Unconfirmed Minutes of the Meeting of the Medical Research Froup of the CRC-Air Pollution Research Advisory Committee, Held in Des Plaines, Illinois on 4/6/77

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COORDINATING RESEARCH COUNCIL THIRTY ROC XE FELLER PLAZA of the Meeting of t h e MEDICAL RESEARCH GROUP CRC-Air Pollution Research Advisory Committee Appendix A - Viewgraphs and supplementary material t o which Dr. Hackney referred during his presentation (Copy attached) Appendix B - List of material brought back from Germany by the team who visited with Dr. von Nieding and his colleagues (Appendices continued on next page)

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(Copies distributed at the meeting and copy attached) Appendix E - Data sheets on Medical College of Wisconsin work (Copies distributed at the meeting and copy attached) Appendix F - Reprint of letters from the May 5 , 1975, issue of Appendix G - Listing of the CY 1978 CRC-APRAC budget proposal along with descriptions of supplementary medical

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Coordinating Research Council ,Inc. Federal Energy Administration Coordinating Research Council, Inc. University of Washington American Petroleum Institute Rancho Los Amigos Hospital Shell Oil Company General Motors Research Laboratories Electric Power Research Institute Coordinating Research Council ,Inc. Energy Research and Development Administration Environment a1 Protection Agency Ford Motor Company Gulf Science and Technology Company Motor Vehicle Manufacturers Association General Motors Corporation 1 Representing J. H. Knelson, EPA Liaison Representative Motion: Dr. Klimisch moved adoption ofthe minutes of the next preceding meeting (November 30-December 1, 1976) inthe form circulated and approved by Page 9 , Paragraph 3 , Lines 2-12 should read : " ...did not think it was important t o work with both relative humid i ties if soluble gases were notto be combined with the aerosol. The particles of concern were probably in or near equilibrium with the much higher relative humidity of the upper airways before reaching the larynx ...as relative humidity increased,was modest until about 95% relative humidity; above the latter level there was a significant increase in the magnitude of growth at equilibrium. The time required for growth was probably long only for larger particles,i.e., over one micrometer in diameter. During Page 1 3 , Paragraph 4 , Line 1: Change "BEEP" t o "National Research Council Medical, Biological and Environmental Effects of Pollutants (BEEP) Study ..."

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The motion was seconded by Dr. Runion and carried without dissenting vote. The Chairman announced that Dr. Spence had submitted his resignation as a member of the Medical Research Group. A replacement for him was actively being MCHO LOS AMIGOS HOSPITAL PROGRZSS REPORT Dr. Hackney ,principal investigator at Rancho Los Amigos Hospital, reviewed that the primary objective of the CAPM-20 study was t o screen selected sulfate and nitrate compounds in aerosol form for their acute effects prior to acute human exposures under Project CAPM-27. Groups of five squirrel monkeys were exposed one ata time for two hours toa pure aerosol compound like (NH4)2SO4 which had a poly disperse size distribution simulating the ambient sulfate aerosols. Studies had been completed with (NH4)zSOq and ZnSOq(NH4)2S04 a t 40 and 85% R.H. a t tion rate and heart rate were the physiological measurements made before,during, and after the exposure t o determine effects. Those results were described in the Final Report for Year 1 which had been distributed previously. With regard to the most recent results,five squirrel monkeys had been exposed during the past two data were not yet analyzed, no dramatic effects due to the aerosol were evident. Dr. Hackney explained that the objective of the CAPM-27 Project was t o acute effects of selected sulfate aerosols upon human cardiopulmonary Groups of normal, sensitive and asthmatic subjects were exposed for two day on two to four successive days to simulate a worst case smog episode. function tests and symptoms were recorded before and after each exposure determine the acute effects. Six asthmatics had recently been exposed t o approximately 200 ug/m’, 0.5 ~ mass median diameter, ammonium sulfate aerosol at 40% relative humidity. The proto - col included one clean - air control day followed by two successive exposure days. Some of the subjects had baseline pulmonary function consistent with chronic obstruct ive lung disease as well as asthma. Many respiratory symptoms were reported during the chamber exposures,butin no case were they obviously worse inthe aeroSol exposures than i n clean air. Group pulmonary function data(for flow-volume, single - breath nitrogen, and respiratory resistance measures) had been analyzed by two-way analysis of variance with repeated measures. No significant group mean function changes were found except for delta nitrogen, which showed a marginally

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three days relative to pre-exposure measurements averaged overall three days. There was no evidence that the change pre- t o post-exposure was significantly different between clean - air and aerosol days (i.e.,there was no sign if i cart interaction between test day and test time). Normally delta nitrogen is expected to increase with pollutant exposure i f adverse effects occur. Overall, no convinci ng evidence of adverse aerosol effects had been found. ERT had completed the calibration of the aerosol characterization system interfaced with RLA's PDP 11/10 computer by using NH4HSO4 aerosol. planning to train RLA personnel in the operation of the computerized data acquis it ion system during April 5-8. During the week of April 11-15, theRIA staff would practice generation of NH4HS04 aerosol and practice using the computerized aerosol data acquisition system during simulated NH4HSO4 exposure runs.Practice and coordination were required for collection and analyzing alternately pulmonary function and aerosol data on-line during exposure runs. After RLA had familiar - ized themselves with the complete system and could demonstrate that it would deliver 85 pc3/m3 of NHqHS04at 40% R.H. and 88'F, they would be ready t o expose the first group of normal human subjects. Dr. Hackney referred to the first of a series of viewgjaphs, copies of which become Appendix A of these minutes, and explained that as part of a contin u ing effort to validate methods convincingly, six members of the RLA staff in - haled 10 breaths of histamine diphosphate aerosol (16 mg/ml buffered to pH 7)to compare change in oscillator yR with change i n body box R. I t looked good. The oscillator yR was completely automated--the body box partially automated. They planned to repeat that after full automation of the body box was achieved. Whether the monkeys would have that kind of correlation was still to be shown, and they would continue t o work on it by comparing oscillator yR toR measured with an Dr. Hackney noted that the overall purpose of the CAPM-21 contract was t o look for possible adverse health effects of ambient photochemical oxidants. The strategy was to relate dose response information for low concentrations of ozone i n clean air with similar ozone concentrations in ambient air.He referred to another viewgraph which presented dose response of ozone and changes in FE Vl with changes i n mechanical function which correlated rather well with symptoms. The numbers represented numbers of subjects. There were obvious questions with regard to the function of ozone i n clean air and more importantly ozone i n amThe first year of the CAPM-21 study was intended as a preliminary invest i - g ation relevant to the question, can acute adverse effects be shown i n people exercising in typical ambient photochemical air pollution ? A total of 2 4 male volunteers, normals and coronary artery disease patients,were studied before and after moderate outdoor exercise in photochemically polluted air in Downey, California. Indoor exercise in an air - conditioned environment and outdoor exercise on days with relatively good air quality provided control studies. Addit ional control studies were performed in a controlled environment chamber for selected subjects (seven normals and eight cardiac s). Health effects measures included pulmonary function,electrocardiograph ic indices, blood biochemical i n - dices considered to be sensitive to oxidant insult, and symptoms reported in a standardized interview. The final report of the first year was almost complete. Ozone and particulate pollutants(including relatively large amounts of sulphates,nitrates, and benzene soluble organics) were the major contributors

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to the pollutant exposures. Effects of oxides of nitrogen and carbon monoxide were not investigated extensively since measured arrbient concentrations were low i n comparison to concentrations causing health effects in laboratory studies. Statistical analyses of results were performed for the normal subject group, for the coronary disease group, and for each individual in the case of pulmonary function tests, for which repeated measures were available under each environmenstatistical results : (1) Effects(significant changes) rel a table to pollutant exposure could also be due to other stresses - - heat,exercise, or psychological factors--which were not controllable independent of pollutant concentrations ; (2) For individuals,small but significant lung function variations overtime are common even inthe absence of obvious environmental stresses; (3)Real but sig - n if i cant ly small effects would likely be missed inthe group statistical analyses, since sample sizes were small and environmental variation contributed to the resi dual error. pollutant - rel a table effects, except for red - cell lactate dehydrogenase (LDH) activity. The LDH tended to decrease during outdoor exercise on clean days,but to increase on polluted days. The changes were smaller than the normal inter - individual range of values for this index. The health significance of this find - ing is not clear. The individual data revealed no obvious pollutant - rel a table effects exce tin the normal subject receiving the most severe exposure (0.31 ppm 03, 370 vg/m' total particulate, 2-hour averages) .He experienced respiratory symptoms and slight function changes. Two additional coronary disease subjects showed possible effects in slightly less severe exposures--excessive fatigue without obvious physiological changes. The following cautions must be observed when interpreting the Within these limitations,the groug statistics showed no obvious They concluded tentatively for that population of Los M ge les residents, effects of ambient exposure t o photochemical oxidant were similar to what would be expected with exposure to03in purified air in laboratory studies,i.e., no evidence was found t o suggest that coexisting ambient pollutants markedly increase the toxicity of ozone. To test the effects of ambient photochemical pollution exposure more rigorously, it would be necessary t o provide more closely matched control experiments ( " blind " exposure conditions, temperature and humidity closely comparable in clean and polluted - air exposures), and possibly to perform exposure s in areas with more extreme photochemical oxidant levels. Also subjects with obstructive airways disease were still to be studied and, with the recent report of von Nieding and associates,a question arose about whether other endpoints, more sensitive than they were using, should also be For flow-volume measures such as FEVl and symptoms, as it turned out,there was little or no controversy--even with the German results.But,the other quest ions raised by the German work remained so that a site visit seemed appropriate. The site visit team consisted of : Dr. Robert Frank, University of Washington; Dr.Peter Mueller, Environmental Research and Technology, and Dr. Jack Hackney, Rancho Director of the American Petroleum Institute, who wasin Europe attending a UN conference, came along as an observer. Dr. Hackney projected a map of Germany showing the area surrounding Moers. H e mentioned that the site visit team had met with Drs. von Nieding and Waqner. The visit had been prompted by the final report on "Studies of the Combined Effects of N02, S 0 2 , and 0 3 on Human Lung Function" by von Nieding and Wagner.

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NOTE : Dr. Hackney projected the first page of that report and copy is included as Page 4 of Appendix A. That report along with other material that had been brought back by the site visit team was put on display at the meeting and those present were asked to sign up i f they wished to receive copies.A complete list of the material is attached as Appendix B of D r - Hackney next projected copy of the fifth page of the translation of that report (Page 5of Appendix A). The next viewgraph presented data from their control studies. The results correspond with pre-exposure, one hour and two hour exposures , and post-exposure levels. Their claim was that arterial oxidant dropped significantly with exposure and then recovered for5 ppm NO2 exposures; the same was true with ozone exposures, and similar with a combination of the two.In addition they reported finding changes i n airway resistance as shown on the seventh Dr. Hackney explained that the primary purpose of the visit was to better understand the recently reported work from that group, "Studies of the combined Effects of NO2 ,S02, and 03 on Human Lung Function." It was felt that a thorough understanding of the work could sharpen interpretation of reported results and optimize planning for future experimental studies. The site visit team gathered further details about air monitoring, air purification,physiological monitoring, and subject characterization, and also attempted to identify any other factor that might confound interpretation of the health - effects study data. The overall impression was that these investigators were serious and highly motivated. Their resources were limited, and were insufficient to deal with several important problems relevant to the conduct and interpretation of their work. They observed physiological changes during pollutant exposure (relative to control),but the interpretation of these changes as a significant adverse health effect of individual well - specified pollutants such as ozone alone,orin cornbination with NO2 o r SO2 is unlikely to be correct and cannot be accepted unless confirmed by further work under more highly controlled conditions. Dr. Hackney projected a summary of Dr. Mueller's report on the visit, and copy becomes Page 8 of Appendix A. H e added that atleast for ozone there was no indication of any serious discrepancy between those investigators ' monitoring techniques and those being used by RLA/ERT. A major weakness was inthe absence of monitoring for gaseous and particulate pollutants other than the test gases which, if present, would complicate interpretation of the health effects. In discussing the air purification system, Dr. Hackney projected a diagram of the chamber used by the German investigators.He explained that topic was also covered more comprehensively inDr.Mueller ' s report, copy of which i s Appendix C of these minutes. He explained that the air purification equipment for the chamber consisted of coarse glass fiber filters and a water scrubber containing ceramic rings in a water bath through which air flowed. No catalytic converter, chemical used. While the available air - purification equipment probably scrubbed the test gases from ambient air, it could not have removed hydrocarbons, carbon monoxide, or small particles efficiently. Furthermore ,the water scrubber itself may have been a source of small particles under some operating conditions,since deposits appeared t o form inside it. The air flow rate through the chamber was said to be sufficient to provide about one change of air per2 minutes and t o provide buildup ofa chosen pollutant concentration within 5-10 minutes. Dr. Hackney then reviewed Dr.Mueller ' s comments on the inhalation chamber a s shown on Page 9of Appendix A .