EPA-SAB/CASAO89-OQ2
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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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C, E0460
December 15, 1§88
The Honorable Lee. M. Thomas
Administrator
U.S, Environmental Protection Agency
401 M Street, S.W,
Washington, DC 20460
Office, of
THE ADMINISTRATOR
RE: Report Qn_AfiisLAerosol Research Needs
Dear Mr, Thomas;
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. Becommendations 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
Eri<:h Bretthauer
Don Clay
Ray Loehr
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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 Jcnowledge 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 taper, the
Committee developed a series of research recommendations for acid
aerosols, prioritising them as high, medium, and low. This
report presents these research recommendations in four parts: l)
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
SCIENC1 ADVISOR* BOARD
CLEAjl AIR _SCIENTIFIC ADVISORY COMMITTEE
Chairman
Dr* Roger 0. 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 Progran,
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-3Q, 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, Wesolovski, Chief, Air and Industrial Hygiene
Laboratory, California Department of Health, 2151 Berkeley
Way, Berkeley, California §4704
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, swf 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
Members
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
Or- Timqthy 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* Qmenn, 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. Phalcn, Professor, Community and Environmental
Medicine, university of California, Irvine, California 92717
Dr. Marc l» Schenker, Director, Occupational and Environmental
Health Unit, University of California, Davis,
• California 95616
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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 Plaak, 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 . . . » l
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.l 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 J Overview . 11
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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.l 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
* 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-terra 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.
* More effort is needed to improve animal to human
extrapolations.
1.2.3 Human Expjgsure 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 ipidemioloov Research
• studies that directly measure health outcomes among
individuals are needed, rather than descriptive or
ecological studies.
• Specific studies warranting highest priority aret
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 PAAQS as well as the air quality criteria
on which they are based. When appropriate, the !PA 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/6QO/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 the 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 H4" and H2SO4,
the currently accepted species of concern. Therefore, the
recommendations given below rest on an uncertain foundation.
3.2 ffpjb.hp.gL Eva 1 uat ion
3,2,1 High Priority Research Needs
3.2.1,1 Evaluating Existing.--Methotis
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 sho«l
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volatile acids from the filter surface, potential penetration of
particulate bases (e.g. soil derived carbonates) past the annular
demider 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-out11 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 Qceanographic
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 be 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 Trans far o f 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 (GARB).
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3.3 Characterization of Acid Aerosols
3.3.1 Indoor,.and Outdoor. Measurements
3.3.1.1 HighPriorityResearch 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 vithin 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 .M.e.eAs
A. If the indoor/outdoor data, the health data, and the
total exposure estimates (discussed below) indicate a potential
health ri«Jc, 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
coraponant 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 Hicfh 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 Hjah 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 (NIM), 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
3.4.2,1 Therroodynamie Equilibria of Ammonia
Using the data base which presently exists, an improved
understanding of therraodynamic equilibria of ammonia with
sulfuric and nitric acid systems should be developed.
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3*4.2,2 ftniytop4a Diffusion/Reaction Kinetics •'""'
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 neutralisation 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 dut
at all, will depend on previous data obtained. Therefore it is
recommended that 1PA develop a comprehensive time-line strategy
for all studies expected to be undertaken.
4*0 ANIMAL TOXICOLOGICAL 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 PriorityResearch 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
8
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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 H2se>4 but HNO3 and/or NH4HSQ4 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 toxicologieal
effects of acidic particles compared to acidic gases. A more
complex issue has arisen from recent research by Dr. Aadur and
her colleagues. They found that H^SO^ adsorbed onto ultrafine
zinc oxide particles was 3 to 10 "times as potent in changing
pulmonary function as an equivalent-sized aerosol of H2SQ4 aist.
This raises several questions, not only for H^SO^ but also for
HC1 since 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 H2SO^ 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 Lung Disease
There are sufficient data to hypothesize that long-term
exposure to low levels of H,S04 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 morphoroetric methods in a time-course
study.
4.2.5 CJ.asses_jof 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^SOi 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 acids, 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 extrapolatibn to man is needed. To achieve the
animal-to-human extrapolation, two primary factors roust 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) microdosiraetry (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 ffeflJMM Priority Research Needs
4.3.1 Susceptible Sutopopulations
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 Ac^ds and co-*occugrlng 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 0^ 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. MEEDS
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 epideniological 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; l) 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 love?
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 Hyperreactivity
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 (l 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
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 epideraiologic 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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In view of these considerations, the studies warranting the
highest priority arei
6.2.1 Harvard Mult^-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 Ridge, 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 Qetatpational Studies of Aci.cLAer.QS.ol 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 MedJLuat '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. NO^)* Other studies of indoor acid
aerosol exposures if identified provide a controlled environment
for studying exposure-response relationships.
6.3.3 Assistanse_..tjg__ForeiQn 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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