Information for Approval of Proposal, Subject: Aerosol Deposition in Human Lungs from Energy Sources and Urban Pollution

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2-3262 R. W. Perkins Radiological SciencesL, A. Ran cite lli NAME OF PROCURING BUREAU I Aerosol Deposition in Human Lungs from Engrgy Sources and Urban Pollution FOR LEGAL AND SPONSOR RELATIONS AEC NOTICE FILED N P E OF CONTRACT TERMS OF PAVMENT SCOPE FILED * 0 GOVT CR4NT 0 SJANDRRO GOVT.

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RICHLAND OPERATIONS OF Fl CE Annual Reports & Open Literature 5. METHOD OF REPORTING Aerosol Deposition in Human Lungs from Energy Sources and 9. MAN YEARS: (DIRECTLY ASSIGNED) 10. FUNDING (DOLLARS IN THOUSANDS) TOTAL OPERATING COSTS CAPITAL EQUIPMENT NOT RELATED

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U.S. ENERGY RESEARCH AND DEVELOPMENT ADMINISTRATION Ad, ONAL JUSTIFICATION FOR OPERATING COST RICHLAND OPERATIONS OFFICE Human Lungs from Energy Sources and 14, Purpose, Need and Scope: In order to realistically assess the potential pollution hazards. from the inhalation of aerosols arising from the production of energy, from transportation, from industry, etc., it is essential to know in both a general and specific way the relationship or "equilibrium" between the deposition, accumulation and concentrations of aerosol residues at various anatomical sites within the human pulmonary system and the aerosol concentrations breathed by human beings under normal living conditions. This proposal aims to provide comprehensive fundamental and baseline infornation on the interaction of an urban population with the ambient air which it breathes that can be used for predicting lung concentrations under specific conditions of interest for evaluation of the impact on a metropolitan population. seen tremendous progress in our knowledge of pulmonary physiology and the toxicological aspects of aerosols and their fate in lungs. This voluminous literature covers exposure in specific industries, and deposition and clearance of specific materials such as beryllium and plutonium, This information has resulted in lung models from which predictions can be made for various situations, Most of the work which has led.to this knowledge has been done with animal experiments. Information on humans is seriously limited and mainly involves acute accident exposures, chronic occupational exposures usually to only one pollutant, and a few human subject experiments using radioactive aerosols. The extensive analysis of human tissues by Tipton and Cook(1) and Tipton et al(2) are simply not sufficiently well documented, nor are most of the measurements of sufficient sensitivity to be useful in a critcal analysis of human exposure to pollutant aerosols. of this present proposal are to obtain specific information on human population exposures and the retention under normal living The past two decades have The proposed study includes carefully characterizing the chemical and physical properties of the atmospheric aerosol within the City of St. Louis and the measurement of aerosol residues in selected tissues from subjects from this region who have been otherwise healthy, but have been the victims of accidental death. The number of sudden deaths in the St. Louis metropolitan area is large enough to draw a suitable sampling of the population. program includes the accumulation of a sample bank containing tissues and aerosol samples collected during approximately a oneyear period. Aerosol sampling will be conducted at representative locations within the City of St. Louis. The specialized analytica and sulfate which are known to be toxic under some conditions, together with some 30 other elements from natural and anthropogeni sources. On the basis of the analytical data from aerosol and

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RICH LA HO OPERATIONS OFFICE Human Lungs from Energy Sources and tissue measurements together with medical and occupational histories, we propose to construct an empirical model relating aerosol composition to accumulation in various -groups (male and - female; young, young adult, old, smokers, non-smokers) of individuals which reside within the urban pollution plume, This model will provide both the basic essential information on which to establish realistic air pollution control stanzards and neasurements and also the essential "exposure term" f r o m which "biological effects studies" of the various pollutants, deposited throughout the respiratory system and,other organisms of the body, can be The detailed discussion of the proposal describing the needs, objectives and research plan is included in Section 20. 15. Relationship to Other Projects: Characterization of the atmospheric aerosol in St. Louis is being conducted under both the ERDA-sponsored METROMEX and EPA-sponsored RAPS. Activation analysis and X-ray fluorescence techniques which have been developed and are conti uously being improved under ERDA out this study. Within the Biology Department of PNL a large Inhalation Toxicology program is being conducted, Technical support and consultation will be obtained from specialists in this field and the infomation generated in this program should be of substantial benefit to their ongoing studies. support will provide the primary 3orking technology for carrying 16, Technical Progress in FY 1975: New program. 17 , Expected Results in FY 1976: The primary objective during the first year of this study will be to establish a preliminary relationship between aerosol concentrations and accumulation within the human pulmonary system, We plan to carry out t h e autopsy tissue sampling effort and an atmospheric sampling project within the St. Louis metropolitan area which should provide most of the necessary bank of samples for the program. This program will require that we carry out some specialized aerosol sampling within the St. Louis metropolitan area together with our acquisition of properly selected autopsy samples, The overall proqram will t h u s include the analysis of physical and- - chemical properties of aerosols from representative areas of the

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U.S.ENERGY RESEARCH AND DEVELOPMENT ADMINISTRATION AD: 5NAL JUSTIFICATION FOR OPERATING COST SICHLAND OPERATIONS OFFICE PROJECT TITLE Aerosol Deposition in . Human Lungs from Energy Sources and Atmospheric Sampling Program We plan to collect samples from 10 stations located throughout the city using the 6-stage Andersen cascade impactors which have backup filters for collection of the very small particles. We plan to sample continuously for 1-month periods throughout the year and this should provide us with over 800 samples. all of these filters by our relatively inexpensive X-ray fluorescence techniques which provide concentrations of about 15 fractions on a quarterly basis for activation analysis. provide concentrations of sulfate and approximately 4 0 trace elements including those which are considered to be the greatest potential hazards in lung deposition (the more toxic trace elements We also plan to carry out special sampling at each of the 10 sampling sites to define aerosol composition changes as a function of time during the day. cade impactors which permit sampling of various particle size separates on a continuously moving drum. Analyses of a few of these samples as a function of time during the day will be made during the first year, but it is anticipated that the majority will be analyzed during the second and third years of the program. We will plan to analyze We will composite aliquots of the various particle size This sampling will be done with Lundgren cascorrelation of exposure with deposition at various-locations within the pulmonary system and other organs of the body. Many of the sampling sites required for this study are already in operation and our analyses of aerosol samples from St. Louis have provided us with the general chemical composition of the urban aerosols. We anticipate that during the first full year of operation we will be able to collect most of the necessary tissue samples and the aerosol samples from which characterization studies during the first year and subsequent years will meet the overall objectives of the program. ICollection and Analysis of Human Autopsy Samples Within the St. Louis metropolitan area there are approximately 2000 accidental death cases per year in which autopsies are performed by the City and County Medical Examiners. We will make arrangements with the responsible pathologists to obtain tissue samples fron a representative group of these cases. The tissue samples, which we feel are essential to this study, include the alveolar parenchyma, sections of the bronchi and trachea, the pleura, thoracic lymph nodes, the kidney and liver. sampled to obtain information indicative of recent oral trace Heart blood will also be

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.ON AL JUSTIFICATION FOR OPERATING COST RICHLAND OPERATIONS OFFICE PROJECT TITLE Aerosol Deposition in Human Lungs from Energy Sources element ingestion through foods. from four groups which include: We plan to collect tissue samples Only tissue samples from the non-smoking female group will be analyzed during the first year, while the other samples will serve to form a tissue bank for studies during the second and third years We anticipate the tissue collection and analytical program will be conducted as follows. Several pathologists who are required to take autopsy samples will collect samples from the appropriate classes of subjects as they become available, Medical and occupational history on each subject will be obtained as outlined in Section 20. If these histories appear adequate for our needs, the samples will be analyzed at our laboratory for trace element content. Only samples from the nonsmoking female group will be analyzed during the first year so that a sufficient number of measurements from one group will be availabl for a reasonable statistical analysis. Samples from the other groups will be stored for analysis in the second and third years. The pathologist conducting the autopsy will also be required to identify the condition of the tissues to determine if there is any indication of disease or other abnormalities. For subsequent correlation analysis and modeling, the subjects will be considered in three age groups: 0 The young (less than 12 years old) 0 Young adults (12 to 25) 0 Mature adults (greater than 25). We plan to obtain approximately 20 cases from each of these age groups. From these 60 individuals in the non-smoking female class, we would secure approximately 500 tissue samples. These samples will be analyzed by neutron activation and X-ray fluorescence techniques for some 30-40 elements which are measured in the aerosol size fractions being studied in the atmosphere. Correlation Analvsis and Modelins Our principal objective of the program is to determine relationships between the atmospheric aerosol and deposition of the trace element pollutants throughout the respiratory system and in other critical organs of the body. The correlation analysis will- -

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RICHLAND OPERATIONS OFFICE PROJECT TITLE Aerosol Deposition i n Human Lungs from Energy Sources an .e s tabl ish the extent of these relationships and also determine what factors are responsible for these relationships. It i s anticipated that from the information gathered during the first - year of the study-, it will be possible to construct a tentative model relating the aerosol composition tothe " equilibrium concent rations " inthe brgans of this group of individuals,the non18. Expected Results for FY 1977 and Beyond: During these two years of the program it should be possible to com plete any additional sampling of autopsy tissue samples and t o complete any air sampling required to provide us with the12 contin u o us months of aerosol collections. It is planned that the collection of autopsy tissue samples will be conducted until we have the 60 cases from each of the following four classes of Tissue samples from the appropriate age classes of each of these groups must be available to permit a good statistical analysis of variations between age classes and within the groups. Once this necessary bank of tissue samples has been collected,the program will deal entirely with the analytical effort of trace element analyses and the correlations of the resulting data in the construct ion of a m & e l which relates atmospheric pollutant concent rations to body deposition. The specific effort in each of the work categories necessary t o accomplish the study is outlined Atmospheric Sampling Program It is essential that atmospheric sampling be conducted for12 contin u o us months so that seasonal variations in pollutant concentrat ions can be considered as they may affect deposition within,the various organs of the body. It i s also important that we develop information describing the diurnal variations. The sampling program will therefore be carried into the second year of the program for a long enough period to collect samples from which these data can b e obtained. Their analysis will be continued so that the total chemical composition of the atmospheric aerosol and the composition as a function of particle size can be clearly defined. This information should also permit us to describe the variations

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A & IONAL JUSTIFICATION FOR OPERATING COS 3 RICHLAND OPERATIONS OFFICE Aerosol Deposition inP RO J ECT TITLE Human Lungs from Energy Sources and in air concentration within the metropolitan area which may be expected, since it is recognized that surface pollutants on aerosol particles may be dissolved in the respiratory system and . thus be available for transfer to other body organs even though the particles may be removed by ciliary action or transposed via the lymphatic system. It is important to establish the solubility of the pollutant elements from the particle size fractions. Surface pollutants may also be removed in the gastro-intestinal tract. We will therefore plan to carry out studies in which various particle size fractions of the aerosols are subjected to dissolution studies with water, simulated lung fluids, and dilute hydrochloric acid. This should provide an estimate as to the rates of removal of surface deposited pollutants on aerosol particles, and thus the extent of their removal from particles in the pulmonary system or in the GI tract. Collection and Analysis of Human Autopsy Samples If we are not able during the first year to complete the necessary collection of human autopsy tissue samples, this will continue into the second year. Once the necessary samples for the tissue bank have been achieved, the sample collection will be discontinuec and our full efforts directed toward their analysis. The analytic; program will continue to be conducted as outlined in our work for the first year. Mainly, we will measure a spectrum of some 30-40 trace elements which are being analyzed from the atmospheric aerosols. These will be measured in the alveolar parenchyma, bronchi and trachea, liver, lymph nodes, kidney, heart blood from the right ventricle and psoas muscle tissue. These samples will be analyzed under our standard "clean-room" conditions which have been demonstrated to permit analysis without any significant conCorrelation Analysis and Modeling During the second and third years of this program the correlation analysis and modeling will be emphasized. The aerosol analyses will have provided us with the chemical composition as a function of particle size, and thus the chemical mass associated with each particle size range. Studies of these particles will also pro- ' vide us with information on the leaching rates of these materials by water and body fluids. These factors, which deal with the nature of exposure material, will be correlated in the model in a manner so as to describe what fraction of each element the pulmonary system actually receives and where in the pulmonary system the material is accumulated. Concentrations in the lymph nodes, the kidney and the liver should provide information on the rates of transfer of these materials from their initial deposition sites, Information on the origin of the aerosol particles, themselves, can be obtained by correlation analyses …