitivity, whereas much higher levels of
pure H2S04 aerosol were needed to produce comparable results. Zinc oxide alone
caused no effects. This suggests that the physical state of acids in pollutant
mixtures is an important determinant of response.
Controlled human exposure studies indicate that asthmatics are more
reactive to inhaled acid aerosols than normals. Small changes in spirometry
have been inconsistently observed in normals with exposures of about
1,000 [jg/m H2S04 for up to 4 hr but no effects at concentrations less than
500 ug/m , whereas asthmatics typically showed modest bronchoconstriction with
exposures of 400 to 1,000 ug/m3. Statistically significant changes in FEV^^
(4.1%, corrected for control) have been observed in adolescent asthmatics at
o
68 ug/m H2S04 (Koenig etal., 1989). Normal adolescents have not been
examined. Recent work by Bauer et al. (1988) with adult asthmatics exposed for
2 hr to 75 ug/m H2S04 shows a trend (although not statistically significant)
for FEV-L decrements (19% for H2S04 versus 15% control) which suggests that
adult asthmatics may also experience mild potentiation of excercise-induced
bronchospasm at these levels. Further work is necessary to more fully
understand effects on respiratory function following acute exposure to acid
aerosols. This should include extending exposures for longer periods or
7-11
-------
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7-13
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repeated exposures at near ambient levels, examination of delayed responses,
and specific examination of the role of concentration, exposure time, and
minute ventilation.
Individual responsiveness to acid aerosols appears to vary substantially
among studies of asthmatics, and even among subjects in any one study,
suggesting that numerous factors may influence susceptibility. Table 5-5
illustrates this to some extent, as it can be seen that a large range of
quantity of acid inhaled has been examined across the various studies, but
there is little consistency in the response. Where statistically significant
effects have been observed, they were typically less than a 10% change in group
mean FEV-,. In any case, while it is difficult to compare studies with different
3
protocols and subjects across concentrations ranging from <100 ug/m to
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>2,000 ug/m , the'available studies of asthmatics generally have not produced
effects that require exposure to be stopped; by contrast, some exercising
asthmatics may respond to short-term (<10 min) SO* exposures such that at low
levels (<0.25 ppm) there is essentially no effect, while at somewhat higher
levels (>0.4 ppm with moderate to heavy exercise) some individuals may
experience distressing effects, finding it necessary to discontinue the exposure
and take medication (U.S. Environmental Protection Agency, 1986).
Effects on airway reactivity have been demonstrated following acute H2$04
exposures in humans (Utell et al., 1983b, 1984) and chronic exposures in animals
(Gearhart and Schlesinger, 1986). The development of hyperresponsive airways
in otherwise normal subjects may be of special concern (see Sections 4.3 and
5.8).
Epidemiology is largely inconclusive for acute effects of acid aerosols on
respiratory function. Two somewhat different possible exposure scenarios can
be addressed by the available studies. First Dockery et al. (1982) and Dassen
et al. (1986) provide evidence of effects on respiratory function in children
(group mean FVC, FEV, change of 2%-5%) following pollution episodes that were
cold weather events with high levels of PM and S02, but apparently low ozone.
Interestingly, both studies provide evidence of an extended depression in
function (2-3 weeks) following a single episode. Neither study has direct
acid measurements, however, and it is not clear that these episodes were
necessarily conducive to the formation or accumulation of high acid levels
(although cold weather conversion of S02 to H2$04 can occur and do so rapidly,
see Section 2.2.3), nor that acids, if present, were an important contributor
7-14
-------
to the observed response. Most other studies discussed in Chapter 6 examining
acute exposure and pulmonary function were summer events in areas removed from
significant local pollution sources where ozone was the principal pollutant and
acid levels, where measured, were low and no effects are clearly attributable
to the acid, or the effect of the acid component is difficult to separate from
the mixture of pollutants present (e.g., Raizenne et al.s 1989).
Chronic exposures have produced functional effects in some animal studies
(see Table 7-2). The five and one-half year chronic exposure of dogs to a
mixture of H2$04 and S02 resulted in several interesting findings (Hyde et al.,
1978; Stara et al., 1980). Changes in pulmonary mechanics and structure were
found at exposure levels considerably lower than in other animal studies. The
functional changes became progressively more severe with time after exposure
had been terminated (2 yr later), at which time a number of morphological
alternations, including airspace enlargement were also found, implying the
development of chronic, irreversible lung disease. It appears that long-term
low level exposures may eventually lead to functional and morphological effects
whereas other studies, limited to shorter exposure durations, have found
effects only with much higher concentrations; or no effects at all.
Ware et al. (1986) from the ongoing Harvard six-city study found the
frequency of cough, bronchitis, and lower respiratory illness in school age
children to be significantly associated with annual mean TSP and total sulfate.
Interestingly, the authors note that city-specific illness rates for Kingston
and Steubenville were consistently highest—subsequent measurements of aerosol
acidity (H ) in four of the six cities show these two cities to be highest on
average (Spengler et al., 1989). In addition, Speizer (1989) indicates that
the subsequently measured H+ data suggest a better correlation with bronchitis
prevalence than does PNLj- in 4 of six cities with H+ data.
The data presented by Speizer (1989) are among the most thought-provoking
for contemporary exposures, but the acid measurements were obtained about 5 to
6 years after the health survey and hence quantitative use of these data are
limited. Moreover, the gradient of exposure, presented as a single long-term
3
mean for each city, was quite small (0.4 to 1.8 ng/m as equivalent HgSO^).
These values reflect the distribution of 24-hr concentrations, but may not
adequately characterize exposures of concern, for example, repeated peak
concentrations. The recently begun Harvard multicity investigation (see
7-15
-------
Section 6.4, 8.5, or Speizer, 1989) will address many key issues directly for
assessing the role of ambient acid exposure on the respiratory health of
children. It is of note that several other studies discussed in Chapter 6 are
generally consistent with the 6-cities data, providing evidence of symptom
associations (but generally not function effects) with chronic exposure to air
pollution (e.g., Chapman et al., 1985; Dodge et al., 1985; Schenker et al.,
1983) but in all cases, no acid exposure data are available. In contrast to
these findings, however, two Canadian studies report finding no significant
differences between high and low sulfate regions in prevalence rates of chronic
respiratory symptoms and illnesses in school children but did find regional
differences in lung function (about 2% in FVC and FEV-^ (Stern et al., 1988a,b).
It is clear there is an urgent need for further epidemiological research, of
which acid exposure characterization is a key component.
7.2.2.2 Host Defense Mechanisms. The lungs have several defense mechanisms to
detoxify and physically remove inhaled material. Nonspecific particle
clearance mechanisms have been well-studied and appear to be sensitive to
inhaled H^SO. at relatively low levels (see Table 7-3). Bronchial mucociliary
clearance appears to be particularly sensitive to the effects of inhaled H9SOA.
3
Single 1-hr exposures to levels as low as 100 pg/m have produced transient
alterations in mucociliary transport rates in humans and animals; repeated
exposures in animals have shown progressive and persistent effects.
Respiratory region clearance in rabbits has been shown to be either accelerated
or retarded, suggesting a graded response that is dependent upon both exposure
concentration and time (see Section 4.5.1.2b). H2$04 may alter alveolar
macrophage (an important defense cell of the lung) function following single or
repeated exposures in animals (Naumann and Schlesinger, 1986; Schlesinger,
1987), but the data are too limited at this time to provide a complete under-
standing of the cellular mechanisms that may underlie changes in respiratory
region clearance.
The pathogenic implications of altered clearance mechanisms have been
discussed previously (see Sections 4.5, 4.8) and, in short, the significance of
transient alterations after short-term exposure is unclear, but such changes
may be an indication of a lung defense response. On the other hand, persistent
impairment of clearance may lead to the inception or progression of chronic
respiratory disease, suggesting a plausible link between inhaled acid aerosols
and respiratory pathology. For example, Lippmann et al. (1982) emphasize the
7-16
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similarities between clearance effects of cigarette smoke and HpSCL; smoking
has a well established role in the development of chronic bronchitis. Lippmann
et al. (1987) recently examined this evidence and other data and hypothesized
a link between H,,S04 exposure and the pathogenesis of chronic bronchitis.
Few other animal studies have provided evidence to indicate that acid
aerosols may compromise lung defense mechanisms. Acid aerosols are apparently
not very potent in enhancing susceptibility to bacterial-mediated respira-
tory disease in mice (see Table 4-6), but two studies indicate significant
interactions with ozone (Gardner et al., 1977; Grose et al., 1982). As with
other endpoints, the effect of mixtures on infectivity needs further examina-
tion. No animal data directly examine the effects of acid on viral infectivity.
Little is known about the effects of acid aerosols on immunologic defense
mechanisms (see Section 4.5.2).
7.2.2.3 Morphological and Biochemical Alterations. Morphological or
biochemical changes are often detected by invasive techniques and hence most
data for acid aerosols are derived from controlled animal tests. Table 7-4
presents relevant studies with exposures <1,000 (jg/m .
Few effects have been demonstrated in animal studies following acute
exposures at levels <1,000 ug/m3 (see Section 4.4). This may be due in part to
different sensitivities of various species or the endpoints studied. However,
daily three-hour exposures to low levels of H^SO. delivered as a coating on
ultrafine zinc oxide particles have produced an increase in the protein content
of pulmonary lavage fluid (peaks after one and three days) and an increase in
neutrophils (peak after three days) indicating tissue damage and an inflammatory
response (Amdur and Chen, 1989). Amdur and colleagues have not yet done animal
exposures to coal combustion products, but suggest that the response produced
by the prototype acid coated zinc oxide aerosols may have considerable relevance
for such exposures. Much higher levels of pure HLSO, droplets were required to
elicit similar responses; the levels of zinc oxide used alone caused no effects.
Chronic or repeated peak exposures to acid aerosols have produced
morphological changes in animals (see Table 7-4). The dog study of Hyde
et al. (1978) provides unique insights into extended exposures (5k yr) to a
mixture of sulfur oxides. Several morphological changes were observed upon
examination 2-3 yr after exposure ceased, including airspace enlargement.
Changes in pulmonary function of the dogs correlated well with the morpholo-
gical effects (Stara et al., 1980). Since the changes in pulmonary function
7-18
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7-19
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were progressive over the post-exposure period, it is likely that morphological
changes were also progressive. There are several points to consider to apply
the dog studies to real world exposures (see U.S. Environmental Protection
Agency 1982a,b) including the possibility that actual acid exposures may have
O
been lower than 90 pg/m due to neutralization by chamber ammonia. Progressive
effects were also found by Gearhart and Schlesinger (1988), on tracheobronchial
clearance in rabbits exposed to H2S04, that continued even after exposure
ceased, again implying progressive, irreversible effects.
It seems reasonable to attribute most of the deep lung effects in the dog
studies, and other studies with S02/H2S04 mixtures, to the acid component,
based on the probability of deep lung deposition of the aerosol. Hyde et al.
(1978) indicates that morphological effects of the SO mixture are more pro-
X
nounced with extended lower level exposure than with much higher concentrations
for a shorter exposure period.
The studies of rabbits (see Table 7-4) provide evidence that low level
(250 ug/m ) chronic exposure to H2$04 results in hypertrophy and/or hyperplasia
of mucus secretory cells in the epithelium; these alterations extend to the
small bronchi and bronchioles, where secretary cells are normally rare or
absent (Gearhart and Schlesinger, 1988). These findings are consistent with
the results of Alarie et al. (1973, 1975) for monkeys chronically exposed to
mixtures of H,,S04 and S02. In addition, Gearhart and Schlesinger found that
there was a shift in the chemistry of mucus towards a greater content of acidic
glycoproteins, which would tend to make mucus more viscous. Similar
morphological and biochemical changes in small airways in humans, along with
mucociliary clearance effects discussed previously, may be part of the
pathogenic sequence leading to the development of chronic bronchitis (see
Lippmann et al., 1987).
In a disease such as chronic bronchitis, the degree to which small airways
are affected may be the most significant feature in determining disability
(Reid, 1980). Because of the small size of their lumen, the peripheral airways
are more easily blocked than the larger airways. The possible dissociation
between mucus hypersecretion in the large airways (probably the primary
contributor to sputum production) and changes in the small airways, including
mucus secretion in these airways normally free of it, may explain why no
consistent correlation has emerged between the amount or duration of sputum
7-20
-------
production and a patients disability (Reid, 1980). It is essential to study
further a possible link between long-term exposure to acid aerosols and the
development of chronic lung disease.
3
Low levels of H,,S04 (40 ug/m ) have been shown to react synergistically
with ozone in altering biochemical indices (Warren and Last, 1987). In this
case, the disease associated with these changes is speculated to be pulmonary
fibrosis (Last et a!., 1983). As mentioned earlier, acid aerosols will
frequently be associated with elevated ozone levels, and there is a need for
further research addressing pollutant mixtures.
7.2.2.4 Aggravation of Existing Disease or Illness. Evidence linking acid
aerosol exposure to aggravation of existing disease or illness is reviewed in
Table 7-5. As is evident, animal data are limited. However, since broncho-
constriction may be an important mechanism by which acid aerosols aggravate
existing respiratory disease, animal and human clinical studies indicating
effects on respiratory mechanics are relevant here (see Table 7-2). In any
event, controlled human studies indicate that asthmatics are more sensitive to
inhaled acid aerosols, but epidemiology provides evidence that other
individuals may be particularly sensitive to air pollution that includes acid
aerosols.
Lawther et al. (1970), in a classic study of chest clinic patients (mostly
bronchitics, but some patients had asthma or emphysema), found day-to-day
changes in health status to depend on daily variations in London pollution (SCL
and British Smoke), measured at seven sampling sites. (This study is discussed
at some length in U.S. Environmental Protection Agency 1982a,b.)
Interestingly, daily sulfuric acid, measured from one central site beginning in
the winter of 1963, was most strongly correlated with effects in a group of
patients for the winter of 1964-1965, but less so for 1967-1968. The authors
suggest that sulfuric acid may be of special interest as a respiratory
irritant. Pollution levels had declined substantially from previous years by
this time, although still quite high compared to current U.S. conditions.
The ongoing correlational study of Bates and Sizto (1983, 1986, 1987,
1989) relating hospital admissions in Southern Ontario to air pollutant levels
is of interest for more contemporary exposures. These analyses demonstrate a
consistent summer relationship between sulfates, ozone and temperature, and
acute respiratory admissions with or without asthma (see Section 6.2.4).
Multiple regression analysis indicates temperature alone accounts for less than
7-21
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1% of the variance, sulfate accounts for about 3%, and when those factors
together with ozone are included in the analysis, 5.6% of the variability in
respiratory admissions is accounted for (Bates and Sizto, 1989). There is a
continuing lack of association of these variables with non-respiratory condi-
tions. Bates and Sitzo (1987) indicate that it is not clear whether the
association of increased respiratory admissions can be ascribed to ozone or
sulfates (the only two pollutants monitored on a regular basis which show a
consistent association) or possibly to some unmeasured species that "travels"
with them over the region in the summer. Recent monitoring efforts in the area
indicate peaks of H+ of small particle size (about 0.2 urn) on days when ozone
and sulfate levels were elevated. These data are interesting and are of
particular relevance for possible health effects at current ambient levels of
acid aerosols, but as yet, the hypothesis that hospital admissions in this area
are more readily attributed to acid aerosols is untested because of a lack of
H+ data.
A significant pollution event occurred in Europe in January 1985 (see
Section 6.2.2). Notable increases in several measures of morbidity were
observed in Germany (Wichmann et al., 1989), especially for cardiovascular
disease. Acid levels for the study area were not determined, but the levels of
PM, SO2 and N02 were qui'te high.
The available epidemiological studies, taken as a whole, suggest that
certain individuals or groups may be sensitive to air pollution that includes
acid aerosols, but ascribing the observed health effects to acid exposure is
difficult for these studies because of a lack of sufficient ambient acid
measurements.
7.2.2.5 Mortality. Evidence linking mortality to acid aerosol exposures at
O
concentrations <1,000 pg/m is limited to epidemiological studies (Table 7-6).
This strongly suggests that a mixture of pollutants may be important or that
individual sensitivity is crucial.
Excess mortality clearly resulted from acute exposures during the severe
pollution episodes of Meuse Valley, Donora, and London. Of greater relevance
for the present discussion, however, are studies such as those of Schwartz and
Marcus (1986) that show mortality associations in London continuing to periods
of much lower pollution, with no evidence of a threshold, and a preliminary
analysis of the London mortality data for which daily acid aerosol measurements
are available from a central site (Thurston et al., 1989). The results of the
7-23
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7-24
-------
latter study indicate that the log of acid aerosol concentrations is more
strongly associated with raw total mortality in bivariate analyses than is
British Smoke (BS) or SCU. The acid aerosol results may be more readily
applied to other environments than is the case for existing BS results, yet
differences in the composition and levels of pollutants between current condi-
tions in the U.S. and those in London at the time the mortality data were
gathered still limits the applicability of the London mortality data to
contemporary North American atmospheres. In addition, there are uncertainties
regarding the quality of the acid measurements; for example, there may have
been substantial positive or negative artifacts.
A more recent study (Ozkaynak and Spengler, 1985) provides qualitative
support for an association between daily mortality and particle concentrations
in nearly contemporary U.S. atmospheres (14 years of New York city data,
1963-1976). The limited data available for the New York City region show very
low levels of strong acid present for urban New York City, indicating substan-
tial neutralization of acid sulfates from urban ammonia sources (Tanner et a!.,
1981).
The recent study by Wichmann et al. (1989) indicated increased mortality
following a European pollution episode, but the levels of several pollutants
were quite high and it is not clear what part acid aerosols may have played, if
any, in this event.
Several ecological analyses have attempted to relate mortality rates to
chronic exposures of sulfate and other pollution measures (see Table 7-6 and
U.S. Environmental Protection Agency, 1982a,b, 1986). There are significant
problems with these kinds -of analyses that limit both quantitative and
qualitative conclusions (see U.S. Environmental Protection Agency, 1986). The
more recent cross-sectional analyses of Ozkaynak and Spengler (1985) and
Ozkaynak and Thurston (1987) address some of these problems. The predictors of
mortality due to air pollution examined in their analyses were expressed in
terms of four aerosol pollutant measures: TSP, IP (inhalable particles), FP
(fine particles), and SoJ" (sulfate). Among these, FP and soj" were most
consistently and significantly associated with the reported SMSA-specific total
annual mortality rates, while TSP and IP were often nonsignificant predictors
of mortality.
Taken as a whole, the above studies are suggestive of an association
between mortality and particles or sulfates at or near contemporary North
7-25
-------
American levels, but assessing the possible role of acid aerosols in this
association is hampered without adequate acid data.
7.2.2.6 Summary of Health Effects. As is evident, there are many possible
health effects associated with acid aerosols, both with acute and chronic
exposures, but the available animal and controlled human data to assess
concentration-response relationships are limited, particularly for assessing
health risk at ambient or near ambient exposures. While the controlled studies
provide the best quantitative data at this time, very few of the studies have
examined (or found effects at) concentrations that approach known peak ambient
levels, and too few concentration-response or concentration times time studies
have been performed. However, chronic studies of ambient acid levels using
sensitive measurement techniques have not been performed. Thus the no
measurable effect level is not adequately defined for risk assessment purposes.
At present, epidemiology provides no clear quantitative relationships because
of a lack of sufficient ambient acid measurements by which to define
exposure-response effects levels.
While the data base is sparse overall, there are some notable features in
the available information including interactive effects of HUSO, with ozone at
near ambient levels on biochemical indices (Last and colleagues), pulmonary
function and inflammatory effects at relatively low levels (20-50 ug/m3) when
HgSO^ is delivered as a coating on ultrafine zinc oxide particles (Amdur and
colleagues), and perhaps most striking, the consistency of some effects across
various studies and disciplines.
Studies of mucociliary clearance, in both humans and animals, for example,
show transient alterations in clearance following single 1-hour exposures to
2
100 ug/m H2SO^; when animals are exposed repeatedly for 1 hr/day to levels of
100 to 250 ug/m for weeks or months, the alterations become progressive and
persistent. Morphological changes, such as increased number and density of
mucus secretory cells, are also evident with these repeated exposures
2
(250 ug/m ) in animals. For respiratory function as the measured endpoint,
animal data are mixed for acute exposures, with most studies showing no effects
2
at concentrations <1,000 ug/m ; guinea pigs, however, have shown functional
2
changes at H?SO. levels of 100 ug/m . In controlled studies of normal humans,
3
few effects on function are evident with exposures <1,000 ug/m . Asthmatics
appear to be more reactive. The lowest level to show small functional effects
3
is 68 ug/m in exercising adolescent asthmatics. Increased airway reactivity
7-26
-------
has been demonstrated in normal humans following a single 4-hr exposure to
450 ug/m HpSCL, and in animals, following repeated 1-hr exposures to
250 [jg/m . In any case, the animal and controlled human exposure studies are
limited for assessing respiratory function effects for ambient exposures, where
o
known peak H,,S04 levels (1 hr) are <50 ug/m . The available epidemiological
studies are also largely inconclusive for functional effects following acute
exposure to acid aerosols. With chronic exposure, there is a degree of con-
sistency across several epidemiological studies in the reported results for
symptoms such as cough for the various pollutants measured. The major limita-
tion of these studies for their use in the current context, however, is a lack
of acid exposure data.
Several factors that are not well understood at this time influence con-
centration-response relationships of acid aerosols, and controlled studies,
therefore, may not yet have adequately characterized potential effects in the
general population. These factors include:
Exposure concentration times exposure time (CxT) relationships
have received limited study for acid aerosols. At high levels
(8-20 mg/m3 H2S04), concentration appears to be the key variable
for mortality, whereas histologic damage appears to depend upon
total dose (i.e., CxT) rather than concentration alone (Amdur
et al., 1952). Schlesinger (1989) has observed that slowing or
speeding of clearance is dependent upon both concentration and
time (Schlesinger1s regression results indicate that C contrib-
utes more to the effect that T, but both are significant
contributors). Similarly, Spektor et al. (1989) found that
human tracheobronchial clearance halftimes tripled from control
with a 2-hr exposure to 100 ug/m3 H2S04, while halftime doubled
with a 1-hr, 100 ug/m3 exposure. With some major assumptions
(e.g., regional dosimetry not included), one can calculate
quantity of acid inhaled for controlled human studies as was
done in Table 5-5. Some of these studies have found effects
with an inhaled dose that is in the range of possible calculated
peak ambient inhaled dose; for example, Spengler et al. (1989)
calculate that a 1 hr peak ambient exposure at an outdoor camp
in southern Ontario resulted in an inhaled dose on on the order
of 1,300 nmol/m3 (or 1,050 nmol/m3 "delivered dose", assuming
80% retention). The CxT concept implies that there is some
accumulation of the pollutant or the effect above mitigating
processes. Several variables may influence this relationship
for acid aerosols, such as ammonia neutralization and airways
buffering, respiratory tract deposition variables, particle
size, and so forth. In any event, this important concept has
received limited specific study for acid aerosols and its
importance for assessing risk of ambient exposures is uncertain
at this time.
7-27
-------
Acutely sensitive groups may not yet be sufficiently identified.
Data from animal studies (e.g., Schlesinger et al., 1979; Wolff
et al., 1979) and human clinical studies (e.g., Avol et al.,
1979; Utell et al., 1983a) suggest that certain individuals, even
within selected subgroups, may be particularly sensitive to acid
aerosols. Where possible, these "hyperresponders" should
receive increased study to allow extrapolation to populations at
greatest risk in the general public. For chronic exposures it
may be difficult to identify a sensitive group, rather all
sufficiently exposed people may be at risk.
Delayed or progressive effects, which may be linked to acute
exposure or to cumulative processes of repeated exposure, may
have been missed. There are some data to suggest that such
effects may occur including delayed development of airway
hypersensitivity (Gearhart and Schlesinger, 1986; Utell et al.,
1983b) and progressive functional and morphological effects
(Stara et al., 1980; Gearhart and Schlesinger, 1988).
Breathing mode (see Chapter 3) and breathing mechanics may
significantly alter deposition (and thus possible response) of
acid aerosols. For example, exercise exacerbates the effects of
inhaled H2S04 (Utell et al., 1986). Additionally, disease
states (e.g., asthma, bronchitis) or age-related factors influ-
ence deposition (see U.S. Environmental Protection Agency,
1982a,b, 1986).
Oral and respiratory tract ammonia may be critical in neutral-
izing inhaled acids and mitigating responses (Larson et al.,
1977; Utell et al., 19§6; see also Section 3.4). In addition,
reduced buffering and H ion absorption capacity of airway mucus
may predispose certain individuals to effects of inhaled acids
(Hoima, 1985, 1989).
Few data on ambient particle size are available. Animal data
indicate that particle size influences the potency and temporal
pattern of response (see Chapter 4); controlled human exposure
data indicate that submicrometer particles are more effective
per mass in altering respiratory mechanics than large particles
more typical at acid fogs (see Table 5-1). Regional mucociliary
clearance effects are apparently related to regional deposition
of H and hence particle size (Lippmann, 1985). In addition,
deposition depends on hydrated, rather than initial, particle
size, but the net effect of hygroscopicity is not adequately
understood (see Section 3.3).
There is inconclusive evidence on the effect of mixtures of
pollutants. Levels as low as 40 yg/m3 H2S04 may act synergis-
tically with 03 on several biochemical endpoints in rats (Warren
and Last, 1987) and H2S04 delivered as a coating on ultrafine
ZnO particles has produced pulmonary function and inflammatory
effects in guinea pigs (Amdur and Chen, 1989); as yet, other
animal or controlled human studies have shown minimal effects
7-28
-------
due to H2S04 at low levels in mixtures (see Sections 4.6 and
5.4). Acid aerosols will often be associated with multiple
pollutants, especially 03. Epidemiology studies show effects in
the presence of elevated levels of acids and ozone (Raizenne
et al., 1987, 1989).
In summary, the available information derived from animal and controlled
human studies clearly indicates that exposure to acid aerosols at high enough
concentrations can produce health effects of concern, particularly in sensitive
subgroups of the population and after chronic exposure. The bulk of these
studies, however, have examined H,,S04 exposures. Data for other acid species
and mixtures are extremely limited. The effects seen range from mild and
transient changes, such as small, reversible functional effects in exercising
asthmatics, to more substantial effects that may have acute or chronic health
consequences, such as persistently altered clearance and structural changes
that may be suggestive of chronic lung disease. In addition, there are some
notable consistencies in the health effects information across various studies
and disciplines. However, there are significant limitations in the available
data to assess the health risk of current ambient exposures. The available
animal and controlled human exposure studies provide good quantitative
information on a range of possible health effects, but most of these studies
have examined ^SO^ levels well above known peak ambient concentrations and
hence provide limited information for possible ambient exposures. Several
relevant epidemiological studies indicate effects consistent with those
observed in the controlled studies but lack direct or concurrent acid exposure
data, substantially limiting their usefulness for quantitative assessment of
health risk of current ambient exposures. The few epidemiological studies that
do have direct acid measurements generally recorded low acid levels (see
Section 6.2.3) or, where acid levels were elevated, ozone was also elevated
(Raizenne et al., 1987, 1989) and the contribution of the acid component for
affecting endpoint measured (pulmonary function) is not clear. Finally, there
are several factors that may significantly influence concentration-response
relationships that are not completely understood.
7.2.3 Sources of Acid Aerosols
A major consideration in reaching a decision to list a pollutant for
regulation under Sections 108 and 109 of the Act is whether the pollutant is
derived from numerous or diverse mobile or stationary sources.
7-29
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The major atmospheric strong acids of concern (acid sulfates and nitric
acid) are principally transformation products of SOp and NOp. Other acids such
as HC1 and some organic acids are generally minor contributors to ambient
strong acid aerosols.
The major precursors of acid aerosols (SOp, N02) are emitted from
ubiquitous sources. S02 is emitted principally from combustion or processing
of sulfur-containing fossil fuels and ores. Emissions of NO result mainly
/\
from combustion of fossil fuels such as coal, oil, or gasoline from mobile or
stationary sources.
Both SOp and N02 are currently regulated under Sections 108 and 109 of the
Act.
7.2.4 Implications of Listing Acid Aerosols
While the subject is not a major focus of this paper, it is important to
recognize and briefly consider the implications of a decision to list acid
aerosols as a criteria air pollutant when assessing the available data. Once a
pollutant is listed, Sections 108 and 109 of the Act require issuance of air
quality criteria and the proposal of air quality standards within 12 months.
The practical effect of these requirements is that the scientific and
technical data available at the time a decision to list is made must be
sufficiently developed to serve as the basis for criteria and standards.
Therefore, when assessing the existing data on acid aerosols, consideration
should also be given to whether it is adequate to provide the kind and amount
of technical information needed to:
1) define a pollutant indicator and associated measurement methodology;
2) select appropriate averaging times and forms for standards; and
3) establish appropriate standard levels.
7.3 ALTERNATIVE APPROACHES FOR A LISTING DECISION
The focus of this chapter has been on those critical elements that EPA
staff believe should be considered in a listing decision. The major consider-
ations included: 1) characterizing and defining acid aerosols as a pollutant
entity for purposes of regulation; 2) possible health effects of acid aerosols
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at current ambient levels; and 3) the sources of acid aerosols. Each of these
elements is of central relevance for listing decisions under Section 108 of the
Act.
The key findings of this assessment are summarized below:
1)
2)
Atmospheric strong acids consist principally of acid sulfates
(particles at typical ambient conditions) and nitric acid (a gas
at typical ambient conditions in the absence of fog) derived
from the oxidation of sulfur dioxide and nitrogen oxides. At
present, however, acid aerosols have not been defined as single
pollutant entity; rather different measures and measurement
techniques have been employed. While there are many promising
measurement methods, efforts must be made to develop and refine
techniques further and to gather more data. In any event, few
data are available at this time to quantify ambient acid levels
and acid events, thus possible human exposures are not well
documented.
Available information from animal and controlled human studies.
is limited, but clearly indicates.that at high enough concentra-
tions acid aerosols can produce health effects of concern,
particularly in sensitive subgroups of the population and after
chronic exposure. These studies provide the best quantitative
information at this time on the range of possible effects and
show some degree of consistency across the various studies and
disciplines for some health endpoints. It is less clear, how-
ever, whether effects of concern are occurring at current peak
ambient levels. Very few of the controlled human studies have
examined (or found effects at) concentrations that approach
known peak ambient levels. Animal studies indicate chronic,
irreversible effects but require replication and extension to
lower concentrations and improved quantitative extrapolation
models for adequate risk assessment. Several relevant community
epidemiological studies indicate that effects consistent with
those observed in animal and controlled human studies may occur
at current ambient levels, but have significant limitations
because of their lack of direct or concurrent acid measurements.
The few studies with concurrent acid measurements provide
limited information for the specific importance of the acid
component of the atmosphere. Epidemiological studies, therefore,
have limited value at this time for quantitative assessment of
the health risk associated with current ambient levels of acid
aerosols.
3)
The principal precursors (S02 and N02) of
emitted from numerous and diverse sources.
acid aerosols are
As indicated earlier, the central question to be addressed in this review
is whether the available scientific and technical information provides suffi-
cient and compelling evidence to proceed with the separate listing of acid
7-31
-------
aerosols. When assessing the adequacy of the available data in light of this
question, consideration must be given to the fact that acid aerosols and their
principal precursors are currently regulated to varying degrees by the existing
national ambient air quality standards (NAAQS) for particulate matter, sulfur
oxides and nitrogen oxides. Thus, a decision to list acid aerosols should be
based on a clearly established need to provide additional public health
protection beyond that afforded by the current NAAQS. Finally, the
implications of a listing decision should be considered. Because the statutory
schedule requires the issuance of air quality criteria and standards within
12 months of such a decision, the available scientific and technical
information must be sufficient to serve as the basis for criteria and provide
the kind and amount of technical information needed to set standards.
Given the above information, three alternative courses of action should be
considered.
1) Recommend that the Administrator consider listing acid aerosols
under Section 108 of the Act. This implies a judgement that the
available health effects information is compelling enough to
require additional protection beyond the current NAAQS. Within
12 months of a listing decision, EPA must issue air quality
criteria and propose standards.
2) Recommend that the Administrator not consider listing acid
aerosols under Section 108.. The available health effects
information as well as any new research would be considered
during the next review of the particulate matter standards.
3) Recommend that the Administrator defer judgement regarding
action to list acid aerosols pending further research on the
critical needs identified in Chapter 8.
Based on the staff's assessment of the available information, it appears
that the scientific and technical basis is not sufficient at this time to
proceed to list acid aerosols as a criteria pollutant and to develop a national
ambient air quality standard. Large uncertainties exist to characterize
current ambient exposures, stemming primarily from the lack of a "standard"
monitoring approach and from a lack of collected data. Similarly, the health
effects data is sparse, particularly for assessing the health risk of current
ambient exposures. The most convincing data clearly indicate that at high
enough concentrations, health effects of concern are associated with exposure
to acid aerosols, but these data are limited for assessing ambient exposures.
7-32
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Nevertheless, data of a more qualitative nature suggest some risk at ambient
levels. This uncertainty regarding health risks at ambient exposures, coupled
with the need to better characterize and define acid aerosols, suggests that it
is difficult to make conclusions regarding the level of protection provided by
existing NAAQS and therefore adoption of either alternative 1) or 2) would be
premature. However, as a whole, the data raise very clear concerns and the
staff believes that additional research is warranted and therefore the most
appropriate course of action would be to recommend that the Administrator defer
judgement pending further research on the critical needs identified in
Chapter 8.
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8. RESEARCH NEEDS
Throughout earlier chapters in this issue paper, numerous gaps in the
current data base for acid aerosols are detectable. The present chapter
summarizes some of the more crucial research needs that are critical to be
addressed in order to provide a firmer basis by which to judge the need for
listing ambient acid aerosols as a criteria air pollutant and for developing
any consequent criteria and standards. The research needs discussed reflect
inputs from chapter authors of this report, external peer reviewers of drafts
of this document, and EPA scientists and represent critical areas where signi-
ficant gaps exist in the data base concerning acid aerosols and associated
health effects. They are identified below by subject area and include needs
related to: characterization and exposure; animal toxicology studies; control-
led human exposure studies, and epidemiological research. Appendix C to this
document contains the CASAC Report on Acid Aerosol Research Needs.
8.1 CHARACTERIZATION AND EXPOSURE
Development and Evaluation of Measurement Methods — Currently, there are
a multitude of techniques to detect various acid species in the atmosphere.
Ideally, before initiating extensive studies to characterize components,
levels, and distribution of ambient acid aerosols, it would be desirable to
have a consensus by the scientific community on measurement techniques that are
accepted as reliable and that reflect the indicator(s) of concern from health
effects studies. Available health studies have not unequivocally identified a
unique entity as the "correct" indicator, although the available evidence
suggests that either the H+ of strong acids or sulfuric acid (H2S04) specifi-
cally is the toxicologically important component. Therefore, until and unless
health studies can define the species of concern more explicitly, it is
desirable to measure individual acid species (both in particles and gases) and
more inclusive measurements of titratable H+, which can include strong acidity
and weak acidity, if desired.
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There are a number of similar techniques, used by different research
groups, which are based on removal of acidic and basic gases by various types
of denuders, collection of acid particles on filters, preservation of the
samples from NFL, and analysis for H+ by pH measurements or titration, and
2-
analysis of SO^ , N03, N02, Cl , and NH4+ by ion chromatography. These can
give time resolution of as low as one or a few hours or for periods of 24 hours
or longer.
H2SO^ may be determined semi continuously by flame photometry using a
temperature-cycled diffusion denuder tube. However, 95% of the aerosol acid
sulfate is typically not in the form of H2S04- Other techniques utilizing
thermal treatment applications have been used for semi continuous measurements
and measure most of H2S04 and possibly NH4HS04. In any event, a program is
needed to evaluate existing methods and to develop or modify techniques, with a
goal of developing recommended approaches that are accepted by the scientific
community and which will thereby provide some uniformity by which to evaluate
ambient conditions and, ultimately, human exposures to acid aerosols.
Application of Measurement Techniques — There are a variety of applica-
tions that place different requirements on measurement techniques. In con-
junction with methods development and evaluation, the range of potential
applications needs to be considered. Research applications require a variety
of special measurements but do not necessarily require low cost, unattended
use, or easy operation. Characterization studies, which need to be conducted
over longer time periods for ambient, indoor, and personal exposure, place
additional constraints on measurement techniques in terms of time resolution,
reliability and accuracy, and ease of operation. For these purposes, scien-
tific acceptance and good quality control are essential. Measurements must be
as complete as possible in terms of species measured.
Both batch and continuous (or at least semicontinuous) techniques will be
needed for research and characterization studies. Continuous techniques are
typically more expensive to setup and more difficult to operate than batch
techniques, but provide information not available from batch measurements and
may be cheaper on a per-sample basis.
An overriding concern for various applications and sampling strategies is
their relevance to available health effects information. For example, there
appears to be a significant diurnal variation in acid levels; the time
resolution of batch measurements ideally would differentiate this variation
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(e.g., 6-hour intervals) yet would still be compatible with longer term
integrated measurement, and thus allow extrapolation to a variety of possible
exposure scenarios.
Characterization of Ambient Acid Levels -- At present, there are extremely
limited data to characterize ambient acid aerosol levels. Once appropriate
measurement techniques are 'available, an ambient characterization study should
be conducted to give a better indication of the potential exposure to atmo-
spheric acids. Sampling sites should include, as a minimum, an urban and an
upwind (in terms of expected acidity) station. Species measured should include
HpSO. and strong acidity, and for gases, HMO,, HNO,,, and NH.,. Measurement of
other species and parameters would be useful, especially fine particle mass,
2-
SO. , NO,, Oo, SOp, and N02- Time resolution should be adequate to charac-
terize the diurnal cycle. Geographic coverage should include, as a minimum, a
site in the mid-west source region, a site in the sulfate impacted NY or PA
area, and two sites farther south in the east. At least two should be in areas
with acid soil and therefore presumably low NH-.
Additional Characterization Needs — Several factors that may affect
concentration-response relationships for ambient acid aerosols need further
study. These include ambient size distributions of acid particles, ammonia
neutralization, aerosol dynamics and chemistry, and spatial and temporal
relationships.
Deposition in the respiratory tract is, to a large degree, a function of
particle size. Acidity is expected to be confined to the fine particles
(0 - 2.5 pm) but the possibility of acidity in coarse particles capable of
penetrating the tracheobronchial region of the respiratory tract should be
examined. Within the fine fraction, the exact particle size, and the distri-
bution between the nuclei mode (0-0.1 urn) and the fine mode (0.1 - 2.5 urn)
needs to be determined for various concentrations and pollutant conditions.
With respect to acid fog, current research is limited to characterization
of bulk fog or cloud water. Unfortunately the efficiency of the collectors
are low and not well known for sizes where lung deposition is high. Measure-
ment techniques are adequate but need to be applied to size-differentiated
samples.
Measurements have shown that NhU reacts rapidly with pure HUSO, aerosol.
However, in the atmosphere acid particles may be coated with a film which will
impede the diffusion of NH3 into the liquid droplet. Thus, it may be that acid
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particles can coexist with NH3. Information on the rate of neutralization is
needed for design of new measurement techniques, to model acid air quality,
to calculate exposure, and to understand the role of endogenous NH, in
influencing the acidity of acid particles in the respiratory system.
Current research suggests the occurrence, especially during summer
episodes, of a strong diurnal pattern with sulfate and acidity both peaking
between 12 noon and 6 pm. Since health effects may depend on the short-term,
high-level exposures, over a threshold, measurement techniques must be adequate
to resolve these peaks. Thus, batch measurements with one-hour resolution or
continuous or semicontinuous measurements may be required.
Acidity may come from regional scale sulfate pollution which is almost
continuous in some parts of the country and more episodic in others. Acidity
may also come from near-source impacts of plumes. Exposure studies will need
to cover these spatial determinants of ambient acidity.
Exposure ~ If health effects studies support health concerns with acid
aerosol at expected ambient exposure levels, personal monitors and personal
exposure studies will be needed to augment available ambient data. This should
include indoor measurements to study penetration of outdoor acidity into indoor
environments in homes, schools, and offices;, the influence of indoor NH3
sources; and the possible generation of acid aerosol by indoor combustion
sources. Activity models should be available from other studies.
Air Quality Models — At some point, it may become necessary to model acid
aerosol air quality. Over the next few years, major advances in air quality
models are expected in terms of transport and removal processes and sulfuric
acid formation (from the Regional Acid Deposition Model), and aerosol size
distribution from Visibility and Fine Particle Models. There are several
considerations which will be especially important for an acid aerosol model
which may not be adequately addressed in existing programs. It may be appro-
priate to add or put more emphasis on these considerations. They include NH3
emissions and influence of soil acidity on NH, emissions and removal, and
diurnal variations in acidity and sulfate concentration. More effort may be
needed to differentiate between pollutant processes in the near ground-level
well-mixed layer, and in that portion of the well-mixed layer which is isolated
from the ground during night-time and early morning.
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8.2 EXTRAPOLATION AND DOSIMETRY
Quantitative Animal-to-Man Extrapolation of Effective Acid Exposures and
Regional Pulmonary Deposition In Man — It is reasonably expected that animal
studies will provide cause-effect data on the chronic effects of acids, mecha-
nisms of effects, and the full range of effects, thereby providing information
unavailable from epidemiological or human clinical studies. These animal data
are therefore of great importance to risk assessment, but quantitative extrapo-
lation to man is required. This extrapolation must be rigorous inasmuch as
small differences in effective concentrations have major impacts on risk
management. To achieve the quantitative animal-to-man extrapolation, two
primary factors must be considered: dosimetry and species sensitivity.
Research on the relationship between concentration and delivered dose in
animals and man will be complex since 1) acids are hygroscopic aerosols for
which more fundamental data are needed, 2) neutralization by breath ammonia
and, in whole body exposure, ammonia from excrement, can be important, 3)
tissue dose will be highly dependent on regional mucus buffering capacity,
requiring data on mucus biochemistry, and 4) microdosimetry (i.e., dose within
lung regions) is quite important since health studies on a single endpoint
(i.e., clearance) show responses to be dependent on regional dose. Of course,
other dosimetric factors are equally important, but acids present some special
cases. It is also of interest to compare dosimetric relationship within
subpopulations of "man", e.g., normal, asthmatic, exercising, etc. Understand-
ing these relationships will enhance the accuracy of predicting susceptibility
factors, since ultimately it is dose that causes an effect. Even once dose-
equivalency in different species is known, species sensitivity to a given dose
is likely to have some differences which must be quantified and linked with
dosimetry to provide a full extrapolation. It is already recognized that the
guinea pig is more sensitive for some endpoints than other animal species to a
given inhaled concentration. How does the sensitivity of a guinea pig compare
to "man", whether "he" be normal, asthmatic, or otherwise more susceptible?
8.3 ANIMAL TOXICOLOGICAL STUDIES
Identification of the Hazardous Chemical Species — Concern about the
health risks of acidic aerosols is derived from epidemiological studies, most
of which did not include direct acid measurements in their exposure assessment,
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and controlled human and animal studies of FLSCh and other less acidic sulfate
species. While this work forms the basis for numerous research needs, there is
a major need to identify the causative chemical species so that future health
and monitoring studies are properly directed and that ultimately the causative
species can be controlled. The relative potency of various acid species needs
further study; most work has focused on H2S04 but NH4HS04 may dominate ambient
aerosol acidity at times. In addition, there is a need to understand the rela-
tive role of the cation and the anion associated with various acid species, and
the toxicological effects of acidic particles compared to acidic gases. A more
complex issue has arisen from recent research by Dr. Amdur and her colleagues
(see Chapter 4). They found that H2$04 adsorbed onto ultrafine zinc oxide
particles was 3 to 10 times as potent in changing pulmonary function as an
equivalent-sized aerosol of FUSO. mist. This raises several questions, not
only for HgSO,, but also for HC1 since it is emitted from hazardous and
municipal waste incinerators, perhaps in association with particles.
Determination of Concentration Times Time (C x T) Relationships -- Health
effect outcomes are dependent on many factors, with C x T being one of the
major ones. Ambient air patterns of acids, as of other pollutants, are not
steady-state, so it is critical to determine which exposure patterns are of
greater risk and hence must be used/monitored in research studies, and be
controlled if control is warranted. Given the paucity of C x T health and
monitoring data, it is important to develop a research strategy between both
health and monitoring scientists so that each may be guided by the other
iteratively. The alternative is a plethora of health data bearing no relation-
ship to ambient exposures or a plethora of monitoring data with averaging times
uninterpretable with respect to health risk. Health study components would
focus on only a few sensitive indicators of response, perhaps clearance and/or
pulmonary function. Focus is necessary to simplify what will be a complex
matrix design.
Determine Influence of Pattern of Exposure on Effects — This topic has
elements in common with the C x T studies described above, but focuses more on
the effects of timing of the pattern of exposure vis-a-vis pattern of response.
Only rarely are delayed responses studied, although they can occur and may
provide important guidance to design and interpretation of human clinical and
epidemic!ogical studies. In the Cincinnati dog study in which dogs exposed to
HpSO. plus S02 were examined 2 years post-exposure, pulmonary function effects
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were progressive, and in the chronic rabbit studies of New York University
several effects were progressive (see Chapter 4) arguing further for the
incorporation of delayed response studies in experimental designs. Another
issue of importance to explore is the response to short-term repeated exposures.
Over a week, the pattern of pulmonary function responses changes, in some cases
worsening and in others plateauing. To interpret the degree of adversity, it
is necessary to know whether there are "silent" changes to one endpoint that
progress while other endpoints adapt, as is the case with ozone.
Determine the Effects of Acids(s) on Development of Chronic Lung
Disease -- There are sufficient data to hypothesize that long-term exposure to
low levels of H2$04 may cause chronic bronchitis. Because of the significance
of these findings, it is essential to test the hypothesis. Several approaches
are of interest. A few would include conducting a study similar to the rabbit
study of Schlesinger et al. (see Chapter 4) in at least one additional species;
repeating the Schlesinger et al., study at a lower concentration; increasing
the knowledge of the relationship between alterations in lung clearance and the
development of chronic bronchitis; applying state-of-the-art lung morphometric
methods in a time-course study.
Define a Fuller Range of Classes of Effects of Acids -- Generally, the
literature on the health effects of acids is sparse, with the more important
findings resulting from the application of newer methods and technologies.
Recently, low levels of H2$04 have been observed to result in inflammatory
responses and effects on alveolar macrophages. These changes have implications
to the development of chronic lung disease. The alveolar macrophage effects
and lung clearance effects may portend decrements in host resistance to infec-
tion, most probably viral infection since bacterial infectivity is apparently
not affected. Taking the literature as a base, several findings require
follow-up so that risk potential can be understood. As examples, is the influx
of neutrophils associated with other inflammatory changes; are defenses against
viral infection compromised?
Determination of Susceptible Subpopulations — Several subpopulations are
known or suspected to be more susceptible to acid aerosols. While some of this
research is incorporated under extrapolation modeling discussed earlier, animal
toxicological research on this topic is needed to supplement human studies to
explore mechanisms more fully.
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Interaction of HpSO. With Other Co-occurring Common Pollutants -- The
issue of the enhanced potency of HpSO, adsorbed onto particles was discussed
briefly under the first recommendation in this section and will not be repeated
here. Sulfuric acid in association with other pollutants such as ammonium
sulfate, 0-, and NO,, has been found to be additive, synergistic, antagonistic
or non-influential, depending upon the endpoint, the co-pollutant, and whether
the exposure was in sequence or in mixture. From a risk perspective, under-
standing the synergism is of major importance. Such studies need to be
designed to mimic ambient occurrences of H2S04 and co-pollutant exposures,
insofar as possible. For example, the temporal relationship and concentration
ratios of 0_ and FLSO. that actually occur should be investigated for effects
using sensitive endpoints such as edema, lung clearance, and other endpoints as
well, since there can be a dependence on endpoint. Once the phenomenon is
understood better, mechanism studies are needed to enable predictions of
interactions in risk assessments. Such predictions are important since it is
not feasible to collect data on every potential interaction of interest.
8.4 CONTROLLED HUMAN EXPOSURE STUDIES
Titratable Acids — All studies should report the titratable acidity of
the aerosol in addition to particle size distribution, acid concentration of
liquid that is aerosolized, and mass concentration of aerosol.
Studies of Adolescent Asthmatics — Further studies of adolescent asth-
matics are required to confirm the apparent susceptibility of this patient
group. Specific attention should be focused on exposures to acid aerosols in
the concentration range of 0-200 ug/m . As an adjunct to such studies, deter-
mination of differences in mucus buffering capacity or oral and airway ammonia
levels in young asthmatics should be made.
Studies of Hucociliary Clearance in Humans — Further work on mucociliary
clearance measurements in humans is needed, emphasizing standardization of
measurement methods and independent confirmation of findings. This work should
focus on estimation of airway acid burdens and, ultimately, identification of
acid deposition "hot spots". Effects of longer (2-8 h) exposures to lower
o
concentrations (0-100 pg/m ) of acid aerosol are necessary to examine further
the predictive validity of the concentration-time product model. Further basic
work is needed to attempt to understand the large "normal" range of mucociliary
clearance rates.
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Studies of Airway Hyperreactivity — Further work on the relationship
between induction of airway hyperreactivity and acid aerosol exposure is
needed. It is important to determine whether acids induce airway inflammatory
responses that may be associated with hyperreactivity. At present, only
hyperresponsiveness to carbachol has been demonstrated. Investigation of
post-exposure reactivity to other stimuli, such as histamine, methacholine, or
antigens, would help to clarify the specific or general nature of the airway
response.
Studies of Hyperresponsive Subjects ~ Efforts should be made to focus on
the susceptible members of the population. Specifically, responses of
hyperreactive subjects should be confirmed. Further study of hyperresponsive
individuals should be initiated to attempt to discern possible mechanisms of
reactivity. Both longer-duration and repeated-exposure studies in humans with
acid aerosols will be necessary to evaluate cumulative effects and possible
adaptive responses. The possibility that repeated acid aerosol exposure may
result in airway hyperresponsiveness should be evaluated.
Buffering Capacity of Airway Secretions — More information is needed
regarding the ability of airway secretions to buffer inhaled acids. Suscepti-
ble subjects need to be identified. Regional variation within the lung of
buffer capacity needs to be better defined. Buffering capacity of mucus from
asthmatics needs to be further evaluated.
Variation of Ammonia Production — Interindividual, regional, and species
variation in ammonia production must also be evaluated. When possible, studies
should measure ammonia levels in conjunction with acid aerosol exposures.
Effects on Respiratory Epithelium — The effects of acid aerosols on the
respiratory epithelium need to be studied more extensively. Changes in epithe-
lial permeability are expected to occur as a result of acute acid inhalation.
Small Airway Effects — Improved methodology for non-invasive evaluation
of small-airway responses is necessary because aerosol deposition models
indicate that a large portion of inhaled acid in the ambient size range is
deposited in the vicinity of the alveoli and respiratory bronchioles.
Effects of Mixtures of Pollutants -- Effects of acid in mixtures of other
pollutants need to be studied in more detail. Specifically, exposure sequences
and simulation of ambient exposures should be examined. Both ozone and H?SO.
appear to cause increased epithelial permeability. Further examination of the
effects of ozone and hSO mixture's thus appears warranted. Further work with
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asthmatics exposed to mixtures of SCL and acid or possibly NCL and acid is also
needed.
Delayed Responses — Further study of delayed response, seen in studies of
normals and asthmatics, is needed to evaluate possible mechanisms of delayed
effects of potential importance. Specifically, a series of follow-up measure-
ments is necessary to evaluate delayed effects and their time course.
Other Acids — There have been a substantial number of studies on sulfuric
acid aerosols. Further work should be conducted using other acids such as
HN03, HC1, and NH4HS04-
8.5 EPIDEMIOLOGY STUDIES
Epidemiology provides an approach for directly studying the effects of
ambient acid aerosol mixtures on human health endpoints. Such studies con-
ducted to date, however, have been markedly limited due to the lack or sparsity
of actual acid measurements or to the relatively low concentrations of acids
present at the time of particular studies. Nevertheless, the data derived from
epidemiological and other types of studies thus far do suggest that certain
health endpoints are more likely than others to be affected by acid aerosols.
Based on the available epidemiological, controlled human exposure, and
animal toxicological studies, future research should clearly include evaluation
of pulmonary function and respiratory diseases as possible health endpoints.
Increased incidence or aggravation of respiratory diseases or symptoms, such
as persistently increased cough and phlegm, bronchitis, and asthma have all
been indirectly implicated. Specifically, chronic bronchitis rates have been
consistently elevated in those situations where it was also likely or confirmed
that ambient air acid levels were elevated. It is also possible that well-
conducted epidemiological studies of short-term exposure effects on lung
function may yield significant effects, especially if geographic study loca-
tions can be found with higher ambient acid aerosol levels than those typically
seen thus far in the summer camp studies discussed in Chapter 6. As for
asthmatics, a reactive population not taking medication may be indicated as
a group to study. Hyperresponsiveness and delayed responses may need to be
evaluated. Also, since inflammatory processes are found toe increase in the
airways following exposure to acid, studies examining reversible changes in
pulmonary function may be appropriate.
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Further development of better methods to more accurately measure ambient
acid levels (see Section 8.1) and the deployment of adequate monitoring sites
are crucial for the success of future epidemiological study efforts. Realis-
tically, given anticipated funding limitations, increasing support to already
ongoing large-scale epidemiology investigations, so that they can be expanded
to include sufficient acid aerosol aerometric measurements and analysis of
health endpoints in relationship to such measurements will probably provide
the best near-term opportunity to notably improve the acid aerosols health
data base. For example, existing ongoing or planned epidemiology studies
should be extended to include additional health endpoints, larger numbers of
subjects, increased numbers of chemical species measured, additional study
areas, and greater numbers of monitoring sites in study areas. Some specific
examples of what might be done are concisely highlighted below.
New Harvard Multicity Investigation — (Primary Sponsors NIEHS and Health
and Welfare, Canada). This study is to directly assess the chronic effects of
acid aerosol on the respiratory health of children. This prevalence cross-
sectional study is discussed in Section 6.4. It is designed to clarify the
possible role acid aerosols may play in chronic respiratory disease that was
suggested in earlier epidemiology studies. Additional funding could be used
to improve acid aerosol exposure assessment and expedite reporting of results.
Canadian Hospital Admissions Study — As discussed in Section 6.2.4, there
is a suggestion that acid aerosol levels may be related to respiratory
admissions to hospital in Southern Ontario, Canada. Acid aerosol measurements
have been obtained in this area during the past two years. Hospital admissions
data will become available to the researchers in the near future. Additional
funding to expedite analyses and reporting of results would be beneficial.
Studies in the Netherlands — Several studies underway and planned in the
Netherlands would benefit from additional funding and potentially produce
data related to the health effects of acid aerosols in a shorter time frame.
One ongoing study is designed to examine the long-term effects of pollutants
on normal and sensitive adults. Every three years, this prospective study
examines respiratory function and symptoms of respiratory disease. The overall
goal is to examine the decline of pulmonary function and the onset of chronic
respiratory disease. Additional assistance related to the acid aerosol
component of the study would be beneficial, e.g., to expand acid aerosol
monitoring.
8-11
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The above study results may be influenced by short-term effects from
acute pollutant exposures that affect the general long-term trends. These
short-term effects will be examined to clarify this problem. Acid aerosol data
would be an important addition to this analysis.
Another acute study in the planning stage is examination of the respira-
tory effects on children of exposure to pollutant events. Acid aerosol data
would be important in this study as well. Of special importance would be to
develop monitoring and measurement capabilities sufficient to characterize
peak exposures.
Studies in Other Countries — European study settings provide an oppor-
tunity to assess winter excursions of pollutants, including acid aerosols which
are not accompanied by elevated ozone as is typical of the summertime episodes
in the U.S. Respiratory morbidity in patients of general practitioners in
England (see Section 6.2.2) is a potential area of study. Examining acute
bronchitis rates in children in relation to acid aerosol exposure is suggested.
Preliminary data from a study in West Germany (see Section 6.2.2) suggest that
study of respiratory disease and exposure to acid aerosols may be indicated in
that country. Another possible location for a study of respiratory disease in
relation to acid aerosol exposure is in Italy in the area of the largest power
plant in Europe. Additional study opportunities should be explored in other
European countries and elsewhere, e.g., China.
Indoor Exposures — Preliminary results from chamber studies at Yale
University indicate that high indoor exposures to acid aerosols may result from
the use of kerosene heaters. Additional research is needed to determine the
extent to which these exposures occur in residential settings and if indicated
to assess their health effects.
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APPENDIX A: GLOSSARY OF TERMS AND SYMBOLS
Absorption: Penetration of a substance into the bulk of a solid or liquid fcf
adsorption). ^ v •
Accumulation mode: Particles formed principally by coagulation or growth
vapor condensation of short-lived particles in nuclei mode (see
Acetylcholine (ACh): A naturally occurring substance in the body havina
important parasympathetic effects; often used as a bronchoconstrictor.
Acidic deposition: See Deposition.
Acidity: The quantity of hydrogen ions in solution; having a pH less than 7
(.see pH).
Acute toxic effects: Effects of, relating to, or caused by a poison or toxin
and having a sudden onset, sharp rise, and short course.
Adsorption: Solid, liquid, or gas molecules, atoms, or ions retained on the
surface of a solid or liquid, as opposed to absorption, the penetration of
a substance into the bulk of the solid or liquid.
Aerodynamic diameter: The diameter of a unit density sphere having the same
settling speed (under gravity) as the particle in question of whatever
shape and density.
Aerometry: Relating to measurement of the properties or contaminants of air.
Aerosol: A suspension of liquid or solid particles in a gas.
Air spaces: All alveolar ducts, alveolar sacs, and alveoli. To be contrasted
with AIRWAYS.
Airway conductance (Gaw): Reciprocal of airway resistance. Gaw = (I/Raw)
Airway resistance (Raw): The (frictional) resistance to airflow afforded by
the airways between the airway opening at the mouth and the alveoli.
Airways: All passageways of the respiratory tract from mouth or nares down to
and including respiratory bronchioles. To be contrasted with AIR SPACES.
Allergen: A material that, as a result of coming into contact with appropriate
tissues of an animal body, induces a state of allergy or hypersensitivity;
generally associated with idiosyncratic hypersensitivities.
Alveolar septum (pi. septa): A thin tissue partition between two adjacent
pulmonary alveoli, consisting of a close-meshed capillary network and
interstitium covered on both surfaces by alveolar epithelial cells.
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Alveolitis: (interstitial pneumonia): Inflammation of the lung distal to the
terminal non-respiratory bronchiole. Unless otherwise indicated, it is
assumed that the condition is diffuse. Arbitrarily, the term is not used
to refer to exudate in air spaces resulting from bacterial infection of
the lung.
Am'on: A negatively charged ion.
Artifact: 1. A structure in a,fixed cell or tissue formed by manipulation or
by the reagent. 2. An erroneous estimate of the atmospheric concentra-
tion of a gaseous or particulate species due to chemical or physical
modification during sampling, storage, or analysis. 3. A structure or
substance not normally present, but produced by some external agency or
action.
Asthma: A disease characterized by an increased responsiveness of the airways
to various stimuli and manifested by slowing of forced expiration which
changes in severity either spontaneously or as a result of therapy. The
term asthma may be modified by words or phrases indicating its etiology,
factors provoking attacks, or its duration.
Atelectasis: State of collapse of air spaces with elimination of the gas
phase.
Atmospheric aerosols: A suspension in the atmosphere of microscopic particles
of a liquid or a solid.
ATPS condition (ATPS): Ambient temperature and pressure, saturated with water
vapor. These are the conditions existing in a water spirometer.
Breathing pattern: A general term designating the characteristics of the
ventilatory activity, e.g., tidal volume, frequency of breathing, and
shape of the volume time curve.
British Smokeshade (BS) sampler: Device used to measure the reflectance of
particles collected on a filter and to predict mass concentrations.
Bronchiole: One of the finer subdivisions of the airways, less than 1 mm in
diameter, and having no cartilage in its wall.
Bronchiolitis: Inflammation of the bronchioles which may be acute or chronic.
If the etiology is known, it should be stated. If permanent occlusion of
the lumens is present, the term bronchiolitis obliterans may be used.
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Bronchitis: A non-neoplastic disorder of structure or function of the bronchi
resulting from infectious or noninfectious irritation. The term bronchi-
tis should be modified by appropriate words or phrases to indicate its
etiology, its chronicity, the presence of associated airways dysfunction,
or type of anatomic change. The term chronic bronchitis, when unquali-
fied, refers to a condition associated with prolonged exposure to nonspe-
cific bronchial irritants and accompanied by mucous hypersecretion and
certain structural alterations in the bronchi. Anatomic changes may
include hypertrophy of the mucous-secreting apparatus and epithelial
metaplasia, as well as more classic evidences of inflammation. In epidem-
iologic studies, the presence of cough or sputum production on most days
for at least three months of the year has sometimes been accepted as a
criterion for the diagnosis.
Bronchoconstriction: Constriction relative to or associated with the bronchi
or their ramifications in the lungs.
Bronchoconstrictor: An agent that causes a reduction in the caliber (diameter)
of airways.
Bronchodilator: An agent that causes an increase in the caliber (diameter) of
airways.
Bronchus: One of the subdivisions of the trachea serving to convey air to and
from the lungs. The trachea divides into right and left main bronchi
which in turn form lobar, segmental, and subsegmental bronchi.
Bronchospasm: Temporary narrowing of the bronchi due to violent, involuntary
contraction of the smooth muscle of the bronchi.
BTPS conditions (BTPS): Body temperature, barometric pressure, and saturated
with water vapor. These are the conditions existing in the gas phase of
the lungs. For man the normal temperature is taken as 37°C, the pressure
as the barometric pressure, and the partial pressure of water vapor as
47 torr.
Carbachol (C6H15 CIN202): The choline ester, carbamycholine chloride, used a
bronchoconstrictor.
Cascade impactors: A device for sampling an aerosol that consists of sets of
jets of progressively smaller size and collection plates designed so that
each plate collects particles of one size range.
Cation: A positively charged ion.
Chemoreceptor: Any sensory organ that responds to chemical stimuli.
Chemiluminescence: Emission of light as a result of a chemical reaction
without an apparent change in temperature. Used in determining
concentration of some pollutant gases.
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Chronic obstructive lung disease (COLD): This term refers to diseases of
uncertain etiology characterized by persistent slowing of airflow during
forced expiration. It is recommended that a more specific term, such as
chronic obstructive bronchitis or chronic obstructive emphysema, be used
whenever possible. Synonymous with chronic obstructive pulmonary disease
(COPD).
Chronic toxic effects: Characterized by a slow progressive course of toxicity
of indefinite duration.
Ciliary beat frequency: Rate of pulsation of the minute vibratile, hair!ike
processes attached to the cells lining some airways.
Closing capacity (CC): Closing volume plus residual volume, often expressed as
a ratio of TLC, i.e. (CC/TLC%).
Closing volume (CV): The volume exhaled after the expired gas concentration is
inflected from an alveolar plateau during a controlled breathing maneuver.
Since the value obtained is dependent on the specific test technique, the
method used must be designated in the text, and when necessary, specified
by a qualifying symbol. Closing volume is often expressed as a ratio of
the VC, i.e. (CV/VC%).
Cloud: A free aerodisperse system of any type having a definite form and
without regard to particle size.
Coarse particles: Airborne particles larger than 2 to 3 micrometers (urn) in
diameter.
Coefficient of haze (CoH): Measurement of the optical density of a sample of
suspended particulates collected by the AISI light transmittance methods.
Cohort: A group of individuals or vital statistics about them having a statis-
tical factor in common in a demographic study (as year of birth).
CoH: See Coefficient of haze.
Collateral resistance (Rcol1): Resistance to flow through indirect pathways.
See COLLATERAL VENTILATION and RESISTANCE.
Collateral ventilation: Ventilation of air spaces via indirect pathways, e.g.,
through pores in alveolar septa, or anastomosing respiratory bronchioles.
Compliance (C.,C .): A measure of distensibility. Pulmonary compliance is
given by thi slope of a static volume-pressure curve at a point, or the
linear approximation of a nearly straight portion of such a curve,
expressed in liters/cm H20 or ml/cm H20. Since the static volume-pressure
characteristics of lungs are nonlinear (static compliance decreases as
lung volume increases) and vary according to the previous volume history
(static compliance at a given volume increases immediately after full
inflation and decreases following deflation), careful specification of the
conditions of measurement are necessary. Absolute values also depend on
organ size. See also DYNAMIC COMPLIANCE.
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Condensation nuclei: Those particles and ions measured by means of an
instrument in which water vapor is made to condense on particles by
supersaturating the vapor; the term "aitken nuclei" is often used
synonymously.
Conductance (G): The reciprocal of RESISTANCE. See AIRWAY CONDUCTANCE.
Cyclone samplers: A centrifugal device for separating particles from an
aerosol. . •
Deposition:
Acidic—Removal of acidic pollutants from the atmosphere by dry and wet
deposition.
Dry—Removal of pollutants from the atmosphere through interactions with
various surfaces of plants, land, and water.
Respiratory tract—Removal of inhaled particles by the respiratory tract
which depends on breathing patterns, airway geometry, and the physi-
cal and chemical properties of the inhaled particles.
Wet—Removal of pollutants from the atmosphere by precipitation.
Dichotomous sampler: A device used to collect separately fine and coarse
particles from an aerosol.
Diffusing capacity of the lung (DL, DL02, DLC02, D,_CO): Amount of gas (02, CO,
C02) commonly expressed as ml gas (STPD) diffusing between alveolar gas
and pulmonary capillary blood per torr mean gas pressure difference per
min, i.e., ml 02/(min-torr). Synonymous with transfer factor and
diffusion factor.
Dust: Dispersion aerosols with solid particles formed by comminution or
disintegration, without regard to particle size.
Dynamic compliance (Cd ): The ratio of the tidal volume to the change in
intrapleural pressure between the points of zero flow at the extremes of
tidal volume in liters/cm H20 or ml/cm H20. Since at the points of zero
airflow at the extremes of tidal volume, volume acceleration is usually
other than zero, and since, particularly in abnormal states, flow may
still be taking place within lungs between regions which are exchanging
volume, dynamic compliance may differ from static compliance, the latter
pertaining to condition of zero volume acceleration and zero gas flow
throughout the lungs. In normal lungs at ordinary volumes and respiratory
frequencies, static and dynamic compliance are the same.
Elastance (E): The reciprocal of COMPLIANCE;-expressed in cm H20/liter or cm
H20/ml.
Emphysema: A condition of the lung characterized by abnormal, permanent
enlargement of airspaces distal to the terminal bronchiole, accompanied by
the destruction of their walls, and without obvious fibrosis.
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Epithelium: A primary animal tissue, distinguished by closely packed cells
with little intercellular substance; covers free surfaces and lines body
cavities and ducts, such as in the respiratory tract.
Expiratory flowrate: See Pulmonary measurements.
Expiratory reserve volume (ERV): The maximal volume of air exhaled from the
end- expiratory level.
FEV./FVC: A ratio of timed (t = 0.5, 1, 2, 3 s) forced expiratory volume
(FEV.) to forced vital capacity (FVC). The ratio is often expressed in
percent 100 x FEVt/FVC. It is an index of airway obstruction.
Fine particles: Airborne particles smaller than 2 to 3 micrometers in
diameter.
Flame photometric detection: A process by which a spray of metallic salts in
solution is vaporized in a very hot flame and subjected to quantitative
analysis by measuring the intensities of the spectrum lengths of the
metals present.
Flow volume curve: Graph of instantaneous forced expiratory flow recorded at
the mouth, against corresponding lung volume. When recorded over the full
vital capacity, the curve includes maximum expiratory flow rates at all
lung volumes in the VC range and is called a maximum expiratory flow-
volume curve (MEFV). A partial expiratory flow-volume curve (PEFV) is
one which describes maximum expiratory flow rate over a portion of the
vital capacity only.
Fluorescence analysis: A method of chemical analysis in which a sample,
exposed to radiation of one wavelength, absorbs this radiation and reemits
radiation of the same or longer wavelength in about 10 9 second. The
intensity of reemitted radiation is almost directly proportional to the
concentration of the fluorescing material. Also known as fluorometry.
Fogs: Suspension of liquid droplets formed by condensation of vapor or atom-
ization; the concentration of particles is sufficiently high to obscure
visibility.
Forced expiratory flow (FEFx): Related to some portion of the FVC curve.
Modifiers refer to the amount of the FVC already exhaled when the measure-
ment is made. For example:
FEF75c£ = instantaneous forced expiratory flow after 75% of the FVC
has been exhaled.
= "lean forced expiratory flow between 200 ml and 1200 ml
of the FVC (formerly called the maximum expiratory flow rate (MEFR).
= mean forced expiratory flow during the middle half of
the FVC [formerly called the maximum mid-expiratory flow rate
(MMFR)].
FEF = the maximal forced expiratory flow achieved during an FVC.
HI 3.X
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Forced expiratory volume (FEV): Denotes the volume of gas which is exhaled in
a given time interval during the execution of a forced vital capacity.
Conventionally, the times used are 0.5, 0.75, or 1 sec, symbolized FEV0.5,
FEVo-75> FEVj.Q. These values are often expressed as a percent of the
forced vital capacity, e.g. (FEV^o/VC) X 100.
Forced inspiratory vital capacity (FIVC): The maximal volume of air inspired
with a maximally forced effort from a position of maximal expiration.
Forced vital capacity (FVC): Vital capacity performed with a maximally forced
expiratory effort.
Functional residual capacity (FRC): The sum of RV and ERV (the volume of air
remaining in the lungs at the end-expiratory position). The method of
measurement should be indicated as with RV.
FVC: The volume of air that can be forcibly expelled from the lungs after the
deepest inspiration.
Gas exchange: Movement of oxygen from the alveoli into the pulmonary capillary
blood as carbon dioxide enters the alveoli from the blood. In broader
terms, the exchange of gases between alveoli and lung capillaries.
Gas exchange ratio (R): See RESPIRATORY QUOTIENT.
Gas trapping: Trapping of gas behind small airways that were opened during
inspiration but closed during forceful expiration. It is a volume differ-
ence between FVC and VC.
Gravimetric mass method: Measurement technique in which the amount of the
constituents is determined by weighing.
Gravimetry: Measurement of a weight or density.
High volume (hi-vol) sampler: A high flow-rate device used to collect parti-
cles from the atmosphere.
Histamine: . A depressor amine derived from the amino acid histidine and found
in all body tissues, with the highest concentration in the lung; a power-
ful stimulant of gastric secretion, a constrictor of bronchial smooth
muscle, and a vasodilator that causes a fall in blood pressure.
Hydroxyl radical: Chemical prefix indicative of the [OH] group.
Hygroscopic growth: Growth induced by moisture.
Inspiratory capacity (1C): The sum of IRV and TV.
Inspiratory reserve volume (IRV): The maximal volume of air inhaled from the
end-inspiratory level.
Inspiratory vital capacity (IVC): The maximum volume of air inhaled from the
point of maximum expiration.
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Intratracheal instillation:
trachea.
Process of placing material within or through the
Ion exchange chromatography: A chromatographic procedure in which the station-
ary phase consists of ion-exchange resins which may be acidic or basic.
Irritant potency: The relative strength of an agent that produces irritation.
Kilogram-meter/min (kg-m/min): The work performed each min to move a mass of
1 kg through a vertical distance of 1 m against the force of gravity.
Synonymous with kilopond-meter/min.
LC50: Concentration of a substance lethal to 50 percent of tested species.
Linear model: A model where all the interrelationships among the quantities
involved are expressed by linear equations which may be algebraic, differ-
ential, or integral.
Lung volume (V,): Actual volume of the lung, including the volume of the
conducting airways.
Maximal aerobic capacity (max V02): The rate of oxygen uptake by the body
during repetitive maximal respiratory effort. Synonymous with maximal
oxygen consumption.
Maximum breathing capacity (MBC): Maximal volume of air which can be breathed
per minute by a subject breathing as quickly and as deeply as possible.
This tiring lung function test is usually limited to 12-20 sec, but given
in liters (BTPS)/min. Synonymous with maximum voluntary ventilation
(MVV).
Maximum expiratory flow (Vmax x):
Forced expiratory flow, related to the total
lung capacity or the actual volume of the lung at which the measurement is
made. Modifiers refer to the amount of lung volume remaining when the
measurement is made. For example:
»•/
Vmax
= instantaneous forced expiratory flow when the
" of its TLC.
flow when the
w o n = instantaneous forced expiratory
Vmax 3.U ., volume is 3.0 liters
Maximum expiratory flow rate (MEFR): Synonymous with FEF20o"i20o-
Maximum mid-expiratory flow rate (MMFR or MMEF): Synonymous with FEF25~75%-
Maximum ventilation (max VP): The volume of air breathed in one minute during
repetitive maximal respiratory effort. Synonymous with maximum ventila-
tory minute volume.
Maximum voluntary ventilation (MVV): The volume of air breathed by a subject
during voluntary maximum hyperventilation lasting a specific period of
time. Synonymous with maximum breathing capacity (MBC). ,^
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Mechanical clearance: See Mucociliary action.
MEFR: See Pulmonary measurement.
Middle turbinate region: Area encompassed by the concha nasal is media ossea.
Minute ventilation (VV): Volume of air breathed in one minute. It is a
CruTTf*™, t1daf Vo1ume (V and breathing frequency (fD). See
VENTILATION. B
Minute volume (Ve): See Pulmonary measurements.
Minute volume: Synonymous with minute ventilation.
Mist: Suspension of liquid droplets formed by condensation of vapor or atom-
ization; the droplet diameters exceed 10 urn and in general the concentra-
tion of particles is not high enough to obscure visibility.
MMFR: See Pulmonary measurements. . .. ..>
mm: Micrometer.
Morbidity: 1. The quantity or state of being diseased; 2. The ratio of the
number of sick individuals to the total population of a community.
Morphology: Structure and form of an organism at any staqe of its life
history. '
I . i .••;••;•
Mortality rate: For a given period of time, the ratio of the number of deaths
occurring per 1000 population. Also known as death rate.
Mucociliary action: Ciliary action of the mucous membranes lining'the airway
that aids in cleansing and removing irritants and aids in moving particles
to the pharyngeal regions.
Mucociliary transport: The process by which mucus is transported, by ciliarv
action, from the lungs. *
Mucus: The clear, viscid secretion of mucous membranes, consisting of mucin,
epithelial cells, leukocytes, and various inorganic salts suspended in'
water.
Mutagenesis: An abrupt change in the genotype of an organism, not resulting
from recombinations; genetic material may undergo qualitative or quantita-
tive alteration, or rearrangement. ; •....,.
\Nasal Power: Energy expenditure during usual breathing (area under the nasal
flow-nasal driving pressure curve).
Nasopharyngeal: Relating to the nose or the nasal cavity and the pharynx
. s (throat). ' ., ; ••''••' • < "' ->• •••
Nasopharyngeal absorption:' The taking up of fluids, gases, or particles by and
within the nasopharynx.
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Nephelometry: 1. The study of aerosols using the techniques of light scatter-
ing. 2. Measurement of light scattering coefficient by certain optical
instruments.
Nitrogen oxides: Compounds of N and 0 in ambient air; i.e., nitric oxide (NO)
and others with a higher oxidation state of N, of which N02 is the most
important toxicologically.
Nitrogen washout (WN2, dN2): The curve obtained by plotting the fractional
concentration of N2 in expired alveolar gas vs. time, for a subject
switched from breathing ambient air to an inspired mixture of pure 02. A
progressive decrease of N2 concentration ensues which may be analyzed into
two or more exponential components. Normally, after 4 min of pure 02
breathing the fractional N2 concentration in expired alveolar gas is down
to less than 2%.
Optical particle morphology method: Techniques for identifying the character
and sources of collected particles.
Oronasal breathing: Breathing through the nose and mouth.
Oxidant: A chemical compound that has the ability to remove, accept, or share
electrons from another chemical species, thereby oxidizing it.
Oxidation (various types): A chemical reaction in which a compound or radical
loses electrons 1/m that is, in which the positive valence is increased.
Oxygen saturation (S02): The amount of oxygen combined with hemoglobin,
expressed as a percentage of the oxygen capacity of that hemoglobin. In
arterial blood, Sa02.
Oxygen uptake (V02): Amount of oxygen taken up by the body from the
environment, by the blood from the alveolar gas, or by an organ or tissue
from the blood. When this amount of oxygen is expressed per unit of time
one deals with an "oxygen uptake rate." "Oxygen consumption" refers more
specifically to the oxygen uptake rate by all tissues of the body and is
equal to the oxygen uptake rate of the organism only when the 02 stores
are constant.
Particle: Any object, solid or liquid, having definite physical boundaries in
all directions; in air pollution, practical interest concentrates on
particles less than 1 mm in diameter.
Particulates: Fine solid particles such as dust, smoke, fumes, or smog, found
in the air or in emissions.
Particulate matter (PM): Matter in the form of small airborne liquid or solid
particles.
Pathogen: Any virus, microorganism, or etiologic agent causing disease.
Peak expiratory flow (PEF): The highest forced expiratory flow measured with a
peak flow meter.
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Peroxyacetyl nitrate (PAN): Pollutant created by action of UV component of
sunlight on hydrocarbons and N0v in the air; an ingredient of
photochemical smog. x
Personnel dosimeter sampling: Determination of the degree of exposure on
individuals, using survey meters, and determination of the dose received
by means of dosimeters.
*•.
pH: A measure of the effective acidity or alkalinity of a solution. It is
expressed as the negative logarithm of the hydrogen-ion concentration.
Pure water has a hydrogen ion concentration equal to l(f7 moles per liter
at standard conditions (25°C). The negative logarithm of this quantity is
7. Thus, pure water has a pH value of 7 (neutral). The pH scale is
usually considered as extending for 0 to 14. A pH less than 7 denotes
acidity; more than 7, alkalinity.
Phagocytosis: A mechanism by which macrophages engulf and carry away
particles.
Pharyngeal regions: The chamber at the oral end of the vertebrate alimentary
canal, leading to the esophagus.
Physical damage functions: The mathematical expression linking exposure to
damage, expressed in terms appropriate to the interaction of the pollutant
and material.
Physiological dead space (VD): Calculated volume which accounts for the
difference between the 'pressures of C02 in expired and alveolar gas (or
arterial blood). Physiological dead space reflects the combination of
anatomical dead space and alveolar dead space, the volume of the latter
increasing with the importance of the nonuniformity of the
ventilation/perfusion ratio in the lung.
Plethysmograph: A rigid chamber placed around a living structure for the
purpose of measuring changes in the volume of the structure. In respira-
tory measurements, the entire body is ordinarily enclosed ("body plethys-
mograph ) and the plethysmograph is used to measure changes in volume of
gas in the system produced 1) by solution and volatilization (e.g., uptake
of foreign gases into the blood), 2) by changes in pressure or temperature
(e.g., gas compression in the lungs, expansion of gas upon passing into
the warm, moist lungs), or 3) by breathing through a tube to the outside
Three types of plethysmograph are used: a) pressure, b) volume, and c)
pressure-volume. In type a, the body chambers have fixed volumes and
volume changes are measured in terms of pressure change secondary to gas
compression (inside the chamber, outside the body). In type b the body
chambers serve essentially as conduits between the body surface and
devices (spirometers or integrating flowmeters) which measure gas dis-
placements. Type c combines a and b by appropriate summing of chamber
pressure and volume displacements.
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Pneumotachograph: A device for measuring instantaneous gas flow rates in
breathing by recording the pressure drop across a fixed flow resistance of
known pressure-flow characteristics, commonly connected to the airway by
means of a mouthpiece, face mask, or cannula. The flow resistance usually
consists either of parallel capillary tubes (Fleisch type) or of
fine-meshed screen (Silverman-Lilly type).
Potentiation: The combined action of two drugs, greater than the sum of the
effects of each used alone.
Primary particles (or primary aerosols): Dispersion aerosols formed from
particles that are emitted directly into the air that do not change form
in the atmosphere.
Pulmonary alveolar proteinosis: A chronic or recurrent disease characterized
by the filling of alveoli with an insoluble exudate, usually poor in
cells, rich in lipids and proteins, and accompanied by minimal histologic
alteration of the alveolar walls.
Pulmonary edema: An accumulation of excessive amounts of fluid in the lung
extravascular tissue and air spaces.
Pulmonary emphysema: An abnormal, permanent enlargement of the air spaces
distal to the terminal nonrespiratory bronchiole, accompanied by destruc-
tive changes of the alveolar walls and without obvious fibrosis. The term
emphysema may be modified by words or phrases to indicate its etiology,
its anatomic subtype, or any associated airways dysfunction.
Pulmonary Measurements: Measurements of the volume of air moved during a
normal or forced inspiration or expiration, which is a reflection of
pulmonary compliance. Atmospheric: pollutants can seriously impair the
volumes of air/gas exchanged during the ventilatory function. Specific
lung volume measurements include:
Tidal volume (TV)—The volume of air moved during normal inspiration.
Functional residual capacity (FRC)—The amount of air left in the lung at
the end of a normal expiration.
Expiratory reserve volume (ERV)—Air removed from the lung by forced
expiration.
Residual volume (RV)—Air that cannot be expelled from the lung.
Vital capacity—The sum of ERV, TV, and inspirational reserve volume
(IRV).
Rales: An abnormal sound accompanying the normal sounds of respiration within
the air passages and heard on auscultation of the chest.
Residual volume (RV): That volume of air remaining in the lungs after maximal
exhalation. The method of measurement should be indicated in the text or,
when necessary, by appropriate qualifying symbols.
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Resistance flow (R): The ratio of the flow-resistive components of pressure to
simultaneous flow, in cm H20/liter per sec. Flow-resistive components of
pressure are obtained by subtracting any elastic or inertia! components,
proportional respectively to volume and volume acceleration. Most flow
resistances in the respiratory system are nonlinear, varying with the
magnitude and direction of flow, with lung volume and lung volume history,
and possibly with volume acceleration. Accordingly, careful specification
of the conditions of measurement is necessary; see AIRWAY RESISTANCE,
TISSUE RESISTANCE, TOTAL PULMONARY RESISTANCE, COLLATERAL RESISTANCE.
Respiratory cycle: A respiratory cycle is constituted by the inspiration
followed by the expiration of a given volume of gas, called tidal volume.
The duration of the respiratory cycle is the respiratory or ventilatory
period, whose reciprocal is the ventilatory frequency.
Respiratory exchange ratio: See RESPIRATORY QUOTIENT.
Respiratory frequency (fp): The number of breathing cycles per unit of time.
Synonymous with breathing frequency (fb).
D
Respiratory quotient (RQ, R): Quotient of the volume of C02 produced divided
by the volume of 02 consumed by an organism, an organ, or a tissue during
a given period of time. Respiratory quotients are measured by comparing
the_composition of an incoming and an outgoing medium, e.g., inspired and
expired gas, inspired gas and alveolar gas, or arterial and venous blood.
Sometimes the phrase "respiratory exchange ratio" is used to designate the
ratio .of C02 output to the 02 uptake by the lungs, "respiratory quotient"
being restricted to the actual metabolic C02 output and 02 uptake by the
tissues. With this definition, respiratory quotient and respiratory
exchange ratio are identical in the steady state, a condition which
implies constancy of the 02 and C02 stores.
RH (Relative Humidity): The dimensionless ratio of the actual vapor pressure
of water in the air to the saturation vapor pressure.
Secondary particles (or secondary aerosols): Dispersion aerosols that form in
the atmosphere as a result of chemical reactions, often involving gases.
Smog: A combination of "smoke" and "fog". Originally, this term referred to
episodes in Great Britain that were attributed to coal burning during
persistent foggy conditions. In the United States, "smog" has become
associated with urban aerosol formation during periods of high oxidant
concentrations.
Smoke: Dispersion aerosol containing both liquid and solid particles formed by
condensation from supersaturated vapors.
Specific airway conductance (SGaw): Airway conductance divided by the lung
volume at which it was measured, i.e., normalized airway conductance.
SGaw = Gaw/TGV.
v . " .1 • I'., j • ^
Specific airway resistance (SRaw): Airway resistance multiplied by the volume
at which it was measured. SRaw = Raw x TGV.
A-13
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Spirograph: Mechanical device, including bellows or other scaled, moving part,
which collects and stores gases and provides a graphical record of volume
changes. See BREATHING PATTERN, RESPIRATORY CYCLE.
Spirometer: An apparatus similar to a spirograph but without recording
facility.
Spirometry: The measurement, by a form of gas meter (spirometer), of volumes
of air that can be moved in and out of the lungs.
Static lung compliance (C. .): Lung compliance measured at zero flow
(breathholding) over linear portion of the volume-pressure curve above
FRC. See COMPLIANCE.
Static transpulmonary pressure (P.t): Transpulmonary pressure measured at a
specified lung volume; e.g., PstTLC is static recoil pressure measured at
TLC (maximum recoil pressure).
STPD conditions (STPD): Standard temperature and pressure, dry. These are the
conditions of a volume of gas at 0°C, at 760 torr, without water vapor. A
STPD volume of a given gas contains a known number of moles of that gas.
2-
Sulfate: 1. A compound containing the [S04 ] group, as in sodium sulfate
(Na2S04); 2. A salt of sulfuric acid.
Sulfur dioxide (S02): Colorless gas with pungent odor, released primarily from
burning of fossil fuels, such as coal, containing sulfur.
Sulfur oxides: Oxides of sulfur, such as sulfur dioxide (S02) and sulfur
trioxide (S03).
Surfactant, pulmonary: Protein-phospholipid (mainly dipalmitoyl lecithin)
complex which lines alveoli (and possibly small airways) and accounts for
the low surface tension which makes air space (and airway) patency possi-
ble at low transpulmonary pressures.
Synergism: The joint action of agents so that their combined effect is greater
than the algebraic sum of their individual effects.
Systemic: Pertaining to or affecting the body as a whole.
Thoracic: Of or pertaining to the chest.
Thoracic gas volume (TGV): Volume of communicating and trapped gas in the
lungs measured by body plethysmography at specific lung volumes. In
normal subjects, TGV determined at end expiratory level corresponds to
FRC.
Thorax: The chest.
Tidal volume (TV): That volume of air inhaled or exhaled with each breath
during quiet breathing, used only to indicate a subdivision of lung
volume. When tidal volume is used in gas exchange formulations, the
symbol VT should be used.
A-14
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Tissue resistance (Rt«):
tissues.
Fractional resistance of the pulmonary and thoracic
Total lung capacity (TLC): The sum of all volume compartments or the volume of
air in the lungs after maximal inspiration. The method of measurement
should be indicated, as with RV.
Total pulmonary resistance (R.): Resistance measured by relating flow-
dependent transpulmonary pressure to airflow at the mouth. Represents
the total (frictional) resistance of the lung tissue (R..) and the airways
(Raw). RL = Raw + Rtr *
Trachea: Commonly known as the windpipe; a cartilaginous air tube extending
from the larynx (voice box) into the thorax (chest) where it divides into
left and right branches.
Tracheobronchial region: The area encompassed by the trachea and bronchi.
Transpulmonary pressure (P.): Pressure difference between airway opening
(mouth, nares, or cannbla opening) and the visceral pleura! surface, in cm
H20. Transpulmonary in the sense used includes extrapulmonary structures,
e.g., trachea and extrathoracic airways. This usage has come about for
want of an anatomic term which includes all of the airways and the lungs
together.
Turbidimetry: A scattered-light procedure for the determination of the weight
concentration of particles in cloudy, dull, or muddy solutions; uses a
device that measures the loss in intensity of a light beam as it passes
through the solution.
Ventilation: Physiological process by which gas is renewed in the lungs. The
word ventilation sometimes designates ventilatory flow rate (or ventila-
tory minute volume) which is the product of the tidal volume by the
ventilatory frequency. Conditions are usually indicated as modifiers;
i.e.,
Vp = Expired volume per minute (BTPS),
. and
Vj = Inspired volume per minute (BTPS).
Ventilation is often referred to as "total ventilation" to distinguish it
from "alveolar ventilation" (see VENTILATION, ALVEOLAR).
Ventilation, alveolar (V.): Physiological process by which alveolar gas is
completely removed arid replaced with fresh gas. Alveolar ventilation is
less than total ventilation because when a tidal volume of gas leaves the
alveolar spaces, the last part does not get expelled from the body but
occupies the dead space, to be reinspired with the next inspiration. Thus
the volume of alveolar gas actually expelled completely is equal to the
tidal volume minus the volume of the dead space. This truly complete
expiration volume times the ventilatory frequency constitutes the alveolar
ventilation.
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Ventilation, dead-space (V,,): Ventilation per minute of the physiologic dead
space (wasted ventilation), BTPS, defined by the following equation:
VD = VE(PaC02 - PEC02)/(PaC02 - PjC02)
Ventilation/perfusion ratio (V./Q): Ratio of the alveolar ventilation to the
blood perfusion volume fnow through the pulmonary parenchyma. This ratio
is a fundamental determinant of the 02 and C02 pressure of the alveolar
gas and of the end-capillary blood. Throughout the lungs the local
ventilation/perfusion ratios vary, and consequently the local alveolar gas
and end-capillary blood compositions also vary.
Vital capacity (VC): The maximum volume of air exhaled from the point of
maximum inspiration.
X-ray fluorescence: Emission by a substance of its characteristic X-ray line
spectrum upon exposure to X-rays. Also known as X-ray emission.
A-16
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APPENDIX B:
REPORT OF THE CLEAN AIR SCIENTIFIC
ADVISORY COMMITTEE (CASAC):
ACID AEROSOL HEALTH EFFECTS
WITH TRANSMITTAL LETTER FROM
ROGER 0. MCCLELLAN, CLEAN AIR SCIENTIFIC
ADVISORY COMMITTEE CHAIRMAN, TO
LEE M. THOMAS, EPA ADMINISTRATOR
B-4
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United Statas
tnirirenmantal Prolaotlon
Aganoy
Olllo« o( 1h • Admlnittrator
Seianca Adhitory Soard
Walhinglon DC 204(0
EPA-SAO/CASAC-M-001
Daeambar Uti
(as)EPA
^^^
Report Of The Clean
Air Scientific Advisory
Committee (CASAC)
Acid Aerosol Health
Effects
B-2
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CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
ADVICE CONCERNING
ACID AEROSOL HEALTH EFFECTS
FINAL REPORT
DECEMBER 15, 1988
U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOAUD
WASHINGTON, DC
B-3
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ABSTRACT
Under Section 109 of the Clean Air Act, the U.S.
Environmental Protection Agency (EPA) is required to periodically
review national ambient air quality standards (NAAQS) and the
criteria on which they are based. The Act also requires the
Clean Air Scientific Advisory Committee (CASAC) to provide
scientific advice on any additional knowledge that is required to
evaluate existing, or setting new or revised NAAQS. To evaluate
the health effects of the class of air pollutants known as acid
aerosols, the Committee requested that EPA prepare an "Acid
Aerosol Issue Paper". This Issue Paper was reviewed by the Acid
Aerosol Subcommittee of CASAC in June 1988. In October 1988, the
Issue Paper, and the Subcommittee's two reports (Acid Aerosol
Research Needs, and Report on the Acid Aerosol Issue Paper) were
reviewed by the CASAC. This report presents the conclusions and
recommendations of the CASAC on the potential health effects of
acid aerosols. Included as an enclosure, is the Acid Aerosol
Subcommittee report to the CASAC (Science Advisory Board Report
No. EPA-SAB/CASAC-89-001).
K«v Words; acid aerosols, acid particles, NAAQS
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U.S. Environmental Protection Agency
NOTICE
This report has been written as part of the activities of
the Science Advisory Board, a public advisory group providing
extramural scientific information and advice to the Administrator
and other officials of the Environmental Protection Agency. The
Board is. structured to provide a balanced expert assessment of
scientific matters related to problems facing the Agency. This
report has not been reviewed for approval by the Agency; and,
hence, the contents of this report do not necessarily represent
the views and policies of the Environmental Protection Agency or
other agencies in the Federal Government. Mention of trade names
or commercial products do not constitute a recommendation for
use.
B-5
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October 1987
U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
Chairman
Dr. Roger O. McClellan, President, Chemical Industry Institute
of Toxicology, P.O. Box 12137, Research Triangle Park,
North Carolina 27709
Members
Dr. Robert Frank, Professor of Environmental Health Sciences,
The Johns Hopkins School of Hygiene and Public Health,
615 N. Wolfe Street, Baltimore, Maryland 21205
Dr. Timothy Larson, Environmental Engineering and Science Program,
Department of Civil Engineering FX-10, University of
Washington, Seattle, Washington 98195
Dr. Gilbert S. Omenn, Professor and Dean, School of Public Health
and Community Medicine, SC-30, University of Washington,
Seattle, Washington 98195
Dr. Marc B. Schenker, Director, Occupational and Environmental
Health Unit, University of California, Davis,
California 96516
Dr. Mark J. Utell, Professor of Medicine and Toxicology,
Co-Director, Pulmonary Disease Unit, University of Rochester
School of Medicine, Rochester, New York 14642
Dr. Jerome J. Wesolowski, Chief, Air and Industrial Hygiene
Laboratory, California Department of Health, 2151 Berkeley
Way, Berkeley, California 94704
Dr. George T. Wolff, Senior Staff Research Scientist, General
Motors Research Labs, Environmental Science Department,
Warren, Michigan 48090
Executive Secretary
Mr. A. Robert Flaak, Environmental Scientist, Science Advisory
Board (A-101F), U.S. Environmental Protection Agency,
401 M Street, SW, Washington, D.C. 20460
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UNITED STATES Ev: . -:CN'<1E\ - A_ PROTECTION-AGENCY
W ASr-i NC ~Cf. t 7 20460
December 15, 1988
The Honorable Lee M. Thomas
Administrator
U.S. Environmental Protection
Agency
401 M Street, SW
Washington, D.C. 20460
RE; CASAC Advice on Acid Aerosols
Dear Mr. Thomas:
I am pleased to transmit via this letter the advice of the
Clean Air Scientific Advisory Committee (CASAC) concerning the
potential health effects of acid aerosols. The current activity
is traceable to concerns of CASAC that developed sometime ago
during the Committee's consideration of the Air Quality Criteria
Document on Particulates and Sulfur Oxides. To facilitate
consideration of the potential health effects of acidic aerosols
by the Agency, the CASAC recommended that the EPA staff prepare an
"Acid Aerosols Issue Paper". A CASAC Subcommittee on Acid Aerosols
was created to review the Issue Paper and prepare a report on acid
aerosol research needs. Enclosed are copies of the Subcommittee's
report to CASAC on the Issue Paper, and its report on acid aerosol
research needs.
In addition to consideration by the Subcommittee, the full
CASAC at a meeting on October 6, 1988 reviewed the Issue Paper, the
Subcommittee's research needs report, and deliberated on the advice
to be provided to you.
In the opinion of the CASAC, the issue of the potential health
effects of acid aerosols is a matter of substantial concern that
clearly warrants additional attention by the Agency. This is
particularly true for the particle phase of the aerosol. Although
the Committee also recognized that the aerosol vapor phase may also
be implicated in adverse health effects, the health and monitoring
data available at this time ate insufficient to warrant more than
recommendations for further research.
B-7
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Letter to Mr. Thomas - Pace 2
Information from animal toxicological experiments and
controlled exposure of human subjects is developing on the health
effects of acid particles in a range of concentrations approaching
that observed in the ambient environment. Preliminary evidence
from epidemiological investigations also implicates acid particles
as a factor contributing to human health effects. Additional
research of this type is underway and should receive continued
support since it is urgently needed to clarify the effects of acid
particles at ambient exposure concentrations.
Limited data are available on the concentrations and
characteristics of acid particles in various parts of the United
States. These data have largely been gathered using research
procedures rather than standardized monitoring methods and thus it
is not possible at this time to adequately characterize the
exposure of the U.S. population to acid particles. To remedy this
deficiency, the CASAC urges the Agency to develop and deploy for
use a standardized method for monitoring air concentrations of
acidic particles. The Committee recognized that the most useful
method would be one which speciated all acids present. Since this
is impractical for monitoring purposes at this time, the Committee
believed that monitoring for total particle acidity would be a
reasonable compromise. A final decision on the measurement method
should await the method workshop recommended by the CASAC in its
report on Acid Aerosol Research Needs.
The CASAC strongly recommends that the Agency initiate in an
expeditious manner the preparation of a detailed substantive
analysis of the available and emerging scientific information on
acid particles, and at the appropriate time prepare an associated
Staff Position Paper. This detailed substantive analysis, with the
rigor used in preparation of a Criteria Document, should provide
a factual basis for determining the degree which acid particles
concentrations in ambient air will endanger public health. The
Staff Position Paper should, among the various topics covered,
address the issue of whether the potential health effects of acid
particles warrant additional action to protect public health,
either through use of one of the existing standards, such as the
PM,0 standard for airborne particulates or by developing a separate,
unique standard for acid particles. The process of preparing and
reviewing these documents widl introduce a degree of rigor that
should help assure that the. Administrator receives the best
possible a'dvice.
B-8
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Letter to Mr. Thomas - Page 3
The CASAC specifically recommends proceeding on multiple
fronts: (a) support of additional research on health effects, (b)
development of a standardized measurement procedure, (c) collection
of monitoring data across the United States, and (d) initiation of
the preparation of the analytical documents described above. It
is the Committee's opinion that this multifaceted approach with
activities proceeding in parallel when possible, assures that this
important public health issue will be dealt with in a timely
manner. The Committee was strongly opposed to an alternative
approach of only conducting additional research in the absence of
action in the other areas.
The CASAC would appreciate receiving a response concerning
the Agency's plans for dealing with the acid particle issue.
Please do not hesitate to contact me if the CASAC can be of further
assistance on this matter.
:oger O. McClellan, D.V.M.
Chairman
Enclosure
cc: Donald Barnes
Erich Bretthauer
Don Clay
Ray Loehr
B-9
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ENCLOSURE
CAS AC Acid Aerosol Subcommittee
Report to the
Clean Air Scientific Advisory Committee
(Science Advisory Board Report No.. EPA-SAB/CASAC-89-001)
BIO
-------
EPA-SAB/CASAC-89-001
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D.C. 20460
October 6, 1988
OFFICE OF
THE ADMINISTRATOR
Dr. Roger McClellan, Chairman
Clean Air Scientific Advisory Committee
Science Advisory Board (A-101F)
U.S. Environmental Protection Agency
Washington, DC 20460
Dear Dr. McClellan:
This letter transmits the conclusions of the CASAC Acid
Aerosol Subcommittee concerning listing acid particles as a
criteria pollutant. The Subcommittee met on June 14-15, 1988 in
Washington, DC to review the draft "Acid Aerosols Issue Paper"
(EPA/600/8-88/005A) prepared by EPA's Office of Research and
Development.
The Subcommittee concensus, although not unanimous, was that
CASAC recommend to the Administrator that he consider listing
acid particles under Section 108 of the Clean Air Act. In
the Subcommittee's view, the cumulative evidence provided by the
available animal, controlled human exposure, and epidemiologic
studies clearly suggests possible health effects associated
with exposure to acid particles. The Subcommittee recognizes
that the available data base is not complete but is concerned
by the potential health risks resulting from exposures under
typical ambient conditions. The ••Subcommittee conculded that
the weight of the evidence from the disciplines of animal
toxicology, controlled clinical studies, and epidemiology is
sufficient at this time to recommend that the Administrator
consider listing of acid particles as a criteria pollutant.
In summary, it should be noted that the majority vote was
cast on th« basis of the weight of the evidence from the three
health related disciplines rather than on any single study
A more detailed discussion of the Subcommittee position is
included in the attached report.
Sincerely,
Mark J. Utell, MD
Chairman
Acid Aerosol Subcommittee
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ABSTRACT
Under Section 109 of the Clean Air Act, the U.S.
Environmental Protection Agency (EPA) is required to periodically
review national ambient air quality standards (NAAQS) and the
criteria on which they are based. The Act also requires the
Clean Air Scientific Advisory Committee (CASAC) to provide
scientific advice on any additional knowledge that is required to
evaluate existing, or setting new or revised NAAQS. To evaluate
the health effects of the class of air pollutants known as acid
aerosols, the Committee requested that EPA prepare an "Acid
Aerosol Issue Paper". This Issue Paper was reviewed by the Acid
Aerosol Subcommittee of CASAC in June 1988. This report presents
the conclusions and recommendations of that Subcommittee as
transmitted to the CASAC.
Key Wordst acid aerosols, acid particles, NAAQS
B-12
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TABLE OF CONTENTS
1.0
2.0
3.0
4.0
5.0
6.0
BACKGROUND ....
OPTIONS FACING THE SUBCOMMITTEE
1
1
MAJOR RESEARCH FINDINGS THAT SUPPORT
THE SUBCOMMITTEE RECOMMENDATIONS 2
REVIEW OF THE ISSUE -PAPER 3
SUBCOMMITTEE RECOMMENDATIONS TO CASAC . . 3
5.1 Recommendation to Defer Decision . . 4
5.2 Recommendation Not to List 4
5.3 Majority Conclusions - Recommendation
to List 5
LITERATURE CITED . . . . . . g
APPENDICES
A - Roster of the CASAC Acid Aerosol
Subcommittee
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U.S. Environmental Protection Agency
Clean Air Scientific Advisory Committee
Acid Aerosol Subcommittee
Recommendations on Listing Acid
Particles as a Criteria Pollutant
1»0 Background
Under section 109(d) of the Clean Air Act the EPA must
periodically review the national ambient air quality standards
(NAAQS) and the air quality criteria on which they are based, and
must revise such criteria and standards as appropriate. In the
process of reviewing new scientific studies concerning health
effects of particulate matter and sulfur oxides in 1986, it
became apparent that researchers had identified acid aerosols as
a constituent of the airborne mix of these pollutants that may be
associated with observed health effects. As a result, the Clean
Air Scientific Advisory Committee (CASAC) recommended that the
Agency prepare ah Acid Aerosols Issue Paper to evaluate the
emerging literature concerning health effects directly associated
with acid aerosols.
The Agency completed this draft Issue Paper in early 1988
and presented it to the CASAC Acid Aerosol Subcommittee on June
14-15, 1988. The Subcommittee faced three primary tasks.
First, whether available scientific information provided
sufficient and compelling evidence for a listing of acid .
particles as a prelude to development of a separate criteria
pollutant, second, to assess the adequacy of the Issue Paper,
and third, to identify and prioritize research needed to
respond to the critical issues identified in the draft Issue
Paper as well as any additional issues identified by the
Subcommittee itself. The first and second issues are addressed
in this report, the third is discussed in a separate research
recommendations report (EPA-SAB/CASAC-89-002).
2.0 Options facing the Subcommittee
In addressing the listing issue, the Subcommittee considered
the three options presented by EPA in the draft Issue Paper:
• - , . . !
1) Recommend that the Administrator consider listing
acid aerosol* under Section 108 of the Act. This implies a
judgment that the available health effects information is
compelling enough to require additional protection beyond the
current NAAQS. Within 12 months of a listing decision, EPA-must
issue air quality criteria and? propose standards.
2) Recommend that the Administrator not consider
listing acid aerosols under Section 108 of the Act. The
available health effects information as well as any new research
would be considered during the' next review of the particulate
matter standards.
B-14
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3) Recommend that the Administrator defer judgment
regarding action to list acid aerosols pending further research
on the critical needs identified in Chapter 8 (Research Needs)
of the draft Acid Aerosols Issue Paper.
In its discussion of research issues, the Subcommittee
considered research needs identified by the Agency in the Issue
Paper, research needs identified by the members of the
Subcommittee, and presentations from the interested public at
the June 14-15, 1988 meeting.
3.0 Ma-I or Research Findings that Support the Subcommittee
Recommendations
The majority vote was based on the weight of evidence from
research involving the three disciplines of animal toxicology,
controlled clinical exposures, and epidemiologic studies. The
key findings from recent toxicology research include: in chronic
daily exposures of rabbits (250 jag/m3 for 1-hr/day, 5 days/week
for one year) persistent alterations of mucociliary and
alveolar particle clearance, airway reactivity, airway
secretory cell density and characteristics, and airway
caliber changes were produced (Gearhart and Schlesinger, 1988).
Such changes were similar to those produced by chronic exposure
to cigarette smoke, suggesting that chronic bronchitis could
result from more prolonged exposures. Furthermore, in single
3-hour and 5 days of 3-hour daily exposures to ultrafine ,acid
coated zinc oxide particles with sulfuric acid concentrations
in the range of 20-3lQ pg/m3, guinea pigs developed
persistent changes in vital capacity, airway compliance,
lung permeability, and carbon-monoxide diffusing capacity
(Amdur and Chen, 1988). Similar results were obtained with
200 pg/mj of ultrafine droplets of pure sulfuric acid. These
findings suggest that primary and secondary sulfuric acid
occurring as coatings on ultrafine fly ash particles may
be considerably more toxic than secondary acidic aerosol which
is found in the atmosphere in solution droplets.
Recent data from controlled clinical studies lends
additional support for a relationship between exposure to near
ambient levels of acid aerosols and adverse respiratory effects.
In 1983, Koenig «t al., (1983) identified allergic adolescent
asthmatics as a subgroup responsive to inhalation of 100 pg/m3
sulfuric acid aerosols (30 minutes at rest followed by 10 minutes
of exercise). These researchers have extended further their
observation in allergic adolescent asthmatics linking exposure to
near ambient levels of sulfuric acid at 68 jig/m3 with significant
alterations in lung function (Koenig et al., 1988). The FEV,
decreased 6% after inhalati'on of sulfuric acid using the
previously tdescribed exposure protocol va 1% decrease after
breathing air. Furthermore, the most recent findings from Bauer
et al. (1988) support Koenig's findings in that adult allergic
asthmatics showed greater decrements in FEV, breathing 75 ug/m3
sulfuric acid vs. NaCl (control) for 2 hours in an environmental
chamber. Based on our understanding of the current
B-15
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data base, extrapolation to longer exposures coupled with
more rigorous exercise could serve to intensify the response.
Data linking acid aerosols with respiratory health
effects emerges from the ongoing field studies. Speizer
(1988) showed that bronchitis in 10-12 year old children in
four U.S. cities varied from about 3-11% from standardized
questionnaire responses in direct relation to annual average
concentration of aerosol H , with the highest prevalence in the
community with the highest annual average H4" concentration
which was 1.8 ug/m3 (expressed as sulfuric acid
equivalents). Similar associations were seen for other
respiratory symptom responses in the same population. While the
prevalence data were for the 1981 school year and the
concentration data were for 1985-1988, it has been
established in other studies from the six cities group that the
bronchitis prevalence in these cities were in similar
proportion in this population in other years, and that there
was little variation in annual average pollution levels during
these years. There were occasional exceedences of the current
NAAQS for FM and SO, in some of these communities during some of
the years covered by these studies, nevertheless, the
Subcommittee is concerned that the current NAAQS may not
provide adequate protection against such health effects.
4.0 Review of Issue Paper
The draft Issue Paper was generally considered to be well
prepared and comprehensive. Most members of the Subcommittee
provided detailed written comments concerning the draft to the
Agency during and following the June 14-15, 1988 meeting.
Extensive discussion occurred during the meeting which pointed
out the need to address certain issues further. An example of
such an issue is to define the pollutant indicator to regulate,
its form, and measurement methodology.
5.0 Subcommittee Recommendations to CASAC
Following a careful review of the Issue Paper and extensive
deliberations, members of the Subcommittee voted and reached the
nearly unanimous conclusion1 that the Clean Air Scientific
Advisory Committ«« should recommend that the Administrator
consider listing acid particles as a criteria pollutant.
However, one Subcommittee member was in favor of recommending
that the Administrator not consider listing acid particles, and
one member was in favor of recommending that the Administrator
defer such a decision until further research van completed.
The minority positions are presented first.
The Subcommittee vote was: 9 in favor of recommending that the
Administrator consider listing, 1 in favor of recommending
that the Administrator not consider listing, and 1 in favor
of recommending that ,the Administrator defer judgment
pending further .research.
D1C
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5-1 Recommendation -to Defer Decision (Dr. Robert Phalen)
1) -Although there is scientific evidence that airborne
acidity at or near levels found in the environment is capable of
harming respiratory tract tissues, I recommend that the decision
to list acid aerosols as a NAAQS be deferred pending further
research directed at resolving several basic issues. First, it
is not at all clear just what the relevant air contaminant is.
Airborne acidity can be in vapor forms and in particulate forms.
In some cases, the acid vapor exceeds the particles in total
mass. The full combination - that is the total acid present in
all forms - is the logical agent to consider for listing because
that is what is inhaled. This is also valid scientifically as
many of us believe that an aerosol consists of a two-phase system
of particles and a surrounding gas. However, the Subcommittee
did not agree to include vapor phase acidity. Further research
will very likely show that "total available hydrogen ion per unit
volume of ambient air" is the entity that relates to adverse
biological effects. Until this research is done our
recommendation to list will possibly ignore a major fraction of
the potentially hazardous agent and thus may under-protect
exposed populations.
2) Next, the presently available human clinical
exposure studies are for short periods - usually less than two
hours. Because populations will be exposed for very prolonged
periods additional studies are desperately needed. Longer
exposures may show that effects increase upon longer exposure or
alternatively that effects disappear upon longer exposure. Such
studies are critical to defining whether peak levels of acidity
or some integrated measure of acid exposure should be listed.
Without this clarification substantial over-protection or under-
protect ion could result.
^ . , 3) Finally, we do not presently have enough animal
toxicology data to identify the most sensitive sites in the body
with respect to acid injury. One must have such information in
order to project what human sub-populations are at greatest risk
and what the expected risks are.
4) Certainly the acid aerosol issue should not be
dropped. The available evidence indicates the real potential for
airborne acidity contributing to adverse effects in human
populations. However, until the above basic issues are better
understood it is difficult to envision the establishing of a
proper NAAQS. ,
5.2 Recommendation Not to List fDr. Georae Wolffl ,
1) Health effects ' due to acid aerosols have been
demonstrated in controlled exposures but only at concentrations
which are much greater than an order of magnitude higher than
typical ambient levels. Even the highest concentration ever
reported in the ambient air is significantly lower than the
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lowest documented concentration ever associated with a
physiological response.
2) The assumption that the threshold dose for an
adverse health effect is 100 jag/m3-hr (i.e., 100 ;ug/m3 x 1 hour =
10 /ug/m3 x 10 hours) is not supported by any of the data. In
fact, it is contrary to conventional wisdom because the body
produces ammonia which will neutralize a certain amount of the
acidity.
3) I question the accuracy of the ambient data,
particularly the extreme values, since there is no standard
procedure for measuring acid aerossols and the techniques used
have not been subjected to rigorous quality assurance protocols.
5.3 Majority Conclusions - Recommendation to List2
Based on its assessment of the technical and scientific
information presented in the Issue Paper, the Subcommittee
reached a nearly unanimous conclusion that the Clean Air
Scientific Advisory Committee should recommend that the
Administrator consider listing acid particles as a
criteria pollutant. In the Subcommittee's view, the cumulative
evidence provided by the available animal, controlled human
exposure, and epidemiologic studies clearly suggests possible
health effects associated with exposure to acid particles.
The Subcommittee recognizes that the available data base is not
complete but is concerned by the potential health risks
resulting from exposures under typical ambient conditions.
The Subcommittee concluded that the weight of the evidence
from the disciplines of animal toxicology, controlled
clinical studies, and epidemiology is sufficient at this time
to recommend that the Administrator consider listing of acid
particles as a criteria pollutant.
In arriving at its recommendation, the Subcommittee took
into account that research currently underway should begin to
provide needed supplemental information in the next several
years. To further augment these ongoing efforts, the
Subcommittee has also identified key research needs that the
Agency should begin to address immediately through a balanced and
adequately funded research program. These are discussed in the
separate report on acid aerosol research recommendations.
These nine members were: Dr. Mary Amdur, Dr. Doug Dockery, Dr.
Robert Frank, Dr. Timothy Larson, Dr. Morton Lippmann, Dr.
Gilbert Omenn, Dr. Marc Schenker, Dr. Jerome Wesolowski, and
Dr. Mark Utell..
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6.0 Literature Cited
Amdur, M.O.-and Chen, L.C. (1988) Furnace generated acid
aerosols: speciation and pulmonary effects. |n-
International symposium on the health effects of acid
aerosols: addressing obstacles in an emerging data base-
October 1987; Research Triangle Park, NC. EHP Environ
Health Perspect.: In press.
Bauer et al., (198?) Am. Rev. Respir. Dis. 137:167.
Gearhart, j M and Schlesinger, R.B. (1988) Response of the
tracheobronchial mucociliary clearance system to repeated
irritant exposure: effect of sulfuric acid mist on
structure and function. Exp. Lung Res.: In press.
Koenig, J.Q. Pierson, W.E., and Horike, M. (1983) The effects
of inhaled sulfuric acid on pulmonary function in adolescent
asthmatics. Am. Rev. Respir. Dis. 128:221-225.
Koenig, J.Q., Covert, D.S., and Pierson, W.E. (1988) The effects
of inhalation of acid compounds on pulmonary function in
allergic adolescent subjects. EHP Environ. Health
Perspect.: In press.
' *
Spiezer, F.E. (1988) Studies of acid aerosols in six cities and
in a new multicity investigation: design issues. In-
International symposium on the health effects of acid
aerosols? addressing, obstacles in an emerging data base.
SCt??vr«1987; Research Triangle Park, NC. EHP Environ.
Health Perspect.: In press.
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APPENDIX A
Roster of the CASAC Acid Aerosol Subcommittee
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Chairman
February 1523
U.S. Environmental Protection Agency
Science Advisory Board
Clean Air Scientific Advisory Committee
Acid Aerosol Subcommi11ee
Members
Dr. Mary Amdur Senior Research Scientist, Energy Laboratory, MIT,
Room 16-339, Cambridge, MA 02139 /•«•*»
Dr. Doug Dockery, Harvard University, School of Public Health
sclen"
Dr. Robert Frank, Professor of Environmental Health Sciences, Johns
Baltimore * °f H7gi"e *nd Public Health, 615 N. Wolfe Street,
Dr. Timothy Larson, Environmental Engineering and Science Program
m"l Ent4M«rt«i»X-10. University of Washington,
Dr. Morton Lippmann, Professor, Institute of Environmental Medicine.
NYU Medical Center, Tuxedo, NY 10987
Dr. Gilbert Omenn, Professor and Dean, School of Public Health and
Community Medicine SC-30, University of Washington.
Seattle, WA 98195
Dr. Robert F. Phalen, Community and Environmental Medicine, College of
Medicine, University of California-Irvine, Irvine, CA 92717
Dr. Marc Schenker, Director, Occupational and Environmental Health Unit.
University of California, Davis, CA 95616
Dr. Jerry Vcsolowskl, Air and Industrial Hygiene Laboratory, California
Department of Health, 2151 Berkeley Way, Berkeley, CA 94704
Dr. George, Wolff, Senior Staff Research Scientist, General Motors
Research Labs, Environmental Science Department, Warren, MI 48090
Executive Secretary
Mr. A. Robert Flaak, .Environmental Scientist, Science Advisory Board
(£~^1?)> u-s* Environmental Protection Agency, Washington, D.C.
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APPENDIX C:
CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
SUBCOMMITTEE ON ACID AEROSOLS
REPORT ON ACID AEROSOL RESEARCH NEEDS
WITH TRANSMITTAL LETTER FROM
, ROGER 0. MCCLELLAN, CASAC CHAIRMAN, AND
MARK J. UTELL, CASAC SUBCOMMITTEE CHAIRMAN,
TO LEE M. THOMAS, EPA ADMINISTRATOR
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UnitieJ St«l«f
Environmental Pretaetlon
Agancy
OHIo« o< th« Administrator
Selene* Advisory Board
W«>hlng1on. DC 20460
EPA-SAB'CASAC-89-002
O«c«mb«r USD
*••, Z •••A. A
SW EPA
Report Of The Clean
Air Scientific Advisory
Committee (CASAC)
Recommendations for
Future Research on
Acid Aerosols
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D C 20460
December 15, 1988
The Honorable Lee. M. Thomas
Administrator
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, DC 20460
OFFICE OF
THE ADMINISTRATOR
Dear Mr. Thomas:
Report on Acid Aerosol Research Needs
We are pleased to transmit via this letter the advice of
the Clean Air Scientific Advisory Committee (CASAC) concerning
research needs for acidic aerosols. As part of its review of the
potential health effects of acidic aerosols, the CASAC and its
Acid Aerosol Subcommittee, reviewed the Acid Aerosol Issue Paper
prepared by EPA and prepared this report to present its research
recommendations for acid aerosols. A separate report has been
prepared by the Committee concerning the potential health effects
of acidic aerosols.
The research recommendations for acid aerosols are presented
in four parts: characterization and exposure; animal toxicology;
human exposure studies; and epidemiology. Recommendations are
classified as high, medium and low.
The Committee appreciates this opportunity to present our
views on acid aerosol research. We look forward to the Agency's
response to our report.
Sincerely,
Roger O. McClellan, D.V.M.
Chairman
Clean Air Scientific Advisory
Committee
Mark J. Utell, M.D.
Chairman
CASAC Acid Aerosol Subcommittee
cc: Don Barnes
Erich Bretthauer
Don Clay
Ray Loehr
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EPA-SAB/CASAC-89-002
CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
SUBCOMMITTEE ON ACID AEROSOLS
REPORT ON
ACID AEROSOL RESEARCH NEEDS
FINAL SUBCOMMITTEE REPORT
OCTOBER 19, 1988
U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
WASHINGTON, DC
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ABSTRACT
Under Section 109 of the Clean Air Act, the U.S.
Environmental Protection Agency (EPA) is required to periodically
review national ambient air quality standards (NAAQS) and the
criteria on which they are based. The Act also requires the
Clean Air Scientific Advisory Committee (CASAC) to provide
scientific advice on any additional knowledge that is required to
evaluate existing, or setting new or revised NAAQS. To evaluate
the health effects of the class of air pollutants known as acid
aerosols, the Committee requested that EPA prepare an "Acid
Aerosol Issue Paper". In reviewing this Issue Paper, the
Committee developed a series of research recommendations for acid
aerosols, prioritizing them as high, medium, and low. This
report presents these research recommendations in four parts: 1)
characterization and exposure, 2) animal toxicology, 3) human
exposure, and 4) epidemiology.
Key. Words; acid aerosols, acid particles, research needs, NAAQS
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U.S. Environmental Protection Agency
NOTICE
This report has been written as part of the activities of
the Science Advisory Board, a public advisory group providing
extramural scientific information and advice to the Administrator
and other officials of the Environmental Protection Agency. The
Board is structured to provide a balanced expert assessment of
scientific matters related to problems facing the Agency. This
report has not been reviewed for approval by the Agency; and,
hence, the contents of this report do not necessarily represent
the views and policies of the Environmental Protection Agency or
other agencies in the Federal Government. Mention of trade names
or commercial products do not constitute a recommendation for
use.
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U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
Chairman
Dr. Roger O. McClellan, President, Chemical Industry Institute
of Toxicology, P.O. Box 12137, Research Triangle Park,
North Carolina 27709
Members
Dr. Timothy Larson, Environmental Engineering and Science Program,
Department of Civil Engineering FX-10, University of
Washington, Seattle, Washington 98195
Dr. Gilbert S. Omenn, Professor of Medicine and of Environmental
Health, Dean, School of Public Health and Community Medicine,
University of Washington, SC-30, Seattle, Washington 98195
Dr. Marc B. Schenker, Director, Occupational and Environmental
Health Unit, University of California, Davis,
California 95616
Dr. Mark J. Utell, Professor of Medicine and Toxicology,
Co-Director, Pulmonary Disease Unit, University of Rochester
School of Medicine, Rochester, New York 14642
Dr. Jerome J. Wesolowski, Chief, Air and Industrial Hygiene
Laboratory, California Department of Health, 2151 Berkeley
Way, Berkeley, California 94704
Dr. George T. Wolff, Principle Scientist, General Motors
Research Labs, Environmental Science Department,
Warren, Michigan 48090
Executive Secretary
Mr. A. Robert Flaak, Environmental Scientist, Science Advisory
Board (A-101F), U.S. Environmental Protection Agency,
401 M Street, SW, Washington, D.C. 20460
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U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
ACID AEROSOL SUBCOMMITTEE
Chairman
Dr. Mark J. Utell, Professor of Medicine and Toxicology,
Co-Director, Pulmonary Disease Unit, University of
Rochester School of Medicine, Rochester, New York 14642
Dr. Mary Amdur, Senior Research Scientist, Energy Laboratory,
MIT, Room 16-339, Cambridge, Massachusetts 02139
Dr. Douglas W. Dockery, Assistant Professor, Respiratory
Epidemiology Program, Department of Environmental Science
and Physiology, Harvard School of Public Health, 665
Huntington Avenue, Boston, Massachusetts 02115
Dr. Robert Frank, Professor of Environmental Health Sciences,
The Johns Hopkins School of Hygiene and Public Health,
615 N. Wolfe Street, Baltimore, Maryland 21205
Dr. Timothy Larson, Environmental Engineering and Science Program,
Department of Civil Engineering FX-10, University of
Washington, Seattle, Washington 98195
Dr. Morton Lippmann, Professor, Institute of Environmental
Medicine, New York University Medical Center, Tuxedo,
New York 10987
Dr. Gilbert S. Omenn, Professor of Medicine and of Environmental
Health, Dean, School of Public Health and Community Medicine,
University of Washington, SC-30, Seattle, Washington 98195
Dr. Robert F. Phalen, Professor, Community and Environmental
Medicine, University of California, Irvine, California 92717
Dr. Marc B. Schenker, Director, Occupational and Environmental
Health Unit, University of California, Davis,
California 95616
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-2-
Dr. Jerome J. Wesolowski, Chief, Air and Industrial Hygiene
Laboratory, California Department of Health, 2151 Berkeley
Way, Berkeley, California 94704
Dr. George T. Wolff, Principle Scientist, General Motors
Research Labs, Environmental Science Department,
Warren, Michigan 48090
Executive Secretary
Mr. A. Robert Flaak, Environmental Scientist, Science Advisory
Board (A-101F), U.S. Environmental Protection Agency,
401 M Street, SW, Washington, D.C. 20460
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TABLE OF CONTENTS
1.0 EXECUTIVE SUMMARY 1
1.1 Overview and Background 1
1.2 Major Recommendations . ,, 1
1.2.1 Characterization and Exposure Research ... 1
1.2.2 Animal Toxicology Research 2
1.2.3 Human Clinical Research 2
1.2.4 Epidemiological Research 2
2.0 INTRODUCTION 3
2.1 Overview 3
2.2 Purpose of this Report 3
3.0 CHARACTERIZATION AND EXPOSURE RESEARCH NEEDS 3
3.1 Overview 3
3.2 Method Evaluation 4
3.2.1 High Priority Research Needs 4
3.2.2 Medium Priority Research Needs 5
3.2.3 Lower Priority Research Needs 5
3.3 Characterization of Acid Aerosols 6
3.3.1 Indoor and Outdoor Measurements 6
3.3.2 Total Exposure Measurements 7
3.4 Modelling 7
3.4.1 High Priority Research Needs 7
3.4.2 Medium Priority Research Needs 7
3.4.3 Lower Priority Research Needs 8
3.5 Conclusions ..... .... 8
4.0 ANIMAL TOXICOLOGY RESEARCH NEEDS ... 8
4.1 Overview 8
4.2 High Priority Research Needs 8
4.2.1 Hazardous Chemical Species 8
4.2.2 Concentration Times Time Relationships ... 9
4.2.3 Exposure-Response Patterns 9
4.2.4 Development of Chronic Lung Disease . . . . 10
4.2.5 Classes of Effects 10
4.2.6 Extrapolations 10
4.3 Medium Priority Research Needs 11
4.3.1 Susceptible Populations 11
4.3.2 Acid and Co-occurring Pollutant
Interactions 11
5.0 HUMAN EXPOSURE RESEARCH NEEDS 11
5.1 Overview H
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5.2 High Priority Research Needs 12
5.2^1 Respiratory Function Responses and
Airway Hyperreactivity ... 12
5.2.2 Airway Mucus and Mucociliary Clearance
Function 12
5.2.3 Mixed Pollutant Studies ; 12
5.3 Medium Priority Research Needs 13
5.3.1 Measurement of Small Airway Response . . . . 13
6.0 EPIDEMIOLOGY RESEARCH NEEDS 13
6.1 Overview 13
6.2 High Priority Research Needs 13
6.2.1 Harvard Multicity 14
6.2.2 Chestnut Ridge and Other Areas of High
Acute Exposures - .... 14
6.2.3 Occupational Studies of Acid
Aerosol Exposure 14
6.3 Medium Priority Research Needs 14
6.3.1 New York Hospital Admissions ........ 14
6.3.2 Indoor Exposures 14
6.3.3 Assistance to Foreign Studies 14
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1.0 EXECUTIVE SUMMARY
1.1 Overview and Background
This is the third in a series of reports prepared by the
Clean Air Scientific Advisory Committee (CASAC) providing
recommendations to the U.S. Environmental Protection Agency (EPA)
on research needed to develop and support national ambient air
quality standards (NAAQS). The first report, issued in December
1983, provided research recommendations on four of the six
criteria air pollutants: carbon monoxide, nitrogen oxides,
particulate matter, and sulfur oxides. The second report, issued
in September 1987, provided recommendations on the two remaining
criteria air pollutants: ozone and lead. The present report
presents research recommendations for acid aerosols, a class of
air pollutants that are under consideration for possible listing
as a seventh criteria pollutant.
The research recommendations for acid aerosols are presented
in four parts: 1) characterization and exposure; 2) animal
toxicology; 3) human exposure studies; and 4) epidemiology. This
document is only concerned with the health risks of acid aerosols
and does not consider potential welfare issues.
1.2 Maior Recommendations
It should be noted that though we have used high, medium,
and low priorities to define research needs as is customary in
our reports, in most cases the use of the last two designations
simply means that these projects should not be initiated until
the high priority projects have a commitment for support.
The Committee has the following high priority research
recommendations for acid aerosols:.
1.2.1 Characterization and Exposure Research
• A program is needed to evaluate existing measurement
methods, to improve them as needed, and to establish
the precision and accuracy of the best methods.
• Quality assurance/quality control procedures should be
developed with respect to outdoor monitoring networks',
indoor characterization, and personal sampling.
• The spatial and temporal behavior of acid aerosols and
gaseous ammonia should be characterized. This should
include measurement of indoor/outdoor ratios.
• Population exposure estimates are needed for all
microenvironments, not just outdoor air.
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• If important routes of exposure other than outdoors are
identified, a total exposure measurement study should
be:-carried out to ascertain the contributions of each
exposure route to different population subsets.
1.2.2 Animal Toxicology Research
0 Develop more concentration times time (CxT) health and
monitoring data.
• More delayed response studies are needed, as are
studies which examine responses to short-term repeated
exposures.
• Further evaluate the hypothesis that long-term exposure
to low levels of sulfuric acid may cause bronchitis.
• More studies are needed which document the nature of
the various health effects of acids.
a More effort is needed to improve animal to human
extrapolations.
1.2.3 Human Exposure Research
• Studies are needed on the influence of ventilatory
rates and concentration and duration of single and
multiple exposures to acid aerosols on the magnitude
and duration of respiratory function responses,
airway hyperreactivity, and assays dependent on
bronchoalveolar lavage in volunteers, and the influence
of age, gender, pre-existing disease and endogenous
ammonia excretion on these responses.
• Studies are needed on the influence of concentrations
and durations of single and multiple exposure to acid
aerosols on the magnitude and duration of mucociliary
clearance function in healthy volunteers.
• Studies are needed on the separate and combined effects
of acute exposures to ozone and acidic aerosols and
vapors on respiratory function and assays of possible
tissue injury, altered defenses, or inflammation,
including epithelial permeability.
1.2.4 Epidemiology Research
• Studies that directly measure health outcomes among
individuals are needed, rather than descriptive or
ecological studies.
• Specific studies warranting highest priority are:
Harvard Multicity; Chestnut Ridge or other areas of
high acute exposure; and occupational studies of acid
aerosol exposure.
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2.0 INTRODUCTION
2.1 Overview-
Under Section 109 of the Clean Air Act, the EPA is required
to periodically review NAAQS as well as the air quality criteria
on which they are based. When appropriate, the EPA is to update
and revise these standards. New pollutants are to be listed if
the Administrator concludes that they may reasonably be
anticipated to endanger public health or welfare and are emitted
by numerous or diverse mobile or stationary sources. The
Administrator will consider the advice of his staff and the
advice of the CASAC before making a decision. Adequate
scientific information for such a. decision must be available,
including a rigorous data base which supports the basis for the
decision. Additional research will be necessary where gaps exist
in the data base.
A major responsibility of the CASAC, as established in the
Act, is to provide scientific advice on additional knowledge that
is required for evaluating existing, or setting new or revised
NAAQS. Based on its review of Agency documents and relevant
scientific literature and on discussions with Agency staff and
the interested public, CASAC develops research recommendations
designed to fill the gaps in existing research.
2.2 Purpose of this Report
On June 14-15, 1988, the CASAC Acid Aerosol Subcommittee met
in Washington, DC to review the draft "Acid Aerosols Issue Paper"
(EPA/600/8-88/005A) prepared by EPA's Office of Research and
Development (ORD). The three main purposes of the meeting were
as follows: to prepare a Subcommittee recommendation on the acid
aerosol listing issue, to comment on the adequacy of the draft
issue paper, and to identify research needs for acid aerosols.
The Subcommittee recommendations were approved, with minor
changes by the full CASAC at a public meeting in Washington, DC
on October 6, 1988.
This report on acid aerosol research recommendations
represents the first such CASAC report that evaluates research
needs for a potential new criteria pollutant.
3.0 CHARACTERIZATION AND EXPOSURE RESEARCH NEEDS
3.1 Overview
This section recommends priorities for research to
characterize acid species (i.e. to identify and quantify acids
potentially in the breathing zones of U.S. citizens), and
research to determine actual exposures in order to link these
exposures to health end points obtained by animal, clinical, and
epidemiological studies.
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The foundation of any air quality standard is the
measurement method, not only because the standard itself must
specify ther-method, but equally important, because before
establishing a standard, the contaminant must be fully
characterized and exposure measurements made to correlate with
health outcomes. Therefore, it is critical to have measurement
methods which have been thoroughly validated. Often, necessary
validation has not been done until the standard is about to be
promulgated. Thus, much of the characterization and health effect
data relies on measurement techniques which are not as rigorously
validated as they are once the standard is set. This is part of
the 'difficulty in competently establishing a standard in the
first place. This difficulty is especially acute with respect to
the development of an acid aerosol standard.
There are two problems that are specific to an acid
standard. First, current exposure science has advanced
sufficiently since previous standards were set that it is no
longer acceptable to characterize acids or determine exposures in
only one microenvironment, viz. outdoor air. Rather their
presence in other microenvironments must also be estimated, and
in the case of acids, particularly indoor environments using
kerosene heaters. Unfortunately, samplers developed for outdoor
monitoring stations cannot always be used indoors because of
size, noise, air flow, and cost (since the indoor environment
requires more samples to characterize it). Secondly, there is
some uncertainty at the present time regarding the.specific acid
species of concern. Thus, any research program must be flexible
enough to accommodate species other than titratable H+ and H2S04,
the currently accepted species of concern. Therefore, the
recommendations given below rest on an uncertain foundation.
3.2 Method Evaluation
3.2.1 High Priority Research Needs
3.2.1.1 Evaluating Existing Methods
A program is needed to evaluate existing methods, to improve
them as needed, and to establish the precision and accuracy of
the best methods. The goal is to establish standardized methods
so that research and monitoring carried out by different groups
will be comparable. This effort should be of the same
comprehensiveness and quality as that carried out for the present
criteria pollutants. It is recommended that the program begin
with the following three steps:
A. EPA should sponsor a scientific workshop to discuss what
species should be emphasized (total titratable acidity, H2SOx,
pH, other ions, NH3, strong and weak acids, etc.), and to decide
which are the best candidate methods presently available.
Discussions should include the sampler, sampling time, sample
preservation, precision and accuracy, as well as the analytical
method itself. Discussion is required on sampling artifacts,
including possible displacement and subsequent off-gassing of
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volatile acids from the filter surface, potential penetration of
particulate bases (e.g. soil derived carbonates) past the annular
denuder with- subsequent chemical neutralization of filterable
acidity, and possible loss of acidity due to within-particle
reactions of alkaline combustion particles with their acidic
surface coatings.
B. An acid aerosol "shoot-out" should be conducted. EPA
should fund any group with a promising measurement method as
determined by the above workshop to participate in a week-long
methods intercomparison study. Since the National Oceanographic
and Atmospheric Administration (NOAA) is already sponsoring an
ammonia "shoot-out", EPA should consider the results of that
study before including ammonia in the acid aerosol "shoot-out".
C. Following the "shoot-out", a second workshop should be
held to determine the causes of differences in the methods, to
determine what modifications can bet made to improve the methods,
and finally to establish which of the methods should be
standardized for acid aerosol and ammonia research and
monitoring.
This is not only a high priority research component, but
should be carried out before major field studies using untested
methods are begun. Of course, if no existing methods perform
adequately, an intensive effort must then be launched to develop
new methods.
3.2.1.2 Quality Assurance/Quality Control
Quality assurance/quality control (QA/QC) procedures should
be developed with respect to outdoor monitoring networks, indoor
characterization, and personal sampling.
3.2.1.3 Transfer of Standards
EPA should develop suitable transfer standards for accuracy
assessment and determination of experimental (sampling and
analytical) precision targets. This would help assure
compatibility of data among various research and monitoring
groups.
3.2.2 Medium Priority Research Needs
Methods for acid fog need to be evaluated.
3.2.3 Lower Priority Research Needs
Methods must be evaluated for acidic gases, particularly for
nitric acid, the predominant atmospheric species. This effort
should be coordinated with the work of the California Air
Resources Board (CARB).
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3-3 Charact.erizat.ion of Acid Aerosols
3.3.1 Indoor- and Outdoor Measurements
3.3.1.1 High Priority Research Needs
A. The spatial and temporal behavior of acid aerosols and
gaseous ammonia should be characterized. Five or six urban areas
in the country should be selected for this task. For example: one
in the Northeast (Philadelphia), one in the Ohio Valley source
region (Cincinnati), one in the Southeast (Atlanta), Houston, and
Los Angeles. In each of these areas, six to ten monitoring sites
should be established. They should be located upwind, downwind
and within the urban centers. The networks should be operated for
one year. At the end of the year, the data should be analyzed to
determine the spatial distribution of acids, ammonia and products
of neutralization, source-receptor relationships, seasonal
patterns, and local and synoptic meteorological influences.
B. Indoor/outdoor ratios should be measured at one or more
of the urban locations discussed above.
3.3.1.2 Medium Priority Research Needs
A. At one or more of the urban sites discussed above,
intensive aerial measurements of acid-related species should be
made so that acid plumes can be mapped. This will augment the
information needed to define the spatial distributions and
source-receptor relationships.
B. Measure acid particle size distributions, on a more
localized, intensive scale than the monitoring network. This
includes examination of the effect of relative humidity or
presence of fog on size.
C. Measurement of ammonia surface fluxes (emission rates)
are needed for subsequent modelling efforts.
3.3.1.3 Lower Priority Research Needs
A. If the indoor/outdoor data, the health data, and the
total exposure estimates (discussed below) indicate a potential
health risk, a nationwide monitoring network would need to be
established. The criteria used to select the urban areas and the
specific monitoring sites would be developed based on the
information learned from the operation of the five or six-city
monitoring networks.
B. The uncertainties in the chemical mechanisms and rate
constants involved in the formation of acid aerosols need to be
assessed. The key reactions which require better information
must be identified. The appropriate experiments to obtain the
information must then be designed and implemented.
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C. Develop an acid aerosol climatology, if acid aerosols are
found to only be a local problem, this task may not be necessary.
If on the other hand, it is found to have an important regional
component like ozone and sulfates, then a regional scale rural
monitoring network will be needed to obtain the data necessary to
understand the formation mechanisms, behavior, and spatial
distributions.
D. The co-occurrence of nitric acid vapor over the same
acidic particle network should be characterized.
3.3.2 Total Exposure Measurements
3.3.2.1 High Priority Research Needs
If the microenvironmental measurements carried out above
indicate potentially important routes of exposure besides the
outdoors, a total exposure measurement study should be carried
out to ascertain the contributions of various routes of exposure
to different subsets of the population.
3.4 Modelling
3.4.1 High Priority Research Needs
3.4.1.1 Estimate of Population Exposure
A crucial part of the health risk assessment necessary to
determine the need of a standard is the estimate of population
exposure. The exposure estimates should be for all
microenvironments, not just outdoor air. Thus, it will be
necessary to examine the various exposure models, particularly
the NAAQS Exposure Model (NEM), to establish which one will be
most appropriate for estimating the exposure distributions for
the various population groups. Clearly this should be establishsd
before the indoor/outdoor measurement studies are designed and
implemented to assure that the data collected will satisfy the
input requirements of the model.
3.4.1.2 Exposure Distributions
The indoor/outdoor data base should then be used in the
chosen exposure model to obtain exposure distributions to
determine potential population subsets at risk.
3.4.2 Medium Priority Research Needs
3.4.2.1 Therroodynamic Equilibria of Ammonia
*•
Using the data base which presently exists, an improved
understanding of thermodynamic equilibria of ammonia with
sulfuric and nitric acid systems should be developed.
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3.4.2.2 Ammonia Diffusion/Reaction K
There is a need for the measurement of ammonia
diffusion/reaction kinetics with actual atmospheric acid
particles. This information, along with size distribution data
will allow for better assessment of the potential for respiratory
NH3 neutralization during inhalation. The information is also
needed for atmospheric models.
3.4.2.3
Ammonia Emissions Inventory
An ammonia emissions inventory is necessary input to all
models which attempt to describe the formation of the acids.
3.4.3 Lower Priority Research Needs
A. an appropriate aerosol module for incorporation into an
air quality model is needed. The scale of the model into which
the aerosol kinetic model will be incorporated will depend on
whether acid aerosols are a local, urban-scale, or regional-scale
model.
3.5 Conclusions
Clearly the above recommendations represent an ambitious
research plan. Nevertheless it must be implemented because the
very foundation of the standard depends on good methods,
characterization studies, and exposure assessments. Because of
the present weakness in the measurement methodology for acid
aerosols, it is particularly important that large field studies
not be implemented until there is concurrence as to the most
appropriate measurement methods, and reliable information is
available on the accuracy and precision of the methods chosen. It
should also be recognized that not all of the recommended studies
can be carried out in parallel since the detailed design for many
studies, and in some cases whether a study should be carried out
at all, will depend on previous data obtained. Therefore it is
recommended that EPA develop a comprehensive time-line strategy
for all studies expected to be undertaken.
4.0 ANIMAL TOXICOLOQICAL RESEARCH NEEDS
4.1 Overview
The Subcommittee endorses the research needs identified by
the EPA in the draft Acid Aerosols Issue Paper. We have modified
these research needs and prioritized them into high and medium
priorities.
4.2 High Priority Research Needs
4.2.1 Hazardous Chemical Species
There is a major need to identify all of the biologically
active chemical species so that future epidemiology and
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monitoring studies are properly directed and so that ultimately
the proper .causative species can be controlled. The relative
potency of various acid species needs further study; most work
has focused on H2S04 but HNO3 and/or NH4HS04 may dominate ambient
aerosol acidity at times. In addition, there is a need to
understand the relative role of the cation and the anion
associated with various acid species, and the toxicological
effects of acidic particles compared to acidic gases. A more
complex issue has arisen from recent research by Dr. Amdur and
her colleagues. They found that H2S04 adsorbed onto ultrafine
zinc oxide particles was 3 to 10 times as potent in changing
pulmonary function as an equivalent-sized aerosol of H2S04 mist.
This raises several questions, not only for H2S04 but also for
HC1 sine© it is emitted from hazardous and municipal waste
incinerators, in association with particles.
4.2.2 Concentration Times Time Relationships
Health effect outcomes are dependent on many factors, with
exposure concentration and time (C x T) being among the major
ones. Ambient air concentration patterns for acids, as for other
pollutants, are not steady-state, so it is critical to determine
which exposure patterns are of greater risk and hence must be
monitored, and controlled if control is warranted. Given the
paucity of C x T health exposure response data, it is important
to develop a research strategy between both health and monitoring
scientists so that the research of each may be made more
efficient by the results of the other. The alternative is a less
efficient integration of monitoring data and health risk data.
Health studies must include a large variety of doses, endpoints
and exposure times - much basic data is missing and needs to be
generated. Such studies are not routine, so some flexibility and
discretion on the part of the investigators is necessary.
4.2.3 Exposure-Response Patterns
This topic has elements in common with the C x T studies
described above, but focuses more on the effects of timing of the
pattern of exposure vis-a-vis pattern of response. Only rarely
are delayed responses studied, although they can occur and may
provide important guidance to design and interpretation of human
clinical and epidemiological studies. In the Cincinnati dog
study, in which dogs exposed to H-2S04 plus SO, were examined two
years post-exposure, pulmonary function effects were progressive
even after stopping the exposure, arguing further for the
incorporation of delayed response studies in experimental
designs. Another issue of importance to explore is the response
to short-term repeated exposures,, Over a week, the pattern of
pulmonary function responses changes, in some cases worsening and
in others plateauing. To interpret the degree of adversity, it is
necessary to know whether there are 'silent' changes to one
endpoint that progress while other endpoints adapt, as is the
case with ozone.
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4-2.4 Development: of Chronic Luna Disease
o™o sufficient data to hypothesize that long-term
exposure to low levels of H2S04 may cause chronic bronchitis.
Because of the significance of these findings, it is essential to
test the hypothesis. Several approaches are of interest. A few
would include conducting studies similar to the rabbit study of
Schlesinger et al. in at least two additional species; repeating
the Schlesinger et al. study at a lower concentration; increasing
the knowledge of the relationship between alterations in lung
clearance and the development of chronic bronchitis; and applying
state-of-the-art lung morphometric methods in a time-course
study .
4.2.5 Classes of Effects
Generally, the literature on the health effects of acids is
sparse, with the more useful findings resulting from the
application of newer methods and technologies. Recently, low
levels of H,SO^ have been observed to result in inflammatory
responses and effects on alveolar .macrophages. These changes have
implications to the development of chronic lung disease. The
alveolar macrophage effects and lung clearance effects may
portend decrements in host resistance to infection, most probably
viral infection since bacterial infectivity is apparently not
affected. Taking the literature as a base, several findings
require follow-up so that risk potential can be understood. As
examples, is the influx of neutrophils associated with other
inflammatory changes; are defenses against viral infection
compromised?
4.2.6 Extrapolation
It is expected that animal studies will provide cause-effect
data on the chronic effects of acidsv mechanisms of effects, and
the full range of effects, thereby providing information
unavailable from epidemiological or human clinical studies. These
animal data are therefore of great importance to risk assessment,
but quantitative extrapolation to man is needed. To achieve the
animal-to-human extrapolation, two primary factors must be
considered: dosimetry and species sensitivity. Research on the
relationship between concentration and delivered dose will be
complex since 1) acids are frequently in hygroscopic aerosols for
which more fundamental data are needed, 2) neutralization by
breath ammonia and, in whole body exposure, ammonia from
excrement, can be important, 3) tissue dose will be highly
dependent on mucus buffering capacity, requiring data on mucus
biochemistry, and 4) microdosimetry (i.e., dose within lung
regions) is quite important since health studies on a single
endpoint (i.e., clearance) show responses to be dependent on
regional dose.
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4.3 ^edium Priority Research Needs
4.3.1 Susceptible Subpopulations
Several subpopulations are known or suspected to be more
susceptible to acid aerosols. While some of this research is
discussed elsewhere in the report, further animal toxicological
research on this topic is needed to supplement human studies to
explore mechanisms more fully.
4.3.2 Acids and Co-occurring Pollutant Interactions
Acidity in association with other pollutants such as
ammonium sulfate, ozone and N02 has been found to be additive,
synergistic, antagonistic or non-influential, depending upon the
endpoint, the co-pollutant, and whether the exposure was in
sequence or in mixture. From a health risk perspective,
understanding any possible synergism is of major importance. Such
studies need to be designed to mimic ambient occurrences of H2S04
and co-pollutant exposures, insofar as possible. For example, the
temporal relationship and concentration ratios of 03 and H2S04
that actually occur should be investigated for effects using
sensitive endpoints such as edema, lung clearance, and other
endpoints as well, since there can be a dependence on endpoint.
Once the phenomenon is understood better, mechanism studies are
needed to enable predictions of interactions in risk assessments.
Such predictions are important since it is not feasible to
collect data on every potential interaction of interest.
5.0 HUMAN EXPOSURE RESEARCH NEEDS
5.1 Overview
Controlled human exposure studies can provide the best
possible information on the relationship between acute exposures
of humans to acid aerosols and transient responses to such
exposures. Studies of the progression of effects during chronic
exposures cannot be performed for both ethical and practical
reasons, and standards designed to protect against the effects of
chronic exposures must rely primarily on data from toxicological
and epidemiological studies. However, controlled human exposure
studies can provide valuable supplemental information to support
the validity of extrapolations of such data. For example, the
close correspondence of transient changes in lung clearance
function between humans and animals following acute exposures
supports the hypothesis that the persistent functional and
structural changes that occur in chronically exposed animals
would also occur in humans if they were similarly exposed.
Furthermore, the kinds of chronic effects seen in the animal
studies are consistent with the kinds of effects seen in human
populations having chronic exposures to ambient acid aerosols.
Controlled human studies are best able to determine
variations in transient responses associated with: 1) Pre-
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existing diseases, such as asthma, 2) various combinations of
concentration, composition, and duration of acid aerosol
exposure; 3) joint actions of combined exposures to acid aerosols
and irritant vapors such as ozone; and 4) endogenous ammonia
excretion. Recently, using bronchoalveolar lavage brief ozone
exposures have been shown to produce inflammation in the lower
airways of humans; such information on effects of acid aerosols
on inflammation, possible tissue injury, altered defense
mechanisms, and mucus are needed. In the past, controlled human
exposure studies have not generally provided much data on the
temporal dynamics of transient responses, especially delayed
responses. However, repeated measurements of function can
generally be made during and following acute exposures and can,
therefore, readily provide valuable data on the temporal aspects
of delayed and/or persistent responses.
5.2 High Priority Research Needs
5.2.1 Respiratory Function Responses and Airway Hvperreactivity
Studies are needed on the influence of ventilatory rates and
concentration and duration of single and multiple exposures to
acid aerosols on the magnitude and duration of respiratory
function responses, airway hyperreactivity, and assays dependent
on bronchoalveolar lavage in volunteers, and the influence of
age, gender, pre-existing disease and endogenous ammonia
excretion on these responses. Such studies are critical for
determining the need and possible exposure levels for a short-
term standard (1 to 8-hr averaging time) to protect against acute
respiratory function effects, especially in sensitive
populations, such as asthmatics.
5.2.2 Airway Mucus and Mucociliary Clearance Function
Studies are needed to develop better methods for sampling and
analyzing airway mucus, to develop better models of buffering
capacity of airway secretions, and to examine the variation among
population groups who may be especially susceptible to the
effects of acid aerosols. Such studies are critical in
understanding the mechanisms of effects of acid aerosols on
mucociliary clearance. In addition, studies are needed on the
influence of concentrations and durations of single and
multiple exposure to acid aerosols on the magnitude and duration
of mucociliary clearance function in healthy volunteers. Such
studies are needed, in conjunction with coordinated studies in
animals, to develop a basis for the quantitative extrapolation of
chronic animal exposure studies' results to chronic symptom and
disease effects in human populations, especially bronchitis
prevalence and hospital admissions for respiratory diseases.
5.2.3 Mixed Pollutant Studies
Studies are needed on the separate and combined effects of
acute exposures to ozone and acidic aerosols and vapors on
respiratory function and assays for possible tissue injury,
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altered cell function, or inflammation, including epithelial
permeability.. Such studies are needed to determine whether the
substantially- greater functional effects of ozone seen in field
studies in comparison to chamber studies is attributable to
enhanced lung permeability or other mechanisms resulting from
exposures to acidic aerosols.
5.3 Medium Priority Research Needs
5.3.1 Measurement of Small Airway Response
Development of methodologies for non-invasive measurement of
small-airway response are needed to permit improved sensitivity
for the detection of early or minimal responses.
6.0 EPIDEMIOLOGY RESEARCH NEEDS
6.1 Overview
The Subcommittee endorses the introductory statement on
research- needs for epidemiologic studies of acid aerosols in the
draft Acid Aerosols Issue Paper. We wish to particularly
emphasize the need for concurrent measurements of acid aerosols
and other important ambient pollutants, so that the independent
effects of acid aerosols can be directly assessed instead of
inferred or assumed from other measurements. This is a major
deficiency in almost all of the existing epidemiologic studies,
and seriously limits their value for this issue.
6.2 High Priority Research Needs
The highest priority should be for epidemiologic studies
that directly measure health outcomes among individuals, and not
descriptive or ecologic studies. The latter are useful for their
ability to look at large populations in a cost effective manner,
but generally provide less evidence of causal association, and
are less able to control for potential significant confounding
factors.
Health outcomes of highest priority for study are acute and
chronic pulmonary function and respiratory symptoms. Pulmonary
function studies provide important objective data, and are of
value in relating to exposure chamber studies of pulmonary
function. Studies of acute (e.g., daily) changes in pulmonary
function should be directed towards locations with high levels of
ambient acid aerosol exposure. Asthmatics and other subjects with
hyperreactive airways may be an 'efficient' population for these
studies. The inflammatory effects of acid aerosols and
preliminary data consistent with an effect on 'bronchitis'
confirm the need to study acute and chronic effects on cough and
phlegm production.
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. . . ln^ view ?f "these considerations, the studies warranting the
nighest priority are:
6.2.1 Harvard Multi-city
This study has the best prospect of looking at chronic
effects of acid aerosols on respiratory symptoms and function,
with a range of other exposures to allow evaluation of the
independent effects of acid aerosols.
6.2.2 Chestnut Ridae or Other Areas of High Acute Exposures
Study design for an acid aerosol study in this area is
unknown. High daily peaks in acid aerosols with frequent
fluctuation would allow epidemiologic studies of acute effects.
Potential chronic effect studies would depend on available
current and historical data on chronic acid aerosol exposures in
the area, and the divergence of acid aerosols from other ambient
pollutants. Absence of such a divergence might prevent useful
conclusions about the independent effects of acid aerosols. Other
study areas with high acute exposures to primary downwind acid
aerosols should also be a high priority for study.
6.2.3 Occupational Studies of Acid Aerosol Exposure
Many occupational settings exist with acid aerosol exposures
in a range that includes the highest current ambient exposures.
This situation gives the greatest potential for assessing acute
dose-response relationships.
6.3 Medium Priority Research Needs
6.3.1 New York Hospital Admissions
This study may provide useful data on exposure-response
relationships for acute effects associated with inhalation of
secondary acid aerosols over wide regions, but has some of the
limitations noted above for observational studies.
6.3.2 Indoor Exposures
The Yale research on indoor acid aerosols from high-sulfur
kerosene heaters may provide a useful opportunity to study acute
and chronic effects, although the effects may be associated with
other indoor pollutants (e.g. N02). other studies of indoor acid
aerosol exposures if identified provide a controlled environment
for studying exposure-response relationships.
6.3.3 Assistance to Foreign Studies
Support for studies in foreign countries may provide unique
opportunities, including assessment of exposures to higher
ambient concentrations of acid aerosols than are seen in this
country. These studies should be evaluated on an individual
basis.
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•it U.S. GOVERNMENT PRINTING OFFICE: 1989— 648 -163' 00354
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