Epidemiology and Air Pollution (1985)

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EXPOSURE ASSESSMENT 89 3 EXPOSURE ASSESSMENT INTRODUCTION This chapter discusses the relationship of exposure assessment to the design and conduct of epidemiologic studies of air pollution. After presenting a working definition of exposure assessment, it discusses the pertinent history of air pollution monitoring and a framework for contemporary exposure assessment. The chapter then identifies the types of pollutants that the Committee feels require attention, indicating some physical, chemical, and spatiotemporal properties that are relevant to exposure assessment. Sections on special approaches to indoor pollutants and monitoring considerations follow, including opportunities for providing optimal exposure data in future epidemiologic studies. Finally, several important characterization studies are reviewed. Exposure assessment refers to a set of multidisciplinary activities that describe who is exposed to how much of what substances, for how long, and under what conditions.14 Exposure assessment, whether based on direct measurement or modeling, is a vital part of all environmental epidemiology. Exposure assessment of air pollutants is particularly complex, because pollutants do not occur independently, but as mixes of natural, industrial, transportation, and residential emissions. The focus of interest in this chapter is human exposure. Hazards to the environment, such as from acid deposition, are important, but are not the subject of this report. In an epidemiologic study, exposure assessment can be addressed before, during, and after the collection of 

EXPOSURE ASSESSMENT 90 health effects data. Conducted beforehand, it can lead to improvement in study design by treating the issues of subject selection, sample size, scale and frequency of monitoring, and usefulness of such tools as fixed-site monitors and descriptive questionnaires. Exposures can then be remeasured, in conjunction with health effects measurement, to provide a basis for a quantitative estimate of the association between exposure and effect. Exposure assessment has many purposes in air pollution research aside from providing exposure variable measurements for epidemiologic studies. Independent and parallel efforts to describe exposure may aim, for example, to determine the effectiveness of efforts to lower exposures, compare possible risks between various populations with different exposure conditions, develop siting and timing strategies for routine ambient air monitoring, and weigh the importance of various components of multisource and multimedium exposures. Obviously, some of these functions require assumptions about quantitative risk relationships based on previous health effects studies. Also, rather than incorporate new exposure assessment and costs into each epidemiologic study, we can often rely on information and assumptions derived from well-designed, independently conducted exposure assessment research. The central theme of this chapter is that the integration of exposure assessment into an epidemiologic study and the decisions as to which aspects of exposure assessment to emphasize will depend on the nature of the specific research question. To be effective under current conditions, exposure assessment in air pollution epidemiology must be flexibly based on reasonable biologic modeling of exposure and effect and must comprise the degree of detail required by the research question. Thus, environmental monitoring should not be restricted arbitrarily from the outset to indoor or outdoor sources or to fixed or personal monitors. The advance in measurement technology increases the variety of potential epidemiologic studies, but does not in itself provide a valid rationale for a given study. The mere ability to measure exposure to a pollutant precisely is not a sufficient reason to launch a study; indeed, many studies that are possible might be unimportant or of unlikely productivity. 

EXPOSURE ASSESSMENT 91 The ultimate goal of exposure assessment in epidemiologic studies of air pollution is to minimize the misclassification of study subjects by exposure magnitude or type. Common variations in outdoor and indoor concentrations and the proportions of time people spend in different locations can yield substantial overlap in the true total exposure between subjects assigned to high- and low- exposure groups. This applies whether exposure magnitude is assigned on the basis of categorical descriptor variables or ambient monitoring from central stations. Misclassification is a major reason for loss of sensitivity in such studies; it increases the likelihood that a study will fail to detect a real association between an air pollution exposure and a health effect. The problem of exposure misclassification is described in more detail in Appendix C and several recent papers.6 10 18 EXPOSURE, DOSE, AND BIOLOGIC MARKERS Most epidemiologic studies of air pollution have assumed that exposure, however measured, constitutes an adequate surrogate of the dose of a given pollutant. Recent advances in toxicology and molecular epidemiology have clarified the meaning of these terms and emphasized some important distinctions.56 “Exposure” (see Figure 1) commonly refers to concentrations of pollutants measured in the environment. As to dose itself, two distinctions can be made: “internal dose” is the amount of a substance or its metabolites in body tissues, and “biologically effective dose” is the amount that interacts with a particular target tissue or its surrogate.14 In this report, however, “exposure,” unless otherwise specified, refers to all kinds of exposure, from ambient air to critical target organ. Research is required to relate a specific ambient exposure to the dose received by a given target tissue in the respiratory tract and to relate that dose, in turn, to a specific health effect. This research will ultimately benefit future epidemiologic studies of air pollution. One of the major constraints in determining the relationship between exposure to air pollutants and the development of nonneoplastic diseases of the respiratory tract is the lack of biologic markers of exposure. Biologic markers that would indicate the cumulative dose of specific pollutants or types of pollutants to the 

EXPOSURE ASSESSMENT 92 FIGURE 1 Framework for exposure assessment. 

EXPOSURE ASSESSMENT 93 respiratory tract would be invaluable in determining precise relationships between exposures and disease. HISTORICAL BACKGROUND As analytic techniques became available around the turn of the century, air pollution investigations moved beyond crude and subjective forms of exposure assessment (e.g., number of foggy days, amount of coal use, or distance from emission sources) to measurement of pollution surrogates, such as dust fall or total acidity. Air monitoring in major European cities for sulfur dioxide, SO2, and smoke began in the 1930s. In the United States, federally sponsored surveys of urban air pollution began in the middle 1950s, and routine monitoring was common by the late 1960s. Today, air pollution monitoring is a highly developed field of applied science. Sophisticated analytic devices are available for measuring many contaminant gases continuously; and particles can be separated by size and analyzed for chemical composition (see box on instrumentation). However, many of the established air pollution monitoring networks were not designed to test explicit biologic models of the health effects of air pollution. Pollutant monitoring typically provided averaged concentration data, usually over 24 hours or a full year, except for hourly data on ozone, O3, and carbon monoxide, CO. Cumulative exposure, frequency of concentration peaks, lag effects, and combined pollutant exposure indexes could not be explored in the air pollution epidemiology of the 1940s, 1950s, and 1960s. Current standards for SO2 and total suspended particles (TSP), based on past data, can thus be surrogates for other exposure times or pollutant species that are really responsible for the effects of concern. Likely candidates include size-fractionated particles and acid aerosols and gases. Until very recently, most air pollution epidemiology investigated relationships between adverse health outcomes in a population and average ambient air pollution concentrations. Most often, data from relatively few central outdoor monitoring stations were used to represent the exposure of all subjects in an entire residential community. Indoor sources that could contribute to total personal exposures to many of the 

EXPOSURE ASSESSMENT 94 A NOTE ON AVAILABLE INSTRUMENTATION Since the early 1970s, instruments and techniques for monitoring exposure to air pollutants have grown substantially in sophistication. Many types of continuous and integrating (discrete period) samplers have been developed for use in a variety of situations, both indoors and outdoors, and they are easily adaptable for providing data on cumulative exposure, time- lagged responses, and frequency of periodic exposure peaks. Quantitative chemical analysis now offers precision and sensitivity far greater than those required for most epidemiologic studies. Personal monitors are available in two basic types: active monitors, which use a pump to draw a measured volume of air into a collecting medium; and passive monitors, which are small lightweight badges that sample by passive diffusion of chemicals. The recent rapid development of diffusion badges is particularly notable, because they have become inexpensive and inconspicuous enough to be used for large populations. However, personal monitors are still all of the integrating type; the choices of sampling and averaging times are limited by available instrumentation. Detailed information on specific equipment can be found elsewhere.15 31 pollutants encountered outdoors were rarely considered. Studies implicitly assumed that the differences in outdoor concentrations of some pollutants between cities or between regions within a community were more important determinants of individual or population exposures than housing or other personal factors. In past decades, when outdoor concentrations in many urban areas were higher than today, they might in fact have been the most important determinants of population exposure to SO2, TSP, benzo[a]pyrene (BaP), and other major industrial and utility-derived pollutants. If differences in exposure within groups are small, compared with differences between groups, the use of fixed monitors at representative sites in the community might suffice. But pollutants with 

EXPOSURE ASSESSMENT 95 important indoor sources or sharp variations in outdoor concentrations from place to place within people's daily mobility range could yield large differences in exposures within groups and require some incorporation of personal measuring techniques. Therefore, although outdoor ambient measurements might still be appropriate for some current questions in air pollution epidemiology, future studies will have to look at exposure in a more sophisticated context. FRAMEWORK FOR EXPOSURE ASSESSMENT In the last decade, recognition of the complexity of the determinants of individual exposure to air pollutants and the impact of misclassification has led to the need for a new conceptual framework for exposure assessment. Figure 1 depicts the relationship of indoor and outdoor pollutant sources and concentrations to each other and to total personal exposure. “Total personal exposure” refers here not only to the total, time-integrated cumulative exposure, but to the number and character of significant peak exposures, because in air pollution studies exposure assessment can develop from a biologic model of the exposure-effect relationship that involves cumulative exposures, peak exposures, or both. We are beginning to understand the interaction of key factors in determining total exposure to some pollutants. Outdoor emission sources contribute to outdoor concentrations, which in turn penetrate to a degree into indoor environments; and indoor sources also contribute to indoor concentrations. The relative importance of indoor and outdoor concentrations in determining personal exposure (average or peak) to a given pollutant depends on several factors, including the location of the predominant source of the pollutant, the daily time-activity patterns of exposed people, other host factors, and the pollutant's entry into, mixing in, and removal from a structure. More detail on the impact of indoor pollutants on air pollution epidemiology will be provided in a later section. With our present knowledge, we can divide air pollutants into three categories by source: • Outdoor, e.g., SO2, sulfates, O3, and lead. • Outdoor and indoor, e.g., fine particles, nitrogen dioxide, and CO. 

EXPOSURE ASSESSMENT 96 • Indoor, e.g., volatile organic chemicals, formaldehyde, woodsmoke, and radon. Of course, these categories might not apply in exceptional situations, such as in communities near industrial point sources. Total personal exposure to an air pollutant is a conceptually important measure for epidemiology. Among the exposure measures that are practically attainable, total personal exposure is the most valid predictor of the risk of any air-pollution-related health effect in a given person. Ideally, perfect individual exposure data (with no misclassification) could come only from measurement of biologically effective personal dose (see Figure 1). All methods of measuring individual exposure are essentially surrogates and can be ranked according to their crudeness or likelihood of misclassification error: • Total personal exposure: direct personal monitoring in breathing zone. • Total personal exposure: indirect area monitoring. • Predictive models using questionnaire and other data. • Questionnaire data (categorical descriptors) without modeling. To assess total personal exposure to air pollutants, one can sample near the breathing zone of the subject with portable instruments or one can find the time- weighted sum of concentrations measured in a series of locations in which the subject spends the day. The latter, indirect approach requires time-activity logs and portable area monitors (rather than smaller monitors that are worn) for measuring microenvironmental concentrations. It is important to distinguish between direct measurement and indirect estimations of total personal exposure. Indirect estimations necessarily assume that contaminant concentrations within the microenvironment are uniform-for example, that within an office or a particular room in a home the concentration measured at one point accurately represents the entire small area. However, multiple measurements often reveal widely varied concentrations 

EXPOSURE ASSESSMENT 97 within a microenvironment. The design of a monitoring program can mitigate this oversimplication to some extent. Research is also underway to improve the statistical handling of data from indirect personal exposure assessment and to resolve unexplained discrepancies with direct measurements. It might ultimately be more practical and cost-effective to pursue the indirect estimation approach for some epidemiologic studies, inasmuch as accurate, inconspicuous, and affordable personal monitors are not available for all pollutants and quality control of personal monitoring is more difficult than that of area monitoring. Furthermore, on the basis of the pollutants involved, a substantial fraction of the variance in human exposures might be explained by monitoring in relatively few locations. As the complex interaction of the variables becomes clarified in exposure assessment research, accurate predictive models for estimating average or peak exposures can be developed for some types of pollutants.28 These models, which can use various kinds of data to minimize the need for actual measurements, are potentially applicable to epidemiologic studies. Future studies might use combinations of measurement and modeling approaches. Several factors can modify personal exposure or dose and should be addressed in planning exposure assessment for epidemiologic studies: • Activity: The amount of an air pollutant inhaled depends in part on ventilatory rate. Exercise or manual work can influence total dose. • Respiratory tract anatomy and physiology: The relationships among lung volume, ventilatory rate, and body size vary with age and race. Infants have a high ratio of ventilation to body size and can therefore have greater pollutant dose per unit of tissue than older people. The accessibility of various sensitive regions of the lung to pollutants also varies between persons. A smoker with a damaged mucociliary mechanism might receive a greater dose from a given ambient exposure than a nonsmoker. • Weather: Meteorologic conditions can affect the concentrations of pollutants, including those formed 

EXPOSURE ASSESSMENT 98 after emission of precursors. Weather also can produce some respiratory changes that are similar to those produced by pollutants. Climate has obvious effects on activity patterns and on housing characteristics that influence air exchange. Not all epidemiologic studies on air pollution require measurement of total personal exposure. Personal monitoring itself is an option, rather than a prerequisite, for good exposure assessment. Chapter 4 discusses the actual role of personal monitoring in epidemiologic studies on air pollution. Here it need be stated only that the current framework for viewing total exposure offers more precision and improved flexibility in choosing where to measure air pollution and therefore demands more careful planning. SOME POLLUTANTS OF CONCERN PHYSICAL, CHEMICAL, AND BIOLOGIC CHARACTERIZATION Planning of epidemiologic studies requires information on the composition of ambient air in the communities of interest and its variation over space and time. Prior assessment of ambient concentrations can help to define the populations potentially exposed to the contaminants of interest; in some instances, potentially confounding pollutant patterns or other variables can be identified. The degree of prior assessment varies widely, but sometimes it involves obtaining detailed information about the chemical, physical, or even biologic nature of the air in a community. Some emission is “fresh” from local sources; some is “aged” from distant sources. Reactive and unreactive compounds undergo changes in the atmosphere after emission. Most notable is the photochemical transformation of nitrogen oxides and hydrocarbons to O3 and other photochemical oxidants. Some gases are oxidized to aerosol species, such as SO2 to aerosol sulfate, SO4−2 and nitrogen dioxide, NO2, to aerosol nitrate, NO3−2. Wet and dry deposition processes alter the concentration and composition of ambient pollutants. Because emission patterns and the meteorology of transport, transformation, and dispersion vary temporally, as well as spatially, most epidemiologic studies must carefully characterize 

EXPOSURE ASSESSMENT 99 several pollution-related variables in addition to the contaminant of interest. Prior assessment of this nature can help to reduce the scope of effort required in a study. A review of several characterization studies appears at the end of this chapter. The mix of pollutants in the environment includes some “older” regulated pollutants that still present stubborn problems and other, newly emerging or previously ignored pollutants that require attention. The pollutants vary in several critical ways: from primary emission to secondary product, from outdoor source to indoor source or both, from presenting a direct health threat to indicating other pollutants, and from spreading over vast areas to accumulating in specific microenvironments. Pollutants known to be sufficiently widespread or present in sufficiently high concentrations to warrant study in future epidemiologic investigations include: • Acid aerosols, acid gases, and O3. • NO2. • CO. • Lead. • Radon and its progeny. Emerging classes of pollutants that might require epidemiologic and exposure studies include: • Volatile organic chemicals (VOCs) and products of incomplete combustion (PICs) from new or reintroduced sources. Some aspects of these six classes that are relevant for planning of future studies are discussed below. ACID AEROSOLS, ACID GASES, AND OZONE For the secondary pollutants O3 and acid aerosol (for example, sulfuric acid, H2SO4, and ammonium bisulfate, NH4HSO4), the primary source of human exposure is the outdoor environment. Acid aerosol particles constitute a 

EXPOSURE ASSESSMENT 100 highly variable fraction of a regulated pollutant--particulate matter. Almost all acid aerosol is included in the fine particle (FP) and particulate matter 10 (PM10) fractions, although FP and PM10 measurements alone do not differentiate among the inorganic and organic compounds that make up particulate mass.* Recent data, from both laboratory and epidemiologic studies, have suggested that SO4−2 in ambient air can be a particular cause for concern.16 58 Ambient concentrations of O3 and SO4−2 can be highly correlated and relatively uniform over very large geographic areas in the summer and have the potential for affecting large segments of the population downwind of areas of precursor emission, particularly during major regional photochemical smog episodes.9 29 35 45 63 However, during such episodes, the distribution and speciation of H2SO4, NH4HSO4, and the fully neutralized ammonium sulfate, (NH4)2SO4 (in decreasing order of presumed toxicity), have not been examined in a systematic fashion. Therefore, examination of the areas where SO4−2 makes up a substantial portion of FP and PM10 and where widespread exposure to H2SO4 can occur should define the best opportunities for epidemiologic investigations. Mapping of changes in ozone concentrations in the Northeast over a single day has indicated (see Figure 2) that nonurban areas downwind of New York City receive the highest episodic ozone exposures and that locations farthest from this source of precursor emission reach their peak ozone concentrations latest in the day.8 Movement of photochemical plumes is determined in part by meteorologic conditions, such as prevailing windspeed and wind direction. These and other observations concerning the spatiotemporal characteristics of O3 transport should be considered in determining the selection of populations and the timing of health effects measurements in epidemiologic studies. * The FP fraction consists of particles less than 2.5 µm in aerodynamic diameter, and the PM10 fraction, particles of 10 µm or less in aerodynamic diameter. Both PM10 and FP can be easily inspired deep into the lung. 

EXPOSURE ASSESSMENT 101 FIGURE 2 Spatial and temporal variations in ozone concentrations in the northeastern United States, July 2, 1974. During summer, when winds from the Southwest commonly prevail, daily movement of photochemical activity is from the New York City region into southern New England. Ozone concentrations are proportional to circle diameters. Reprinted with permission from Cleveland et al.8 

EXPOSURE ASSESSMENT 102 FIGURE 3 Predicted annual sulfate concentrations in 1990 from the Brookhaven long-distance transport model. Emissions are from major coal-burning facilities and include area sources. Sulfate concentrations are proportional to altitude and spatially averaged over 32 x 32-km grids (x,y). Reprinted with permission from Wilson et al.62 Predicted annual concentration patterns of SO4−2 (Figure 3) indicate that the eastern third of the coterminous United States will be substantially exposed and that the exposure will contrast sharply with that in other parts of the country. In winter and in the presence of specific meteorologic conditions, such as plume fumigation (downward diffusion of stack emission) and fog, primary acidic particulate sulfate can exist independently of O3. However, in such circumstances, the areas selected for study would probably be much smaller than those selected in summer smog episodes and include urban centers or areas downwind of power plants. Exposures to acid aerosols and O3 are modified in accord with the ability of each pollutant to penetrate indoors (e.g., air-conditioned versus non-air- conditioned environments during the summer) and to react with surfaces 

EXPOSURE ASSESSMENT 103 and with other indoor air contaminants. O3 in particular is rapidly dissipated after contact with textured indoor surfaces, such as rugs, curtains, books, and furniture.39 The accumulation of O3 outdoors usually results from a complex series of photochemical reactions that produces other irritant species (aldehydes, peroxyacetylnitrate, etc.). The Environmental Protection Agency has established continuous monitoring networks to determine compliance and detect the presence of O3 in nonurban and urban areas throughout the country. However, concern over potential health effects in groups spending large portions of the summer day outdoors during periods of maximal O3 and SO4−2 exposure will require adjustments in monitor locations for epidemiologic purposes. NITROGEN DIOXIDE NO2 exposure poses different problems for epidemiologic research. Personal exposure to NO2 can have both indoor and outdoor components, with the highest exposures occurring indoors in the presence of unvented combustion sources (e.g., gas stoves).41 A systematic investigation of the health effects of short-term and chronic exposures to NO2 in summer and winter is required. The study designs must include examination of a variety of microenvironments that have and do not have indoor sources of NO2. CARBON MONOXIDE The measurement of CO exposure presents design questions similar to those presented by NO2 measurement, in that both outdoor and indoor sources typically are present. Recent studies of total exposure to CO in Boston, Denver, and Washington, D.C., have indicated a lack of association between outdoor CO concentration and personal-monitor measurements based on diffusion badges.24 65 Personal monitors for CO are reliable, but broader studies of exposure are needed to define populations at risk. Typical and extreme case studies of temporal and spatial variations are required for examination of short-term effects and accumulated burdens and for relation of these exposures to changes in 

EXPOSURE ASSESSMENT 104 carboxyhemoglobin, a well-validated biologic marker of exposure. LEAD The study of lead as a pollutant of epidemiologic concern requires careful consideration of both indoor and outdoor environments. The populations for study could be large, because of the continued presence of lead in gasoline. Inasmuch as average blood lead concentrations have decreased from 1976 through 1980 with the national decrease in lead in gasoline, it will be important to study whether additional declines are associated with the phased-in reduction of lead in gasoline. Future air pollution studies on lead in the United States must also focus on individual point sources, such as smelters.3 Outdoor measurements could well be needed at sites other than a centralized monitoring station; for instance, recent data suggest that people can be substantially exposed to airborne lead in motor vehicles.54 Future studies of environmental lead exposure should differentiate the relative contributions of water, food, workplace, and other sources to total lead exposure, as reflected by such measures as blood or dentin lead. RADON AND ITS PROGENY Radon and its decay products are of much concern, because radon is a primary indoor air pollutant and has common natural environmental sources, such as the earth surrounding residences, building materials used to construct homes, and water that enters homes.36 37 The problem has grown since the 1970s, as homeowners have sealed residential structures to reduce energy consumption. Some investigations of radon exposure will require study sites with maximal potential for exposure (i.e., homes in potential radon hot spots in the earth's crust), and others should be based on representative cross sections of the housing stock in the United States. Estimates of exposures of select populations with high exposures are available, but estimates that are more representative of the general population are needed. Studies of radon exposure should include samples integrated over the course of an entire year. 

EXPOSURE ASSESSMENT 105 VOLATILE ORGANIC CHEMICALS AND PRODUCTS OF INCOMPLETE COMBUSTION VOCs and PICs--large groups of materials that can be toxic, carcinogenic, or both--are associated with small and increasingly numerous sources. An estimated 11 million American homes are now heated at least partially by wood fuel.7 In addition, VOCs are likely to be emitted from new manufacturing processes involving the plastics, chemical, and semiconductor industries, as well as older sources, such as dry-cleaning establishments and filling stations. PICs and VOCs are usually classified on the basis of their organic constituents. In addition to the multitude of individual compounds to be examined, problems arise from the lack of suitable chemical tracers or surrogates. For instance, total polycyclic aromatic compounds and benzo[a]pyrene, two commonly measured surrogates, might give but a poor reflection of the carcinogenic potential of PIC mixtures under some conditions. A relative toxicity ranking of the components of complex mixtures produced by different combustion fuels and combustion conditions could be useful. Important sources of PICs are wood, kerosene, and coal stoves; industrial and utility boilers; and internal-combustion engines.43 Common sources of VOCs are household and commercial solvents, paints, dry-cleaning solvents, plastics manufacturing plants, unburned automotive fuel, and hazardous waste sites.20 33 40 42 Hence, appropriate sites for exposure studies would include homes where solvents are regularly used indoors, homes near single major outdoor sources of PICs or VOCs or clusters of small industrial and commercial sources, and areas where PIC emission is dominated by one type of fuel used for space heating. INDOOR POLLUTANTS: SPECIAL PROBLEMS AND PROSPECTS Documentation of the importance of indoor concentrations of pollutants is profoundly altering air pollution epidemiology. Today in the United States over two-thirds of our time, on the average, is spent indoors. Therefore, the presence of even moderate amounts of pollutants indoors can influence the classification of a person with regard to pollutant exposure. 

EXPOSURE ASSESSMENT 106 The increased energy costs of the 1970s stimulated efforts to conserve fuel through insulation, reduction in air exchange, and fuel switching. Residential and commercial buildings are a prime target for conservation efforts, because together they consume about one-third of this nation's energy, nearly all for heating, cooling, and moving air. Thus, reduction in ventilation or air exchange has become an important energy conservation strategy. But this strategy has tended to increase indoor concentrations of particles, CO, NO2, radon, aldehydes, and other organic compounds. Some housing patterns may also increase concentrations of bacteria, fungal spores, and aeroallergens. In a related development, wood and coal stoves and kerosene heaters have displaced the more expensive oil, gas, and electricity in some areas. Many consumer products, furnishings, and construction materials recently introduced into the commercial market give off VOCs. Other older but unrecognized problems have come to the fore; asbestos in insulation and building materials and radon in soil and water are examples. (A more comprehensive treatment of this subject can be found in the 1981 National Research Council publication, Indoor Pollutants.38) Specific indoor exposures can now be considered in the framework described above for epidemiologic exposure assessment. Respirable particles, which were defined as those with median aerodynamic diameter less than 3.5 µm, were monitored in an extensive indoor air quality survey of over 80 homes in six U.S. cities;44 24-hour samples were collected every sixth day for up to 2 years from stationary samplers in each home. The results of this survey are illustrated in Figure 4. On the average, indoor concentrations were higher and had a much greater range across homes than outdoor concentrations. It is clear from comparisons of smoking and nonsmoking homes that smoking is a very important contributor to the increase in the respirable-particle fraction, which can also contain inert dust, fibers, aerosols (from spray cans), spores, aeroallergens, and viable organisms. Several U.S. epidemiologic studies have reported that the percentage of young school-age children living with one or more smoking family members varied from 54% (in Tucson, Arizona) to 75% (in St. Louis, Missouri).38 However, even in nonsmoking homes, indoor respirable-particle concentrations--due to a variety of unspecified 

EXPOSURE ASSESSMENT 107 FIGURE 4 Monthly mean respirable-particle concentrations across six U.S. cities. Reprinted with permission from Spengler and Soczek.45 activities--can be higher than outdoor concentrations.38 Thus, problems were encountered in attempting to investigate the health effects of these particles in ambient air, because the variation in indoor concentration among homes within cities is far greater than the variation in outdoor concentration between cities. The impact of indoor pollutants on total exposure can also be illustrated with results of some recent personalexposure studies. In the last 10 years, the availability of lightweight portable sampling pumps and diffusion badges has allowed investigators to compare total personal exposure to indoor and outdoor pollution simultaneously. These investigations have revealed low correlations between outdoor concentrations and integrated personal exposure for some important pollutants, such as respirable particles and NO2. In the situations studied for these pollutants, indoor concentrations appear to be better predictors of time-averaged exposure (and the potential for substantial peak exposures) than outdoor concentrations. Preliminary results from EPA's Total Exposure Assessment Method (TEAM) study indicate that personal exposures to VOCs are greatly influenced by consumer product uses. 

EXPOSURE ASSESSMENT 108 FIGURE 5 Daily average indoor, outdoor, and personal concentrations for 46 persons in Topeka, Kansas. Reprinted with permission from Spengler and Tosteson.47 In the personal-exposure studies on respirable particles, subjects (mostly adults) carried portable samplers and recorded time in various places and activities. The data were used to determine how accurately central-site outdoor monitors represented the actual day-to-day personal exposures within a community. In Topeka, Kansas, 45 nonsmoking adults carried monitors during the active 12-hour periods of the day.54 Husband-and-wife teams participated in an 18-day study. Figure 5 illustrates the differences in daily outdoor, in-home, and personal concentrations of respirable particles collected in the study. Note that the indoor concentrations are higher than the outdoor, and the personal exposures higher still. This indicates that somewhere in their daily activities subjects were receiving a greater exposure to particles than could be explained by the measurements taken either in their homes or outdoors. Passive smoke exposure (either outside the home or in rooms other than those monitored) appeared to provide an explanation. In one set of measurements from this group, respirable 

EXPOSURE ASSESSMENT 109 particle concentrations were 20 µg/m3 higher in those reporting some passive smoke exposure than in those reporting none. The personal exposures of neither the husband nor the wife were correlated with the ambient outdoor measurements. Husband and wife concentrations showed considerable common variance; their measurements had a correlation of 0.5. The wives' exposures were significantly correlated (0.7) with home measurements. Although indoor concentrations do not completely explain personal exposures, information from the Kansas study and from other exposure studies5 has indicated the importance of home measurements in understanding total personal exposure to particles. Categorical descriptor variables and ambient outdoor concentrations are notoriously poor predictors of personal exposures. Outdoor measures explain less than 1% of the interindividual variance in personal exposure to respirable particles. The indoor concentration by itself explains over 60% in adults.45 Similar studies have recently examined the role of various sources in determining total exposure to NO2. Indoor residential concentrations correlated poorly with outdoor concentrations, but were related to frequency of gas cooking and variations in air exchange rates (including seasonal variations). In Portage, Wisconsin, where ambient NO2 averages only 15 µg/m3, gas cooking adds, on the average, 45 µg/m3 to indoor concentrations.41 Surprisingly, 3% of homes monitored in Portage, which has relatively clean air, exceeded the National Ambient Air Quality Standard of 100 µg/m3. The important implication is that a substantial portion of the U.S. population, on an average day, is exposed to NO2 at a concentration over the health standard, when both indoor and outdoor sources are considered together. Epidemiologic research on indoor pollutants is only beginning. There have been very few systematic investigations of passive smoke exposure or exposure to aeroallergens, radon, and other common indoor contaminants. The relative contributions of these pollutants to the total indoor air quality problem remain to be determined.44 Even the few reported studies have not adequately characterized exposures to indoor pollutants with direct measurements. The development of simple, lightweight, and inexpensive monitoring instruments will have great 

EXPOSURE ASSESSMENT 110 benefits in this field. Passive collectors that yield time-integrated measurements are useful, but are not always best for a particular application. Short-term peak concentrations, which can be measured only with continuous monitors, have greater biologic relevance for some pollutants. SITING AND TIMING OF AIR POLLUTION MONITORS In past epidemiologic studies, cost considerations and a simple view of exposure have favored the use of routinely collected data on air quality. Siting guidelines for EPA national air monitoring stations are available for primary pollutants (such as SO2, nitrogen oxides, lead, and CO), secondary pollutants (such as O3), and combinations of the two (PM10). As noted earlier, the national network was not established for epidemiologic purposes. Although the data it provides might have been adequate for studies involving larger contrasts in exposure, many current studies must have tighter control over the error involved in estimating individual exposures via remote outdoor stations. Decisions regarding the siting of stations for routine air monitoring were not usually made according to the needs of public health researchers. As a 1964 symposium on environmental measurements aptly noted: Some of the considerations in selecting a suitable (sampling) area were openness of the surroundings, availability of utilities, proximity to atypical sources, and approval of city building commission or other authorities.57 The later introduction of clean air standards promoted the location of monitors near emission sources in the most polluted areas of a given community, where violations would be most likely. The search for ideal sampling locations for epidemiologic purposes has led to the use of complex statistical approaches to siting. A goal, for example, is a location that will represent a homogeneous population unit with regard to magnitude of exposure while minimizing the total number of stations. The complexity and expense of such efforts should not be underestimated. The Nashville 

EXPOSURE ASSESSMENT 111 air pollution study in the early 1960s, perhaps the most ambitious so far, used a regular grid of 123 monitoring stations.64 Subareas with contrasting exposure could be identified, and some stations were determined to be redundant. It was feasible to identify such contrasts for only two pollutants, particles and SO2. In spite of the wealth of data from the Nashville study, generalization to other cities, periods, and pollutants has been very difficult. Within cities, the potential variation in exposure over short distances and the nonuniform distribution of population frustrate statistical sampling strategies, which are limited by the availability of funds. Rather than convert varied exposure to a homogeneous value, epidemiologic studies might need to take advantage of variability itself. Grid approaches to monitor siting appear to have less appeal today than approaches based on expert judgment. Locations for monitors in future studies will require information on meteorologic characteristics, sources and density of emission, and other conditions that indicate potential for accumulating high concentrations of pollutants. For example, a monitoring location suited for obtaining CO exposure estimates would not be appropriate for O3, because direct automobile emission quenches atmospheric O3. Variations in pollutant concentrations over time are a major source of biologically relevant information about exposure. The nature of the questions asked by a particular epidemiologic study and the type of health effect under study dictate important decisions concerning sampling times and intervals. Pollutant concentrations vary substantially from year to year, season to season, and day to day, and from time to time in a given day. Temporal aspects of exposure are also involved in the process of reducing continuous data or sequential samples into single numbers. Theoretically, the ideal sampler would provide continuous measurements from which peaks, integrated exposures over different intervals, and trends might be discerned. But such a sampler would be prohibitively expensive, and it would not absolve researchers of the need to make sense of the limitless data produced. The details of daily or even seasonal variation in pollutant concentrations would mean little in a study whose aim was to relate lifetime exposure with risk of 

EXPOSURE ASSESSMENT 112 chronic effects. Techniques for reconstructing past exposures and creating long- term historical exposure indexes are likely to be more appropriate in such instances. Biologic models concerning the presumed action of air pollutants have not always been explicitly considered in planning epidemiologic studies. For some irritants, such as SO2, the number and duration of peaks might be more relevant than smoothed average concentrations in determining effect. This applies to both chronic and acute effects, in that the role of cumulative acute insults in the development of chronic lung disease remains in question. Laboratory studies on animals and controlled-exposure studies on humans can provide guidance in determining relevant features of temporal variations. CHARACTERIZATION STUDIES Over the last 10 years, a number of studies have successfully characterized indoor and outdoor environments--for example: • Houston Area Oxidants Study (HAOS).4 • Portland Aerosol Characterization Study (PACS).61 • Persistent Elevated Pollution Episodes (PEPE).19 • New York Summer Aerosol Study (NYSAS).27 • California Aerosol Characterization Experiment (ACHEX).21 • Regional Air Pollution Study (RAPS).1 • Denver Brown Cloud.11 • Sulfate Regional Experiment (SURE).35 • Harvard Air Pollution Health Study.46 • Total Exposure Assessment Method (TEAM).59 • New Jersey Project on Airborne Toxic Element and Organic Species (ATEOS).30 

EXPOSURE ASSESSMENT 113 The characteristics of the exposed population and of the pollutants themselves were explored in some cases. These studies had a variety of objectives, but their results can be used to plan the characterization data needed for new epidemiologic studies. Lippmann et al.32 used the design of PEPE, which characterized ambient air in regions near Indiana, Pennsylvania, to design a field study of children's response to regional haze at a summer camp. The Harvard Air Pollution Health Study included a number of characterization experiments that ultimately led to the identification and examination of population exposures to both indoor and outdoor pollutants. The ATEOS project has characterized urban areas with different mixes of industrial, commercial, and residential activities for the presence of potentially mutagenic or carcinogenic species;30 it yielded information that can now be used in the design of epidemiologic studies on ambient carcinogens and mutagens. The VOC studies conducted in the TEAM project have yielded important cross-sectional exposure information that suggests opportunities for future epidemiologic research.59 Although this project measured a wide range of materials, future investigations must focus on specific questions, because there are a large number of potential compounds and sources. Characterization studies should eventually be able to limit the volatile organic hydrocarbons to an important subgroup that might require epidemiologic investigations. The TEAM study has shown that specific microenvironments (e.g., self-service filling stations) will have to be considered in future population studies and that we must include the characterization of populations that could be exposed to high concentrations in either indoor or outdoor environments. Pollutant characterization for epidemiologic purposes must go beyond the standard indexes, which actually stand as surrogates for complex mixtures. The commonly used index TSP is an example. TSP is composed of particles of various sizes, primary and secondary pollutants, and inorganic and organic species. For instance, SO4−2 species53 and organic matter12 are associated primarily with the fine-particle fraction (FP), whereas ammonium nitrate is usually found on both FP and coarse particles (aerodynamic diameter, greater than 2.5 µm).26 Variations in the relative proportions of these components will affect the anticipated biologic effects of breathing 

EXPOSURE ASSESSMENT 114 air that contains them. Characterization of such components is essential in selecting study populations with critical contrasts in exposure. A much improved kind of exposure assessment research, which will assist in the design of epidemiologic studies, is the resolution of sources that contribute to measured air concentrations. Most of the work to date has been done on the outdoor sources of particulate matter. Information on the approach called source-receptor modeling can be found in EPA reports and original research papers.2 13 48 A variety of mathematical techniques are available, including chemical-element balance17 and multiple-regression factor analysis.25 The main product of each technique is an estimate of the percentage of particle mass in a given sample of air that can be attributed to an individual source or type of source. This information will be very useful in the development of measures to regulate the contributions of sources that are found to produce a health effect in an exposed population. It will also be helpful in explaining the variation in personal exposure within a sampled area that could be attributable to variation in individual proximity to sources. EPA has recently published its rationale for converting the TSP standard to one based on PM10, in recognition that not only the concentration of suspended particles but also particle size and site of deposition in the respiratory tract are important determinants of the risk of health effects.55 In the future, it should be recognized that the potential health effects of inhaled particles also depend on the inherent toxicity or biologic activity of the particles, whether fine or coarse. For example, not all particles can be expected to be as toxic as alpha-quartz, a substance known to be highly toxic to the pulmonary alveolar macrophage (PAM) and to be highly fibrogenic. Several groups have compared the ability of mineral dusts to kill cultured cells with their fibrogenicity in whole animals, to validate the ability of the in vitro cytotoxicity test to predict in vivo activity.22 23 51 Recently, Hill and Hobbs compared the toxicity of several types of coal-combustion fly ash with that of a positive reference standard, DQ12 quartz. They found that the fly ash had little or no toxicity to PAM cells at concentrations 

EXPOSURE ASSESSMENT 115 up to 500 µg/ml of culture medium, although the quartz caused a large leak of enzymes from the cells at a concentration of 250 µg/ml.22 Rats were then exposed by inhalation to the same two dusts, and the relative pulmonary toxicities of the dusts were evaluated by analysis of bronchoalveolar lavage (BAL) fluids. Although both dusts caused inflammation, as measured by neutrophil cell counts in BAL fluid, only the quartz increased the protein in BAL fluid, and the increase in enzymes in the fluid was much higher in the quartz-exposed than in the ash- exposed rats.23 Thus, in this study the in vivo test validated the use of the PAM toxicity assay as a predictor of in vivo toxicity. With the use of such end points as cell viability and release of enzymes, it can be suggested that the PAM cytotoxicity test can be used to rank the pulmonary toxicity of environmental dusts. Bioassays could play a very important role in prescreening a community in the design stages of an epidemiologic study. If incorporated into a study, bioassays might provide important clues for interpreting differences in responses (rates of illness or effects on pulmonary function) in the community. Short-term biologic tests to determine exposure to harmful chemicals have been used most successfully to determine exposure to mutagenic-carcinogenic agents in high-risk populations. An example from air pollution research is the recent study of urinary mutagenic activity in children residing near a Montana smelter.60 In contrast, with the notable exceptions of blood lead and carboxyhemoglobin measurements, there are no biologic methods for monitoring the extent of exposure of the general population to EPA criteria air pollutants. Such methods might be particularly difficult to develop for short-lived reactive pollutants that exert their effects in the lung. Biologic measures of oxidant exposure should therefore be sought in surrogate targets, such as red cells or serum proteins.34 When biochemical techniques have been developed much further, they might permit the precise measurement of biologically effective dose. However, measures of external exposure will still be important in determining relationships between environmentally monitored and internally absorbed concentrations of pollutants and will remain vital to epidemiology as long as such measures are the basis for regulation. 

EXPOSURE ASSESSMENT 116 To assist in the characterization of a pollutant sample with respect to predicting the dose received by tissues, information on the effect of its physical and chemical matrix can be obtained. The nature of this matrix affects the bioavailability of inhaled chemical pollutants. The potential health effects of inhaled benzo[a]pyrene, for example, might depend on whether it is inhaled as a pure compound (a rare occurrence), inhaled after adsorption on particles, or inhaled as a component of a droplet of a complex organic mixture. The formulation affects the retention time of organic compounds in the lung.49, 50, 51 and 52 Thus, knowledge of the amount of a specific type of chemical in the atmosphere is often no longer sufficient for predicting its health effects. As the ability to characterize pollutants improves, exposure assessment becomes an increasingly sophisticated tool for epidemiologic studies of air pollution. REFERENCES 1. Allen, P.W. Regional Air Pollution Study: An overview. Preprint No.#73-21. Proceedings of the 66th Annual Meeting of the Air Pollution Control Association. Pittsburgh, Pa.: Air Pollution Control Association, 1973. 2. Anderson, M.K., E.T. Brookman, R.J. Londergan, J.G. Watson, and P.J. Lioy. Receptor Model Technical Series: Source Apportionment Techniques and Considerations in Combining Their Use. Vol. 5. Publication No. EPA/450/4-84/020. Research Triangle Park, N.C.: U.S. Environmental Protection Agency, 1985. 191 pp. [Also available from the National Technical Information Service, Springfield, Va., as NTIS/PB85-111524.] 3. Annest, J.L., J.L. Pirkle, D. Makuc, J.W. Neese, D.D. Bayse, and M.G. Kovar. Chronological trend in blood lead between 1976 and 1980. N. Engl. J. Med. 308:1373-1377, 1983. 4. Beck, W.B., and G.K. Tannahill. An overview of the Houston area oxidant study. #78-30.1. Proceedings of the 71st Annual Meeting of the Air Pollution Control Association. Pittsburgh, Pa.: Air Pollution Control Association, 1978. 

EXPOSURE ASSESSMENT 117 5. Binder, R.E., C.A. Mitchell, H.R. Hosein, and A. Bouhuys. Importance of the indoor environment in air pollution exposure. Arch. Environ. Health 31:277-279, 1976. 6. Bross, I. Misclassification in 2 x 2 tables. Biometrics 10:478-486, 1954. 7. Cannon, J.A. Air quality effects of residential wood combustion. J. Air Pollut. Control Assoc. 34:895-897, 1984. 8. Cleveland, W.S., B. Kleiner, J.E. McRae, and J.L. Warner. Photochemical air pollution: Transport from the New York City area into Connecticut and Massachusetts. Science 191:179-181, 1976. 9. Cobourn, W.G., and R.B. Husar. Diurnal and seasonal patterns of particulate sulfur and sulfuric acid in St. Louis, Missouri, July 1977-June 1978. Atmos. Environ. 16:1441-1450, 1982. 10. Copeland, K.T., H. Checkoway, A.J. McMichael, and R.H. Holbrook. Bias due to misclassification in the estimation of relative risk. Am. J. Epidemiol. 105:488-495, 1977. 11. Countess, R.J., G.T. Wolff, and S.H. Cadle. The Denver winter aerosol: A comprehensive chemical characterization. J. Air Pollut. Control Assoc. 31:1194-1200, 1981. 12. Daisey, J.M. Organic compounds in urban aerosols. Ann. N.Y. Acad. Sci. 338:50-69, 1980. 13. Dattner, S., and P. Hopke, Eds. Receptor Models Applied to Contemporary Pollution Problems. Pittsburgh, Pa.: Air Pollution Control Association, 1983. 368 pp. 14. Davis, D.L., and S. Gusman. Exposure assessment: Introduction. Toxic Subst. J. 4:4-11, 1982. 15. Electric Power Research Institute. Electric Power Research Institute/Gas Research Institute Workshop on Personal and Portable Monitoring Equipment, December 5-8, 1984. Palo Alto, Cal.: Electric Power Research Institute. (in press) 

EXPOSURE ASSESSMENT 118 16. Frezieres, R.G., A.H. Coulson, R.M. Katz, R. Detels, S.C. Siegel, and G.S. Rachelefsky. Response of individuals with reactive airway disease to sulfates and other atmospheric pollutants. Ann. Allergy 48:156-165, 1982. 17. Friedlander, S.K. Chemical element balances and identification of air pollution sources. Environ. Sci. Technol. 7:235-240, 1973. 18. Gladen, B. and W.J. Rogan. Misclassification and the design of environmental studies. Am. J. Epidemiol. 109:607-616, 1979. 19. Hamilton, H.L., Jr., and S.N. Jones. Seminars/Workshop Proceedings: Persistent Elevated Pollution Episodes (PEPE), March 1979. Publication No. EPA-600/9-81-016. Research Triangle Park, N.C.: U.S. Environmental Protection Agency, 1979. 599 pp. 20. Harkov, R., B. Kebbekus, J.W. Bozzelli, P.J. Lioy, and J.M. Daisey. Comparisons of selected volatile organic compounds during the summer and winter at urban sites in New Jersey. Sci. Total Environ. 34:259-274, 1984. 21. Hidy, G.M., P.K. Mueller, D. Grogjean, B.R. Appel, and J. Wesolowski, Eds. The Character and Origins of Smog Aerosols: A Digest of Results from the California Aerosols Characterization Experiments. Vol. 10. Wiley-Interscience, 1980. 776 pp. 22. Hill, J.O., and C.H. Hobbs. Comparative cytotoxicity of DQ12-quartz and fly ash particles from coal combustion. Toxicol. Lett. 10:399-403, 1982. 23. Hobbs, C.H., R.L. Carpenter, D.E. Bice, J.L. Mauderly, J.A. Pickrell, S.A. Silbaugh, F.F. Hahn, R.F. Henderson, and R.K. Wolff. Comparative inhalation toxicity of fly ash from pulverized and fluidized bed combustion of coal, pp. 401-407. In M.B. Snipes, T.C. Marshall, and B.S. Martinez, Eds. Inhalation Toxicology Research Institute Annual Report, 1981-1982. Publication No. LMF-102, 1982. Albuquerque, N.M.: Inhalation Toxicology Research Institute. 

EXPOSURE ASSESSMENT 119 24. Holland, D., and D. Mage. Carbon Monoxide Concentrations in Four U.S. Cities During the Winter of 1981. Publ. No. EPA 600/59-83-025. Research Triangle Park, N.C.: U.S. Environmental Protection Agency, 1983. 75 pp. 25. Kleinman, M.T., B.S. Pasternack, M. Eisenbud, and T.J. Kneip. Identifying and estimating the relative importance of sources of airborne particulates. Environ. Sci. Technol. 14:62-65, 1980. 26. Kleinman, M.T., C. Tomczyk, B.P. Leaderer, and R.L. Tanner. Inorganic nitrogen compounds in New York City air. Ann. N.Y. Acad. Sci. 322:115-123, 1979. 27. Leaderer, B.P., D.M. Bernstein, J.M. Daisey, M.T. Kleinman, T.J. Kneip, E.O. Knutson, M. Lippmann, P.J. Lioy, K.A. Rahn, D. Sinclair, R.T. Tanner, and G.T. Wolff. Summary of the New York Summer Aerosol Study (NYSAS). J. Air Pollut. Control Assoc. 28:321-327, 1978. 28. Leaderer, B.P., R.T. Zagraniski, M. Berwick, and J.A.J. Stolwijk. Assessment of exposure to indoor air contaminants from combustion sources: Methodology and application. Am. J. Epidemiol., 1985. (in press) 29. Lioy, P.J. Ambient Measurements of Sulfate Species in the United States. Preprint #83-8.3. Proceedings of the 76th Annual Meeting of the Air Pollution Control Association. Pittsburgh, Pa.: Air Pollution Control Association, 1983. 30. Lioy, P.J., and J.M. Daisey, with T. Atherholt, J. Bozzelli, F. Darack, R. Fisher, A. Greenberg, R. Harkov, B. Kebbekus, T.J. Kneip, J. Louis, G. McGarrity, L. McGeorge,and N.M. Reiss. The New Jersey Project on Airborne Toxic Elements and Organic Substances (ATEOS): A summary of the 1981 summer and 1982 winter studies. J. Air Pollut. Control Assoc. 33:649-657, 1983. 31. Lioy, P.J., and M.J. Lioy, Eds. Air Sampling Instruments for Evaluation of Atmospheric Contaminants. 6th ed. Cincinnati, Oh.: American Conference of Governmental and Industrial Hygienists, 1983. 600 pp. 

EXPOSURE ASSESSMENT 120 32. Lippmann, M., P.J. Lioy, G. Liekauf, K.B. Green, D. Baxter, M. Morandi, B. Pasternak, D. Fife, and F.E. Speizer. Effects of ozone on the pulmonary function of children, pp. 423-446. In M.A. Melman, S.D. Lee, and M.G. Mustafa, Eds. Advances in Modern Environmental Toxicology. Vol. V. Princeton, N.J.: Princeton Scientific Publishers, 1983. 33. McMillin, C.R., L.B. Mote, and D.G. DeAngelis. Potential Atmospheric Carcinogens: Phase I. Identification and Classification. Publication No. EPA 600/2-80-015. Research Triangle Park, N.C.: U.S. Environmental Protection Agency, 1980. 255 pp. 34. Morgan, D.L., A.F. Dorsey, and D.B. Menzel. Erythrocytes from ozone-exposed mice exhibit decreased deformability. Fund. Appl. Toxicol. 5:137-143, 1985. 35. Mueller, P.K., and G.M. Hidy. The Sulfate Regional Experiment: Report of Findings. Vols. 1-3. EPRI Publ. No. EA-1901. Palo Alto, Cal.: Electric Power Research Institute, 1983. 36. National Council on Radiation Protection and Measurements. Exposures from the Uranium Series with Emphasis on Radon and Its Daughters. NCRP Report No. 77. Bethesda, Md.: National Council on Radiation Protection and Measurements, 1984. 37. National Research Council, Committee on Indoor Pollutants. Indoor Pollutants, pp. 307-322. Washington, D.C.: National Academy Press, 1981. 38. National Research Council, Committee on Indoor Pollutants. Indoor Pollutants. Washington, D.C.: National Academy Press, 1981. 537 pp. 39. National Research Council, Committee on Medical and Biologic Effects of Environmental Pollutants. Ozone and Other Photochemical Oxidants. Washington, D.C.: National Academy of Sciences, 1977. 719 pp. 

EXPOSURE ASSESSMENT 121 40. National Research Council, Committee on Vapor-Phase Organics from Diesels. Vapor-Phase Organic Pollutants: Volatile Hydrocarbons and Oxidation Products. Washington, D.C.: National Academy Press, 1976. 411 pp. 31. Quackenboss, J.J., M.S. Kanarek, J.D. Spengler, and R. Letz. Personal monitoring for nitrogen dioxide exposure: Methodological considerations for a community study. Environ. Int. 8:249-258, 1982. 42. Singh, H.B., L.J. Salas, A.J. Smith, and H. Shigeishi. Measurements of some potentially hazardous organic chemicals in urban environments. Atmos. Environ. 15:601-612, 1981. 43. Smith, K.R., A.L. Aggarwal, and R.M. Dave. Air pollution and rural biomass fuels in developing countries: A pilot village study in India and implications for research and policy. Atmos. Environ. 17:2343-2361, 1983. 44. Spengler, J.D., D.W. Dockery, W.A. Turner, J.M. Wolfson, and B.G. Ferris, Jr. Long-term measurements of respirable sulfates and particles inside and outside homes. Atmos. Environ. 15:23-30, 1981. 45. Spengler, J.D., and M.L. Soczek. Evidence for improved ambient air quality and the need for personal exposure research. Environ. Sci. Technol. 18:268A-280A, 1984. 46. Spengler, J.D., and G.D. Thurston. Mass and elemental composition of fine and coarse particles in six U.S. cities. J. Air Pollut. Control Assoc. 33:1162-1171, 1983. 47. Spengler, J.D., and T.D. Tosteson. Personal Exposure to Respirable Particles. Presented at Environmetries ‘81, Conference of the Society for Industrial and Applied Mathematics, Alexandria, Va. April 8-10, 1981. 48. Stevens, R.K. and T.G. Pace. Overview of the Mathematical and Empirical Receptor Models Workshop (Quail Roost-II). Atmos. Environ. 18:1499-1506, 1984. 

EXPOSURE ASSESSMENT 122 49. Sun, J.D. and R.O. McClellan. Respiratory tract clearance of 14C-labeled diesel exhaust compounds associated with diesel particles or as a particle-free extract. Fund. Appl. Toxicol. 4:388-393, 1984. 50. Sun, J.D., R.K. Wolff, H.M. Aberman, and R.O. McClellan. Inhalation of 1-nitropyrene associated with ultrafine insoluble particles or as a pure aerosol: A comparison of deposition and biological fate. Toxicol. Appl. Pharmacol. 69:185-198, 1983. 51. Sun, J.D., R.K. Wolff, G.M. Kanapilly, and R.O. McClellan. Effect of particle association on the biological fate of inhaled organic pollutants, pp. 1137-1151. In M.W. Cooke and A.J. Dennis, Eds. Polynuclear Aromatic Hydrocarbons. Vol. 7. Columbus, Oh.: Battelle Press, 1982. 52. Sun, J.D., R.K. Wolff, G.M. Kanapilly, and R.O. McClellan. Lung retention and metabolic fate of inhaled benzo(a)pyrene associated with diesel exhaust particles. Toxicol. Appl. Pharmacol. 73:48-59, 1984. 53. Tanner, R.L., R. Garber, W. Marlow, B.P. Leaderer, B.P., and M.A. Leyko. Chemical composition of sulfate as a function of particle size in New York summer aerosol. Ann. N.Y. Acad. Sci. 322:99-113, 1979. 54. Tosteson, T., J.D. Spengler, and R.A. Weker. Aluminum, iron, and lead content of respirable particulate samples from a personal monitoring study. Environ. Int. 2:265-268, 1982. 55. U.S. Federal Register. Proposed Revisions to the National Ambient Air Quality Standard for Particulate Matter. March 20, 1984. Vol. 49, No.5, pp. FR 10408-10462. 56. U.S. National Institute of Environmental Health Sciences. Biochemical and cellular markers of chemical exposure and preclinical indicators of disease. In Human Health and the Environment: Some Research Needs. Research Triangle Park, N.C.: U.S. National Institute of Environmental Health Sciences, 1985. (in press) 

EXPOSURE ASSESSMENT 123 57. U.S. Public Health Service. Symposium: Environmental Measurements: Valid Data and Logical Interpretation, pp. 109-110. Public Health Service Publ. No. 999-AP-15. Washington, D.C.: U.S. Department of Health, Education, and Welfare, Public Health Service, 1964. 58. Utell, M.J., P.E. Morrow, and R.W. Hyde. Airway reactivity to sulfate acid aerosols in normal and asthmatic subjects. J. Air Pollut. Control Assoc. 34:931-935, 1984. 59. Wallace, L.A., E.D. Pellizzari, T.D. Hartwell, C. Sparacino, and H. Zelon. Personal exposure of volatile organics and other compounds indoors and outdoors: The TEAM Study. Preprint #83-9.12. Proceedings of the 76th Annual Meeting of the Air Pollution Control Association. Pittsburgh, Pa.: Air Pollution Control Association, 1983. 60. Warren, G.R., and S.J. Rodgers. Urine mutagen screening as a population monitoring technique: Children in an isolated, high lung cancer mortality area, pp. 39-48. In B.A. Bridges and B.E. Butterworth, Eds. Indicators of Genotoxic Exposure. Banbury 13. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratories, 1982. 61. Watson, J.G. Chemical Element Balance Receptor Model Methodology for Assessing the Source of Fine and Total Suspended Particulate Matter in Portland, Oregon. Ph.D. Dissertation, Oregon Graduate Center, February 1979. 525 pp. 62. Wilson, R., J.D. Spengler, S. Colome, and D. Wilson. Health Effects of Fossil Fuel Burning: Assessment and Mitigation. New York: Ballinger Publishing Co., 1980. 416 pp. 63. Wolff, G.T., and P.J. Lioy. Development of an ozone river associated with synoptic scale episodes in the eastern United States. Environ. Sci. Technol. 14:1257-1261, 1980. 

EXPOSURE ASSESSMENT 124 64. Zeidberg, L.P., J.J. Schuenem, R.A. Prendle, and P.A. Humphrey. Air pollution and health: General description of a study in Nashville, Tennessee. J. Air Pollut. Control. Assoc. 11:289-297, 1961. 65. Ziskind, R.A., K. Fite, and D.T. Mage. Pilot field study: Carbon monoxide exposure monitoring in the general population. Environ. Int. 8:283-293, 1982. 

125 Chapter 4 Concepts and Strategies in Planning Epidemiologic Studies on Air Pollution 

126