Research Priorities for Airborne Particulate Matter I. Immediate Priorities and a Long-Range Research Portfolio (1998) / Chapter Skim
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4. The Committee's 10 Highest-Priority Research Recommendations
4. The Committee's 10 Highest-Priority Research Recommendations
Pages 44-97
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From page 44... ...
to ambient particulate-matter concentrations, actual human exposures, doses cielivereci to the lung, anal, ultimately, to adverse health effects from the most biologically active constituents or characteristics of particulate matter. The ~ O particulate-matter research priorities identified in this chapter inclucie some research activities that shouIci be starter!
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From page 45... ...
This information can then be used to focus on human exposures to biologically important aspects of particulate matter. An iterative process involving interpretation of evicience from toxicological and exposure studies will leaf!
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From page 46... ...
RESEARCH PRIORITIES RESEARCH TOPIC ~ OUTDOOR MEASURES VS. ACTUAL HUMAN EXPOSURES What are the quantitative relationships between concentrations of particulate matter andgaseous copo/lu tan ts measured at stationary outdoor air-monitoring sites, and the contributions of these concentrations to actual personal exposures, especiallyfor potentially susceptible subpopulations and individuals?
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From page 47... ...
while waiting for further health-effects studies. Hypothesis-driven exposure studies must be designed to provide fundamental information on actual human exposure to particulate matter and gaseous pollutants (NRC 1991~.
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· The sampling of particulate matter should include measurements of both PM25 and PM~o SCIENTIFIC VALUE Most epidemiological studies of particulate matter to ciate have been based on outcioor measurements. Therefore, the investigation of relationships between actual personal exposures and outdoor air-particle concentrations is crucial for validating and interpreting the results of epidemiological studies by providing better estimates of actual human exposure.
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From page 49... ...
DECISIONMAKING VALUE Pollutant concentrations in outdoor ambient air oRen are very different from actual personal exposures. Understanding the relationship between particulate-matter mass concentrations measured at fixed outdoor sites and actual human exposure to particulate matter will help guide and improve decisions about ambient pollution control strategies (NRC ~ 991 I
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Because ofthe complex aerometric measurements required, the three studies will require approximately $3.0 million per year for 3 years. Adding potentially susceptible subpopulations to such studies could increase that cost by a factor of 3 or more.
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From page 51... ...
These exposure studies should include members of the general population and potentially susceptible subgroups, using personal-monitoring studies and ambient stationary sites to examine the outdoor contributions to measurements of total personal exposure. · Further refine the sampling and analysis tools developed in Research Topic 3 (below)
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From page 52... ...
At the same time, the identification of critical inclicator species will help in the implementation of cost-effective strategies to protect individuals at high risk, because control resources will be devoted more efficiently to the sources of the specific causal agents of the health effects. FEASIBILITY AND TIMING Some population-exposure studies could be initiated soon, but a more targetec!
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From page 53... ...
These studies are estimated to cost approximately $4.0 million per year for 5 years, depencling on the indicators being measured. RESEARCH TOPIC 3 SOURCE RECEPTOR MEASUREMENT Toots What are the advanced mathematical, modeling, and monitoring tools needed to represent source-response relationships more accurately?
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From page 54... ...
Therefore, accurate and precise analyses are needed for representative samples from emissions and ambient airwith respect to chemical compositions of particulate matter, especially PM25, and gaseous pollutants. It is possible that the organic carbon fraction of particulate matter contains compounds that are biologically important or wouici provicle useful marker compounds to characterize various source emissions.
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From page 55... ...
The following specific research tasks should be undertaken to develop the capability to apply effective tools to understand the sourcereceptor relationships of biologically important particulate-matter components: · Develop advanced modeling techniques for relating source emissions to ambient concentrations of particulate matter by more quantitatively incorporating atmospheric dynamics- including the effects of complex terrain, passages of frontal air masses, vertical mixing of air, and cloud and fog processes-into source-oriented models. The first generation of first-principle models is available.
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From page 56... ...
It is critical that a substantial majority ofthe organic carbon mass be separated and identified to provide the basis for toxicological and epidemiological studies. That will require sampling on various media, in addition to quartz fiber filters, to capture the gaseous and solid phase of carbon compounds.
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From page 57... ...
Such analyses will help to iclentify the significance of specific particulate-matter components that might cause adverse health effects, as well as to evaluate effects of emissions reduction strategies. The development of mathematical tools is also needed for continued development of receptor-mocleling methocis for the quantitative apportionment of particulate-matter mass for secondary and reactive species, as well as for predictions of the intensity of human exposures in various settings.
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However, to have appropriate models in place by the time they are needed, the development effort should start soon. Models are needed both to relate source emissions to ambient concentrations (source-oriented models)
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From page 59... ...
The additional costs could be as high as $2.0 million to $10.0 million per urban area. RESEARCH TOPIC 4 APPLICATION OF METHODS AND MODELS Afrer biologically important components of particulate matter are identifiecl, how can the analytical tools developed in Research Topic 3 be applied to link those components to their sources to provide effective and efficient air-quality management to protect human health?
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Receptor models have been effectively useci to icientify local sources of particulate matter. Most applications of receptor modeling have been to airborne particulate matter.
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From page 61... ...
Also, the samplers shouici be small, lightweight, inexpensive, and easy to operate, allowing them to be used in largescale exposure studies. Because NAAQS have been issued for PM~o and PM25, the samplers should also allow personal exposures to be measured for both particle sizes simultaneously.
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It will improve source and receptor models anti improve the linkage between biological data and human exposure and atmospheric concentrations of particulate matter.
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From page 63... ...
In addition, $1 .0 million per year is needed in the first 2 years for the development of advanced exposure-measurement technology for the epidemiological studies to begin in year 4. Advanced tools for monitoring biological responses to toxic components of particulate matter will also be needed.
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To explore aciverse health effects of particulate matter requires coorciinatec! efforts in epidemiological and controlled exposure studies that provicie adequate exposure metrics that characterize size and chemist~y.
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From page 65... ...
These atmospheres can be well defined and, with the exception of the concentrated ambient particulate matter, reproduced in the laboratory. Because of the exposure variability in studies using concentrated ambient particulate matter, these must include a careful characterization of particle composition (size and chemistry)
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From page 66... ...
It is, therefore, possible that the best dose metric for ambient particulate matter might differ for different particle types, depenciing perhaps upon the physicochemical properties ofthe specific particulate-matter exposure atmospheres. Because ambient air-quality standards are based upon mass concentration, current estimates of exposure derived from atmospheric sampling networks will not relate meaningfully to response in cases where adverse biological effects are causally associated with a ciifferent particle metric for a specific particle type.
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From page 67... ...
In this regard, surface-absorbed, short-lived radicals, such as peroxides, have been suggested as potential contributors to the toxicity of ambient particulate matter, and primary reactive organics, as well as secondary organics derived from the oxidation of hydrocarbons in the atmosphere, should also be considered in this regard. Thus, there is a need to study biological responses to particles having specific chemical compositions, bearing in mind the relevance ofthis chemistry to actual constituents of ambient
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From page 68... ...
Furthermore, identification of particle characteristics that affect responses of experimental animals and humans undergoing controlled exposure studies, followeci by comparison to populations undergoing exposure in the ambient environment, would provide powerful confirmation ofthe role of specific physicochemical properties of particulate matter. The cievelopment of surrogates for ambient particulate matter for use in controlled exposure studies as an outcome of studies of physical and chemical characteristics would!
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From page 69... ...
laboratory animal and human clinical research on the toxic components of particulate matter using controlled exposure studies is estimates} to cost $~.0 million a year for 5 years. This amount includes research to identify relevant close metrics for particulate matterto assess epidemiological results.
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From page 70... ...
This information is not only critical to understanding exposure-dose-response relationships for health risks, but also to extrapolating these relationships between different types of subjects and between experimental animals and humans. At a given airborne concentration in the breathing zone, the deposited dose of particulate matter depends on the amount inhaled (inhaled concentration x volume breathecl)
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0 ~m) in the respiratory tract.
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From page 72... ...
. · Obtain better uncierstanciing of particle deposition patterns within the respiratory tracts of susceptible subpopulations as a function of particle size, hygroscopicity, and breathing rate over the entire range of particle sizes.
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From page 73... ...
Also, it is central to cleaning critical dose terms and then estimating critical closes at the organ, tissue, and cellular levels for particulate matter and its associated compounds in susceptible populations. DECISIONMA~NG VALUE This information will be critical to estimating the relative doses of particulate matter and biologically important constituents in normal and abnormal lungs, thus helping to determine the techniques needed to control the exposures of susceptible subpopulations.
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From page 74... ...
The research will include detailed morphometric measurements on abnormal lungs, development of deposition models based on the morphometric measurements, and validation of the deposition models using in viva studies of individuals with abnormal lungs. RESEARCH TOPIC 7 COMBINED EFFECTS OF PARTICU~TE MATTER AND GASEOUS COPOLLUTANTS How can the effects of particulate matter be disentang/edpom the effects of other po//utants?
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COPOLLUTANTS AND EFFECTS OF LONG-TERM EXPOSURE (EPIDEMIOLOGICAL STUDIES) Epidemiologists have generally followed two approaches to try to characterize the independent effects of particulate matter: using regression models for data analysis that includes pollutants other than particulate matter, and examining the effects of particulate matter across areas having differing levels of other pollutants.
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Further studies to investigate the influence of copollutants on health responses to particulate matter are needed in controlled-experiment laboratory studies (animal and controlled clinical studies) as well as in epidemiology.
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DECISIONMAMNG VALUE It is important to understand tile relative importance of combinations of various pollutants to health responses so that relevant pollutants can be regulated appropriately. It is also critically important to understand better the nature and effects of long-term exposures to particulate matter anti gaseous copollutants, so that the full public health effect of these combineci exposures can be assessed.
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The committee estimates that controlled exposure studies will require $3.0 million per year for the first two years, $4.0 million per year for the third through sixth years, ant! $5.0 million per year for the remain~ng years.
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The committee expects the design and implementation of new long-term epidemiological studies to be a principal activity ofthe university-based research centers. An important long-term objective is the conduct of a large-scale prospective epidemiological study ofthe public health impacts of exposure to particulate air pollution, inching both morbidity and mortality.
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From page 80... ...
At this time, the limited knowlecige about these and related factors in susceptible subpopulations prevents the cievelopment and validation of effective models for exposure assessment or prediction of actual doses. Controllecl human-exposure studies and the development of appropriate animal moclels (that mimic human respiratory anti cardiac disease)
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Clinical and epidemiological studies are neecleci to increase knowledge about the types ant! severity of health responses in susceptible subgroups.
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DESC~PTION The significance of results from epidemiological studies will be great
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Controlled clinical studies afford an opportunity to examine the hypothesis that particulate matter exacerbates pre-existing carctiorespiratory conditions in susceptible subpopulations. Appropriately designed toxicological investigations would provide mechanistic information on particulatematter-induced damage to pulmonary tissue and on the cellular and molecular events involved in the causal pathways responsible for cardiorespiratory morbidity ant} mortality.
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From page 84... ...
FRESCO rioN Associations between exposure to generally low ambient particulate-matter levels with morbidity and mortality have been observed in susceptible subpopulations, but it is not likely that low environmental concentrations of particulate matter will elicit acute health effects in healthy animals, which are the usual models in toxicological studies. Epiciemiological ciata strongly suggest that the associations between particulate matter and mortality and morbidity are manifested in subpopulations having special susceptibility factors.
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From page 85... ...
Low exposure levels and relevant exposure routes and mocies need to be emphasized. It is also necessary to assess deposition of particulate matter in ciifferent regions ofthe respiratory tract and to evaluate subsequent retention characteristics, which then can be correlatecl with specific biological responses and compared with results of exposure studies using healthy animals.
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From page 86... ...
They will also provide valuable information for designing focused clinical and epidemiological studies that will contribute to the review of NAAQS for particulate matter. They will also contribute valuable information in guiding ciecisions on important policy issues such as the indicator for the standard ant!
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From page 87... ...
In vitro studies are useful to examine a specific hypothesis based upon results of in vivo studies and can be tested using target cells of the respiratory tract. However, the method of closing has to be critically evaluated (e.g., via delivery of airborne particles or via particle suspension in the medium)
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From page 88... ...
DECISIONMA~NG VALUE The use of appropriate in vitro mociels will provide valuable inciirect information to support other investigations of the mechanisms of particulate-matter toxicity, which will assist in the interpretation of epidemiological data that show associations between particulate-matter exposure and cardiorespiratory disease. Specifically, disease-related mechanistic information at the cellular and molecular level could add significantly to the weight of evidence regarding a causal relationship between particulate-matter exposure anti human morbidity.
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From page 89... ...
Clearly, clinical models will focus on acute responses that often have implications for chronic effects. SCIENTIFIC VALUE Associations between exposure to generally low ambient particulatematter levels anti morbidity have been observed in susceptible
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From page 90... ...
Carefully clesigneci clinical studies will provide information on symptomatic, physiological, ant! cellular responses in healthy end susceptible subpopulations, namelythose with pre-existing cardiorespiratory conditions.
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Extensive covariate adjustment is required to minimize the possibility of confounding factors. Exposure measurement error can have the effect of understating risk, as well as o~rerstating the precision of risk estimates.
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· Are existing epidemiological cIata aciequate to identify the most relevant timing characteristics of exposure? · Is residual confounding a concern in particulate-matter epidemiological studies?
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FEASIBILIn' AND TIMING Although analytic methods for the evaluation of data from epidemiological studies ofthe health effects of particulate air pollution are rela
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fob. MEASUREMENT ERROR What is the effect of measurement error and misclassification on estimates of the association between air pollution and health?
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The components of this difference include errors in the accuracy and precision of the monitoring instrument; differences in exposure due to the placement of the ambient monitor (related to the zones of representation for a monitor or to the spatial homogeneity of the environmental agent measured) ; differences between ambient concentrations useci to characterize a pollutant exposure and the average personal exposure to that pollutant or, for particulate matter, its mass or the size fractions and chemicals of biological significance; anti the differences between average personal exposure levels and the exposure of a given individual.
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· What are the effects of measurement error on the estimated associations between particulate matter (or its size fractions and biologically important chemical constituents) and health?
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From page 97... ...
COST Much ofthe data required to address the issue of exposure measurement error will be collectecl through personal exposure studies conducted as part ofthe enhanced exposure monitoring component ofthe overall particulate research program. Nonetheless, additional studies designed to characterize ciistribution measurement error distributions will be needled.
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